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Clinical Trial Results:
A Phase II open-label, single-arm, multi-center study of ruxolitinib added to corticosteroids in pediatric subjects with moderate and severe chronic graft vs. host disease after allogeneic stem cell transplantation – final analysis Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com for complete trial results.

Summary
EudraCT number	2018-003296-35
Trial protocol	SK IT CZ LT GR ES SI
Global end of trial date	26 Aug 2024

Results information
Results version number	v1(current)
This version publication date	15 Mar 2025
First version publication date	15 Mar 2025
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

CINC424G12201

ISRCTN number

US NCT number

NCT03774082

WHO universal trial number (UTN)

Sponsor organisation name

Novartis Pharma, AG

Sponsor organisation address

CH-4002, Basel, Switzerland,

Public contact

Clinical Disclosure Office, Novartis Pharma, AG, 41 613241111, novatis.email@novartis.com

Scientific contact

Clinical Disclosure Office, Novartis Pharma, AG, 41 613241111, novatis.email@novartis.com

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

Yes

EMA paediatric investigation plan number(s)

EMEA-000901-PIP04-17

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

25 Feb 2022

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

26 Aug 2024

Was the trial ended prematurely?

Main objective of the trial

The primary objective of this study was to evaluate the activity of ruxolitinib added to standard dose corticosteroids, ± calcineurin inhibitor (CNI), in pediatric subjects with moderate or severe treatment-naïve chronic GvHD or steroid-refractory chronic GvHD, by measuring the overall response rate (ORR) at Cycle 7 Day 1, based on all subjects in the study. ORR was defined as the proportion of subjects demonstrating a complete response (CR) or partial response (PR) without the requirement of additional systemic therapies for an earlier progression, mixed response or non-response.

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.

Background therapy

Evidence for comparator

Actual start date of recruitment

20 May 2020

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Brazil: 3

Country: Number of subjects enrolled

Canada: 1

Country: Number of subjects enrolled

Czechia: 1

Country: Number of subjects enrolled

India: 6

Country: Number of subjects enrolled

Italy: 3

Country: Number of subjects enrolled

Japan: 7

Country: Number of subjects enrolled

Korea, Republic of: 6

Country: Number of subjects enrolled

Russian Federation: 1

Country: Number of subjects enrolled

Slovakia: 1

Country: Number of subjects enrolled

Spain: 2

Country: Number of subjects enrolled

Switzerland: 2

Country: Number of subjects enrolled

Taiwan: 2

Country: Number of subjects enrolled

Thailand: 1

Country: Number of subjects enrolled

Türkiye: 10

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

At least 5 evaluable participants per group were needed for the primary analysis in Groups 1, 2 and 3. No minimum number of evaluable participants were needed in Group 4. Disposition and Demographics are presented by age group.

Screening details

Enrollment initiation into the youngest age group, Group 4, was subject to the availability of data in this age group from study CINC424F12201, as well as a review of available PK, safety, and activity data generated from Groups 1 to 3 in the current study.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

≥ 12y - < 18y RUX 10mg BID (Group 1)

Arm description

Participants received ruxolitinib 10mg orally twice a day (BID).

Arm type

Experimental

Investigational medicinal product name

Ruxolitinib

Investigational medicinal product code

INC424

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

10mg ruxolitinib was taken twice a day (BID)

≥ 6y - < 12y RUX 5mg BID (Group 2)

Arm description

Participants received ruxolitinib 5mg orally twice a day (BID).

Arm type

Experimental

Investigational medicinal product name

Ruxolitinib

Investigational medicinal product code

INC424

Other name

Pharmaceutical forms

Tablet, Oral liquid

Routes of administration

Oral use

Dosage and administration details

5mg ruxolitinib was taken twice a day (BID) as tablet or liquid

≥ 2y - < 6y RUX 4mg/m2 BID (Group 3)

Arm description

Participants received ruxolitinib 4mg/m2 orally twice a day (BID).

Arm type

Experimental

Investigational medicinal product name

Ruxolitinib

Investigational medicinal product code

INC424

Other name

Pharmaceutical forms

Oral liquid

Routes of administration

Oral use

Dosage and administration details

4mg/m2 ruxolitinib was taken twice a day (BID) as liquid

Number of subjects in period 1	≥ 12y - < 18y RUX 10mg BID (Group 1)	≥ 6y - < 12y RUX 5mg BID (Group 2)	≥ 2y - < 6y RUX 4mg/m2 BID (Group 3)
Started	22	17	7
Full Analysis Set	22	16	7
Completed treatment	3 ^[1]	5 ^[2]	3 ^[3]
Discontinued from treatment	19	11	4
Completed	14	10	4
Not completed	8	7	3
Adverse event, serious fatal	6	3	2
Subject decision	-	3	-
Administrative reasons	-	1	-
Lost to follow-up	2	-	-
Guardian decision	-	-	1

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: This is correct as is. These subjects here completed treatment, not study.
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: This is correct as is. These subjects here completed treatment, not study.
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: This is correct as is. These subjects here completed treatment, not study.

Baseline characteristics

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Reporting group title

≥ 12y - < 18y RUX 10mg BID (Group 1)

Reporting group description

Participants received ruxolitinib 10mg orally twice a day (BID).

Reporting group title

≥ 6y - < 12y RUX 5mg BID (Group 2)

Reporting group description

Participants received ruxolitinib 5mg orally twice a day (BID).

Reporting group title

≥ 2y - < 6y RUX 4mg/m2 BID (Group 3)

Reporting group description

Participants received ruxolitinib 4mg/m2 orally twice a day (BID).

Reporting group values	≥ 12y - < 18y RUX 10mg BID (Group 1)	≥ 6y - < 12y RUX 5mg BID (Group 2)	≥ 2y - < 6y RUX 4mg/m2 BID (Group 3)	Total
Number of subjects	22	17	7	46
Age categorical
Units: Subjects
Children (2-11 years)	0	17	7	24
Adolescents (12-17 years)	22	0	0	22
Age Continuous
Units: months
arithmetic mean (standard deviation)	175.2 ( 20.05 )	99.3 ( 18.39 )	47.1 ( 15.08 )	-
Sex: Female, Male
Units: Participants
Female	7	8	2	17
Male	15	9	5	29
Race/Ethnicity, Customized
Units: Subjects
White	8	11	3	22
Black or African American	0	1	0	1
Asian	14	5	4	23

Subject analysis set title

All Participants

Subject analysis set type

Full analysis

Subject analysis set description

All participants from Group 1, Group 2 and Group 3.

Subject analysis set title

≥ 12y - < 18y RUX 10mg BID (Tablet)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants in this group were administered 10mg ruxolitinib tablet twice a day.

Subject analysis set title

≥ 6y - < 12y RUX 5mg BID (Tablet)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants in this group were administered 5mg ruxolitinib tablets twice a day.

Subject analysis set title

≥ 6y - < 12y RUX 5mg BID (Liquid)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants in this group were administered ruxolitinib oral pediatric formulation twice a day.

Subject analysis set title

≥ 2y - < 6y RUX 4mg/m2 BID (Liquid)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants in this group were administered ruxolitinib oral pediatric formulation twice a day.

Subject analysis set title

All Participants

Subject analysis set type

Sub-group analysis

Subject analysis set description

DOR was analyzed for all responders from the three age groups (Groups 1, 2 and 3)

Subject analysis set title

All Participants

Subject analysis set type

Full analysis

Subject analysis set description

FFS was analyzed for all participants from the three age groups (Groups 1, 2 and 3)

Subject analysis set title

All Participants

Subject analysis set type

Sub-group analysis

Subject analysis set description

MR was analyzed for all participants with underlying hematologic malignant disease from the three age groups (Groups 1, 2 and 3).

Subject analysis set title

All Participants

Subject analysis set type

Full analysis

Subject analysis set description

NRM was analyzed for all participants from the three age groups (Groups 1, 2 and 3).

Subject analysis set title

All Participants

Subject analysis set type

Full analysis

Subject analysis set description

OS was analyzed for all participants from the three age groups (Groups 1, 2 and 3).

Subject analysis set title

All Participants

Subject analysis set type

Sub-group analysis

Subject analysis set description

The percentage of participants with ≥50% reduction from baseline in daily corticosteroid dose at least once was analyzed for all participants in Groups 1, 2 and 3 who received corticosteroids at baseline.

Subject analysis set title

All Participants

Subject analysis set type

Sub-group analysis

Subject analysis set description

The percentage of participants with reduction to <=0.2mg/kg/day from baseline in daily corticosteroid dose at least once was analyzed for all participants in Groups 1, 2 and 3 who received corticosteroids at baseline.

Subject analysis set title

All Participants

Subject analysis set type

Full analysis

Subject analysis set description

Graft Failure was analyzed for all participants from the three age groups (Groups 1, 2 and 3).

Subject analysis sets values	All Participants	≥ 12y - < 18y RUX 10mg BID (Tablet)	≥ 6y - < 12y RUX 5mg BID (Tablet)	≥ 6y - < 12y RUX 5mg BID (Liquid)	≥ 2y - < 6y RUX 4mg/m2 BID (Liquid)	All Participants	All Participants	All Participants	All Participants	All Participants	All Participants	All Participants	All Participants
Number of subjects	45	21	13	2	7	37	45	30	45	45	40	40	45
Age categorical
Units: Subjects
Children (2-11 years)
Adolescents (12-17 years)
Age Continuous
Units: months
arithmetic mean (standard deviation)	128.3 ( 52.86 )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )
Sex: Female, Male
Units: Participants
Female
Male
Race/Ethnicity, Customized
Units: Subjects
White
Black or African American
Asian

End points

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Reporting group title

≥ 12y - < 18y RUX 10mg BID (Group 1)

Reporting group description

Participants received ruxolitinib 10mg orally twice a day (BID).

Reporting group title

≥ 6y - < 12y RUX 5mg BID (Group 2)

Reporting group description

Participants received ruxolitinib 5mg orally twice a day (BID).

Reporting group title

≥ 2y - < 6y RUX 4mg/m2 BID (Group 3)

Reporting group description

Participants received ruxolitinib 4mg/m2 orally twice a day (BID).

Subject analysis set title

All Participants

Subject analysis set type

Full analysis

Subject analysis set description

All participants from Group 1, Group 2 and Group 3.

Subject analysis set title

≥ 12y - < 18y RUX 10mg BID (Tablet)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants in this group were administered 10mg ruxolitinib tablet twice a day.

Subject analysis set title

≥ 6y - < 12y RUX 5mg BID (Tablet)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants in this group were administered 5mg ruxolitinib tablets twice a day.

Subject analysis set title

≥ 6y - < 12y RUX 5mg BID (Liquid)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants in this group were administered ruxolitinib oral pediatric formulation twice a day.

Subject analysis set title

≥ 2y - < 6y RUX 4mg/m2 BID (Liquid)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants in this group were administered ruxolitinib oral pediatric formulation twice a day.

Subject analysis set title

All Participants

Subject analysis set type

Sub-group analysis

Subject analysis set description

DOR was analyzed for all responders from the three age groups (Groups 1, 2 and 3)

Subject analysis set title

All Participants

Subject analysis set type

Full analysis

Subject analysis set description

FFS was analyzed for all participants from the three age groups (Groups 1, 2 and 3)

Subject analysis set title

All Participants

Subject analysis set type

Sub-group analysis

Subject analysis set description

MR was analyzed for all participants with underlying hematologic malignant disease from the three age groups (Groups 1, 2 and 3).

Subject analysis set title

All Participants

Subject analysis set type

Full analysis

Subject analysis set description

NRM was analyzed for all participants from the three age groups (Groups 1, 2 and 3).

Subject analysis set title

All Participants

Subject analysis set type

Full analysis

Subject analysis set description

OS was analyzed for all participants from the three age groups (Groups 1, 2 and 3).

Subject analysis set title

All Participants

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

All Participants

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

All Participants

Subject analysis set type

Full analysis

Subject analysis set description

Graft Failure was analyzed for all participants from the three age groups (Groups 1, 2 and 3).

Primary: Overall response rate (ORR) at Cycle 7 Day 1

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End point title

Overall response rate (ORR) at Cycle 7 Day 1 ^[1]

End point description

ORR is defined as the percentage of participants demonstrating a complete response (CR) or partial response (PR) without the requirement of additional systemic therapies for an earlier progression, mixed response or non-response. The response is assessed per National Institute of Health (NIH) consensus criteria and scoring of response was relative to the organ stage at the start of study treatment. Full Analysis Set (FAS) comprised all subjects to whom study treatment has been assigned and who received at least one dose of study treatment.

End point type

Primary

End point timeframe

At Cycle 7 Day 1 (Day 168); Cycle = 28 Days

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 done

End point values	≥ 12y - < 18y RUX 10mg BID (Group 1)	≥ 6y - < 12y RUX 5mg BID (Group 2)	≥ 2y - < 6y RUX 4mg/m2 BID (Group 3)	All Participants
Number of subjects analysed	22	16	7	45
Units: Percentage of participants
number (confidence interval 90%)	36.4 (19.6 to 56.1)	50.0 (27.9 to 72.1)	28.6 (5.3 to 65.9)	40.0 (27.7 to 53.3)

No statistical analyses for this end point

Secondary: Ruxolitinib concentrations by timepoint

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End point title

Ruxolitinib concentrations by timepoint

End point description

Pharmacokinetics (PK) of ruxolitinib by age groups (and formulation tablet vs liquid).

End point type

Secondary

End point timeframe

Cycle 1 Day 1: 0.5, 2 and 6 hours post-dose; Pre-dose on Cycle 1 Day 8, Cycle 1 Day 15, Cycle 1 Day 22, Cycle 3 Day 1, Cycle 5 Day 1 and Cycle 7 Day 1; Cycle = 28 Days

End point values	≥ 12y - < 18y RUX 10mg BID (Tablet)	≥ 6y - < 12y RUX 5mg BID (Tablet)	≥ 6y - < 12y RUX 5mg BID (Liquid)	≥ 2y - < 6y RUX 4mg/m2 BID (Liquid)
Number of subjects analysed	20	13	2	7
Units: ug/ml
geometric mean (geometric coefficient of variation)
Cycle 1 Day 1: 0.5 hr (post-dose) (n =7,9,1,7)	60.0 ( 350.7 )	32.4 ( 471.9 )	78.6 ( 999 )	60.1 ( 98.7 )
Cycle 1 Day 1: 2 hr (post-dose) (n = 7,7,1,7)	112 ( 51.8 )	106 ( 39.2 )	77.0 ( 999 )	49.7 ( 30.7 )
Cycle 1 Day 1: 6hr (post-dose) (n = 7, 8, 1, 7)	56.7 ( 73.9 )	47.8 ( 164.1 )	60.0 ( 999 )	15.3 ( 66.2 )
Cycle 1 Day 8: 0 hr (pre-dose) (n =20, 13, 1, 7)	16.7 ( 208.3 )	10.9 ( 146.5 )	3.47 ( 999 )	3.88 ( 152.4 )
Cycle 1 Day 15: 0 hr (pre-dose) (n = 19, 12, 2, 7)	17.8 ( 195.5 )	12.9 ( 248.2 )	4.14 ( 399.3 )	9.43 ( 121.5 )
Cycle 1 Day 22: 0 hr (pre-dose) (n = 18, 11, 2, 7)	20.8 ( 199.5 )	11.7 ( 165.4 )	4.89 ( 505.2 )	10.3 ( 150.4 )
Cycle 3 Day 1: 0 hr (pre-dose (n = 17, 11, 2, 5)	11.4 ( 193.8 )	11.3 ( 193.1 )	2.66 ( 587.5 )	5.56 ( 180.8 )
Cycle 5 Day 1: 0 hr (pre-dose (n = 14,10, 2, 4)	13.0 ( 176.6 )	16.4 ( 470.7 )	11.0 ( 83.5 )	7.32 ( 102.0 )
Cycle 7 Day 1: 0 hr (pre-dose (n = 12, 8, 2, 4)	14.3 ( 173.7 )	10.7 ( 129.9 )	5.79 ( 120.1 )	4.94 ( 165.9 )

No statistical analyses for this end point

Secondary: Duration of response (DOR)

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End point title

Duration of response (DOR)

End point description

Time from first response until chronic Graft vs. host disease (cGvHD) progression, death, or the date of addition of systemic therapies for cGvHD assessed for responders only based on BOR up to Cycle 7 Day 1. Presented as percentage of participants to still be in response at different time points in months (per Kaplan-Meier estimates). Participants without event will be censored at the date of their last response assessment prior to or at the analysis cut-off date if no events occurred on or before 12 weeks (84 days) after the last GvHD assessment. As planned in the SAP, this outcome measure is provided for all participants instead of per age groups. Full Analysis Set (FAS) comprised all subjects to whom study treatment has been assigned and who received at least one dose of study treatment.

End point type

Secondary

End point timeframe

From baseline up to 39 cycles; Cycle = 28 Days

End point values	All Participants
Number of subjects analysed	37
Units: Percentage of participants
number (confidence interval 95%)
Month 1	94.59 (80.07 to 98.62)
Month 2	86.23 (70.01 to 94.03)
Month 6	74.24 (56.17 to 85.74)
Month 12	63.10 (43.74 to 77.38)
Month 18	58.89 (39.23 to 74.12)
Month 24	58.89 (39.23 to 74.12)
Month 30	58.89 (39.23 to 74.12)
Month 36	58.89 (39.23 to 74.12)

No statistical analyses for this end point

Secondary: Overall Response Rate (ORR) at Cycle 4 Day 1

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End point title

Overall Response Rate (ORR) at Cycle 4 Day 1

End point description

ORR is defined as the percentage of participants demonstrating a complete response (CR) or partial response (PR) without the requirement of additional systemic therapies for an earlier progression, mixed response or non-response. The response is assessed per National Institute of Health (NIH) consensus criteria and scoring of response will be relative to the organ stage at the start of study treatment at Cycle 4 Day 1.

End point type

Secondary

End point timeframe

At Cycle 4 Day 1 (Day 84); Cycle = 28 Days

End point values	≥ 12y - < 18y RUX 10mg BID (Group 1)	≥ 6y - < 12y RUX 5mg BID (Group 2)	≥ 2y - < 6y RUX 4mg/m2 BID (Group 3)	All Participants
Number of subjects analysed	22	16	7	45
Units: Percentage of participants
number (confidence interval 90%)	54.5 (35.3 to 72.9)	62.5 (39.1 to 82.2)	42.9 (12.9 to 77.5)	55.6 (42.3 to 68.3)

No statistical analyses for this end point

Secondary: Best overall response (BOR)

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End point title

Best overall response (BOR)

End point description

Percentage of participants who achieved overall response (complete response (CR) or partial response (PR)) at any time point until Cycle 7 Day 1 or the start of additional systemic therapy for chronic GvHD.

End point type

Secondary

End point timeframe

Until Cycle 7 Day 1 (Day 168) or the start of additional systemic therapy for cGvHD; Cycle = 28 Days

End point values	≥ 12y - < 18y RUX 10mg BID (Group 1)	≥ 6y - < 12y RUX 5mg BID (Group 2)	≥ 2y - < 6y RUX 4mg/m2 BID (Group 3)	All Participants
Number of subjects analysed	22	16	7	45
Units: Percentage of participants
number (confidence interval 90%)	81.8 (63.1 to 93.5)	81.3 (58.3 to 94.7)	85.7 (47.9 to 99.3)	82.2 (70.2 to 90.8)

No statistical analyses for this end point

Secondary: Failure free survival (FFS)

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End point title

Failure free survival (FFS)

End point description

Failure-free survival was defined as the time from date of treatment to any of the following events: i) relapse or recurrence of underlying disease or death due to underlying disease, ii) non-relapse mortality, or iii) addition or initiation of another systemic therapy for cGvHD per Kaplan-Meier estimates. As planned in the SAP, this outcome measure is provided for all participants instead of per age groups.

End point type

Secondary

End point timeframe

From baseline up to 39 cycles; Cycle = 28 Days

End point values	All Participants
Number of subjects analysed	45
Units: Percentage of participants
number (confidence interval 95%)
Month 1	91.11 (78.03 to 96.57)
Month 2	84.44 (70.12 to 92.26)
Month 6	68.89 (53.20 to 80.25)
Month 12	64.44 (48.67 to 76.48)
Month 18	57.78 (42.11 to 70.61)
Month 24	57.78 (42.11 to 70.61)
Month 30	57.78 (42.11 to 70.61)
Month 36	57.78 (42.11 to 70.61)

No statistical analyses for this end point

Secondary: Cumulative incidence of malignancy relapse/recurrence (MR)

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End point title

Cumulative incidence of malignancy relapse/recurrence (MR)

End point description

MR was defined as the time from date of treatment assignment to the date of hematologic malignancy relapse/recurrence. Calculated for subjects with underlying hematologic malignant disease. The cumulative incidence (CI) of malignancy relapse/recurrence at 1, 2, 6, 12, 18, 24, 30 and 36 months after start of treatment has been reported. As planned in the SAP, this outcome measure is provided for all participants instead of per age groups.

End point type

Secondary

End point timeframe

From baseline up to 39 cycles; Cycle = 28 Days

End point values	All Participants
Number of subjects analysed	30
Units: Percentage of participants
number (confidence interval 95%)
Month 1	3.33 (0.23 to 14.80)
Month 2	10.00 (2.47 to 23.88)
Month 6	10.00 (2.47 to 23.88)
Month 12	10.00 (2.47 to 23.88)
Month 18	10.00 (2.47 to 23.88)
Month 24	10.00 (2.47 to 23.88)
Month 30	10.00 (2.47 to 23.88)
Month 36	10.00 (2.47 to 23.88)

No statistical analyses for this end point

Secondary: Non-relapse mortality (NRM)

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End point title

Non-relapse mortality (NRM)

End point description

NRM is defined as the time from date of treatment assignment to date of death not preceded by underlying disease relapse/recurrence calculated for all participants. The cumulative incidence (CI) of non-relapse mortality at 1, 2, 6, 12, 18, 24, 30 and 36 months after start of treatment has been reported. As planned in the SAP, this outcome measure is provided for all participants instead of per age groups.

End point type

Secondary

End point timeframe

From baseline up to 39 cycles; Cycle = 28 Days

End point values	All Participants
Number of subjects analysed	45
Units: Percentage of participants
number (confidence interval 95%)
Month 1	2.22 (0.17 to 10.28)
Month 2	2.22 (0.17 to 10.28)
Month 6	6.67 (1.70 to 16.53)
Month 12	13.33 (5.34 to 25.02)
Month 18	17.78 (8.23 to 30.28)
Month 24	20.07 (9.80 to 32.93)
Month 30	20.07 (9.80 to 32.93)
Month 36	20.07 (9.80 to 32.93)

No statistical analyses for this end point

Secondary: Overall survival (OS)

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End point title

Overall survival (OS)

End point description

OS is defined as the time from the date of treatment assignment to the date of death due to any cause. As planned in the SAP, this outcome measure is provided for all participants instead of per age groups.

End point type

Secondary

End point timeframe

From baseline up to 39 cycles; Cycle = 28 Days

End point values	All Participants
Number of subjects analysed	45
Units: survival probability in percentage
number (confidence interval 95%)
Month 1	97.78 (85.25 to 99.68)
Month 2	97.78 (85.25 to 99.68)
Month 6	91.06 (77.90 to 96.55)
Month 12	84.23 (69.73 to 92.15)
Month 18	79.67 (64.57 to 88.87)
Month 24	77.33 (61.94 to 87.11)
Month 30	77.33 (61.94 to 87.11)
Month 36	74.91 (59.26 to 85.26)

No statistical analyses for this end point

Secondary: Percentage of participants with ≥50% reduction from baseline in daily corticosteroid dose

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End point title

Percentage of participants with ≥50% reduction from baseline in daily corticosteroid dose

End point description

Reduction of at least ≥50% from baseline in daily corticosteroid use by Cycle 7 Day 1 (regardless of reason). As planned in the SAP, this outcome measure is provided for all participants instead of per age groups, for those who received corticosteroids at baseline.

End point type

Secondary

End point timeframe

Baseline to Cycle 7 Day 1 (Day 168); Cycle = 28 Days

End point values	All Participants
Number of subjects analysed	40
Units: Percentage of participants
number (not applicable)	75.0

No statistical analyses for this end point

Secondary: Percentage of participants with a reduction to a low dose corticosteriod

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End point title

Percentage of participants with a reduction to a low dose corticosteriod

End point description

Reduction to low dose corticosteroids, is defined as the percentage of participants with reduction from baseline in daily corticosteroid dose to methylprednisolone-equivalent steroid dose of ≤ 0.2 mg/kg/day (or equivalent dose of ≤ 0.25 mg/kg/day prednisone or prednisolone). As planned in the SAP, this outcome measure is provided for all participants instead of per age groups, for those who received corticosteroids at baseline.

End point type

Secondary

End point timeframe

Baseline to Cycle 7 Day 1 (Day 168); Cycle = 28 Days

End point values	All Participants
Number of subjects analysed	40
Units: Percentage of participants
number (not applicable)	67.5

No statistical analyses for this end point

Secondary: Graft failure

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End point title

Graft failure

End point description

Reported are the number of participants with graft failure from all age groups together. Graft failure was assessed by donor cell chimerism, defined as initial whole blood or marrow donor chimerism for those who had ≥ 5% donor cell chimerism at baseline. If donor cell chimerism declined to < 5% on subsequent measurements, graft failure was declared.

End point type

Secondary

End point timeframe

From baseline up to 39 cycles; Cycle = 28 Days

End point values	All Participants
Number of subjects analysed	45
Units: Participants	2

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

AEs & on-treatment deaths were collected from 1st dose up to 30 days after last dose of study treatment. Post-treatment survival follow-up events were collected 31 days after last dose of study treatment until study end, approx. 36 months/39 cycles.

Adverse event reporting additional description

An Adverse Event (AE) is any sign or symptom that occurs during the conduct of the trial and post-treatment survival follow-up.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

27.0

Reporting group title

On-Treatment >=12y - <18y RUX 10mg BID

Reporting group description

On-Treatment >=12y - <18y RUX 10mg BID

Reporting group title

On-Treatment >=2y - <6y RUX 4mg/m2 BID

Reporting group description

On-Treatment >=2y - <6y RUX 4mg/m2 BID

Reporting group title

On-Treatment >=6y - <12y RUX 5mg BID

Reporting group description

On-Treatment >=6y - <12y RUX 5mg BID

Reporting group title

Post-Treatment >=2y - <6y RUX 4mg/m2 BID

Reporting group description

Post-Treatment >=2y - <6y RUX 4mg/m2 BID

Reporting group title

Post-Treatment >=6y - <12y RUX 5mg BID

Reporting group description

Post-Treatment >=6y - <12y RUX 5mg BID

Reporting group title

Post-Treatment >=12y - <18y RUX 10mg BID

Reporting group description

Post-Treatment >=12y - <18y RUX 10mg BID

Reporting group title

Post-Treatment All subjects

Reporting group description

Post-Treatment All subjects

Reporting group title

On-Treatment All subjects

Reporting group description

On-Treatment All subjects

Serious adverse events	On-Treatment >=12y - <18y RUX 10mg BID	On-Treatment >=2y - <6y RUX 4mg/m2 BID	On-Treatment >=6y - <12y RUX 5mg BID	Post-Treatment >=2y - <6y RUX 4mg/m2 BID	Post-Treatment >=6y - <12y RUX 5mg BID	Post-Treatment >=12y - <18y RUX 10mg BID	Post-Treatment All subjects	On-Treatment All subjects
Total subjects affected by serious adverse events
subjects affected / exposed	15 / 22 (68.18%)	4 / 7 (57.14%)	7 / 16 (43.75%)	0 / 7 (0.00%)	0 / 16 (0.00%)	3 / 22 (13.64%)	3 / 45 (6.67%)	26 / 45 (57.78%)
number of deaths (all causes)	0	1	2	1	1	6	8	3
number of deaths resulting from adverse events	0	0	0	0	0	1	1	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Post transplant lymphoproliferative disorder
subjects affected / exposed	1 / 22 (4.55%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Oedema peripheral
subjects affected / exposed	1 / 22 (4.55%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	2 / 22 (9.09%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	3 / 45 (6.67%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Haemophagocytic lymphohistiocytosis
subjects affected / exposed	1 / 22 (4.55%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Alveolar proteinosis
subjects affected / exposed	1 / 22 (4.55%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumothorax
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	1 / 22 (4.55%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory distress
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Blood creatinine increased
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Transplant failure
subjects affected / exposed	1 / 22 (4.55%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Transfusion-related acute lung injury
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Bradycardia
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	1 / 22 (4.55%)	1 / 45 (2.22%)	0 / 45 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Aura
subjects affected / exposed	1 / 22 (4.55%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Presyncope
subjects affected / exposed	1 / 22 (4.55%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Febrile neutropenia
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Thrombocytopenia
subjects affected / exposed	1 / 22 (4.55%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Retinal vein occlusion
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Pneumatosis intestinalis
subjects affected / exposed	1 / 22 (4.55%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Hepatorenal syndrome
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Urinary retention
subjects affected / exposed	1 / 22 (4.55%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Pain in extremity
subjects affected / exposed	1 / 22 (4.55%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Muscular weakness
subjects affected / exposed	2 / 22 (9.09%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	2 / 45 (4.44%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Aspergillus infection
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
COVID-19
subjects affected / exposed	2 / 22 (9.09%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	1 / 22 (4.55%)	1 / 45 (2.22%)	2 / 45 (4.44%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0
Cytomegalovirus infection reactivation
subjects affected / exposed	1 / 22 (4.55%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dengue fever
subjects affected / exposed	1 / 22 (4.55%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Epstein-Barr virus infection
subjects affected / exposed	1 / 22 (4.55%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis viral
subjects affected / exposed	1 / 22 (4.55%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Herpes zoster
subjects affected / exposed	2 / 22 (9.09%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	2 / 45 (4.44%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Human bocavirus infection
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infectious pleural effusion
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Parainfluenzae virus infection
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia respiratory syncytial viral
subjects affected / exposed	1 / 22 (4.55%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia fungal
subjects affected / exposed	1 / 22 (4.55%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	1 / 22 (4.55%)	1 / 45 (2.22%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	1 / 1	0 / 0
Pneumonia
subjects affected / exposed	1 / 22 (4.55%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	2 / 45 (4.44%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia viral
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory syncytial virus infection
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tooth infection
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Septic shock
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Sepsis
subjects affected / exposed	1 / 22 (4.55%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rhinovirus infection
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Hyponatraemia
subjects affected / exposed	2 / 22 (9.09%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	2 / 45 (4.44%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Steroid diabetes
subjects affected / exposed	1 / 22 (4.55%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	On-Treatment >=12y - <18y RUX 10mg BID	On-Treatment >=2y - <6y RUX 4mg/m2 BID	On-Treatment >=6y - <12y RUX 5mg BID	Post-Treatment >=2y - <6y RUX 4mg/m2 BID	Post-Treatment >=6y - <12y RUX 5mg BID	Post-Treatment >=12y - <18y RUX 10mg BID	Post-Treatment All subjects	On-Treatment All subjects
Total subjects affected by non serious adverse events
subjects affected / exposed	22 / 22 (100.00%)	7 / 7 (100.00%)	15 / 16 (93.75%)	0 / 7 (0.00%)	2 / 16 (12.50%)	4 / 22 (18.18%)	6 / 45 (13.33%)	44 / 45 (97.78%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma
subjects affected / exposed	1 / 22 (4.55%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	2 / 45 (4.44%)
occurrences all number	1	0	1	0	0	0	0	2
Vascular disorders
Hypertension
subjects affected / exposed	3 / 22 (13.64%)	1 / 7 (14.29%)	3 / 16 (18.75%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	7 / 45 (15.56%)
occurrences all number	3	1	3	0	0	0	0	7
Hot flush
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	1	0	0	0	0	0	1
General disorders and administration site conditions
Oedema peripheral
subjects affected / exposed	2 / 22 (9.09%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	2 / 45 (4.44%)
occurrences all number	3	0	0	0	0	0	0	3
Pain
subjects affected / exposed	3 / 22 (13.64%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	3 / 45 (6.67%)
occurrences all number	3	0	0	0	0	0	0	3
Influenza like illness
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Pyrexia
subjects affected / exposed	3 / 22 (13.64%)	0 / 7 (0.00%)	4 / 16 (25.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	7 / 45 (15.56%)
occurrences all number	4	0	6	0	0	0	0	10
Immune system disorders
Allergy to chemicals
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Reproductive system and breast disorders
Acquired phimosis
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Pruritus genital
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Cough
subjects affected / exposed	3 / 22 (13.64%)	0 / 7 (0.00%)	3 / 16 (18.75%)	0 / 7 (0.00%)	0 / 16 (0.00%)	1 / 22 (4.55%)	1 / 45 (2.22%)	6 / 45 (13.33%)
occurrences all number	3	0	7	0	0	2	2	10
Epistaxis
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Oropharyngeal pain
subjects affected / exposed	2 / 22 (9.09%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	2 / 45 (4.44%)
occurrences all number	2	0	0	0	0	0	0	2
Productive cough
subjects affected / exposed	1 / 22 (4.55%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	2 / 45 (4.44%)
occurrences all number	1	0	1	0	0	0	0	2
Rhinorrhoea
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Pneumothorax
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	2	0	0	0	0	2
Psychiatric disorders
Insomnia
subjects affected / exposed	2 / 22 (9.09%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	3 / 45 (6.67%)
occurrences all number	2	0	1	0	0	0	0	3
Investigations
Alanine aminotransferase increased
subjects affected / exposed	3 / 22 (13.64%)	1 / 7 (14.29%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	5 / 45 (11.11%)
occurrences all number	6	1	1	0	0	0	0	8
Amylase increased
subjects affected / exposed	1 / 22 (4.55%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	2 / 45 (4.44%)
occurrences all number	1	0	1	0	0	0	0	2
Aspartate aminotransferase increased
subjects affected / exposed	1 / 22 (4.55%)	1 / 7 (14.29%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	3 / 45 (6.67%)
occurrences all number	3	1	1	0	0	0	0	5
Blood alkaline phosphatase increased
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	2 / 45 (4.44%)
occurrences all number	0	1	1	0	0	0	0	2
Blood cholesterol increased
subjects affected / exposed	2 / 22 (9.09%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	2 / 45 (4.44%)
occurrences all number	2	0	0	0	0	0	0	2
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	2 / 16 (12.50%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	2 / 45 (4.44%)
occurrences all number	0	0	2	0	0	0	0	2
Blood lactate dehydrogenase increased
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Blood magnesium increased
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
C-reactive protein increased
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	2 / 45 (4.44%)
occurrences all number	0	1	1	0	0	0	0	2
Immunoglobulins decreased
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Gamma-glutamyltransferase increased
subjects affected / exposed	2 / 22 (9.09%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	3 / 45 (6.67%)
occurrences all number	3	0	1	0	0	0	0	4
Hepatic enzyme increased
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Herpes simplex test positive
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	1	0	0	0	0	0	1
Epstein-Barr virus test positive
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Lymphocyte count decreased
subjects affected / exposed	2 / 22 (9.09%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	3 / 45 (6.67%)
occurrences all number	3	2	0	0	0	0	0	5
Neutrophil count decreased
subjects affected / exposed	5 / 22 (22.73%)	2 / 7 (28.57%)	2 / 16 (12.50%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	9 / 45 (20.00%)
occurrences all number	9	2	3	0	0	0	0	14
Weight decreased
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	2 / 16 (12.50%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	2 / 45 (4.44%)
occurrences all number	0	0	2	0	0	0	0	2
Serum ferritin increased
subjects affected / exposed	1 / 22 (4.55%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	2 / 45 (4.44%)
occurrences all number	1	0	1	0	0	0	0	2
Vascular access device culture positive
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	2	0	0	0	0	0	2
Platelet count decreased
subjects affected / exposed	5 / 22 (22.73%)	0 / 7 (0.00%)	2 / 16 (12.50%)	0 / 7 (0.00%)	0 / 16 (0.00%)	1 / 22 (4.55%)	1 / 45 (2.22%)	7 / 45 (15.56%)
occurrences all number	6	0	2	0	0	1	1	8
Weight increased
subjects affected / exposed	2 / 22 (9.09%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	2 / 45 (4.44%)
occurrences all number	2	0	0	0	0	0	0	2
White blood cell count decreased
subjects affected / exposed	2 / 22 (9.09%)	1 / 7 (14.29%)	2 / 16 (12.50%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	5 / 45 (11.11%)
occurrences all number	4	1	2	0	0	0	0	7
Injury, poisoning and procedural complications
Arthropod bite
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Extraskeletal ossification
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Ligament sprain
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Head injury
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	1	0	0	0	0	0	1
Fall
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	1	0	0	0	0	0	1
Post procedural haemorrhage
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Procedural pain
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Ulna fracture
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Cardiac disorders
Tachycardia
subjects affected / exposed	3 / 22 (13.64%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	4 / 45 (8.89%)
occurrences all number	4	0	1	0	0	0	0	5
Nervous system disorders
Headache
subjects affected / exposed	5 / 22 (22.73%)	0 / 7 (0.00%)	2 / 16 (12.50%)	0 / 7 (0.00%)	0 / 16 (0.00%)	1 / 22 (4.55%)	1 / 45 (2.22%)	7 / 45 (15.56%)
occurrences all number	15	0	2	0	0	1	1	17
Polyneuropathy
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	7 / 22 (31.82%)	2 / 7 (28.57%)	2 / 16 (12.50%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	11 / 45 (24.44%)
occurrences all number	7	3	3	0	0	0	0	13
Coagulopathy
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Lymphopenia
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	2	0	0	0	0	2
Neutropenia
subjects affected / exposed	2 / 22 (9.09%)	2 / 7 (28.57%)	4 / 16 (25.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	8 / 45 (17.78%)
occurrences all number	2	2	6	0	0	0	0	10
Leukopenia
subjects affected / exposed	2 / 22 (9.09%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	3 / 45 (6.67%)
occurrences all number	3	0	1	0	0	0	0	4
Thrombocytopenia
subjects affected / exposed	3 / 22 (13.64%)	1 / 7 (14.29%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	5 / 45 (11.11%)
occurrences all number	4	1	1	0	0	0	0	6
Ear and labyrinth disorders
Ear canal stenosis
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Ear pain
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Eye disorders
Astigmatism
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	1	0	0	0	0	0	1
Blepharitis
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	2	0	0	0	0	2
Cataract
subjects affected / exposed	1 / 22 (4.55%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	2 / 45 (4.44%)
occurrences all number	1	0	1	0	0	0	0	2
Conjunctivitis allergic
subjects affected / exposed	2 / 22 (9.09%)	1 / 7 (14.29%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	4 / 45 (8.89%)
occurrences all number	2	1	1	0	0	0	0	4
Glaucoma
subjects affected / exposed	2 / 22 (9.09%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	2 / 45 (4.44%)
occurrences all number	2	0	0	0	0	0	0	2
Dry eye
subjects affected / exposed	2 / 22 (9.09%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	2 / 45 (4.44%)
occurrences all number	2	0	0	0	0	0	0	2
Ocular hyperaemia
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	1	0	0	0	0	0	1
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	2 / 22 (9.09%)	1 / 7 (14.29%)	2 / 16 (12.50%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	5 / 45 (11.11%)
occurrences all number	2	1	3	0	0	0	0	6
Dental caries
subjects affected / exposed	1 / 22 (4.55%)	1 / 7 (14.29%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	3 / 45 (6.67%)
occurrences all number	1	1	1	0	0	0	0	3
Constipation
subjects affected / exposed	2 / 22 (9.09%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	3 / 45 (6.67%)
occurrences all number	3	0	1	0	0	0	0	4
Abdominal pain
subjects affected / exposed	2 / 22 (9.09%)	1 / 7 (14.29%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	4 / 45 (8.89%)
occurrences all number	3	3	1	0	0	0	0	7
Vomiting
subjects affected / exposed	3 / 22 (13.64%)	0 / 7 (0.00%)	2 / 16 (12.50%)	0 / 7 (0.00%)	0 / 16 (0.00%)	1 / 22 (4.55%)	1 / 45 (2.22%)	5 / 45 (11.11%)
occurrences all number	4	0	2	0	0	1	1	6
Lip pain
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	1	0	0	0	0	0	1
Hepatobiliary disorders
Liver disorder
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Jaundice
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	1	0	0	0	0	0	1
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	1	0	0	0	0	0	1
Acne
subjects affected / exposed	2 / 22 (9.09%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	2 / 45 (4.44%)
occurrences all number	3	0	0	0	0	0	0	3
Dermatitis contact
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	1	0	0	0	0	0	1
Dry skin
subjects affected / exposed	3 / 22 (13.64%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	3 / 45 (6.67%)
occurrences all number	3	0	0	0	0	0	0	3
Eczema
subjects affected / exposed	2 / 22 (9.09%)	0 / 7 (0.00%)	2 / 16 (12.50%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	4 / 45 (8.89%)
occurrences all number	2	0	2	0	0	0	0	4
Rash
subjects affected / exposed	1 / 22 (4.55%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	2 / 45 (4.44%)
occurrences all number	1	1	0	0	0	0	0	2
Hypertrichosis
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	2 / 45 (4.44%)
occurrences all number	0	1	1	0	0	0	0	2
Pruritus
subjects affected / exposed	1 / 22 (4.55%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	2 / 45 (4.44%)
occurrences all number	1	0	1	0	0	0	0	2
Erythema
subjects affected / exposed	1 / 22 (4.55%)	0 / 7 (0.00%)	2 / 16 (12.50%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	3 / 45 (6.67%)
occurrences all number	1	0	2	0	0	0	0	3
Rash macular
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	1	0	0	0	0	0	1
Skin haemorrhage
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	1	0	0	0	0	0	1
Urticaria
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	2 / 16 (12.50%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	2 / 45 (4.44%)
occurrences all number	0	0	2	0	0	0	0	2
Skin irritation
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	1	0	0	0	0	0	1
Endocrine disorders
Cushing's syndrome
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	3 / 22 (13.64%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	1 / 22 (4.55%)	1 / 45 (2.22%)	3 / 45 (6.67%)
occurrences all number	7	0	0	0	0	1	1	7
Back pain
subjects affected / exposed	3 / 22 (13.64%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	4 / 45 (8.89%)
occurrences all number	3	0	1	0	0	0	0	4
Bone pain
subjects affected / exposed	1 / 22 (4.55%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	2 / 45 (4.44%)
occurrences all number	2	0	1	0	0	0	0	3
Osteoporosis
subjects affected / exposed	1 / 22 (4.55%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	2 / 45 (4.44%)
occurrences all number	1	0	1	0	0	0	0	2
Knee deformity
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Osteopenia
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Foot deformity
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Pain in extremity
subjects affected / exposed	3 / 22 (13.64%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	3 / 45 (6.67%)
occurrences all number	3	0	0	0	0	0	0	3
Infections and infestations
Acarodermatitis
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Bronchiolitis
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
BK virus infection
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Aspergillus infection
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	1	0	0	0	0	0	1
Gastroenteritis
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Fungal skin infection
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	1	0	0	0	0	0	1
Epstein-Barr viraemia
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Cytomegalovirus infection reactivation
subjects affected / exposed	2 / 22 (9.09%)	0 / 7 (0.00%)	2 / 16 (12.50%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	4 / 45 (8.89%)
occurrences all number	2	0	2	0	0	0	0	4
Conjunctivitis
subjects affected / exposed	1 / 22 (4.55%)	1 / 7 (14.29%)	2 / 16 (12.50%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	4 / 45 (8.89%)
occurrences all number	1	1	2	0	0	0	0	4
COVID-19
subjects affected / exposed	4 / 22 (18.18%)	2 / 7 (28.57%)	3 / 16 (18.75%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	9 / 45 (20.00%)
occurrences all number	4	3	3	0	0	0	0	10
Gastroenteritis viral
subjects affected / exposed	1 / 22 (4.55%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	2 / 45 (4.44%)
occurrences all number	1	1	0	0	0	0	0	2
Otitis media
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	2 / 45 (4.44%)
occurrences all number	0	1	1	0	0	0	0	2
Oral viral infection
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Onychomycosis
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	2 / 45 (4.44%)
occurrences all number	0	1	1	0	0	0	0	2
Nasopharyngitis
subjects affected / exposed	1 / 22 (4.55%)	1 / 7 (14.29%)	3 / 16 (18.75%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	5 / 45 (11.11%)
occurrences all number	1	2	3	0	0	0	0	6
Lower respiratory tract infection
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	2	0	0	0	0	2
Influenza
subjects affected / exposed	1 / 22 (4.55%)	1 / 7 (14.29%)	2 / 16 (12.50%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	4 / 45 (8.89%)
occurrences all number	1	1	2	0	0	0	0	4
Parainfluenzae virus infection
subjects affected / exposed	2 / 22 (9.09%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	3 / 45 (6.67%)
occurrences all number	2	1	0	0	0	0	0	3
Pneumonia
subjects affected / exposed	4 / 22 (18.18%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	5 / 45 (11.11%)
occurrences all number	4	0	2	0	0	0	0	6
Rhinovirus infection
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	2	0	0	0	0	0	2
Skin infection
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	1	0	0	0	0	0	1
Streptococcal infection
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	1	0	0	0	0	0	1
Tonsillitis
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 22 (0.00%)	1 / 45 (2.22%)	0 / 45 (0.00%)
occurrences all number	0	0	0	0	1	0	1	0
Upper respiratory tract infection
subjects affected / exposed	1 / 22 (4.55%)	4 / 7 (57.14%)	4 / 16 (25.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	9 / 45 (20.00%)
occurrences all number	2	11	5	0	0	0	0	18
Urinary tract infection
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	1	0	0	0	0	0	1
Viral infection
subjects affected / exposed	0 / 22 (0.00%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	1	0	0	0	0	0	1
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Hypertriglyceridaemia
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Hyperkalaemia
subjects affected / exposed	1 / 22 (4.55%)	0 / 7 (0.00%)	2 / 16 (12.50%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	3 / 45 (6.67%)
occurrences all number	2	0	2	0	0	0	0	4
Hyperphosphataemia
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Hypercholesterolaemia
subjects affected / exposed	2 / 22 (9.09%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	3 / 45 (6.67%)
occurrences all number	2	0	1	0	0	0	0	3
Hypoglycaemia
subjects affected / exposed	2 / 22 (9.09%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	3 / 45 (6.67%)
occurrences all number	5	0	1	0	0	0	0	6
Hypokalaemia
subjects affected / exposed	3 / 22 (13.64%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	1 / 22 (4.55%)	1 / 45 (2.22%)	3 / 45 (6.67%)
occurrences all number	4	0	0	0	0	1	1	4
Hypomagnesaemia
subjects affected / exposed	2 / 22 (9.09%)	0 / 7 (0.00%)	2 / 16 (12.50%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	4 / 45 (8.89%)
occurrences all number	3	0	2	0	0	0	0	5
Vitamin D deficiency
subjects affected / exposed	2 / 22 (9.09%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 22 (0.00%)	1 / 45 (2.22%)	3 / 45 (6.67%)
occurrences all number	2	0	2	0	1	0	1	4
Hypozincaemia
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Obesity
subjects affected / exposed	0 / 22 (0.00%)	0 / 7 (0.00%)	1 / 16 (6.25%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	1 / 45 (2.22%)
occurrences all number	0	0	1	0	0	0	0	1
Steroid diabetes
subjects affected / exposed	2 / 22 (9.09%)	1 / 7 (14.29%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	3 / 45 (6.67%)
occurrences all number	2	1	0	0	0	0	0	3
Hypophosphataemia
subjects affected / exposed	2 / 22 (9.09%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 7 (0.00%)	0 / 16 (0.00%)	0 / 22 (0.00%)	0 / 45 (0.00%)	2 / 45 (4.44%)
occurrences all number	2	0	0	0	0	0	0	2

More information

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Were there any global substantial amendments to the protocol? Yes

19 Nov 2020

Update of the guidance regarding the management of ruxolitinib. Update the inclusion criteria to allow for nasogastric tube administration of the oral. pediatric formulation Ruxolitinib tapering management clarification Guidance inclusion for the assessment of organ involvement and response. Ruxolitinib post-trial access requirements clarification. Contraception guidelines and pregnancy reporting requirements update. An assessment of benefit, risk and trial integrity related to SARS-CoV-2 virus and the COVID-19 pandemic was conducted and determined no substantial risk for subject safety or additional measures regarding study design or conduct was warranted.

09 Sep 2022

Public health emergency disruption proofing language inclusion. Clarification on ruxolitinib treatment management and to subject withdrawal of consent.

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.

Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com for complete trial results.

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Overall response rate (ORR) at Cycle 7 Day 1

Primary: Overall response rate (ORR) at Cycle 7 Day 1

Secondary: Ruxolitinib concentrations by timepoint

Secondary: Ruxolitinib concentrations by timepoint

Secondary: Duration of response (DOR)

Secondary: Duration of response (DOR)

Secondary: Overall Response Rate (ORR) at Cycle 4 Day 1

Secondary: Overall Response Rate (ORR) at Cycle 4 Day 1

Secondary: Best overall response (BOR)

Secondary: Best overall response (BOR)

Secondary: Failure free survival (FFS)

Secondary: Failure free survival (FFS)

Secondary: Cumulative incidence of malignancy relapse/recurrence (MR)

Secondary: Cumulative incidence of malignancy relapse/recurrence (MR)

Secondary: Non-relapse mortality (NRM)

Secondary: Non-relapse mortality (NRM)

Secondary: Overall survival (OS)

Secondary: Overall survival (OS)

Secondary: Percentage of participants with ≥50% reduction from baseline in daily corticosteroid dose

Secondary: Percentage of participants with ≥50% reduction from baseline in daily corticosteroid dose

Secondary: Percentage of participants with a reduction to a low dose corticosteriod

Secondary: Percentage of participants with a reduction to a low dose corticosteriod

Secondary: Graft failure

Secondary: Graft failure

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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