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Clinical Trial Results:
A Phase 3, Randomised, Multicenter, Open-Label, Crossover Study Assessing Subject Perception of Treatment Burden With Use of Weekly Growth Hormone (Somatrogon) Versus Daily Growth Hormone (Genotropin) Injections in Children With Growth Hormone Deficiency

Summary
EudraCT number	2018-000918-38
Trial protocol	GB SK CZ BG
Global end of trial date	28 Aug 2020

Results information
Results version number	v1(current)
This version publication date	04 Mar 2021
First version publication date	04 Mar 2021
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

C0311002

ISRCTN number

US NCT number

NCT03831880

WHO universal trial number (UTN)

Sponsor organisation name

Pfizer Inc.

Sponsor organisation address

235 E 42nd Street, New York, United States, NY 10017

Public contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Scientific contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

17 Dec 2020

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

28 Aug 2020

Was the trial ended prematurely?

Main objective of the trial

To evaluate the treatment burden of a weekly Somatrogon injection schedule and a daily Genotropin injection schedule.

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

07 Feb 2019

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Bulgaria: 10

Country: Number of subjects enrolled

Czechia: 16

Country: Number of subjects enrolled

Slovakia: 5

Country: Number of subjects enrolled

United Kingdom: 4

Country: Number of subjects enrolled

United States: 52

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

A total of 107 subjects were enrolled and 87 subjects aged 3 to less than (<) 18 years, with growth hormone deficiency (GHD) who were stable on treatment with daily Genotropin were randomised in this study.

Period 1 title

Baseline Period

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Daily Genotropin Then Weekly Somatrogon

Arm description

Subjects were randomised to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects received Somatrogon, weekly subcutaneously at a dose of 0.66 milligram per kilogram per week (mg/kg/week) for 12 weeks. Subjects were followed up maximum for 35 days (5 weeks) after last dose of study drug.

Arm type

Experimental

Investigational medicinal product name

Genotropin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects received Genotropin, daily subcutaneous at the same dose as their daily hGH which they were receiving at the time of enrollment.

Weekly Somatrogon Then Daily Genotropin

Arm description

Subjects were randomised to receive Somatrogon, weekly subcutaneously at a dose of 0.66 mg/kg/week, for 12 weeks in Period 1. Period 1 was followed by Period 2, where subjects continued to receive Genotropin, daily subcutaneously at the same dose which they were receiving at the time of enrollment, for 12 weeks. Subjects were followed up maximum for 35 days after last dose of study drug.

Arm type

Experimental

Investigational medicinal product name

Somatrogon

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects received Somatrogon, weekly subcutaneously at a dose of 0.66 mg/kg/week.

Number of subjects in period 1	Daily Genotropin Then Weekly Somatrogon	Weekly Somatrogon Then Daily Genotropin
Started	43	44
Completed	43	44

Period 2 title

Period 1 (12 Weeks)

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Daily Genotropin Then Weekly Somatrogon

Arm description

Arm type

Experimental

Investigational medicinal product name

Genotropin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects received Genotropin, daily subcutaneous at the same dose as their daily hGH which they were receiving at the time of enrollment.

Weekly Somatrogon Then Daily Genotropin

Arm description

Arm type

Experimental

Investigational medicinal product name

Somatrogon

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects received Somatrogon, weekly subcutaneously at a dose of 0.66 mg/kg/week.

Number of subjects in period 2	Daily Genotropin Then Weekly Somatrogon	Weekly Somatrogon Then Daily Genotropin
Started	43	44
Completed	43	43
Not completed	0	1
Adverse event, not serious	-	1

Period 3 title

Period 2 (12 Weeks)

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Daily Genotropin Then Weekly Somatrogon

Arm description

Arm type

Experimental

Investigational medicinal product name

Genotropin

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects received Genotropin, daily subcutaneous at the same dose as their daily hGH which they were receiving at the time of enrollment.

Weekly Somatrogon Then Daily Genotropin

Arm description

Arm type

Experimental

Investigational medicinal product name

Somatrogon

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects received Somatrogon, weekly subcutaneously at a dose of 0.66 mg/kg/week.

Number of subjects in period 3	Daily Genotropin Then Weekly Somatrogon	Weekly Somatrogon Then Daily Genotropin
Started	43	43
Completed	43	42
Not completed	0	1
Protocol Deviation	-	1

Period 4 title

Follow-up

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Daily Genotropin Then Weekly Somatrogon

Arm description

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Weekly Somatrogon Then Daily Genotropin

Arm description

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Number of subjects in period 4	Daily Genotropin Then Weekly Somatrogon	Weekly Somatrogon Then Daily Genotropin
Started	43	42
Completed	43	43
Joined	0	1
Continued Follow-up	-	1

Baseline characteristics

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Reporting group title

Daily Genotropin Then Weekly Somatrogon

Reporting group description

Reporting group title

Weekly Somatrogon Then Daily Genotropin

Reporting group description

Reporting group values	Daily Genotropin Then Weekly Somatrogon	Weekly Somatrogon Then Daily Genotropin	Total
Number of subjects	43	44	87
Age categorical
Units: Subjects
In Utero	0	0	0
Pre-term newborn - gestational age < 37 wk	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	21	25	46
Adolescents (12-17 years)	22	19	41
Adults (18-64 years)	0	0	0
From 65-84 years	0	0	0
85 years and over	0	0	0
Age Continuous
Units: Years
arithmetic mean (standard deviation)	10.8 ± 3.4	10.7 ± 3.7	-
Sex: Female, Male
Units: Subjects
Female	9	6	15
Male	34	38	72
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0
Asian	0	1	1
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	3	1	4
White	39	42	81
More than one race	0	0	0
Unknown or Not Reported	1	0	1
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	3	2	5
Not Hispanic or Latino	39	42	81
Unknown or Not Reported	1	0	1

End points

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Reporting group title

Daily Genotropin Then Weekly Somatrogon

Reporting group description

Reporting group title

Weekly Somatrogon Then Daily Genotropin

Reporting group description

Reporting group title

Daily Genotropin Then Weekly Somatrogon

Reporting group description

Reporting group title

Weekly Somatrogon Then Daily Genotropin

Reporting group description

Reporting group title

Daily Genotropin Then Weekly Somatrogon

Reporting group description

Reporting group title

Weekly Somatrogon Then Daily Genotropin

Reporting group description

Reporting group title

Daily Genotropin Then Weekly Somatrogon

Reporting group description

Reporting group title

Weekly Somatrogon Then Daily Genotropin

Reporting group description

Subject analysis set title

Genotropin

Subject analysis set type

Full analysis

Subject analysis set description

Subjects received Genotropin, daily subcutaneously, in overall study (either in Period 1 or in Period 2).

Subject analysis set title

Somatrogon

Subject analysis set type

Full analysis

Subject analysis set description

Subjects received Somatrogon, weekly subcutaneously, at a dose of 0.66 mg/kg/week, in overall study (either in Period 1 or in Period 2).

Primary: Total Score Related to Overall Life Interference Assessed at Baseline, Using Dyad Clinical Outcomes Assessment 1 (DCOA 1) Questionnaire

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End point title

Total Score Related to Overall Life Interference Assessed at Baseline, Using Dyad Clinical Outcomes Assessment 1 (DCOA 1) Questionnaire ^[1]

End point description

Subjects were assessed for their treatment burden using DCOA 1 questionnaire completed by subject/caregiver dyads. The subject life interference questionnaire component of the DCOA 1 had 7 questions (life interference [5 questions]: a measure of life interference [daily activities/social activities/leisure/night away from home/travel]; life interference-changes to life routine [1 question]: a measure of how often changes are made to life routine; and life interference-bother of growth hormone [GH] injections [1 question]: a measure of how often the growth hormone injections cause bother) and all questions used a 5-point scale: 1= never, 2= rarely, 3= sometimes, 4= often, 5= always. The overall life interference total score was sum of all 7 questions, scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant less life interference (better outcome). FAS was analysed. ‘Number of Subjects Analysed’ = subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Baseline

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was planned for this endpoint

End point values	Daily Genotropin Then Weekly Somatrogon	Weekly Somatrogon Then Daily Genotropin
Number of subjects analysed	42	40
Units: units on a scale
arithmetic mean (standard deviation)	29.5 ± 18.0	27.1 ± 19.8

No statistical analyses for this end point

Primary: Total Score Related to Overall Life Interference Assessed at Week 12, Using DCOA 1 Questionnaire

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End point title

Total Score Related to Overall Life Interference Assessed at Week 12, Using DCOA 1 Questionnaire ^[2]

End point description

End point type

Primary

End point timeframe

Week 12

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was planned for this endpoint

End point values	Daily Genotropin Then Weekly Somatrogon	Weekly Somatrogon Then Daily Genotropin
Number of subjects analysed	43	40
Units: units on a scale
arithmetic mean (standard deviation)	25.2 ± 17.3	7.1 ± 7.8

No statistical analyses for this end point

Primary: Total Score Related to Overall Life Interference Assessed at Week 24, Using DCOA 1 Questionnaire

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End point title

Total Score Related to Overall Life Interference Assessed at Week 24, Using DCOA 1 Questionnaire ^[3]

End point description

End point type

Primary

End point timeframe

Week 24

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was planned for this endpoint

End point values	Daily Genotropin Then Weekly Somatrogon	Weekly Somatrogon Then Daily Genotropin
Number of subjects analysed	42	42
Units: units on a scale
arithmetic mean (standard deviation)	9.5 ± 13.3	23.0 ± 22.6

No statistical analyses for this end point

Primary: Total Score Related to Overall Life Interference by Treatment in Overall Study, Using DCOA 1 Questionnaire

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End point title

Total Score Related to Overall Life Interference by Treatment in Overall Study, Using DCOA 1 Questionnaire

End point description

End point type

Primary

End point timeframe

Baseline up to Week 24

End point values	Genotropin	Somatrogon
Number of subjects analysed	85	82
Units: units on a scale
arithmetic mean (confidence interval 95%)	24.13 (20.61 to 27.65)	8.63 (5.05 to 12.22)

Genotropin versus Somatrogon

Comparison groups

Genotropin v Somatrogon

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[4]

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-15.49

Confidence interval

level

95%

sides

2-sided

lower limit

-19.71

upper limit

-11.27

Notes
[4] - 95% CI: Model-based difference in means. Results were based on a linear mixed effects model including sequence, period, and treatment as fixed effects and subject within sequence and within-subject error as random effects.

Secondary: Total Score Related to Pen Ease of Use Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

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End point title

Total Score Related to Pen Ease of Use Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

End point description

Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked 5 questions from Section I of the Injection Pen Assessment Questionnaire (IPAQ) patient-reported outcome (PRO) tool related to pen ease of use and used a 5-point scale: 1= very easy, 2= somewhat easy, 3= neither easy nor difficult, 4= somewhat difficult, 5= very difficult. The total score related to pen ease of use was sum of all 5 questions; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant a better outcome. FAS was analysed. Here 'n' signifies number of subjects evaluable for specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 12, Week 24

End point values	Daily Genotropin Then Weekly Somatrogon	Weekly Somatrogon Then Daily Genotropin
Number of subjects analysed	43	44
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n= 42, 40)	10.6 ± 11.3	11.6 ± 12.8
Week 12 (n= 43, 40)	12.0 ± 13.8	5.1 ± 7.6
Week 24 (n= 42, 42)	5.5 ± 9.3	9.4 ± 13.0

No statistical analyses for this end point

Secondary: Total Score Related to Pen Ease of Use by Treatment in Overall Study, Using DCOA 1 Questionnaire

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End point title

Total Score Related to Pen Ease of Use by Treatment in Overall Study, Using DCOA 1 Questionnaire

End point description

Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked 5 questions from Section I of the IPAQ PRO tool related to pen ease of use and used a 5-point scale: 1= very easy, 2= somewhat easy, 3= neither easy nor difficult, 4= somewhat difficult, 5= very difficult. The total score related to pen ease of use was sum of all 5 questions; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant a better outcome. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline up to Week 24

End point values	Genotropin	Somatrogon
Number of subjects analysed	85	82
Units: units on a scale
arithmetic mean (confidence interval 95%)	10.71 (8.27 to 13.14)	5.32 (2.84 to 7.80)

Genotropin versus Somatrogon

Comparison groups

Genotropin v Somatrogon

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0017 ^[5]

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-5.39

Confidence interval

level

95%

sides

2-sided

lower limit

-8.69

upper limit

-2.09

Notes
[5] - 95% CI: Model-based difference in means. Results were based on a linear mixed effects model including sequence, period, and treatment as fixed effects and subject within sequence and within-subject error as random effects.

Secondary: Total Score Related to Ease of the Injection Schedule Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

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End point title

Total Score Related to Ease of the Injection Schedule Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

End point description

Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked a question from Section I of the IPAQ PRO tool related to ease of injection schedule and used a 5-point scale: 1= very easy, 2= somewhat easy, 3= neither easy nor difficult, 4= somewhat difficult, 5= very difficult. The total score related to ease of the injection schedule ranged from 1 to 5; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant a better outcome. FAS was analysed. Here 'n' signifies number of subjects evaluable for specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 12, Week 24

End point values	Daily Genotropin Then Weekly Somatrogon	Weekly Somatrogon Then Daily Genotropin
Number of subjects analysed	43	44
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n= 42, 40)	18.5 ± 20.0	16.3 ± 17.5
Week 12 (n= 43, 40)	23.3 ± 25.2	4.4 ± 11.2
Week 24 (n= 42, 42)	9.5 ± 18.3	17.9 ± 22.3

No statistical analyses for this end point

Secondary: Total Score Related to Ease of the Injection Schedule by Treatment in Overall Study, Using DCOA 1 Questionnaire

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End point title

Total Score Related to Ease of the Injection Schedule by Treatment in Overall Study, Using DCOA 1 Questionnaire

End point description

Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked a question from Section I of the IPAQ PRO tool related to ease of injection schedule and used a 5-point scale: 1= very easy, 2= somewhat easy, 3= neither easy nor difficult, 4= somewhat difficult, 5= very difficult. The total score related to ease of the injection schedule ranged from 1 to 5; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant a better outcome. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline up to Week 24

End point values	Genotropin	Somatrogon
Number of subjects analysed	85	82
Units: units on a scale
arithmetic mean (confidence interval 95%)	20.56 (16.22 to 24.89)	6.96 (2.54 to 11.37)

Genotropin versus Somatrogon

Comparison groups

Genotropin v Somatrogon

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[6]

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-13.6

Confidence interval

level

95%

sides

2-sided

lower limit

-19.74

upper limit

-7.45

Notes
[6] - 95% CI: Model-based difference in means. Results were based on a linear mixed effects model including sequence, period, and treatment as fixed effects and subject within sequence and within-subject error as random effects.

Secondary: Total Score Related to Convenience of the Injection Schedule Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

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End point title

Total Score Related to Convenience of the Injection Schedule Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

End point description

Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked a question from Section I of the IPAQ PRO tool related to ease of injection schedule and used a 7-point scale: 1=extremely convenient to 7=extremely inconvenient. The total score related to convenience of injection schedule ranged from 1 to 7; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant a better outcome. FAS was analysed. Here 'n' signifies number of subjects evaluable for specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 12, Week 24

End point values	Daily Genotropin Then Weekly Somatrogon	Weekly Somatrogon Then Daily Genotropin
Number of subjects analysed	43	44
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n= 42, 40)	34.5 ± 21.0	32.5 ± 21.3
Week 12 (n= 43, 40)	35.3 ± 23.9	7.9 ± 10.7
Week 24 (n= 42, 42)	11.9 ± 14.4	33.3 ± 24.1

No statistical analyses for this end point

Secondary: Total Score Related to Convenience of the Injection Schedule by Treatment in Overall Study, Using DCOA 1 Questionnaire

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End point title

Total Score Related to Convenience of the Injection Schedule by Treatment in Overall Study, Using DCOA 1 Questionnaire

End point description

Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked a question from Section I of the IPAQ PRO tool related to ease of injection schedule and used a 7-point scale: 1=extremely convenient to 7=extremely inconvenient. The total score related to convenience of injection schedule ranged from 1 to 7; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant a better outcome. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline up to Week 24

End point values	Genotropin	Somatrogon
Number of subjects analysed	85	82
Units: units on a scale
arithmetic mean (confidence interval 95%)	34.30 (30.13 to 38.47)	9.96 (5.71 to 14.21)

Genotropin versus Somatrogon

Comparison groups

Genotropin v Somatrogon

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[7]

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-24.34

Confidence interval

level

95%

sides

2-sided

lower limit

-30.1

upper limit

-18.57

Notes
[7] - 95% CI: Model-based difference in means. Results were based on a linear mixed effects model including sequence, period, and treatment as fixed effects and subject within sequence and within-subject error as random effects.

Secondary: Total Score Related to Satisfaction With Overall Treatment Experience Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

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End point title

Total Score Related to Satisfaction With Overall Treatment Experience Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

End point description

Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked a question from Section I of the IPAQ PRO tool related to subject satisfaction with treatment and used a 5-point scale: 1=very satisfied to 5=very dissatisfied. The total score related to satisfaction with overall treatment ranged from 1 to 5; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant a better outcome. FAS was analysed. Here 'n' signifies number of subjects evaluable for specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 12, Week 24

End point values	Daily Genotropin Then Weekly Somatrogon	Weekly Somatrogon Then Daily Genotropin
Number of subjects analysed	43	44
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n= 42, 40)	28.0 ± 21.5	29.4 ± 23.3
Week 12 (n= 43, 40)	27.3 ± 27.2	20.0 ± 31.1
Week 24 (n= 42, 42)	22.0 ± 32.3	30.4 ± 27.9

No statistical analyses for this end point

Secondary: Total Score Related to Satisfaction With Overall Treatment Experience by Treatment in Overall Study, Using DCOA 1 Questionnaire

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End point title

Total Score Related to Satisfaction With Overall Treatment Experience by Treatment in Overall Study, Using DCOA 1 Questionnaire

End point description

Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked a question from Section I of the IPAQ PRO tool related to subject satisfaction with treatment and used a 5-point scale: 1=very satisfied to 5=very dissatisfied. The total score related to satisfaction with overall treatment ranged from 1 to 5; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant a better outcome. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline up to Week 24

End point values	Genotropin	Somatrogon
Number of subjects analysed	85	82
Units: units on a scale
arithmetic mean (confidence interval 95%)	28.95 (22.55 to 35.36)	21.13 (14.61 to 27.65)

Genotropin versus Somatrogon

Comparison groups

Genotropin v Somatrogon

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0739 ^[8]

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-7.83

Confidence interval

level

95%

sides

2-sided

lower limit

-16.42

upper limit

0.77

Notes
[8] - 95% CI: Model-based difference in means. Results were based on a linear mixed effects model including sequence, period, and treatment as fixed effects and subject within sequence and within-subject error as random effects.

Secondary: Total Scores Related to Willingness to Continue Injection Schedule Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

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End point title

Total Scores Related to Willingness to Continue Injection Schedule Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

End point description

Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked a question from Section I of the IPAQ PRO tool related to subject willingness to continue treatment and used a 5-point scale: 1=extremely willing to 5=not at all willing. The total score related to willingness to continue injection schedule ranged from 1 to 5; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant a better outcome. FAS was analysed. Here 'n' signifies number of subjects evaluable for specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 12, Week 24

End point values	Daily Genotropin Then Weekly Somatrogon	Weekly Somatrogon Then Daily Genotropin
Number of subjects analysed	43	44
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n= 42, 40)	18.5 ± 20.0	22.5 ± 23.9
Week 12 (n= 43, 40)	28.5 ± 27.6	10.6 ± 21.1
Week 24 (n= 42, 42)	13.1 ± 24.8	30.4 ± 29.0

No statistical analyses for this end point

Secondary: Total Scores Related to Willingness to Continue Injection Schedule by Treatment in Overall Study, Using DCOA 1 Questionnaire

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End point title

Total Scores Related to Willingness to Continue Injection Schedule by Treatment in Overall Study, Using DCOA 1 Questionnaire

End point description

Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked a question from Section I of the IPAQ PRO tool related to subject willingness to continue treatment and used a 5-point scale: 1=extremely willing to 5=not at all willing. The total score related to willingness to continue injection schedule ranged from 1 to 5; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score meant a better outcome. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline up to Week 24

End point values	Genotropin	Somatrogon
Number of subjects analysed	85	82
Units: units on a scale
arithmetic mean (confidence interval 95%)	29.54 (23.95 to 35.12)	11.93 (6.24 to 17.62)

Genotropin versus Somatrogon

Comparison groups

Genotropin v Somatrogon

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[9]

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-17.6

Confidence interval

level

95%

sides

2-sided

lower limit

-25.15

upper limit

-10.06

Notes
[9] - 95% CI: Model-based difference in means. Results were based on a linear mixed effects model including sequence, period, and treatment as fixed effects and subject within sequence and within-subject error as random effects.

Secondary: Total Scores Related to Injection Signs and Symptoms for Subjects Aged 8 Years and Above Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

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End point title

Total Scores Related to Injection Signs and Symptoms for Subjects Aged 8 Years and Above Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

End point description

Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subjects (8-17 years old). Subjects were asked 4 questions from Section I of the IPAQ PRO tool related to subject's injection signs and symptoms and used a 11-point scale: 0=no pain to 10=worst possible pain; 0=no stinging to 10=worst possible stinging; 0=no bruising to 10=worst possible bruising; and 0=no bleeding to 10=worst possible bleeding, respectively. The total score was sum of all questions; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score for injection signs and symptoms meant a better outcome. FAS was analysed. Here 'n' signifies number of subjects evaluable for specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 12, Week 24

End point values	Daily Genotropin Then Weekly Somatrogon	Weekly Somatrogon Then Daily Genotropin
Number of subjects analysed	43	44
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n= 35, 29)	15.0 ± 10.4	13.8 ± 11.9
Week 12 (n= 34, 25)	16.2 ± 12.2	13.7 ± 10.3
Week 24 (n= 32, 32)	13.6 ± 12.2	10.9 ± 9.6

No statistical analyses for this end point

Secondary: Total Scores Related to Injection Signs and Symptoms for Subjects Aged 8 Years and Above by Treatment in Overall Study, Using DCOA 1 Questionnaire

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End point title

Total Scores Related to Injection Signs and Symptoms for Subjects Aged 8 Years and Above by Treatment in Overall Study, Using DCOA 1 Questionnaire

End point description

Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subjects (8-17 years old). Subjects were asked 4 questions from Section I of the IPAQ PRO tool related to subject's injection signs and symptoms and used a 11-point scale: 0=no pain to 10=worst possible pain; 0=no stinging to 10=worst possible stinging; 0=no bruising to 10=worst possible bruising; and 0=no bleeding to 10=worst possible bleeding, respectively. The total score was sum of all questions; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score for injection signs and symptoms meant a better outcome. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline up to Week 24

End point values	Genotropin	Somatrogon
Number of subjects analysed	66	57
Units: units on a scale
arithmetic mean (confidence interval 95%)	13.56 (10.78 to 16.34)	14.27 (11.32 to 17.21)

Genotropin versus Somatrogon

Comparison groups

Genotropin v Somatrogon

Number of subjects included in analysis

123

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6137 ^[10]

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.71

Confidence interval

level

95%

sides

2-sided

lower limit

-2.09

upper limit

3.51

Notes
[10] - 95% CI: Model-based difference in means. Results were based on a linear mixed effects model including sequence, period, and treatment as fixed effects and subject within sequence and within-subject error as random effects.

Secondary: Total Scores Related to Assessment of Signs, Completed by Caregiver for Children Aged <8 Years Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

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End point title

Total Scores Related to Assessment of Signs, Completed by Caregiver for Children Aged <8 Years Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

End point description

Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by caregiver for children under 8 years. Subjects were asked 2 questions from Section I of the IPAQ PRO tool related to subject's assessment of signs and used a 11-point scale: 0=no bruising to 10=worst possible bruising and 0=no bleeding to 10=worst possible bleeding, respectively. The total score was sum of all questions; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score for assessment of signs meant a better outcome. FAS was analysed. Here 'n' signifies number of subjects evaluable for specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 12, Week 24

End point values	Daily Genotropin Then Weekly Somatrogon	Weekly Somatrogon Then Daily Genotropin
Number of subjects analysed	43	44
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n= 6, 10)	14.2 ± 14.6	13.5 ± 11.3
Week 12 (n= 7, 10)	9.3 ± 10.6	13.0 ± 15.8
Week 24 (n= 8, 9)	5.6 ± 7.8	9.4 ± 8.8

No statistical analyses for this end point

Secondary: Total Scores Related to Assessment of Signs, Completed by Caregiver for Children Aged <8 Years by Treatment in Overall Study, Using DCOA 1 Questionnaire

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End point title

Total Scores Related to Assessment of Signs, Completed by Caregiver for Children Aged <8 Years by Treatment in Overall Study, Using DCOA 1 Questionnaire

End point description

Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by caregiver for children under 8 years. Subjects were asked 2 questions from Section I of the IPAQ PRO tool related to subject's assessment of signs and used a 11-point scale: 0=no bruising to 10=worst possible bruising and 0=no bleeding to 10=worst possible bleeding, respectively. The total score was sum of all questions; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score for assessment of signs meant a better outcome. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline up to Week 24

End point values	Genotropin	Somatrogon
Number of subjects analysed	16	18
Units: units on a scale
arithmetic mean (confidence interval 95%)	8.75 (2.65 to 14.86)	9.31 (3.47 to 15.16)

Genotropin versus Somatrogon

Comparison groups

Genotropin v Somatrogon

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8404 ^[11]

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

0.56

Confidence interval

level

95%

sides

2-sided

lower limit

-5.29

upper limit

6.41

Notes
[11] - 95% CI: Model-based difference in means. Results were based on a linear mixed effects model including sequence, period, and treatment as fixed effects and subject within sequence and within-subject error as random effects.

Secondary: Total Scores Related to Caregiver Life Interference, Including Family Life Interference Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

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End point title

Total Scores Related to Caregiver Life Interference, Including Family Life Interference Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

End point description

Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by caregiver. Subjects were asked 13 questions from Section I of the IPAQ PRO tool related to caregiver life interference and used a 5-point scale: 1= never to 5= always. The total score ranged was sum of scores from all questions; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score for caregiver and family life interference meant less life interference (a better outcome). FAS was analysed. Here 'n' signifies number of subjects evaluable for specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 12, Week 24

End point values	Daily Genotropin Then Weekly Somatrogon	Weekly Somatrogon Then Daily Genotropin
Number of subjects analysed	43	44
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n= 41, 40)	17.8 ± 17.5	20.0 ± 20.1
Week 12 (n= 43, 40)	15.9 ± 16.7	3.1 ± 5.5
Week 24 (n= 42, 42)	3.8 ± 6.0	18.1 ± 23.4

No statistical analyses for this end point

Secondary: Total Scores Related to Caregiver Life Interference, Including Family Life Interference by Treatment in Overall Study, Using DCOA 1 Questionnaire

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End point title

Total Scores Related to Caregiver Life Interference, Including Family Life Interference by Treatment in Overall Study, Using DCOA 1 Questionnaire

End point description

Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by caregiver. Subjects were asked 13 questions from Section I of the IPAQ PRO tool related to caregiver life interference and used a 5-point scale: 1= never to 5= always. The total score ranged was sum of scores from all questions; scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score for caregiver and family life interference meant less life interference (a better outcome). FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline up to Week 24

End point values	Genotropin	Somatrogon
Number of subjects analysed	85	82
Units: units on a scale
arithmetic mean (confidence interval 95%)	17.01 (13.77 to 20.25)	3.54 (0.24 to 6.84)

Genotropin versus Somatrogon

Comparison groups

Genotropin v Somatrogon

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[12]

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-13.47

Confidence interval

level

95%

sides

2-sided

lower limit

-17.59

upper limit

-9.35

Notes
[12] - 95% CI: Model-based difference in means. Results were based on a linear mixed effects model including sequence, period, and treatment as fixed effects and subject within sequence and within-subject error as random effects.

Secondary: Total Scores Related to Missed Injections Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

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End point title

Total Scores Related to Missed Injections Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

End point description

Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked a question from Section I of the IPAQ PRO tool related to number of missed injections (daily or weekly administration) during past 4 weeks. The total scores ranged from 0 to 31 for daily administration (Genotropin) and from 0 to 5 for weekly administration (Somatrogon). All scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score for missed injections meant a better outcome. FAS was analysed. Here 'n' signifies number of subjects evaluable for specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 12, Week 24

End point values	Daily Genotropin Then Weekly Somatrogon	Weekly Somatrogon Then Daily Genotropin
Number of subjects analysed	43	44
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n= 41, 40)	7.8 ± 15.1	7.3 ± 16.1
Week 12 (n= 43, 40)	4.3 ± 8.2	0.0 ± 0.0
Week 24 (n= 42, 42)	1.9 ± 7.4	3.1 ± 10.8

No statistical analyses for this end point

Secondary: Total Scores Related to Missed Injections by Treatment in Overall Study, Using DCOA 1 Questionnaire

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End point title

Total Scores Related to Missed Injections by Treatment in Overall Study, Using DCOA 1 Questionnaire

End point description

Subjects were assessed for their treatment experience using DCOA 1 questionnaire completed by subject/caregiver dyads. Subjects were asked a question from Section I of the IPAQ PRO tool related to number of missed injections (daily or weekly administration) during past 4 weeks. The total scores ranged from 0 to 31 for daily administration (Genotropin) and from 0 to 5 for weekly administration (Somatrogon). All scores were transformed from raw scores and converted to a 0 to 100 scale; a lower score for missed injections meant a better outcome. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline up to Week 24

End point values	Genotropin	Somatrogon
Number of subjects analysed	85	82
Units: units on a scale
arithmetic mean (confidence interval 95%)	3.71 (2.03 to 5.39)	0.95 (-0.76 to 2.66)

Genotropin versus Somatrogon

Comparison groups

Genotropin v Somatrogon

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0245 ^[13]

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-2.76

Confidence interval

level

95%

sides

2-sided

lower limit

-5.16

upper limit

-0.36

Notes
[13] - 95% CI: Model-based difference in means. Results were based on a linear mixed effects model including sequence, period, and treatment as fixed effects and subject within sequence and within-subject error as random effects.

Secondary: Number of Subjects as per Responses to Choice of Injection Pen Assessed at Week 24, Using DCOA 2 Questionnaire

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End point title

Number of Subjects as per Responses to Choice of Injection Pen Assessed at Week 24, Using DCOA 2 Questionnaire

End point description

Subjects were assessed for their treatment experience using DCOA 2 questionnaire completed by subject/caregiver dyads. Subjects/caregivers responded to question from Section II of the IPAQ PRO tool “If you were given the choice between the daily growth hormone injection pen and the weekly growth hormone injection pen, which pen would you choose?” Response was: 1) the daily injection pen (Genotropin) or 2) the weekly injection pen (Somatrogon). FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Week 24

End point values	Daily Genotropin Then Weekly Somatrogon	Weekly Somatrogon Then Daily Genotropin
Number of subjects analysed	42	42
Units: subjects
Somatrogon	38	36
Genotropin	4	6

No statistical analyses for this end point

Secondary: Number of Subjects as per Responses to Preferred Injection Schedule Assessed at Week 24, Using DCOA 2 Questionnaire

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End point title

Number of Subjects as per Responses to Preferred Injection Schedule Assessed at Week 24, Using DCOA 2 Questionnaire

End point description

Subjects were assessed for their treatment experience using DCOA 2 questionnaire completed by subject/caregiver dyads. Subjects/caregivers responded to question from Section II of the IPAQ PRO tool “Which growth hormone injection schedule do you prefer overall?” by choosing from any 1 option from: 1) prefer the daily injection schedule; 2) prefer the weekly injection schedule; 3) no preference. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Week 24

End point values	Daily Genotropin Then Weekly Somatrogon	Weekly Somatrogon Then Daily Genotropin
Number of subjects analysed	42	42
Units: subjects
Somatrogon	40	37
Genotropin	2	4
No Preference	0	1

No statistical analyses for this end point

Secondary: Number of Subjects as per Responses to Convenience of the Injection Schedule Assessed at Week 24, Using DCOA 2 Questionnaire

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End point title

Number of Subjects as per Responses to Convenience of the Injection Schedule Assessed at Week 24, Using DCOA 2 Questionnaire

End point description

Subjects were assessed for their treatment experience using DCOA 2 questionnaire completed by subject/caregiver dyads. Subjects/caregivers responded to question from Section II of the IPAQ PRO tool “Which growth hormone injection schedule was more convenient overall?” by choosing from any 1 option from: 1) daily injection schedule was more convenient; 2) weekly injection schedule was more convenient; 3) no difference. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Week 24

End point values	Daily Genotropin Then Weekly Somatrogon	Weekly Somatrogon Then Daily Genotropin
Number of subjects analysed	42	42
Units: subjects
Somatrogon	40	40
Genotropin	2	2
No Difference	0	0

No statistical analyses for this end point

Secondary: Number of Subjects as per Responses to Ease of Following Injection Schedule Assessed at Week 24, Using DCOA 2 Questionnaire

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End point title

Number of Subjects as per Responses to Ease of Following Injection Schedule Assessed at Week 24, Using DCOA 2 Questionnaire

End point description

Subjects were assessed for their treatment experience using DCOA 2 questionnaire completed by subject/caregiver dyads. Subjects/caregivers responded to question from Section II of the IPAQ PRO tool “Which growth hormone injection schedule was easier to follow overall?” by choosing from any 1 option from: 1) easier to follow daily injection schedule; 2) easier to follow weekly injection schedule; 3) no difference. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Week 24

End point values	Daily Genotropin Then Weekly Somatrogon	Weekly Somatrogon Then Daily Genotropin
Number of subjects analysed	42	42
Units: subjects
Somatrogon	38	34
Genotropin	4	4
No Difference	0	4

No statistical analyses for this end point

Secondary: Number of Subjects as per Responses to Pen Ease of Use Assessed at Week 24, Using DCOA 2 Questionnaire

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End point title

Number of Subjects as per Responses to Pen Ease of Use Assessed at Week 24, Using DCOA 2 Questionnaire

End point description

Subjects were assessed for their treatment experience using DCOA 2 questionnaire completed by subject/caregiver dyads. Subjects/caregiver were asked a question “Which pen was easier to use?” from Section II of the IPAQ PRO tool. Question had 4 parts: preparing the injection pen (Part I), setting the dose (Part II), injecting the medicine (Part III) and storing the pen (Part IV). Subjects/caregiver expressed their preference by choosing from any 1 option for each activity from: 1) daily pen easier to use; 2) weekly pen easier to use; 3) no difference. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Week 24

End point values	Daily Genotropin Then Weekly Somatrogon	Weekly Somatrogon Then Daily Genotropin
Number of subjects analysed	42	42
Units: subjects
Part I: Somatrogon	29	25
Part I: Genotropin	3	4
Part I: No difference	10	13
Part II: Somatrogon	21	17
Part II: Genotropin	6	8
Part II: No Difference	15	17
Part III: Somatrogon	13	18
Part III: Genotropin	16	12
Part III: No Difference	13	12
Part IV: Somatrogon	12	14
Part IV: Genotropin	2	2
Part IV: No Difference	28	26

No statistical analyses for this end point

Secondary: Number of Subjects as per Responses to Subject Life Interference Assessed at Week 24, Using DCOA 2 Questionnaire

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End point title

Number of Subjects as per Responses to Subject Life Interference Assessed at Week 24, Using DCOA 2 Questionnaire

End point description

Subjects were assessed for their treatment experience using DCOA 2 questionnaire completed by subject/caregiver dyads. Subjects/caregiver were asked a question “Which injection schedule interfered less?” from Section II of the IPAQ PRO tool related to subject life interference. Subjects were assessed for 5 activities: daily activities (Activity 1), social activities (Activity 2), recreation/leisure activities (Activity 3), spending night away from home (Activity 4) and travel (Activity 5). The subjects expressed their preference by choosing from any 1 option for each activity from: 1) daily injection schedule interfered less; 2) weekly injection schedule interfered less; 3) no difference. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Week 24

End point values	Daily Genotropin Then Weekly Somatrogon	Weekly Somatrogon Then Daily Genotropin
Number of subjects analysed	42	42
Units: subjects
Activity 1: Somatrogon	35	31
Activity 1: Genotropin	2	1
Activity 1: No Difference	5	10
Activity 2: Somatrogon	34	34
Activity 2: Genotropin	2	0
Activity 2: No Difference	6	8
Activity 3: Somatrogon	34	33
Activity 3: Genotropin	2	1
Activity 3: No Difference	6	8
Activity 4: Somatrogon	36	37
Activity 4: Genotropin	2	1
Activity 4: No Difference	4	4
Activity 5: Somatrogon	33	37
Activity 5: Genotropin	3	0
Activity 5: No Difference	6	5

No statistical analyses for this end point

Secondary: Number of Subjects as per Responses to Caregiver Life Interference Assessed at Week 24, Using DCOA 2 Questionnaire

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End point title

Number of Subjects as per Responses to Caregiver Life Interference Assessed at Week 24, Using DCOA 2 Questionnaire

End point description

Caregivers of subjects were asked a question “Which injection schedule interfered less?” from Section II of the IPAQ PRO tool related to caregiver life interference and were assessed for 5 activities: daily activities (Activity 1), social activities (Activity 2), recreation/leisure activities (Activity 3), spending night away from home (Activity 4) and travel (Activity 5). Preference was expressed by choosing from any 1 option for each activity from: 1) daily injection schedule interfered less; 2) weekly injection schedule interfered less; 3) no difference. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Week 24

End point values	Daily Genotropin Then Weekly Somatrogon	Weekly Somatrogon Then Daily Genotropin
Number of subjects analysed	42	42
Units: subjects
Activity 1: Somatrogon	36	31
Activity 1: Genotropin	2	0
Activity 1: No Difference	4	11
Activity 2: Somatrogon	36	32
Activity 2: Genotropin	2	0
Activity 2: No Difference	4	10
Activity 3: Somatrogon	35	34
Activity 3: Genotropin	2	0
Activity 3: No Difference	5	8
Activity 4: Somatrogon	35	37
Activity 4: Genotropin	1	0
Activity 4: No Difference	6	5
Activity 5: Somatrogon	35	37
Activity 5: Genotropin	2	0
Activity 5: No Difference	5	5

No statistical analyses for this end point

Secondary: Number of Subjects as per Responses to Family Life Interference Assessed at Week 24, Using DCOA 2 Questionnaire

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End point title

Number of Subjects as per Responses to Family Life Interference Assessed at Week 24, Using DCOA 2 Questionnaire

End point description

Subjects were assessed for their treatment experience using DCOA 2 questionnaire completed by subject/caregiver dyads. Subjects/ caregiver were asked a question “Which injection schedule interfered less?” from Section II of the IPAQ PRO tool related to family life interference and assessed for 5 activities: daily activities (Activity 1), social activities (Activity 2), recreation/leisure activities (Activity 3), spending night away from home (Activity 4) and travel (Activity 5). Preference was expressed by choosing from any 1 option for each activity from: 1) daily injection schedule interfered less; 2) weekly injection schedule interfered less; 3) no difference. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Week 24

End point values	Daily Genotropin Then Weekly Somatrogon	Weekly Somatrogon Then Daily Genotropin
Number of subjects analysed	42	42
Units: subjects
Activity 1: Somatrogon	32	29
Activity 1: Genotropin	1	0
Activity 1: No Difference	9	13
Activity 2: Somatrogon	32	30
Activity 2: Genotropin	1	0
Activity 2: No Difference	9	12
Activity 3: Somatrogon	32	32
Activity 3: Genotropin	1	0
Activity 3: No Difference	9	10
Activity 4: Somatrogon	31	34
Activity 4: Genotropin	1	0
Activity 4: No Difference	10	8
Activity 5: Somatrogon	31	36
Activity 5: Genotropin	1	0
Activity 5: No Difference	10	6

No statistical analyses for this end point

Secondary: Number of Subjects as per Response to Benefit Relating to the Injection Schedule Assessed at Week 24, Using DCOA 2 Questionnaire

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End point title

Number of Subjects as per Response to Benefit Relating to the Injection Schedule Assessed at Week 24, Using DCOA 2 Questionnaire

End point description

Subjects were assessed for their treatment experience using DCOA 2 questionnaire completed by subject/caregiver dyads. Subjects/ caregiver were asked a question “How beneficial was to take injections less often?” from Section II of the IPAQ PRO tool pertaining to benefit relating to the Injection schedule and used a 5-point scale: 1= extremely beneficial, 2= very beneficial, 3= moderately beneficial, 4= slightly beneficial and 5= not at all beneficial. Lower score of benefit relating to injection schedule meant a better outcome. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Week 24

End point values	Daily Genotropin Then Weekly Somatrogon	Weekly Somatrogon Then Daily Genotropin
Number of subjects analysed	42	42
Units: subjects
Extremely Beneficial	28	20
Very Beneficial	11	14
Moderately Beneficial	1	3
Slightly Beneficial	0	3
Not At All Beneficial	2	2

No statistical analyses for this end point

Secondary: Number of Subjects as per Responses to Intention to Comply Assessed at Week 24, Using DCOA 2 Questionnaire

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End point title

Number of Subjects as per Responses to Intention to Comply Assessed at Week 24, Using DCOA 2 Questionnaire

End point description

Subjects/caregiver dyads were asked 4 questions “Which schedule would be better able to follow?” (Question 1), “Which schedule would be more likely to follow for a longer time?” (Question 2), “Which schedule would be better able to follow for a longer time?” (Question 3) and “Which schedule would be more likely to follow?” (Question 4) from Section II of the IPAQ PRO tool related to subject intention to comply with treatment. Options for each question were: 1) daily injection (Genotropin), 2) weekly injection (Somatrogon) or 3) no difference. FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Week 24

End point values	Daily Genotropin Then Weekly Somatrogon	Weekly Somatrogon Then Daily Genotropin
Number of subjects analysed	42	42
Units: subjects
Question 1: Somatrogon	33	31
Question 1: Genotropin	2	2
Question 1: No Difference	7	9
Question 2: Somatrogon	29	32
Question 2: Genotropin	1	2
Question 2: No Difference	12	8
Question 3: Somatrogon	34	35
Question 3: Genotropin	1	1
Question 3: No Difference	7	6
Question 4: Somatrogon	26	31
Question 4: Genotropin	3	2
Question 4: No Difference	13	9

No statistical analyses for this end point

Secondary: Patient Global Impression Severity-Impact on Daily Activities (PGIS-IDA) Score Assessed at Baseline, Week 12 and Week 24

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End point title

Patient Global Impression Severity-Impact on Daily Activities (PGIS-IDA) Score Assessed at Baseline, Week 12 and Week 24

End point description

The PGIS-IDA rated the severity of the impact on daily activities due to the treatment administration during the past 4 weeks on a 7-point scale (1= not present to 7= extremely severe). Scores were transformed from raw scores to a 0 to 100 scale. Lower scores meant less impact on daily activities (better outcome). FAS was analysed. Here 'n' signifies number of subjects evaluable for specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 12, Week 24

End point values	Daily Genotropin Then Weekly Somatrogon	Weekly Somatrogon Then Daily Genotropin
Number of subjects analysed	43	44
Units: units on a scale
arithmetic mean (standard deviation)
Baseline (n= 41, 40)	15.0 ± 14.8	16.3 ± 16.2
Week 12 (n= 43, 40)	19.0 ± 19.4	4.6 ± 7.5
Week 24 (n= 42, 42)	7.1 ± 9.8	22.2 ± 20.4

No statistical analyses for this end point

Secondary: Patient Global Impression Severity-Impact on Daily Activities (PGIS-IDA) Score by Treatment in Overall Study

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End point title

Patient Global Impression Severity-Impact on Daily Activities (PGIS-IDA) Score by Treatment in Overall Study

End point description

The PGIS-IDA rated the severity of the impact on daily activities due to the treatment administration during the past 4 weeks on a 7-point scale (1= not present to 7= extremely severe). Scores were transformed from raw scores to a 0 to 100 scale. Lower scores meant less impact on daily activities (better outcome). FAS was analysed. Here ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline up to Week 24

End point values	Genotropin	Somatrogon
Number of subjects analysed	85	82
Units: units on a scale
arithmetic mean (confidence interval 95%)	20.64 (17.30 to 23.99)	6.06 (2.66 to 9.46)

Genotropin versus Somatrogon

Comparison groups

Genotropin v Somatrogon

Number of subjects included in analysis

167

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[14]

Method

Mixed models analysis

Parameter type

Mean difference (final values)

Point estimate

-14.58

Confidence interval

level

95%

sides

2-sided

lower limit

-18.72

upper limit

-10.44

Notes
[14] - 95% CI: Model-based difference in means. Results were based on a linear mixed effects model including sequence, period, and treatment as fixed effects and subject within sequence and within-subject error as random effects.

Other pre-specified: Number of Subjects With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Emergent Treatment Related AEs and SAEs

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End point title

Number of Subjects With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Emergent Treatment Related AEs and SAEs

End point description

An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. SAE was any untoward medical occurrence at any dose that: resulted in death, was life threatening (immediate risk of death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions), resulted in congenital anomaly/birth defect. Treatment-emergent AEs (TEAEs) were defined as events that occurred between first dose of study drug up to 35 days after last dose of study drug. Related TEAEs were those AEs who had relation to the study treatment and was judged by investigator. The safety analysis set was analysed, included all randomised subjects who received at least 1 dose of study drug.

End point type

Other pre-specified

End point timeframe

Baseline up to 29 Weeks

End point values	Genotropin	Somatrogon
Number of subjects analysed	86	87
Units: subjects
Treatment-Emergent AEs	38	47
Treatment-Emergent SAEs	0	0
Treatment-Emergent Treatment Related AEs	14	21
Treatment-Emergent Treatment Related SAEs	0	0

No statistical analyses for this end point

Other pre-specified: Number of Subjects With Adverse Events per Severity

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End point title

Number of Subjects With Adverse Events per Severity

End point description

AE was assessed according to severity; mild (did not interfered with subject's usual function), moderate (interfered to some extent with subject's usual function) and severe (interfered significantly with subject's usual function). The safety analysis set was analysed, included all randomised subjects who received at least 1 dose of study drug.

End point type

Other pre-specified

End point timeframe

Baseline up to 29 Weeks

End point values	Genotropin	Somatrogon
Number of subjects analysed	86	87
Units: subjects
Mild	34	41
Moderate	4	6
Severe	0	0

No statistical analyses for this end point

Other pre-specified: Number of Subjects With Discontinuations due to Adverse Events (AEs)

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End point title

Number of Subjects With Discontinuations due to Adverse Events (AEs)

End point description

An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. The discontinuations due to adverse events was defined for subjects. The safety analysis set was analysed, included all randomised subjects who received at least 1 dose of study drug.

End point type

Other pre-specified

End point timeframe

Baseline up to 29 Weeks

End point values	Genotropin	Somatrogon
Number of subjects analysed	86	87
Units: subjects	0	1

No statistical analyses for this end point

Other pre-specified: Number of Subjects With Laboratory Abnormalities

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End point title

Number of Subjects With Laboratory Abnormalities

End point description

The laboratory abnormality parameters included Hematology: erythrocyte (ery.) mean corpuscular volume, ery. mean corpuscular hemoglobin:<0.9*lower limit normal (LLN), leukocytes:<0.6*LLN, lymphocytes:<0.8*LLN, neutrophils:<0.8*LLN greater than (>) 1.2*upper limit normal (ULN), eosinophils, monocytes:>1.2*ULN. Clinical chemistry: bilirubin, direct bilirubin, indirect bilirubin:>1.5*ULN, gamma glutamyl transferase:>3.0*ULN, albumin:>1.2*ULN, blood urea nitrogen:>1.3*ULN, urate:>1.2*ULN, high-density lipoprotein (HDL) cholesterol:<0.8*LLN, potassium, magnesium:>1.1*ULN, phosphate:>1.2*ULN, bicarbonate:<0.9*LLN, creatine kinase:>2.0*ULN. Urinalysis: specific gravity:>1.030, ketones, urine protein, urine hemoglobin, nitrite, leukocyte esterase:>=1. The safety analysis set was analysed, included all randomised subjects who received at least 1 dose of study drug. Here 'n' signifies number of subjects evaluable for specified time points.

End point type

Other pre-specified

End point timeframe

Week 1 to Week 12, Week 13 to Week 24

End point values	Daily Genotropin Then Weekly Somatrogon	Weekly Somatrogon Then Daily Genotropin
Number of subjects analysed	43	44
Units: subjects
Week 1 to Week 12 (n= 41, 36)	19	19
Week 13 to Week 24 (n= 42, 43)	24	21

No statistical analyses for this end point

Other pre-specified: Number of Subjects With Positive Anti-Recombinant Human Growth Hormone (rhGH) Antibodies and Neutralising Antibodies (NAb)

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End point title

Number of Subjects With Positive Anti-Recombinant Human Growth Hormone (rhGH) Antibodies and Neutralising Antibodies (NAb)

End point description

Blood samples were collected for determination of rhGH and NAb. The subjects who tested positive for antibodies were reported. The safety analysis set was analysed, included all randomised subjects who received at least 1 dose of study drug.

End point type

Other pre-specified

End point timeframe

Baseline, Week 12, Week 24

End point values	Daily Genotropin Then Weekly Somatrogon	Weekly Somatrogon Then Daily Genotropin
Number of subjects analysed	43	44
Units: subjects
Baseline: Non-neutralising	5	0
Baseline: Neutralising	0	0
Week 12: Non-neutralising	3	3
Week 12: Neutralising	0	0
Week 24: Non-neutralising	4	6
Week 24: Neutralising	0	0

No statistical analyses for this end point

Other pre-specified: Number of Subjects With Positive Anti-Somatrogon Antibodies and Neutralising Antibodies (NAb)

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End point title

Number of Subjects With Positive Anti-Somatrogon Antibodies and Neutralising Antibodies (NAb)

End point description

Blood samples were collected for determination of anti-somatrogon antibodies and NAb. The subjects who tested positive for antibodies were reported. The safety analysis set was analysed, included all randomised subjects who received at least 1 dose of study drug. Here, “99999” signifies subjects were not tested for anti-somatrogon antibodies.

End point type

Other pre-specified

End point timeframe

Baseline, Week 12, Week 24

End point values	Daily Genotropin Then Weekly Somatrogon	Weekly Somatrogon Then Daily Genotropin
Number of subjects analysed	43	44
Units: subjects
Baseline: Non-neutralising	0	0
Baseline: Neutralising	0	0
Week 12: Non-neutralising	99999	4
Week 12: Neutralising	99999	0
Week 24: Non-neutralising	0	99999
Week 24: Neutralising	0	99999

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Baseline up to 35 days after last dose (up to 29 weeks)

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

23.0

Reporting group title

Genotropin

Reporting group description

Subjects received Genotropin, daily subcutaneously, in overall study (either in Period 1 or in Period 2).

Reporting group title

Somatrogon

Reporting group description

Subjects received Somatrogon, weekly subcutaneously, at a dose of 0.66 mg/kg/week, in overall study (either in Period 1 or in Period 2).

Serious adverse events	Genotropin	Somatrogon
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 86 (0.00%)	0 / 87 (0.00%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events	0	0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Genotropin	Somatrogon
Total subjects affected by non serious adverse events
subjects affected / exposed	38 / 86 (44.19%)	47 / 87 (54.02%)
General disorders and administration site conditions
Administration site oedema
subjects affected / exposed	0 / 86 (0.00%)	1 / 87 (1.15%)
occurrences all number	0	1
Administration site pain
subjects affected / exposed	0 / 86 (0.00%)	2 / 87 (2.30%)
occurrences all number	0	2
Application site pruritus
subjects affected / exposed	1 / 86 (1.16%)	0 / 87 (0.00%)
occurrences all number	1	0
Fat tissue increased
subjects affected / exposed	0 / 86 (0.00%)	1 / 87 (1.15%)
occurrences all number	0	1
Influenza like illness
subjects affected / exposed	1 / 86 (1.16%)	1 / 87 (1.15%)
occurrences all number	1	1
Injection site bruising
subjects affected / exposed	2 / 86 (2.33%)	1 / 87 (1.15%)
occurrences all number	3	3
Injection site erythema
subjects affected / exposed	1 / 86 (1.16%)	1 / 87 (1.15%)
occurrences all number	1	1
Injection site haematoma
subjects affected / exposed	8 / 86 (9.30%)	4 / 87 (4.60%)
occurrences all number	10	5
Injection site haemorrhage
subjects affected / exposed	2 / 86 (2.33%)	0 / 87 (0.00%)
occurrences all number	3	0
Injection site pain
subjects affected / exposed	11 / 86 (12.79%)	13 / 87 (14.94%)
occurrences all number	23	19
Injection site reaction
subjects affected / exposed	0 / 86 (0.00%)	1 / 87 (1.15%)
occurrences all number	0	1
Injection site swelling
subjects affected / exposed	2 / 86 (2.33%)	2 / 87 (2.30%)
occurrences all number	2	2
Pyrexia
subjects affected / exposed	4 / 86 (4.65%)	2 / 87 (2.30%)
occurrences all number	4	2
Immune system disorders
Hypersensitivity
subjects affected / exposed	1 / 86 (1.16%)	0 / 87 (0.00%)
occurrences all number	1	0
Social circumstances
Excessive exercise
subjects affected / exposed	0 / 86 (0.00%)	1 / 87 (1.15%)
occurrences all number	0	1
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	2 / 86 (2.33%)	4 / 87 (4.60%)
occurrences all number	3	4
Nasal congestion
subjects affected / exposed	1 / 86 (1.16%)	2 / 87 (2.30%)
occurrences all number	1	2
Oropharyngeal pain
subjects affected / exposed	1 / 86 (1.16%)	0 / 87 (0.00%)
occurrences all number	1	0
Respiratory tract congestion
subjects affected / exposed	0 / 86 (0.00%)	1 / 87 (1.15%)
occurrences all number	0	1
Rhinitis allergic
subjects affected / exposed	0 / 86 (0.00%)	1 / 87 (1.15%)
occurrences all number	0	1
Rhinorrhoea
subjects affected / exposed	1 / 86 (1.16%)	1 / 87 (1.15%)
occurrences all number	1	1
Psychiatric disorders
Emotional distress
subjects affected / exposed	1 / 86 (1.16%)	1 / 87 (1.15%)
occurrences all number	1	4
Insomnia
subjects affected / exposed	0 / 86 (0.00%)	1 / 87 (1.15%)
occurrences all number	0	1
Irritability
subjects affected / exposed	0 / 86 (0.00%)	1 / 87 (1.15%)
occurrences all number	0	1
Investigations
Body temperature increased
subjects affected / exposed	1 / 86 (1.16%)	3 / 87 (3.45%)
occurrences all number	2	3
Insulin-like growth factor increased
subjects affected / exposed	0 / 86 (0.00%)	1 / 87 (1.15%)
occurrences all number	0	1
Injury, poisoning and procedural complications
Ligament sprain
subjects affected / exposed	0 / 86 (0.00%)	1 / 87 (1.15%)
occurrences all number	0	1
Limb injury
subjects affected / exposed	0 / 86 (0.00%)	1 / 87 (1.15%)
occurrences all number	0	1
Procedural pain
subjects affected / exposed	0 / 86 (0.00%)	1 / 87 (1.15%)
occurrences all number	0	1
Nervous system disorders
Headache
subjects affected / exposed	5 / 86 (5.81%)	6 / 87 (6.90%)
occurrences all number	6	6
Lethargy
subjects affected / exposed	0 / 86 (0.00%)	1 / 87 (1.15%)
occurrences all number	0	1
Migraine
subjects affected / exposed	0 / 86 (0.00%)	1 / 87 (1.15%)
occurrences all number	0	1
Paraesthesia
subjects affected / exposed	0 / 86 (0.00%)	1 / 87 (1.15%)
occurrences all number	0	1
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	0 / 86 (0.00%)	1 / 87 (1.15%)
occurrences all number	0	1
Hyperacusis
subjects affected / exposed	0 / 86 (0.00%)	1 / 87 (1.15%)
occurrences all number	0	1
Eye disorders
Eye pruritus
subjects affected / exposed	1 / 86 (1.16%)	0 / 87 (0.00%)
occurrences all number	1	0
Vision blurred
subjects affected / exposed	1 / 86 (1.16%)	0 / 87 (0.00%)
occurrences all number	1	0
Gastrointestinal disorders
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 86 (0.00%)	1 / 87 (1.15%)
occurrences all number	0	1
Nausea
subjects affected / exposed	0 / 86 (0.00%)	1 / 87 (1.15%)
occurrences all number	0	1
Tongue ulceration
subjects affected / exposed	0 / 86 (0.00%)	1 / 87 (1.15%)
occurrences all number	0	1
Vomiting
subjects affected / exposed	0 / 86 (0.00%)	2 / 87 (2.30%)
occurrences all number	0	2
Skin and subcutaneous tissue disorders
Blister
subjects affected / exposed	0 / 86 (0.00%)	1 / 87 (1.15%)
occurrences all number	0	1
Endocrine disorders
Adrenocortical insufficiency acute
subjects affected / exposed	0 / 86 (0.00%)	1 / 87 (1.15%)
occurrences all number	0	1
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 86 (0.00%)	3 / 87 (3.45%)
occurrences all number	0	3
Muscle twitching
subjects affected / exposed	0 / 86 (0.00%)	1 / 87 (1.15%)
occurrences all number	0	1
Neck pain
subjects affected / exposed	0 / 86 (0.00%)	1 / 87 (1.15%)
occurrences all number	0	1
Pain in extremity
subjects affected / exposed	1 / 86 (1.16%)	2 / 87 (2.30%)
occurrences all number	1	3
Infections and infestations
Conjunctivitis
subjects affected / exposed	0 / 86 (0.00%)	1 / 87 (1.15%)
occurrences all number	0	1
Conjunctivitis viral
subjects affected / exposed	1 / 86 (1.16%)	0 / 87 (0.00%)
occurrences all number	1	0
Ear infection
subjects affected / exposed	2 / 86 (2.33%)	3 / 87 (3.45%)
occurrences all number	2	3
Gastroenteritis
subjects affected / exposed	1 / 86 (1.16%)	0 / 87 (0.00%)
occurrences all number	1	0
Impetigo
subjects affected / exposed	1 / 86 (1.16%)	0 / 87 (0.00%)
occurrences all number	1	0
Influenza
subjects affected / exposed	0 / 86 (0.00%)	1 / 87 (1.15%)
occurrences all number	0	1
Laryngitis
subjects affected / exposed	1 / 86 (1.16%)	0 / 87 (0.00%)
occurrences all number	1	0
Nasopharyngitis
subjects affected / exposed	5 / 86 (5.81%)	6 / 87 (6.90%)
occurrences all number	5	6
Otitis media
subjects affected / exposed	1 / 86 (1.16%)	0 / 87 (0.00%)
occurrences all number	1	0
Pharyngitis
subjects affected / exposed	0 / 86 (0.00%)	1 / 87 (1.15%)
occurrences all number	0	1
Pharyngitis streptococcal
subjects affected / exposed	1 / 86 (1.16%)	0 / 87 (0.00%)
occurrences all number	1	0
Pneumonia
subjects affected / exposed	1 / 86 (1.16%)	0 / 87 (0.00%)
occurrences all number	1	0
Respiratory tract infection
subjects affected / exposed	1 / 86 (1.16%)	1 / 87 (1.15%)
occurrences all number	2	1
Rhinitis
subjects affected / exposed	0 / 86 (0.00%)	1 / 87 (1.15%)
occurrences all number	0	1
Tonsillitis
subjects affected / exposed	1 / 86 (1.16%)	0 / 87 (0.00%)
occurrences all number	1	0
Upper respiratory tract infection
subjects affected / exposed	2 / 86 (2.33%)	4 / 87 (4.60%)
occurrences all number	2	4
Urinary tract infection
subjects affected / exposed	1 / 86 (1.16%)	0 / 87 (0.00%)
occurrences all number	1	0
Viral infection
subjects affected / exposed	3 / 86 (3.49%)	1 / 87 (1.15%)
occurrences all number	3	1
Viral rash
subjects affected / exposed	1 / 86 (1.16%)	0 / 87 (0.00%)
occurrences all number	1	0
Viral upper respiratory tract infection
subjects affected / exposed	2 / 86 (2.33%)	0 / 87 (0.00%)
occurrences all number	2	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

18 Jul 2018

(A) Schedule of Activities. Medication dispensation added for Genotropin at Visits 3 and 6. (B) Schedule of Activities. DYAD Questionnaire (completed by Clinical Site Staff) added at Visits 1, 4 and 7. (C) Section 4.1. Inclusion criterion #2 (Currently on treatment with either Genotropin Pen®, Genotropin GoQuick Pen®, HumatroPen® [United States of America {USA} only], or Omnitrope® Pen [USA only]) >=3 months and had been compliant on a stable dose (+/-10%) for at least 3 months prior to screening), was modified to allow for GHD subjects on a wider range of doses to enroll in the study. (D) Section 4.2. Exclusion criterion #5 (Other causes of short stature such as uncontrolled primary hypothyroidism and rickets), was modified to remove celiac disease as exclusionary. As this is not an efficacy study assessing linear growth, children with celiac disease (which can impact growth) need not be excluded. (E) Section 5. Clarification added regarding which body weight measurement is to be used for dosing of somatrogon at Visits 1 and 4. (F) Sections 6.2.3 and 6.2.6. Genotropin drug dispensation added.

28 Aug 2018

(A) Schedule of Activities. Anti-rhGH antibodies (and neutralising antibodies) added at Screening, and Visits 4 and 7 at the request of the FDA. (B) Section 2 and Protocol Summary. Detection of anti-rhGH antibodies (and neutralising antibodies) added to align with FDA request. (C) Section 5.4. Arm included as an allowable injection site for Genotropin; its prior omission was in error.

08 Nov 2018

(A) Added free thyroxine (FT4) testing at Screening and at Visits 4 and 7 at the request of the MHRA. (B) Modified Section 13, definition of end of trial to be last subject last visit (LSLV) at the request of the MHRA.

03 May 2019

(A) Section 4.2. Addition of children with closed epiphyses to the Exclusion Criteria to address the request of EU Health Authorities. (B) Section 4.2. Exclusion criteria regarding allowable injectable medications clarified. (C) Sections 5.5, 6.1.1, 6.2.3, & 6.2.4. Dosing windows expanded for Genotropin (36 hours +/- 24 hours) and somatrogon (7 days +/- 72 hours) prior to Visits 1 and 4 providing increased flexibility in dosing for subjects/caregivers prior to visits. (D) Section 5.8.1. Allowable injectable concomitant medications clarified.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Phase 3, Randomised, Multicenter, Open-Label, Crossover Study Assessing Subject Perception of Treatment Burden With Use of Weekly Growth Hormone (Somatrogon) Versus Daily Growth Hormone (Genotropin) Injections in Children With Growth Hormone Deficiency

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Total Score Related to Overall Life Interference Assessed at Baseline, Using Dyad Clinical Outcomes Assessment 1 (DCOA 1) Questionnaire

Primary: Total Score Related to Overall Life Interference Assessed at Baseline, Using Dyad Clinical Outcomes Assessment 1 (DCOA 1) Questionnaire

Primary: Total Score Related to Overall Life Interference Assessed at Week 12, Using DCOA 1 Questionnaire

Primary: Total Score Related to Overall Life Interference Assessed at Week 12, Using DCOA 1 Questionnaire

Primary: Total Score Related to Overall Life Interference Assessed at Week 24, Using DCOA 1 Questionnaire

Primary: Total Score Related to Overall Life Interference Assessed at Week 24, Using DCOA 1 Questionnaire

Primary: Total Score Related to Overall Life Interference by Treatment in Overall Study, Using DCOA 1 Questionnaire

Primary: Total Score Related to Overall Life Interference by Treatment in Overall Study, Using DCOA 1 Questionnaire

Secondary: Total Score Related to Pen Ease of Use Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

Secondary: Total Score Related to Pen Ease of Use Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

Secondary: Total Score Related to Pen Ease of Use by Treatment in Overall Study, Using DCOA 1 Questionnaire

Secondary: Total Score Related to Pen Ease of Use by Treatment in Overall Study, Using DCOA 1 Questionnaire

Secondary: Total Score Related to Ease of the Injection Schedule Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

Secondary: Total Score Related to Ease of the Injection Schedule Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

Secondary: Total Score Related to Ease of the Injection Schedule by Treatment in Overall Study, Using DCOA 1 Questionnaire

Secondary: Total Score Related to Ease of the Injection Schedule by Treatment in Overall Study, Using DCOA 1 Questionnaire

Secondary: Total Score Related to Convenience of the Injection Schedule Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

Secondary: Total Score Related to Convenience of the Injection Schedule Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

Secondary: Total Score Related to Convenience of the Injection Schedule by Treatment in Overall Study, Using DCOA 1 Questionnaire

Secondary: Total Score Related to Convenience of the Injection Schedule by Treatment in Overall Study, Using DCOA 1 Questionnaire

Secondary: Total Score Related to Satisfaction With Overall Treatment Experience Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

Secondary: Total Score Related to Satisfaction With Overall Treatment Experience Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

Secondary: Total Score Related to Satisfaction With Overall Treatment Experience by Treatment in Overall Study, Using DCOA 1 Questionnaire

Secondary: Total Score Related to Satisfaction With Overall Treatment Experience by Treatment in Overall Study, Using DCOA 1 Questionnaire

Secondary: Total Scores Related to Willingness to Continue Injection Schedule Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

Secondary: Total Scores Related to Willingness to Continue Injection Schedule Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

Secondary: Total Scores Related to Willingness to Continue Injection Schedule by Treatment in Overall Study, Using DCOA 1 Questionnaire

Secondary: Total Scores Related to Willingness to Continue Injection Schedule by Treatment in Overall Study, Using DCOA 1 Questionnaire

Secondary: Total Scores Related to Injection Signs and Symptoms for Subjects Aged 8 Years and Above Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

Secondary: Total Scores Related to Injection Signs and Symptoms for Subjects Aged 8 Years and Above Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

Secondary: Total Scores Related to Injection Signs and Symptoms for Subjects Aged 8 Years and Above by Treatment in Overall Study, Using DCOA 1 Questionnaire

Secondary: Total Scores Related to Injection Signs and Symptoms for Subjects Aged 8 Years and Above by Treatment in Overall Study, Using DCOA 1 Questionnaire

Secondary: Total Scores Related to Assessment of Signs, Completed by Caregiver for Children Aged <8 Years Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

Secondary: Total Scores Related to Assessment of Signs, Completed by Caregiver for Children Aged <8 Years Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

Secondary: Total Scores Related to Assessment of Signs, Completed by Caregiver for Children Aged <8 Years by Treatment in Overall Study, Using DCOA 1 Questionnaire

Secondary: Total Scores Related to Assessment of Signs, Completed by Caregiver for Children Aged <8 Years by Treatment in Overall Study, Using DCOA 1 Questionnaire

Secondary: Total Scores Related to Caregiver Life Interference, Including Family Life Interference Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

Secondary: Total Scores Related to Caregiver Life Interference, Including Family Life Interference Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

Secondary: Total Scores Related to Caregiver Life Interference, Including Family Life Interference by Treatment in Overall Study, Using DCOA 1 Questionnaire

Secondary: Total Scores Related to Caregiver Life Interference, Including Family Life Interference by Treatment in Overall Study, Using DCOA 1 Questionnaire

Secondary: Total Scores Related to Missed Injections Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

Secondary: Total Scores Related to Missed Injections Assessed at Baseline, Week 12 and Week 24, Using DCOA 1 Questionnaire

Secondary: Total Scores Related to Missed Injections by Treatment in Overall Study, Using DCOA 1 Questionnaire

Secondary: Total Scores Related to Missed Injections by Treatment in Overall Study, Using DCOA 1 Questionnaire

Secondary: Number of Subjects as per Responses to Choice of Injection Pen Assessed at Week 24, Using DCOA 2 Questionnaire

Secondary: Number of Subjects as per Responses to Choice of Injection Pen Assessed at Week 24, Using DCOA 2 Questionnaire

Secondary: Number of Subjects as per Responses to Preferred Injection Schedule Assessed at Week 24, Using DCOA 2 Questionnaire

Secondary: Number of Subjects as per Responses to Preferred Injection Schedule Assessed at Week 24, Using DCOA 2 Questionnaire

Secondary: Number of Subjects as per Responses to Convenience of the Injection Schedule Assessed at Week 24, Using DCOA 2 Questionnaire

Secondary: Number of Subjects as per Responses to Convenience of the Injection Schedule Assessed at Week 24, Using DCOA 2 Questionnaire

Secondary: Number of Subjects as per Responses to Ease of Following Injection Schedule Assessed at Week 24, Using DCOA 2 Questionnaire

Secondary: Number of Subjects as per Responses to Ease of Following Injection Schedule Assessed at Week 24, Using DCOA 2 Questionnaire

Secondary: Number of Subjects as per Responses to Pen Ease of Use Assessed at Week 24, Using DCOA 2 Questionnaire

Secondary: Number of Subjects as per Responses to Pen Ease of Use Assessed at Week 24, Using DCOA 2 Questionnaire

Secondary: Number of Subjects as per Responses to Subject Life Interference Assessed at Week 24, Using DCOA 2 Questionnaire

Secondary: Number of Subjects as per Responses to Subject Life Interference Assessed at Week 24, Using DCOA 2 Questionnaire

Secondary: Number of Subjects as per Responses to Caregiver Life Interference Assessed at Week 24, Using DCOA 2 Questionnaire

Secondary: Number of Subjects as per Responses to Caregiver Life Interference Assessed at Week 24, Using DCOA 2 Questionnaire

Secondary: Number of Subjects as per Responses to Family Life Interference Assessed at Week 24, Using DCOA 2 Questionnaire

Secondary: Number of Subjects as per Responses to Family Life Interference Assessed at Week 24, Using DCOA 2 Questionnaire

Secondary: Number of Subjects as per Response to Benefit Relating to the Injection Schedule Assessed at Week 24, Using DCOA 2 Questionnaire

Secondary: Number of Subjects as per Response to Benefit Relating to the Injection Schedule Assessed at Week 24, Using DCOA 2 Questionnaire

Secondary: Number of Subjects as per Responses to Intention to Comply Assessed at Week 24, Using DCOA 2 Questionnaire

Secondary: Number of Subjects as per Responses to Intention to Comply Assessed at Week 24, Using DCOA 2 Questionnaire

Secondary: Patient Global Impression Severity-Impact on Daily Activities (PGIS-IDA) Score Assessed at Baseline, Week 12 and Week 24

Secondary: Patient Global Impression Severity-Impact on Daily Activities (PGIS-IDA) Score Assessed at Baseline, Week 12 and Week 24

Secondary: Patient Global Impression Severity-Impact on Daily Activities (PGIS-IDA) Score by Treatment in Overall Study

Secondary: Patient Global Impression Severity-Impact on Daily Activities (PGIS-IDA) Score by Treatment in Overall Study

Other pre-specified: Number of Subjects With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Emergent Treatment Related AEs and SAEs

Other pre-specified: Number of Subjects With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Emergent Treatment Related AEs and SAEs

Clinical Trial Results:
A Phase 3, Randomised, Multicenter, Open-Label, Crossover Study Assessing Subject Perception of Treatment Burden With Use of Weekly Growth Hormone (Somatrogon) Versus Daily Growth Hormone (Genotropin) Injections in Children With Growth Hormone Deficiency