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Clinical Trial Results:
A Randomized, Double-blind, Placebo-controlled, Multi-center Study of the Safety and Efficacy of 3-month Subcutaneous REGN1033 Treatment in Patients with Sarcopenia

Summary
EudraCT number	2013-003134-33
Trial protocol	ES NL
Global end of trial date	27 Feb 2015

Results information
Results version number	v1(current)
This version publication date	01 May 2018
First version publication date	01 May 2018
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

R1033-SRC-1239

ISRCTN number

US NCT number

NCT01963598

WHO universal trial number (UTN)

Sponsor organisation name

Regeneron Pharmaceuticals, Inc.

Sponsor organisation address

777 Old Saw Mill River Rd., Tarrytown, United States, 10591

Public contact

Clinical Trial Management, Regeneron Pharmaceuticals, Inc., clinicaltrials@regeneron.com

Scientific contact

Clinical Trial Management, Regeneron Pharmaceuticals, Inc., clinicaltrials@regeneron.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?

Analysis stage

Final

Date of interim/final analysis

15 Sep 2016

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

27 Feb 2015

Was the trial ended prematurely?

Main objective of the trial

The primary objective of the study was to evaluate the effect of multiple doses of REGN1033 administered subcutaneously (SC) for 12 weeks on total lean body mass (LBM), as measured by dual energy X-ray absorptiometry (DXA) in subjects with sarcopenia.

Protection of trial subjects

This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with the International Conference on Harmonisation (ICH) guidelines for Good Clinical Practice (GCP) and applicable regulatory requirements.

Background therapy

Evidence for comparator

Actual start date of recruitment

30 Dec 2013

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Netherlands: 1

Country: Number of subjects enrolled

France: 5

Country: Number of subjects enrolled

Spain: 3

Country: Number of subjects enrolled

United States: 244

Worldwide total number of subjects

253

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

221

85 years and over

Subject disposition

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Recruitment details

The study was conducted at 56 centers in 4 countries between 30 December 2013 and 27 February 2015. A total of 939 subjects were screened in the study, of whom, 686 were screen failures.

Screening details

A total of 253 subjects were randomized in 1:1:1:1 ratio to Placebo (for REGN1033) every 2 weeks (q2w), REGN1033 100 mg q2w, REGN1033 300 mg every 4 weeks (q4w) and REGN1033 300 mg q2w arms.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer, Assessor

Are arms mutually exclusive

Yes

Placebo

Arm description

Single SC injection of Placebo q2w for 12 weeks

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

SC injection in separate abdominal quadrants for all doses.

REGN1033 100 mg q4w

Arm description

Single SC injection of REGN1033 100 mg q4w alternating with placebo q4w for 12 weeks.

Arm type

Experimental

Investigational medicinal product name

Trevogrumab

Investigational medicinal product code

REGN1033

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

SC injection in separate abdominal quadrants for all doses.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

SC injection in separate abdominal quadrants for all doses.

REGN1033 300 mg q4w

Arm description

Single SC injection of REGN1033 300 mg q4w alternating with placebo q4w for 12 weeks.

Arm type

Experimental

Investigational medicinal product name

Trevogrumab

Investigational medicinal product code

REGN1033

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

SC injection in separate abdominal quadrants for all doses.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

SC injection in separate abdominal quadrants for all doses.

REGN1033 300 mg q2w

Arm description

Single SC injection of REGN1033 300 mg q2w for 12 weeks.

Arm type

Experimental

Investigational medicinal product name

Trevogrumab

Investigational medicinal product code

REGN1033

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

SC injection in separate abdominal quadrants for all doses.

Number of subjects in period 1	Placebo	REGN1033 100 mg q4w	REGN1033 300 mg q4w	REGN1033 300 mg q2w
Started	65	63	65	60
Completed	64	60	61	56
Not completed	1	3	4	4
Consent withdrawn by subject	-	-	1	1
Adverse events	1	3	2	-
Adverse event, non-fatal	-	-	-	2
Death	-	-	-	1
Lost to follow-up	-	-	1	-

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Single SC injection of Placebo q2w for 12 weeks

Reporting group title

REGN1033 100 mg q4w

Reporting group description

Single SC injection of REGN1033 100 mg q4w alternating with placebo q4w for 12 weeks.

Reporting group title

REGN1033 300 mg q4w

Reporting group description

Single SC injection of REGN1033 300 mg q4w alternating with placebo q4w for 12 weeks.

Reporting group title

REGN1033 300 mg q2w

Reporting group description

Single SC injection of REGN1033 300 mg q2w for 12 weeks.

Reporting group values	Placebo	REGN1033 100 mg q4w	REGN1033 300 mg q4w	REGN1033 300 mg q2w	Total
Number of subjects	65	63	65	60	253
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	78.5 ± 6.02	77.3 ± 4.94	77.7 ± 5.1	77.7 ± 6.32	-
Gender categorical
Units: Subjects
Female	33	33	35	31	132
Male	32	30	30	29	121

End points

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Reporting group title

Placebo

Reporting group description

Single SC injection of Placebo q2w for 12 weeks

Reporting group title

REGN1033 100 mg q4w

Reporting group description

Single SC injection of REGN1033 100 mg q4w alternating with placebo q4w for 12 weeks.

Reporting group title

REGN1033 300 mg q4w

Reporting group description

Single SC injection of REGN1033 300 mg q4w alternating with placebo q4w for 12 weeks.

Reporting group title

REGN1033 300 mg q2w

Reporting group description

Single SC injection of REGN1033 300 mg q2w for 12 weeks.

Primary: Percent Change in Total Lean Body Mass by DXA From Baseline to Week 12

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End point title

Percent Change in Total Lean Body Mass by DXA From Baseline to Week 12

End point description

Lean body mass, a measurement of body composition, was assessed by DXA scan. Full analysis set (FAS): includes all randomized subjects who received any study medication, had a baseline assessment and at least one post-baseline primary efficacy assessment. Here "Number of subjects analyzed" = subjects with lean body mass assessment at specified time-points.

End point type

Primary

End point timeframe

Baseline to Week 12

End point values	Placebo	REGN1033 100 mg q4w	REGN1033 300 mg q4w	REGN1033 300 mg q2w
Number of subjects analysed	63	62	62	56
Units: percent change
least squares mean (standard error)	-0.474 ± 0.4377	1.191 ± 0.4441	1.308 ± 0.442	1.816 ± 0.4662

REGN1033 300mg q2w vs. Placebo

Statistical analysis description

Null and alternative hypotheses were tested as: H0: no treatment difference between REGN1033 group and placebo; H1: treatment difference between REGN1033 group and placebo. Multiplicity was controlled for the primary endpoint using hierarchical testing procedure from highest dose (REGN1033 300 mg q2w) to lowest dose (REGN1033 100 mg q4w). Hierarchical testing sequence continued only if the null hypothesis was rejected for the higher dose tested at 0.05 level.

Comparison groups

REGN1033 300 mg q2w v Placebo

Number of subjects included in analysis

119

Analysis specification

Pre-specified

Analysis type

superiority ^[1]

P-value

= 0.0004 ^[2]

Method

Mixed models Repeated Measures (MMRM)

Parameter type

Least square (LS) mean difference

Point estimate

2.289

Confidence interval

level

95%

sides

2-sided

lower limit

1.042

upper limit

3.537

Variability estimate

Standard error of the mean

Dispersion value

0.6333

Notes
[1] - Analysis was performed using mixed-effect repeated measures model (MMRM) with treatment,visit, treatment-by-visit interaction, stratification factors (i.e. sex and body mass index (BMI >27.4 or ≤27.4) as fixed effect and relevant baseline value as a covariate.
[2] - Threshold for significance at 0.05 level.

REGN1033 300mg q4w vs. Placebo

Statistical analysis description

Hierarchical testing sequence continued only if the null hypothesis was rejected for the higher dose tested previously at 0.05 level.

Comparison groups

REGN1033 300 mg q4w v Placebo

Number of subjects included in analysis

125

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0043 ^[3]

Method

Mixed models Repeated Measures (MMRM)

Parameter type

LS mean difference

Point estimate

1.781

Confidence interval

level

95%

sides

2-sided

lower limit

0.565

upper limit

2.998

Variability estimate

Standard error of the mean

Dispersion value

0.6175

Notes
[3] - Threshold for significance at 0.05 level.

REGN 1033 100mg q4w vs. Placebo

Statistical analysis description

Hierarchical testing sequence continued only if the null hypothesis was rejected for the higher dose tested previously at 0.05 level.

Comparison groups

Placebo v REGN1033 100 mg q4w

Number of subjects included in analysis

125

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0077 ^[4]

Method

Mixed models Repeated Measures (MMRM)

Parameter type

LS mean difference

Point estimate

1.664

Confidence interval

level

95%

sides

2-sided

lower limit

0.445

upper limit

2.884

Variability estimate

Standard error of the mean

Dispersion value

0.6191

Notes
[4] - Threshold for significance at 0.05 level.

Secondary: Percent Change in Appendicular Lean Body Mass from Baseline to Week 6, 10, 12 and 20

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End point title

Percent Change in Appendicular Lean Body Mass from Baseline to Week 6, 10, 12 and 20

End point description

Appendicular lean body mass was assessed by DXA scan. Percent change: (Appendicular lean body mass at visit minus Appendicular lean body mass at baseline) divided by Appendicular lean body mass at baseline, multiplied by 100. Analysis was performed on FAS population. Here "n" signifies number of subjects with available data at specified time points.

End point type

Secondary

End point timeframe

Baseline, Week 6, 10, 12 and 20

End point values	Placebo	REGN1033 100 mg q4w	REGN1033 300 mg q4w	REGN1033 300 mg q2w
Number of subjects analysed	65	63	65	60
Units: Percent Change
least squares mean (standard error)
Change at Week 6 (n= 63, 62, 64, 58)	-0.749 ± 0.5501	1.725 ± 0.5573	0.926 ± 0.5503	1.449 ± 0.5798
Change at Week 10 (n= 61, 62, 62, 55)	-0.923 ± 0.5631	2.441 ± 0.5654	1.736 ± 0.5635	2.127 ± 0.598
Change at Week 12 (n= 63, 62, 62, 56)	-0.249 ± 0.5605	2.162 ± 0.5678	2.033 ± 0.5668	2.502 ± 0.599
Change at Week 20 (n= 63, 60, 60, 56)	0.054 ± 0.7284	2.039 ± 0.7465	2.693 ± 0.7467	2.487 ± 0.7764

No statistical analyses for this end point

Secondary: Percent Change in Total Lean Mass from Baseline to Week 6, 10, 12, and 20

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End point title

Percent Change in Total Lean Mass from Baseline to Week 6, 10, 12, and 20

End point description

Total lean mass, was assessed by DXA scan. Percent change: (Total lean mass at visit minus total lean mass at baseline) divided by total lean mass at baseline, multiplied by 100. Analysis was performed on FAS population. Here "Number of subjects analyzed" = Number of subjects evaluated for this outcome measure and"n" signifies number of subjects with available data at specified time-points.

End point type

Secondary

End point timeframe

Baseline, Week 6, 10, 12 and 20

End point values	Placebo	REGN1033 100 mg q4w	REGN1033 300 mg q4w	REGN1033 300 mg q2w
Number of subjects analysed	65	62	64	59
Units: Percent Change
least squares mean (standard error)
Change at Week 6 (n= 63, 62, 64, 58)	-0.54 ± 0.4299	1.167 ± 0.4362	0.755 ± 0.4299	1.058 ± 0.4523
Change at Week 10 (n= 61, 62, 62, 55)	-0.538 ± 0.4576	1.65 ± 0.4601	1.242 ± 0.4575	1.62 ± 0.4845
Change at Week 12 (n= 63, 62, 62, 56)	-0.474 ± 0.4377	1.191 ± 0.4441	1.308 ± 0.442	1.816 ± 0.4662
Change at Week 20 (n= 63, 60, 60, 56)	-0.137 ± 0.61	1.28 ± 0.6249	2.401 ± 0.6243	1.775 ± 0.6488

No statistical analyses for this end point

Secondary: Percent Change in Total and Regional (Android and Gynoid) Fat Mass from Baseline to Week 6, 10, 12, and 20

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End point title

Percent Change in Total and Regional (Android and Gynoid) Fat Mass from Baseline to Week 6, 10, 12, and 20

End point description

Total and regional (Android and Gynoid) fat mass, was assessed by DXA scan. Annual percent change: (Total mass at visit minus total mass at baseline) divided by total mass at baseline, multiplied by 100. Analysis was performed on FAS population. Here "n" signifies number of subjects with available data at specified time-points.

End point type

Secondary

End point timeframe

Baseline, Week 6, 10, 12 and 20

End point values	Placebo	REGN1033 100 mg q4w	REGN1033 300 mg q4w	REGN1033 300 mg q2w
Number of subjects analysed	65	63	65	60
Units: Percent Change
least squares mean (standard error)
Total fat mass:Change at Week 6(n= 63,62,64,58)	0.621 ± 0.6447	-0.335 ± 0.6525	-1.383 ± 0.6552	-0.831 ± 0.6769
Total fat mass:Change at Week 10(n= 61,62,62,55)	0.049 ± 0.7172	-0.237 ± 0.7214	-2.377 ± 0.7273	-1.321 ± 0.7574
Total fat mass:Change at Week 12(n= 63,62,62,56)	-0.076 ± 0.7077	-0.077 ± 0.7167	-2.666 ± 0.7232	-0.947 ± 0.7503
Total fat mass:Change at Week 20(n= 63,60,60,56)	-0.151 ± 1.0109	-1.881 ± 1.0345	-5.185 ± 1.0394	-1.749 ± 1.0743
Android fat mass:Change at Week 6(n= 63,62,64,58)	2.341 ± 1.1918	0.063 ± 1.2089	-1.153 ± 1.2046	-1.756 ± 1.2535
Android fat mass:Change at Week 10(n= 61,62,62,55)	0.557 ± 1.1988	0.7 ± 1.2064	-3.288 ± 1.2122	-2.118 ± 1.2695
Android fat mass:Change at Week 12(n= 63,62,62,56)	2.501 ± 1.1177	-0.496 ± 1.1339	-3.164 ± 1.1422	-2.209 ± 1.1897
Android fat mass:Change at Week 20(n= 63,60,60,56)	1.442 ± 1.4723	-2.617 ± 1.5083	-8.245 ± 1.5163	-2.429 ± 1.5684
Gynoid fat mass:Change at Week 6(n= 63,62,64,58)	0.875 ± 0.7541	-0.482 ± 0.7634	-1.035 ± 0.7625	-1.116 ± 0.7916
Gynoid fat mass:Change at Week 10(n= 61,62,62,55)	0.218 ± 0.8226	-0.012 ± 0.8288	-2.51 ± 0.8321	-2.282 ± 0.8693
Gynoid fat mass:Change at Week 12(n= 63,62,62,56)	0.156 ± 0.7976	0.022 ± 0.8079	-2.594 ± 0.813	-2.185 ± 0.8469
Gynoid fat mass:Change at Week 20(n= 63,60,60,56)	0.386 ± 1.1487	-0.741 ± 1.1753	-4.78 ± 1.1809	-1.791 ± 1.2217

No statistical analyses for this end point

Secondary: Percent Change in Maximal Leg Press Strength (1-RM) from Baseline to Week 6, 10, 12 and 20

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End point title

Percent Change in Maximal Leg Press Strength (1-RM) from Baseline to Week 6, 10, 12 and 20

End point description

For leg press assessments, subjects performed a series of repetitions of the exercises using equipment fitted with progressively heavier weight loads until repetition failure was achieved. Repetition failure was defined as the inability to move against the resistance to the required range of motion, or not using proper technique, or the subject not feeling safe in trying a heavier resistance. Muscle strength in the leg press was expressed in units of 1-RM, defined as the greatest resistance (weight) that could be overcome through a defined range of motion using proper techniques. Analysis was performed on FAS population. Here 'n' signifies number of subjects with available data at specified time-points.

End point type

Secondary

End point timeframe

Baseline, Week 6, 10, 12 and 20

End point values	Placebo	REGN1033 100 mg q4w	REGN1033 300 mg q4w	REGN1033 300 mg q2w
Number of subjects analysed	65	63	65	60
Units: Percent Change
least squares mean (standard error)
Change at Week 6 (n= 59,56,57,54)	6.7 ± 3.67	11.3 ± 3.71	10.7 ± 3.67	6.4 ± 3.79
Change at Week 10 (n= 55,58,57,53)	12.3 ± 4.46	18.6 ± 4.47	13.6 ± 4.43	8.2 ± 4.56
Change at Week 12 (n= 56,58,54,51)	14.7 ± 5.65	27.1 ± 5.67	16.5 ± 5.63	15.3 ± 5.78
Change at Week 20 (n= 54,57,53,53)	13.1 ± 7.05	29.5 ± 7.06	14.6 ± 7.01	12.9 ± 7.12

No statistical analyses for this end point

Secondary: Percent Change in Maximal Chest Press Strength (1-RM) from Baseline to Week 6, 10, 12 and 20

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End point title

Percent Change in Maximal Chest Press Strength (1-RM) from Baseline to Week 6, 10, 12 and 20

End point description

For chest press assessments, subjects performed a series of repetitions of the exercises using equipment fitted with progressively heavier weight loads until repetition failure was achieved. Repetition failure was defined as the inability to move against the resistance to the required range of motion, or not using proper technique, or the subject not feeling safe in trying a heavier resistance. Muscle strength in the chest press was expressed in units of 1-RM, defined as the greatest resistance (weight) that could be overcome through a defined range of motion using proper techniques. Analysis was performed on FAS population. Here "Number of subjects analyzed" = Number of subjects evaluated for this outcome measure and "n" signifies number of subjects with available data at specified time-points.

End point type

Secondary

End point timeframe

Baseline, Week 6, 10, 12 and 20

End point values	Placebo	REGN1033 100 mg q4w	REGN1033 300 mg q4w	REGN1033 300 mg q2w
Number of subjects analysed	65	62	64	59
Units: Percent Change
least squares mean (standard error)
Change at Week 6 (n= 61,55,57,51)	13.5 ± 10.8	31.8 ± 11.02	15.1 ± 10.94	25 ± 11.51
Change at Week 10 (n= 56,58,58,50)	17.3 ± 9.76	37.9 ± 9.8	24.9 ± 9.78	19.3 ± 10.33
Change at Week 12 (n= 57,60,55,51)	19.6 ± 10.16	44.7 ± 10.21	24.5 ± 10.25	21 ± 10.74
Change at Week 20 (n= 56,57,54,50 )	15.8 ± 9.48	38 ± 9.53	22.5 ± 9.57	12.8 ± 10.08

No statistical analyses for this end point

Secondary: Percent Change in Hand Grip Strength (Dominant and Non-Dominant Hands) from Baseline to Week 6, 10, 12 and 20

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End point title

Percent Change in Hand Grip Strength (Dominant and Non-Dominant Hands) from Baseline to Week 6, 10, 12 and 20

End point description

Hand Grip Strength Test measures maximum isometric strength of hand and forearm muscles. Subject was required to squeeze dynamometer with maximum isometric effort while sitting with shoulder adducted and neutrally rotated, elbow flexed at 90 degrees and forearm in neutral position and wrist between 0 to 30 degrees dorsiflexion and a 0 to 15 degrees ulnar deviation. subject performed this task 3 times with each hand, starting with non-paretic hand. If difference between scores for 3 trials were within 3 kg, test was considered complete and if difference in score between any 2 measurement trials was more than 3 kg, procedure was repeated after a resting period. The performance measure for this task was average score measured in pounds of pressure exerted. Analysis was performed on FAS population. Here "Number of subjects analyzed" = Number of subjects evaluated for this outcome measure and "n" signifies number of subjects with available data at specified time-points.

End point type

Secondary

End point timeframe

Baseline, Week 6, 10, 12 and 20

End point values	Placebo	REGN1033 100 mg q4w	REGN1033 300 mg q4w	REGN1033 300 mg q2w
Number of subjects analysed	65	62	64	59
Units: Percent Change
least squares mean (standard error)
Dominant: Change at Week 6 (n= 64,60,62,57)	6.9 ± 2.62	11 ± 2.72	5.9 ± 2.68	3.4 ± 2.8
Dominant: Change at Week 10 (n= 61,61,60,55)	7.4 ± 4.36	16.8 ± 4.46	8.1 ± 4.43	4.8 ± 4.6
Dominant: Change at Week 12 (n= 62,61,60,56)	8.2 ± 4.28	18.8 ± 4.39	10.4 ± 4.36	5.7 ± 4.52
Dominant: Change at Week 20 (n= 62,59,61,56)	7.8 ± 4.07	12.5 ± 4.18	6.2 ± 4.11	4 ± 4.3
Non-Dominant: Change at Week 6 (n= 64,61,62,57)	6.3 ± 3.55	13 ± 3.64	9.8 ± 3.61	7.4 ± 3.78
Non-Dominant: Change at Week 10 (n= 61,62,61,55)	6.1 ± 3.66	14.9 ± 3.7	7.4 ± 3.7	8.3 ± 3.88
Non-Dominant: Change at Week 12 (n= 62,62,61,56)	10.7 ± 3.57	17.5 ± 3.62	17.2 ± 3.62	9.8 ± 3.79
Non-Dominant: Change at Week 20 (n= 62,60,61,56)	7.6 ± 4.17	12.9 ± 4.25	9.6 ± 4.22	6.2 ± 4.41

No statistical analyses for this end point

Secondary: Changes in Short Physical Performance Battery (SPPB): Total Score from Baseline to Week 6, 10, 12 and 20

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End point title

Changes in Short Physical Performance Battery (SPPB): Total Score from Baseline to Week 6, 10, 12 and 20

End point description

SPPB is a performance measure consisting of 3 components: a 4-meter (4M) gait speed test, a timed repeated chair stand test, and 3 increasingly difficult balance tests. Each component of the SPPB was assigned a categorical score ranging from 0 (inability to complete the test) to 4 (best performing). Total score, which rated the performance of subjects from 0 (worst) to 12 (best), was calculated by summing the 3 component scores. Analysis was performed on FAS population. Here "Number of subjects analyzed" = Number of subjects evaluated for this outcome measure and "n" signifies number of subjects with available data at specified time-points.

End point type

Secondary

End point timeframe

Baseline, Week 6, 10, 12 and 20

End point values	Placebo	REGN1033 100 mg q4w	REGN1033 300 mg q4w	REGN1033 300 mg q2w
Number of subjects analysed	65	62	64	59
Units: units on a scale
least squares mean (standard error)
Change at Week 6 (n= 64, 61, 63, 58)	0.2 ± 0.06	0.1 ± 0.06	0 ± 0.06	0.1 ± 0.06
Change at Week 10 (n=62, 62, 62, 55)	0.2 ± 0.06	0.1 ± 0.06	0.1 ± 0.06	0.1 ± 0.07
Change at Week 12 (n=62, 62, 62, 56)	0.3 ± 0.06	0.2 ± 0.06	0.2 ± 0.06	0.1 ± 0.06
Change at Week 20 (n=61, 60, 61, 56)	0.3 ± 0.06	0.2 ± 0.06	0.3 ± 0.06	0.2 ± 0.06

No statistical analyses for this end point

Secondary: Changes in SPPB Subscore: Repeated Chair Stand Test from Baseline to Week 6, 10, 12 and 20

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End point title

Changes in SPPB Subscore: Repeated Chair Stand Test from Baseline to Week 6, 10, 12 and 20

End point description

SPPB is performance measure consisting of 3 components: 4M gait speed test, repeated chair stand test & balance tests. In repeated chair stand test, subjects were seated on straight-backed armless chair placed next to a wall with their arms folded across chest and asked to stand up straight while keeping their arms folded across their chest, for 5 times without stopping in between. Length of time required for subjects to stand up 5 times was measured with stop-watch,beginning from when subjects were told to start standing test to when they stood up straight for 5th time.Subjects were given scores: 0(unable to complete 5 stands in >60 seconds),1(completed 5 stands in ≥16.70 seconds),2(completed 5 stands in 13.70 to 16.69 second), 3(completed 5 stands in 11.20 to 13.69 seconds) or 4 (completed 5 chair stands in ≤11.19 seconds). FAS population. Here "Number of subjects analyzed" were subjects evaluated for this outcome measure and "n" signifies number of subjects with available data.

End point type

Secondary

End point timeframe

Baseline, Week 6, 10, 12 and 20

End point values	Placebo	REGN1033 100 mg q4w	REGN1033 300 mg q4w	REGN1033 300 mg q2w
Number of subjects analysed	65	62	64	59
Units: units on a scale
least squares mean (standard error)
Change at Week 6 (n= 59,57,62,54)	0.2 ± 0.1	0.4 ± 0.1	0.3 ± 0.1	0.4 ± 0.11
Change at Week 10 (n=58,58,60,53)	0.4 ± 0.11	0.5 ± 0.11	0.4 ± 0.11	0.6 ± 0.11
Change at Week 12 (n=57,59,62,54 )	0.5 ± 0.11	0.5 ± 0.11	0.5 ± 0.11	0.7 ± 0.12
Change at Week 20 (n= 56,57,59,54)	0.5 ± 0.1	0.5 ± 0.1	0.5 ± 0.1	0.7 ± 0.11

No statistical analyses for this end point

Secondary: Changes in SPPB Subscore: Balance Testing from Baseline to Week 6, 10, 12 and 20

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End point title

Changes in SPPB Subscore: Balance Testing from Baseline to Week 6, 10, 12 and 20

End point description

SPPB is a performance measure consisting of 3 components: 4-meter (4M) gait speed test, repeated chair stand test and balance tests. Balance testing component of SPPB consists of side-by-side stand test (subjects were asked to stand with feet together for 10 seconds); a semi-tandem stand test (standing with side of heel of one foot touching other foot for 10 seconds); and tandem stand test (stand with heel of one foot in front of and touching toes of other foot for 10 seconds). Total score for balance testing component range from 0 (inability to complete the test) to 4 (best performing). Analysis was performed on FAS population. Here "Number of subjects analyzed" = Number of subjects evaluated for this outcome measure and "n" signifies number of subjects with available data at specified time-points.

End point type

Secondary

End point timeframe

Baseline, Week 6, 10, 12 and 20

End point values	Placebo	REGN1033 100 mg q4w	REGN1033 300 mg q4w	REGN1033 300 mg q2w
Number of subjects analysed	65	62	64	59
Units: units on a scale
least squares mean (standard error)
Change at Week 6 (n=64,61,53,58)	0.1 ± 0.08	0.1 ± 0.08	0.1 ± 0.08	0.1 ± 0.08
Change at Week 10 (n=62,62,62,55)	0.1 ± 0.09	0 ± 0.09	0.1 ± 0.09	0 ± 0.1
Change at Week 12 (n=62,62,62,56)	0.2 ± 0.09	0 ± 0.09	0.2 ± 0.09	0.1 ± 0.09
Change at Week 20 (n=61,60,61,56)	0.2 ± 0.08	0.1 ± 0.09	0.2 ± 0.09	0.1 ± 0.09

No statistical analyses for this end point

Secondary: Changes in SPPB Subscore: 4-Meter Walk from Baseline to Week 6, 10, 12 and 20

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End point title

Changes in SPPB Subscore: 4-Meter Walk from Baseline to Week 6, 10, 12 and 20

End point description

The 4-Minute Walk Test (4-MWT), which measures the maximum distance a person can walk in 4 minutes, is a test of exercise endurance in elderly subjects with cardiovascular or pulmonary disease. Analysis was performed on FAS population. Here "Number of subjects analyzed" = Number of subjects evaluated for this outcome measure and "n" signifies number of subjects with available data at specified time-points.

End point type

Secondary

End point timeframe

Baseline, Week 6, 10, 12 and 20

End point values	Placebo	REGN1033 100 mg q4w	REGN1033 300 mg q4w	REGN1033 300 mg q2w
Number of subjects analysed	65	62	64	59
Units: units on a scale
least squares mean (standard error)
Change at Week 6 (n= 64,61,63,58)	0.2 ± 0.06	0.1 ± 0.06	0 ± 0.06	0.1 ± 0.06
Change at Week 10 (n= 62,62,62,55)	0.2 ± 0.06	0.1 ± 0.06	0.1 ± 0.06	0.1 ± 0.07
Change at Week 12 (n= 62,62,62,56)	0.3 ± 0.06	0.2 ± 0.06	0.2 ± 0.06	0.1 ± 0.06
Change at Week 20 (n= 61,60,61,56)	0.3 ± 0.06	0.2 ± 0.06	0.3 ± 0.06	0.2 ± 0.06

No statistical analyses for this end point

Secondary: Percent Change in 4-Meter Gait Speed from Baseline to Week 6, 10, 12 and 20

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End point title

Percent Change in 4-Meter Gait Speed from Baseline to Week 6, 10, 12 and 20

End point description

SPPB is a performance measure consisting of 3 components: 4-meter (4M) gait speed test, repeated chair stand test and balance tests. 4-meter (4M) gait speed component of the SPPB test was determined on a flat indoor surface marked at the start and at 4 meters from the start. Subjects were instructed to walk from a standing start past the 4-meter mark at their usual pace without hesitation. Completion time was recorded to the nearest 0.01 second using photoelectric cells and timers. Subjects completed 3 trials of the test, and the fastest time of 3 trials was used to calculate the walking speed. Total score for 4M gait speed component range from 0 (inability to complete the test) to 4 (best performing). Analysis was performed on FAS population. Here "Number of subjects analyzed" = Number of subjects evaluated for this outcome measure and "n" signifies number of subjects with available data at specified time-points.

End point type

Secondary

End point timeframe

Baseline, Week 6, 10, 12 and 20

End point values	Placebo	REGN1033 100 mg q4w	REGN1033 300 mg q4w	REGN1033 300 mg q2w
Number of subjects analysed	65	62	64	59
Units: Percent Change
least squares mean (standard error)
Percent change at Week 6 (n= 64,61,63,58)	7.25 ± 1.988	3.31 ± 2.033	5.47 ± 2.004	10.78 ± 2.096
Percent change at Week 10 (n= 62,62,62,55)	7.7 ± 2.122	8.88 ± 2.136	10.25 ± 2.125	12.47 ± 2.25
Percent change at Week 12 (n= 62,62,62,56)	11.65 ± 2.131	11.89 ± 2.144	13.06 ± 2.135	15.17 ± 2.249
Percent change at Week 20 (n= 61,60,61,56)	10.42 ± 2.23	11.02 ± 2.251	14.21 ± 2.235	12.51 ± 2.345

No statistical analyses for this end point

Secondary: Percent Change in Distance Walked in the 6-Minute Walk Test (6MWT) from Baseline to Week 6, 10, 12 and 20

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End point title

Percent Change in Distance Walked in the 6-Minute Walk Test (6MWT) from Baseline to Week 6, 10, 12 and 20

End point description

The 6-Minute Walk Test (6-MWT), which measures the maximum distance a person can walk in 6 minutes, is a test of exercise in elderly subjects with cardiovascular or pulmonary disease. Analysis was performed on FAS population. Here "Number of subjects analyzed" = Number of subjects evaluated for this outcome measure and "n" signifies number of subjects with available data at specified time-points.

End point type

Secondary

End point timeframe

Baseline, Week 6, 10, 12 and 20

End point values	Placebo	REGN1033 100 mg q4w	REGN1033 300 mg q4w	REGN1033 300 mg q2w
Number of subjects analysed	65	62	64	59
Units: Percent Change
least squares mean (standard error)
Percent change at Week 6 (n=64,61,63,58)	5.2 ± 2.01	7 ± 2.06	4.8 ± 2.03	2.6 ± 2.13
Percent change at Week 10 (n=60,62,62,55)	7.1 ± 2.29	7.5 ± 2.28	6 ± 2.27	7.9 ± 2.41
Percent change at Week 12 (n=61,61,61,55)	7 ± 2.52	9.9 ± 2.53	9.8 ± 2.52	7.6 ± 2.65
Percent change at Week 20 (n=60,59,60,56)	6.3 ± 2.55	5.4 ± 2.57	7.8 ± 2.56	3.3 ± 2.68

No statistical analyses for this end point

Secondary: Percent Change in Loaded and Unloaded Stair Climb Power from Baseline to Week 6, 10, 12 and 20

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End point title

Percent Change in Loaded and Unloaded Stair Climb Power from Baseline to Week 6, 10, 12 and 20

End point description

The stair climb test comprising of 8 steps unloaded and 8 steps loaded (performed with an extra weight of approximately 20% of the subject’s body weight) involves using step switch pads placed on the bottom and the top steps to record the time required to climb the stairs. Subjects were instructed to climb 1 step at a time without assistance, only using the handrail if they lost their balance. Stair height, subject’s weight (including clothing worn during test), and time interval between each step pad, were recorded. The power exerted was calculated as: Power (watts) = Weight (kg) x rise in stairs over the interval (meters) divided by 9.804 m/^2 divided by time over the interval (seconds). Analysis was performed on FAS population. Here "Number of subjects analyzed" = Number of subjects evaluated for this outcome measure and "n" signifies number of subjects with available data at specified time-points.

End point type

Secondary

End point timeframe

Baseline, Week 6, 10, 12 and 20

End point values	Placebo	REGN1033 100 mg q4w	REGN1033 300 mg q4w	REGN1033 300 mg q2w
Number of subjects analysed	65	62	64	59
Units: Percent Change
least squares mean (standard error)
Loaded; Change at Week 6 (n= 42,43,44,43)	16.5 ± 4.39	8.9 ± 4.37	15.7 ± 4.31	4.4 ± 4.41
Loaded; Change at Week 10 (n= 36,41,41,36)	10.8 ± 7.69	14.1 ± 7.29	29.4 ± 7.26	9 ± 7.75
Loaded; Change at Week 12 (n= 45,47,48,41)	28.6 ± 7.02	24 ± 6.89	29.8 ± 6.83	19 ± 7.33
Loaded; Change at Week 20 (n= 43,46,46,40)	22.5 ± 6.4	15.8 ± 6.25	20.9 ± 6.19	13.5 ± 6.66
Unloaded; Change at Week 6 (n= 52,53,57,56)	7.2 ± 2.83	11.7 ± 2.81	7.6 ± 2.71	8.1 ± 2.78
Unloaded; Change at Week 10 (n= 46,51,55,47)	10.5 ± 3.35	18.2 ± 3.26	12.1 ± 3.16	13.5 ± 3.35
Unloaded; Change at Week 12 (n= 55,57,59,54)	11.5 ± 3.99	21 ± 3.93	20 ± 3.85	16 ± 4.02
Unloaded; Change at Week 20 (n= 54, 56,57,53)	9.7 ± 3.68	18.2 ± 3.63	15.3 ± 3.57	14.6 ± 3.73

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational product.

Adverse event reporting additional description

Reported AEs and deaths are treatment emergent that developed/worsened and deaths that occurred during 'treatment emergent period’ (from the first dose of study drug up to the end of study visit [8 weeks after last study dose]). Analysis was performed on safety population that included all randomized subjects who received any study drug.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

Reporting group title

Placebo

Reporting group description

Single subcutaneous (SC) injection of Placebo q2w for 12 weeks.

Reporting group title

REGN1033 100 mg q4w

Reporting group description

Single SC injection of REGN1033 100 mg q4w alternating with placebo q4w for 12 weeks.

Reporting group title

REGN1033 300 mg q4w

Reporting group description

Single SC injection of REGN1033 300 mg q4w alternating with placebo q4w for 12 weeks.

Reporting group title

REGN1033 300 mg q2w

Reporting group description

Single SC injection of REGN1033 300 mg q2w for 12 weeks.

Serious adverse events	Placebo	REGN1033 100 mg q4w	REGN1033 300 mg q4w	REGN1033 300 mg q2w
Total subjects affected by serious adverse events
subjects affected / exposed	5 / 65 (7.69%)	5 / 63 (7.94%)	5 / 65 (7.69%)	4 / 60 (6.67%)
number of deaths (all causes)	0	0	0	1
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic squamous cell carcinoma
subjects affected / exposed	0 / 65 (0.00%)	0 / 63 (0.00%)	0 / 65 (0.00%)	1 / 60 (1.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma of lung
subjects affected / exposed	0 / 65 (0.00%)	0 / 63 (0.00%)	1 / 65 (1.54%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Femur fracture
subjects affected / exposed	1 / 65 (1.54%)	0 / 63 (0.00%)	0 / 65 (0.00%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hip fracture
subjects affected / exposed	1 / 65 (1.54%)	1 / 63 (1.59%)	0 / 65 (0.00%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Periprosthetic fracture
subjects affected / exposed	0 / 65 (0.00%)	1 / 63 (1.59%)	0 / 65 (0.00%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Wound dehiscence
subjects affected / exposed	0 / 65 (0.00%)	1 / 63 (1.59%)	0 / 65 (0.00%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Hypertension
subjects affected / exposed	0 / 65 (0.00%)	0 / 63 (0.00%)	0 / 65 (0.00%)	1 / 60 (1.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Atrial tachycardia
subjects affected / exposed	1 / 65 (1.54%)	0 / 63 (0.00%)	0 / 65 (0.00%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sinus bradycardia
subjects affected / exposed	0 / 65 (0.00%)	0 / 63 (0.00%)	0 / 65 (0.00%)	1 / 60 (1.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Syncope
subjects affected / exposed	0 / 65 (0.00%)	1 / 63 (1.59%)	0 / 65 (0.00%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Haematochezia
subjects affected / exposed	1 / 65 (1.54%)	0 / 63 (0.00%)	0 / 65 (0.00%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatic cyst
subjects affected / exposed	0 / 65 (0.00%)	0 / 63 (0.00%)	1 / 65 (1.54%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Upper gastrointestinal haemorrhage
subjects affected / exposed	0 / 65 (0.00%)	0 / 63 (0.00%)	1 / 65 (1.54%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
subjects affected / exposed	1 / 65 (1.54%)	1 / 63 (1.59%)	0 / 65 (0.00%)	1 / 60 (1.67%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumothorax
subjects affected / exposed	0 / 65 (0.00%)	0 / 63 (0.00%)	0 / 65 (0.00%)	1 / 60 (1.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Musculoskeletal and connective tissue disorders
Osteoarthritis
subjects affected / exposed	0 / 65 (0.00%)	0 / 63 (0.00%)	1 / 65 (1.54%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Gastroenteritis viral
subjects affected / exposed	0 / 65 (0.00%)	0 / 63 (0.00%)	1 / 65 (1.54%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haemophilus sepsis
subjects affected / exposed	0 / 65 (0.00%)	1 / 63 (1.59%)	0 / 65 (0.00%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pharyngitis streptococcal
subjects affected / exposed	0 / 65 (0.00%)	1 / 63 (1.59%)	0 / 65 (0.00%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 65 (0.00%)	1 / 63 (1.59%)	0 / 65 (0.00%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Hyponatraemia
subjects affected / exposed	0 / 65 (0.00%)	0 / 63 (0.00%)	1 / 65 (1.54%)	0 / 60 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Placebo	REGN1033 100 mg q4w	REGN1033 300 mg q4w	REGN1033 300 mg q2w
Total subjects affected by non serious adverse events
subjects affected / exposed	32 / 65 (49.23%)	27 / 63 (42.86%)	30 / 65 (46.15%)	35 / 60 (58.33%)
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	1 / 65 (1.54%)	1 / 63 (1.59%)	2 / 65 (3.08%)	3 / 60 (5.00%)
occurrences all number	1	1	2	3
Excoriation
subjects affected / exposed	4 / 65 (6.15%)	0 / 63 (0.00%)	0 / 65 (0.00%)	1 / 60 (1.67%)
occurrences all number	4	0	0	1
Fall
subjects affected / exposed	8 / 65 (12.31%)	7 / 63 (11.11%)	5 / 65 (7.69%)	6 / 60 (10.00%)
occurrences all number	11	9	6	7
Nervous system disorders
Dizziness
subjects affected / exposed	2 / 65 (3.08%)	1 / 63 (1.59%)	6 / 65 (9.23%)	3 / 60 (5.00%)
occurrences all number	2	1	7	3
Headache
subjects affected / exposed	5 / 65 (7.69%)	3 / 63 (4.76%)	4 / 65 (6.15%)	1 / 60 (1.67%)
occurrences all number	5	3	6	1
General disorders and administration site conditions
Asthenia
subjects affected / exposed	1 / 65 (1.54%)	2 / 63 (3.17%)	0 / 65 (0.00%)	4 / 60 (6.67%)
occurrences all number	1	2	0	4
Fatigue
subjects affected / exposed	1 / 65 (1.54%)	1 / 63 (1.59%)	6 / 65 (9.23%)	3 / 60 (5.00%)
occurrences all number	1	1	6	3
Injection site erythema
subjects affected / exposed	5 / 65 (7.69%)	4 / 63 (6.35%)	4 / 65 (6.15%)	10 / 60 (16.67%)
occurrences all number	6	6	4	19
Injection site oedema
subjects affected / exposed	4 / 65 (6.15%)	1 / 63 (1.59%)	0 / 65 (0.00%)	2 / 60 (3.33%)
occurrences all number	4	1	0	2
Injection site pruritus
subjects affected / exposed	0 / 65 (0.00%)	1 / 63 (1.59%)	1 / 65 (1.54%)	3 / 60 (5.00%)
occurrences all number	0	2	1	3
Injection site reaction
subjects affected / exposed	1 / 65 (1.54%)	0 / 63 (0.00%)	4 / 65 (6.15%)	6 / 60 (10.00%)
occurrences all number	1	0	6	13
Gastrointestinal disorders
Nausea
subjects affected / exposed	2 / 65 (3.08%)	1 / 63 (1.59%)	2 / 65 (3.08%)	3 / 60 (5.00%)
occurrences all number	2	2	2	3
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	0 / 65 (0.00%)	1 / 63 (1.59%)	6 / 65 (9.23%)	0 / 60 (0.00%)
occurrences all number	0	1	6	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	5 / 65 (7.69%)	4 / 63 (6.35%)	5 / 65 (7.69%)	4 / 60 (6.67%)
occurrences all number	6	4	5	4
Back pain
subjects affected / exposed	4 / 65 (6.15%)	0 / 63 (0.00%)	3 / 65 (4.62%)	2 / 60 (3.33%)
occurrences all number	4	0	3	2
Muscle spasms
subjects affected / exposed	4 / 65 (6.15%)	4 / 63 (6.35%)	0 / 65 (0.00%)	3 / 60 (5.00%)
occurrences all number	4	4	0	4
Myalgia
subjects affected / exposed	3 / 65 (4.62%)	1 / 63 (1.59%)	4 / 65 (6.15%)	2 / 60 (3.33%)
occurrences all number	3	1	4	2
Pain in extremity
subjects affected / exposed	0 / 65 (0.00%)	4 / 63 (6.35%)	4 / 65 (6.15%)	2 / 60 (3.33%)
occurrences all number	0	5	4	2
Infections and infestations
Nasopharyngitis
subjects affected / exposed	2 / 65 (3.08%)	1 / 63 (1.59%)	0 / 65 (0.00%)	4 / 60 (6.67%)
occurrences all number	2	1	0	4
Sinusitis
subjects affected / exposed	1 / 65 (1.54%)	1 / 63 (1.59%)	2 / 65 (3.08%)	3 / 60 (5.00%)
occurrences all number	1	1	2	3
Urinary tract infection
subjects affected / exposed	4 / 65 (6.15%)	4 / 63 (6.35%)	0 / 65 (0.00%)	2 / 60 (3.33%)
occurrences all number	4	4	0	2

More information

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Were there any global substantial amendments to the protocol? Yes

10 Jan 2014

Following changes were done: •Added description of the independent Data Monitoring Committee (IDMC). •Clarifications to Inclusion/Exclusion criteria based on requests by health authorities. •Added detail about the severity of injection reactions and adverse events (AEs) that resulted in study drug dosing being permanently stopped. •Added detail about the severity of AEs that resulted in study drug dosing being temporarily stopped. •Clarified the prohibited medications section to specify ‘new prescription’ medications, to remove the prohibition for over-the-counter medications, and not require discussion in advance. •Clarified the description of the stair climb and 4-meter gait speed function measures. •Added a secondary endpoint. •Clarified the subject confidentiality statement. •Clarified the reasons for premature termination of the study.

10 Mar 2014

•Increased the number of study sites from 40 sites to 50 sites. •Added The European Quality of Life-5 Dimensions 3 Level System (EQ-5D-3L) Questionnaire. •Updated study procedures and endpoints. •Added the definition of adverse reactions and serious adverse reactions. •Added the definition of and reporting requirements for suspected unexpected serious adverse reactions.

23 Jul 2014

•Changes in the exclusion criteria, including decreases in the exclusion thresholds for sitting blood pressure and for HbA1C. •Added a 2% variance in the calculated appendicular lean mass to account for test-retest variability in whole-body DXA. •Added language for a first analysis of efficacy and safety assessments after subjects completed week 12 assessments. •Revised language stating that all subjects should attempt, or be asked to attempt, the stair climb test, but allowing subjects to choose not to perform the test, while still remaining eligible to participate in the study.

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 Randomized, Double-blind, Placebo-controlled, Multi-center Study of the Safety and Efficacy of 3-month Subcutaneous REGN1033 Treatment in Patients with Sarcopenia

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percent Change in Total Lean Body Mass by DXA From Baseline to Week 12

Primary: Percent Change in Total Lean Body Mass by DXA From Baseline to Week 12

Secondary: Percent Change in Appendicular Lean Body Mass from Baseline to Week 6, 10, 12 and 20

Secondary: Percent Change in Appendicular Lean Body Mass from Baseline to Week 6, 10, 12 and 20

Secondary: Percent Change in Total Lean Mass from Baseline to Week 6, 10, 12, and 20

Secondary: Percent Change in Total Lean Mass from Baseline to Week 6, 10, 12, and 20

Secondary: Percent Change in Total and Regional (Android and Gynoid) Fat Mass from Baseline to Week 6, 10, 12, and 20

Secondary: Percent Change in Total and Regional (Android and Gynoid) Fat Mass from Baseline to Week 6, 10, 12, and 20

Secondary: Percent Change in Maximal Leg Press Strength (1-RM) from Baseline to Week 6, 10, 12 and 20

Secondary: Percent Change in Maximal Leg Press Strength (1-RM) from Baseline to Week 6, 10, 12 and 20

Secondary: Percent Change in Maximal Chest Press Strength (1-RM) from Baseline to Week 6, 10, 12 and 20

Secondary: Percent Change in Maximal Chest Press Strength (1-RM) from Baseline to Week 6, 10, 12 and 20

Secondary: Percent Change in Hand Grip Strength (Dominant and Non-Dominant Hands) from Baseline to Week 6, 10, 12 and 20

Secondary: Percent Change in Hand Grip Strength (Dominant and Non-Dominant Hands) from Baseline to Week 6, 10, 12 and 20

Secondary: Changes in Short Physical Performance Battery (SPPB): Total Score from Baseline to Week 6, 10, 12 and 20

Secondary: Changes in Short Physical Performance Battery (SPPB): Total Score from Baseline to Week 6, 10, 12 and 20

Secondary: Changes in SPPB Subscore: Repeated Chair Stand Test from Baseline to Week 6, 10, 12 and 20

Secondary: Changes in SPPB Subscore: Repeated Chair Stand Test from Baseline to Week 6, 10, 12 and 20

Secondary: Changes in SPPB Subscore: Balance Testing from Baseline to Week 6, 10, 12 and 20

Secondary: Changes in SPPB Subscore: Balance Testing from Baseline to Week 6, 10, 12 and 20

Secondary: Changes in SPPB Subscore: 4-Meter Walk from Baseline to Week 6, 10, 12 and 20

Secondary: Changes in SPPB Subscore: 4-Meter Walk from Baseline to Week 6, 10, 12 and 20

Secondary: Percent Change in 4-Meter Gait Speed from Baseline to Week 6, 10, 12 and 20

Secondary: Percent Change in 4-Meter Gait Speed from Baseline to Week 6, 10, 12 and 20

Secondary: Percent Change in Distance Walked in the 6-Minute Walk Test (6MWT) from Baseline to Week 6, 10, 12 and 20

Secondary: Percent Change in Distance Walked in the 6-Minute Walk Test (6MWT) from Baseline to Week 6, 10, 12 and 20

Secondary: Percent Change in Loaded and Unloaded Stair Climb Power from Baseline to Week 6, 10, 12 and 20

Secondary: Percent Change in Loaded and Unloaded Stair Climb Power from Baseline to Week 6, 10, 12 and 20

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A Randomized, Double-blind, Placebo-controlled, Multi-center Study of the Safety and Efficacy of 3-month Subcutaneous REGN1033 Treatment in Patients with Sarcopenia