An Extension Study of the Efficacy, Safety and Tolerabili... | NCT02573467

NCT02573467

ID	Type	Description	Link
2015-001411-12	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Brief Summary

This extension study will provide data to further evaluate the efficacy, safety, and tolerability of three doses of BYM338 and to assess the long-term effects of BYM338 in patients with sporadic inclusion body myositis. The extension study was planned to consist of a Screening epoch (to assess patient eligibility), followed by a Treatment Period 1 epoch (double-blind and placebo-controlled), and a Treatment Period 2 epoch (open-label). A Post-treatment Follow-up (FUP) epoch was also planned for patients who discontinued prematurely. Patients who complete the core study and qualify for this extension study entered Treatment Period 1 and continued on the study drug to which they were randomized in the core study (either to one of the three bimagrumab doses (1 mg/kg, 3 mg/kg, and 10mg/kg) or placebo) during Treatment Period 1. Thus, Treatment Period 1 was double-blind and placebo-controlled. Participants were to continue in Treatment Period 1 until the dose with the best benefit-risk profile was determined from the core study data and selected (duration of Treatment Period 1 was estimated to be between 6 and 8 months). Once the dose with the best benefit-risk profile was selected, all participants (including those who were receiving placebo) were planned to enter Treatment Period 2 and switch to open-label treatment with bimagrumab at the selected dose. The core study has been completed but since the core study did not meet the primary end point (no bimagrumab dose was identified based on the core study efficacy results) the extension study was terminated as per protocol/sponsor's decision; therefore, no patients had entered Treatment Period 2. Instead, all patients were to return for the End of Treatment Period 1 (EOT1) visit at their next scheduled visit. As per protocol, all patients who discontinued study medication during Treatment Period 1 for any reason, including due to the study having been stopped as per protocol/sponsor's decision, were to have entered and complete the 6-month FUP after their EOT1 visit.

Due to the nature of the design of the core and extension studies and termination of study medication in the extension study, the treatment duration for individual patients varied considerably. Consequently, the number of patients contributing data to the efficacy analyses at Week 104 and later timepoints was decreased.

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
BYM338/bimagrumab 10 mg/kg	Experimental	Participants received BYM338 10 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period.	Drug: Bimagrumab
BYM338/bimagrumab 3 mg/kg	Experimental	Participants received BYM338 3 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period.	Drug: Bimagrumab
BYM338/bimagrumab 1 mg/kg	Experimental	Participants received BYM338 1 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period.	Drug: Bimagrumab
Placebo	Placebo Comparator	Participants received placebo administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period.	Drug: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Bimagrumab	Drug	BYM338, a 150 mg/mL concentrate for solution for i.v. infusion, was provided in colorless glass vials with a rubber stopper and aluminum flip-off caps.	BYM338/bimagrumab 1 mg/kg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths.	Safety monitoring was conducted throughout the study. AEs starting on or after the day of first administration of extension study drug until last administration of study drug + 56 days are considered. SAEs starting on or after the day of first administration of extension study drug are considered. Deaths which occurred on or after the day of first administration of extension study drug are considered.	to end of study (up to 14 months, including the 6-month treatment-free follow-up period)
Change From Core Study Baseline in 6 Minute Walking Distance Test (6MWD)	The 6MWD test measures the distance (in meters) that a participant can walk in a 6 minute time frame. A positive change from baseline indicates improvement. The efficacy analysis and time points were based on windowed visits relative to the first dose of the double-blind treatment in the core study.	Core study baseline, weeks 52, 78, 104, and >=117

Secondary Outcomes

Measure	Description	Time Frame
Change From Core Study Baseline in Quadriceps Quantitative Muscle Testing (QMT) on the Right Side	Quantitative Muscle Testing (QMT) was used to describe the long-term evolution of quadriceps muscle strength on the right side. The QMT was performed using the same portable fixed dynamometry (PFD) used in the core study. A negative change from baseline indicates deterioration. The efficacy analysis and time points were based on windowed visits relative to the first dose of the double-blind treatment in the core study.

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		Phoenix	Arizona	85028	United States
Novartis Investigative Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
33597289	Derived	Amato AA, Hanna MG, Machado PM, Badrising UA, Chinoy H, Benveniste O, Karanam AK, Wu M, Tanko LB, Schubert-Tennigkeit AA, Papanicolaou DA, Lloyd TE, Needham M, Liang C, Reardon KA, de Visser M, Ascherman DP, Barohn RJ, Dimachkie MM, Miller JAL, Kissel JT, Oskarsson B, Joyce NC, Van den Bergh P, Baets J, De Bleecker JL, Karam C, David WS, Mirabella M, Nations SP, Jung HH, Pegoraro E, Maggi L, Rodolico C, Filosto M, Shaibani AI, Sivakumar K, Goyal NA, Mori-Yoshimura M, Yamashita S, Suzuki N, Aoki M, Katsuno M, Morihata H, Murata K, Nodera H, Nishino I, Romano CD, Williams VSL, Vissing J, Zhang Auberson L; RESILIENT Study Extension Group. Efficacy and Safety of Bimagrumab in Sporadic Inclusion Body Myositis: Long-term Extension of RESILIENT. Neurology. 2021 Mar 23;96(12):e1595-e1607. doi: 10.1212/WNL.0000000000011626. Epub 2021 Feb 17.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	BYM338/Bimagrumab 10 mg/kg	Participants received BYM338 10 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period.
FG001	BYM338/Bimagrumab 3 mg/kg

Periods

Title

Milestones

Reasons Not Completed

Double-blind Treatment Epoch

Type	Comment	Milestone Data
STARTED	Mean duration of exposure during the extension double-blind treatment period was 197.2 to 212.3 days

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

BYM338/bimagrumab 10 mg/kg

BYM338/bimagrumab 3 mg/kg

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	BYM338/Bimagrumab 10 mg/kg	Participants received BYM338 10 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period.
BG001	BYM338/Bimagrumab 3 mg/kg	Participants received BYM338 3 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period..
BG002	BYM338/Bimagrumab 1 mg/kg	Participants received BYM338 1 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period.
BG003	Placebo	Participants received BYM338 1 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period.
BG004	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Adverse events

Title	Measurements
	OG00048 OG00150 OG00244 OG003

Primary

Change From Core Study Baseline in 6 Minute Walking Distance Test (6MWD)

The 6MWD test measures the distance (in meters) that a participant can walk in a 6 minute time frame. A positive change from baseline indicates improvement. The efficacy analysis and time points were based on windowed visits relative to the first dose of the double-blind treatment in the core study.

The full analysis set, which consisted of all participants who were assigned to treatment in the core study and who received at least one dose of study drug during the extension, was considered for the analysis. Participants with both core baseline (BL) and post core-BL values for each time point were analyzed for that time point.

Posted

Mean

Standard Deviation

meters

Core study baseline, weeks 52, 78, 104, and >=117

ID	Title	Description
OG000	BYM338/Bimagrumab 10 mg/kg	Participants received BYM338 10 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period.
OG001	BYM338/Bimagrumab 3 mg/kg	Participants received BYM338 3 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period..
OG002	BYM338/Bimagrumab 1 mg/kg

Secondary

Change From Core Study Baseline in Quadriceps Quantitative Muscle Testing (QMT) on the Right Side

Quantitative Muscle Testing (QMT) was used to describe the long-term evolution of quadriceps muscle strength on the right side. The QMT was performed using the same portable fixed dynamometry (PFD) used in the core study. A negative change from baseline indicates deterioration. The efficacy analysis and time points were based on windowed visits relative to the first dose of the double-blind treatment in the core study.

Posted

Mean

Standard Deviation

newtons

Core study baseline, week 52, week 78, week 104 and >=week 117

ID	Title	Description
OG000	BYM338/Bimagrumab 10 mg/kg	Participants received BYM338 10 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period.
OG001	BYM338/Bimagrumab 3 mg/kg	Participants received BYM338 3 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period..

Secondary

Change From Core Study Baseline in Sporadic Inclusion Body Myositis (sIBM) Functional Assessment (sIFA) Score

Self-reported physical function was assessed by a newly developed patient reported outcome named sporadic inclusion body myositis (sIBM) functional assessment (sIFA). The sIFA consists of 11 items scored on an 11 point numerical rating scale from 0 (no difficulty) to 10 (unable to do) across 3 domains: upper body functioning, lower body functioning and general functioning. Participants completed the assessment where the recall period was the past week prior to completing the patient reported outcome (PRO). The total score on the sIFA scale ranges from 0 (minimum) to 110 (maximum). Higher values represent a worse outcome. A positive change from baseline indicates deterioration. The efficacy analysis and time points were based on windowed visits relative to the first dose of the double-blind treatment in the core study.

Posted

Mean

Standard Deviation

score on a scale

Core study baseline, week 52, week 78, week 104, and >=week 117

ID	Title	Description
OG000	BYM338/Bimagrumab 10 mg/kg	Participants received BYM338 10 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period.

Secondary

Estimated Annual Number of Falls Per Participant Within Treatment Group

Participants documented any fall occurrences in a paper diary during the study.

Safety set: The safety set consisted of all participants who were assigned to treatment in the core study and who received at least one dose of study drug during the extension.

Posted

Number

Annual number of falls per participant

Core baseline to end of extension double-blind treatment (up to a maximum of 32 months)

ID	Title	Description
OG000	BYM338/Bimagrumab 10 mg/kg	Participants received BYM338 10 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period.
OG001	BYM338/Bimagrumab 3 mg/kg	Participants received BYM338 3 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period..
OG002	BYM338/Bimagrumab 1 mg/kg	Participants received BYM338 1 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period.

Secondary

Change From Core Study Baseline in Short Physical Performance Battery (SPPB) Score

The SPPB evaluated lower extremities function by testing gait speed, ability to keep standing balance and time to rise from a chair five times. The sub-score for each test ranged from 0 to 4. The summary score, which was a summation of scores from the 3 tests, ranged from 0 to 12. An increase in score indicates improvement in physical performance. A negative change from baseline indicates deterioration. The efficacy analysis and time points were based on windowed visits relative to the first dose of the double-blind treatment in the core study.

Posted

Mean

Standard Deviation

score on a scale

Core study baseline, week 52, week 78, week 104 and >=week 117

ID	Title	Description
OG000	BYM338/Bimagrumab 10 mg/kg	Participants received BYM338 10 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period.
OG001	BYM338/Bimagrumab 3 mg/kg	Participants received BYM338 3 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period..

Secondary

Change in Muscles of the Thigh

Magnetic resonance imaging (MRI) was planned to be used to characterize changes in muscles of the thigh in a subset of patients.

No participants were analyzed. The optional MRI assessment was not initiated as the study was stopped.

Posted

up to 1 year, up to 2 years

ID	Title	Description
OG000	BYM338/Bimagrumab 10 mg/kg	Participants received BYM338 10 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period.
OG001	BYM338/Bimagrumab 3 mg/kg	Participants received BYM338 3 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period..
OG002	BYM338/Bimagrumab 1 mg/kg	Participants received BYM338 1 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period.
OG003	Placebo

Secondary

Number of Patients With Anti-BYM338 Antibodies

Investigated the development of immunogenicity against BYM338.

Safety set: The safety set consisted of all participants who were assigned to treatment in the core study and who received at least one dose of study drug during the extension. Only those participants who provided a sample were analyzed.

Posted

Number

Participants

end of double-blind treatment (up to 8 months)

ID	Title	Description
OG000	BYM338/Bimagrumab 10 mg/kg	Participants received BYM338 10 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period.
OG001	BYM338/Bimagrumab 3 mg/kg	Participants received BYM338 3 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period..
OG002	BYM338/Bimagrumab 1 mg/kg	Participants received BYM338 1 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	BYM338/Bimagrumab 10 mg/kg	Participants received BYM338 10 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period.	1	53	12	53	40	53
EG001	BYM338/Bimagrumab 3 mg/kg	Participants received BYM338 3 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period..	1	52	10	52	46	52
EG002	BYM338/Bimagrumab 1 mg/kg	Participants received BYM338 1 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period.	1	51	7	51	38	51
EG003	Placebo	Participants received BYM338 1 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period.	2	55	8	55	43	55
EG004	Pooled Active Treatment Groups	Participants from all 3 BYM338 groups	3	156	29	156	124	156

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected53 at risk EG0010 affected52 at risk EG0020 affected51 at risk EG0031 affected55 at risk EG0040 affected156 at risk
Colitis	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected53 at risk EG0010 affected52 at risk EG0020 affected51 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected53 at risk EG0010 affected52 at risk EG0020 affected51 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected53 at risk EG0010 affected52 at risk EG0020 affected51 at risk EG003
Oesophageal achalasia	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected53 at risk EG0011 affected52 at risk EG0020 affected51 at risk EG003
Asthenia	General disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected53 at risk EG0010 affected52 at risk EG0020 affected51 at risk EG003
Cellulitis	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0000 affected53 at risk EG0011 affected52 at risk EG0020 affected51 at risk EG003
Pneumonia	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0001 affected53 at risk EG0011 affected52 at risk EG0021 affected51 at risk EG003
Sepsis	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0001 affected53 at risk EG0010 affected52 at risk EG0020 affected51 at risk EG003
Urosepsis	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0000 affected53 at risk EG0010 affected52 at risk EG0021 affected51 at risk EG003
Ankle fracture	Injury, poisoning and procedural complications	MedDRA (19.1)	Systematic Assessment	EG0001 affected53 at risk EG0011 affected52 at risk EG0020 affected51 at risk EG003
Avulsion fracture	Injury, poisoning and procedural complications	MedDRA (19.1)	Systematic Assessment	EG0000 affected53 at risk EG0010 affected52 at risk EG0021 affected51 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA (19.1)	Systematic Assessment	EG0000 affected53 at risk EG0010 affected52 at risk EG0021 affected51 at risk EG003
Head injury	Injury, poisoning and procedural complications	MedDRA (19.1)	Systematic Assessment	EG0000 affected53 at risk EG0010 affected52 at risk EG0020 affected51 at risk EG003
Hip fracture	Injury, poisoning and procedural complications	MedDRA (19.1)	Systematic Assessment	EG0001 affected53 at risk EG0010 affected52 at risk EG0020 affected51 at risk EG003
Lower limb fracture	Injury, poisoning and procedural complications	MedDRA (19.1)	Systematic Assessment	EG0001 affected53 at risk EG0010 affected52 at risk EG0020 affected51 at risk EG003
Patella fracture	Injury, poisoning and procedural complications	MedDRA (19.1)	Systematic Assessment	EG0000 affected53 at risk EG0011 affected52 at risk EG0020 affected51 at risk EG003
Pelvic fracture	Injury, poisoning and procedural complications	MedDRA (19.1)	Systematic Assessment	EG0000 affected53 at risk EG0010 affected52 at risk EG0020 affected51 at risk EG003
Subarachnoid haemorrhage	Injury, poisoning and procedural complications	MedDRA (19.1)	Systematic Assessment	EG0000 affected53 at risk EG0010 affected52 at risk EG0020 affected51 at risk EG003
Subdural haemorrhage	Injury, poisoning and procedural complications	MedDRA (19.1)	Systematic Assessment	EG0001 affected53 at risk EG0010 affected52 at risk EG0020 affected51 at risk EG003
Ulna fracture	Injury, poisoning and procedural complications	MedDRA (19.1)	Systematic Assessment	EG0001 affected53 at risk EG0010 affected52 at risk EG0020 affected51 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected53 at risk EG0010 affected52 at risk EG0020 affected51 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected53 at risk EG0010 affected52 at risk EG0020 affected51 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected53 at risk EG0011 affected52 at risk EG0020 affected51 at risk EG003
Inclusion body myositis	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected53 at risk EG0010 affected52 at risk EG0020 affected51 at risk EG003
Joint effusion	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected53 at risk EG0010 affected52 at risk EG0020 affected51 at risk EG003
Mobility decreased	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected53 at risk EG0011 affected52 at risk EG0020 affected51 at risk EG003
Muscle haemorrhage	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected53 at risk EG0010 affected52 at risk EG0020 affected51 at risk EG003
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected53 at risk EG0011 affected52 at risk EG0020 affected51 at risk EG003
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (19.1)	Systematic Assessment	EG0000 affected53 at risk EG0010 affected52 at risk EG0021 affected51 at risk EG003
Bladder cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (19.1)	Systematic Assessment	EG0000 affected53 at risk EG0011 affected52 at risk EG0020 affected51 at risk EG003
Bowen's disease	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (19.1)	Systematic Assessment	EG0000 affected53 at risk EG0011 affected52 at risk EG0020 affected51 at risk EG003
Haemangioma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (19.1)	Systematic Assessment	EG0001 affected53 at risk EG0010 affected52 at risk EG0020 affected51 at risk EG003
Skin cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (19.1)	Systematic Assessment	EG0000 affected53 at risk EG0011 affected52 at risk EG0020 affected51 at risk EG003
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (19.1)	Systematic Assessment	EG0001 affected53 at risk EG0011 affected52 at risk EG0020 affected51 at risk EG003
Headache	Nervous system disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected53 at risk EG0010 affected52 at risk EG0020 affected51 at risk EG003
Migraine	Nervous system disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected53 at risk EG0011 affected52 at risk EG0020 affected51 at risk EG003
Presyncope	Nervous system disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected53 at risk EG0011 affected52 at risk EG0020 affected51 at risk EG003
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected53 at risk EG0010 affected52 at risk EG0022 affected51 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected53 at risk EG0010 affected52 at risk EG0020 affected51 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected53 at risk EG0010 affected52 at risk EG0020 affected51 at risk EG003
Peripheral arterial occlusive disease	Vascular disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected53 at risk EG0010 affected52 at risk EG0021 affected51 at risk EG003
Peripheral venous disease	Vascular disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected53 at risk EG0010 affected52 at risk EG0021 affected51 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain upper	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected53 at risk EG0014 affected52 at risk EG0020 affected51 at risk EG0030 affected55 at risk EG0044 affected156 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (19.1)	Systematic Assessment	EG0009 affected53 at risk EG0015 affected52 at risk EG0029 affected51 at risk EG003
Seasonal allergy	Immune system disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected53 at risk EG0010 affected52 at risk EG0023 affected51 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0000 affected53 at risk EG0014 affected52 at risk EG0021 affected51 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA (19.1)	Systematic Assessment	EG0003 affected53 at risk EG0013 affected52 at risk EG0024 affected51 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA (19.1)	Systematic Assessment	EG0009 affected53 at risk EG0017 affected52 at risk EG00212 affected51 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA (19.1)	Systematic Assessment	EG00030 affected53 at risk EG00136 affected52 at risk EG00230 affected51 at risk EG003
Foot fracture	Injury, poisoning and procedural complications	MedDRA (19.1)	Systematic Assessment	EG0003 affected53 at risk EG0011 affected52 at risk EG0020 affected51 at risk EG003
Injury	Injury, poisoning and procedural complications	MedDRA (19.1)	Systematic Assessment	EG0003 affected53 at risk EG0011 affected52 at risk EG0020 affected51 at risk EG003
Joint injury	Injury, poisoning and procedural complications	MedDRA (19.1)	Systematic Assessment	EG0003 affected53 at risk EG0010 affected52 at risk EG0020 affected51 at risk EG003
Laceration	Injury, poisoning and procedural complications	MedDRA (19.1)	Systematic Assessment	EG0001 affected53 at risk EG0017 affected52 at risk EG0024 affected51 at risk EG003
Ligament sprain	Injury, poisoning and procedural complications	MedDRA (19.1)	Systematic Assessment	EG0005 affected53 at risk EG0012 affected52 at risk EG0022 affected51 at risk EG003
Limb injury	Injury, poisoning and procedural complications	MedDRA (19.1)	Systematic Assessment	EG0003 affected53 at risk EG0011 affected52 at risk EG0021 affected51 at risk EG003
Skin abrasion	Injury, poisoning and procedural complications	MedDRA (19.1)	Systematic Assessment	EG0006 affected53 at risk EG0017 affected52 at risk EG0024 affected51 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected53 at risk EG0015 affected52 at risk EG0026 affected51 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0002 affected53 at risk EG0014 affected52 at risk EG0023 affected51 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0004 affected53 at risk EG0018 affected52 at risk EG0023 affected51 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected53 at risk EG0013 affected52 at risk EG0020 affected51 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0003 affected53 at risk EG0012 affected52 at risk EG0020 affected51 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0002 affected53 at risk EG0012 affected52 at risk EG0024 affected51 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0002 affected53 at risk EG0014 affected52 at risk EG0022 affected51 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected53 at risk EG0010 affected52 at risk EG0020 affected51 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected53 at risk EG0015 affected52 at risk EG0023 affected51 at risk EG003
Dizziness	Nervous system disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected53 at risk EG0010 affected52 at risk EG0020 affected51 at risk EG003
Headache	Nervous system disorders	MedDRA (19.1)	Systematic Assessment	EG0001 affected53 at risk EG0012 affected52 at risk EG0024 affected51 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA (19.1)	Systematic Assessment	EG0000 affected53 at risk EG0011 affected52 at risk EG0021 affected51 at risk EG003
Acne	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0002 affected53 at risk EG0011 affected52 at risk EG0023 affected51 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0003 affected53 at risk EG0010 affected52 at risk EG0022 affected51 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA (19.1)	Systematic Assessment	EG0002 affected53 at risk EG0013 affected52 at risk EG0023 affected51 at risk EG003
Haematoma	Vascular disorders	MedDRA (19.1)	Systematic Assessment	EG0002 affected53 at risk EG0010 affected52 at risk EG0022 affected51 at risk EG003
Hypertension	Vascular disorders	MedDRA (19.1)	Systematic Assessment	EG0005 affected53 at risk EG0012 affected52 at risk EG0022 affected51 at risk EG003

ID	Term
D018979	Myositis, Inclusion Body
D009133	Muscular Atrophy

Ancestor Terms

ID	Term
D009220	Myositis
D009135	Muscular Diseases
D009140	Musculoskeletal Diseases
D009468	Neuromuscular Diseases
D009422	Nervous System Diseases
D020879	Neuromuscular Manifestations
D009461	Neurologic Manifestations
D001284	Atrophy
D020763	Pathological Conditions, Anatomical
D013568	Pathological Conditions, Signs and Symptoms
D012816	Signs and Symptoms

ID	Term
C000596367	bimagrumab

EG0040 affected156 at risk

EG0041 affected156 at risk

EG0040 affected156 at risk

EG0041 affected156 at risk

EG0040 affected156 at risk

EG0041 affected156 at risk

EG0043 affected156 at risk

EG0041 affected156 at risk

EG0042 affected156 at risk

EG0041 affected156 at risk

EG0040 affected156 at risk

EG0041 affected156 at risk

EG0040 affected156 at risk

EG0041 affected156 at risk

EG0040 affected156 at risk

EG0041 affected156 at risk

EG0040 affected156 at risk

EG0041 affected156 at risk

EG0042 affected156 at risk

EG0041 affected156 at risk

EG0043 affected156 at risk

EG0041 affected156 at risk

EG00423 affected156 at risk

EG0043 affected156 at risk

EG0045 affected156 at risk

EG00410 affected156 at risk

EG00428 affected156 at risk

EG00496 affected156 at risk

EG0044 affected156 at risk

EG0043 affected156 at risk

EG00412 affected156 at risk

EG0049 affected156 at risk

EG0045 affected156 at risk

EG00417 affected156 at risk

EG00412 affected156 at risk

EG0049 affected156 at risk

EG00415 affected156 at risk

EG0044 affected156 at risk

EG0045 affected156 at risk

EG0048 affected156 at risk

EG0040 affected156 at risk

EG0049 affected156 at risk

EG0041 affected156 at risk

EG0047 affected156 at risk

EG0042 affected156 at risk

EG0046 affected156 at risk

EG0045 affected156 at risk

EG0048 affected156 at risk

EG0044 affected156 at risk

EG0049 affected156 at risk

Title	Measurements
	OG000-5.25± 122.002 OG001-9.73± 68.302 OG002-18.66± 81.536 OG003-32.78± 96.494

Title	Measurements
	OG000-22.68± 102.549 OG001-50.58± 118.012 OG002-25.08± 95.737 OG003-61.30± 107.399

Title	Measurements
	OG000-206.65± 281.923 OG001-5.0± NAStandard deviation (SD) does not apply when n = 1. OG002-53.65± 114.322 OG00331.60± NASD does not apply when n = 1.

Title	Measurements
	OG000-9.43± 41.285 OG001-23.76± 73.729 OG002-17.04± 25.696 OG003-21.02± 31.391

Title	Measurements
	OG000-11.92± 35.243 OG001-16.99± 34.379 OG002-18.63± 37.968 OG003-21.91± 39.985

Title	Measurements
	OG00067.64± NASD does not apply when n = 1. OG00133.38± NASD does not apply when n = 1. OG002-19.36± 18.475 OG003-18.24± NASD does not apply when n = 1.

Title	Measurements
	OG000-0.27± 13.745 OG0015.33± 13.099 OG0026.52± 12.918 OG0037.41± 14.410

Title	Measurements
	OG0003.54± 14.998 OG0018.04± 16.861 OG0025.97± 12.849 OG0037.39± 15.580

Title	Measurements
	OG000-16.37± 21.857 OG00110.91± NASD does not apply when n = 1. OG0021.37± 17.655 OG0036.36± NASD does not apply when n = 1.

Title	Measurements
	OG000-0.5± 2.58 OG001-0.1± 1.54 OG002-0.4± 1.69 OG003-0.9± 1.92

Title	Measurements
	OG000-1.4± 3.29 OG001-0.9± 2.77 OG002-1.1± 2.56 OG003-1.3± 2.35

Title	Measurements
	OG000-3.0± 4.24 OG0010.0± NASD does not apply when n = 1. OG0020.3± 2.06 OG0030.0± NASD does not apply when n = 1.