NCT02573467

An Extension Study of the Efficacy, Safety and Tolerability of BYM338 (Bimagrumab) in Patients With Sporadic Inclusion Body Myositis Who Previously Participated in the Core Study CBYM338B2203

Completed Phase 3 Results posted Last updated 13 March 2018

What this trial tests

Phase 3 trial testing Bimagrumab in Sporadic Inclusion Body Myositis in 211 participants. Completed in 13 February 2017.

Timeline

2 November 2015

Primary endpoint
17 August 2016

13 February 2017

Quick facts

Lead sponsor	Novartis Pharmaceuticals
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	211
Start date	2 November 2015
Primary completion	17 August 2016
Estimated completion	13 February 2017
Sites	38 locations across Denmark, France, Italy, Japan, Netherlands, Belgium, United Kingdom, Switzerland

Drugs / interventions tested

• Bimagrumab — full drug profile →
• Placebo

Conditions studied

• Sporadic Inclusion Body Myositis — all drugs for Sporadic Inclusion Body Myositis →

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

36 and older, any sex, with Sporadic Inclusion Body Myositis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths. Primary · to end of study (up to 14 months, including the 6-month treatment-free follow-up period)

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.

Adverse events

Group	Value	95% CI
BYM338/Bimagrumab 10 mg/kg	48
BYM338/Bimagrumab 3 mg/kg	50
BYM338/Bimagrumab 1 mg/kg	44
Placebo	49

Serious adverse events

Group	Value	95% CI
BYM338/Bimagrumab 10 mg/kg	12
BYM338/Bimagrumab 3 mg/kg	10
BYM338/Bimagrumab 1 mg/kg	7
Placebo	8

Deaths

Group	Value	95% CI
BYM338/Bimagrumab 10 mg/kg	1
BYM338/Bimagrumab 3 mg/kg	1
BYM338/Bimagrumab 1 mg/kg	1
Placebo	2

Change From Core Study Baseline in 6 Minute Walking Distance Test (6MWD) Primary · Core study baseline, weeks 52, 78, 104, and >=117

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.

Week 52 (n=53,52,51,54)

Group	Value	95% CI
BYM338/Bimagrumab 10 mg/kg	6.88	± 68.948
BYM338/Bimagrumab 3 mg/kg	9.48	± 81.676
BYM338/Bimagrumab 1 mg/kg	-14.26	± 81.029
Placebo	-5.98	± 78.817

Week 78

Group	Value	95% CI
BYM338/Bimagrumab 10 mg/kg	-5.25	± 122.002
BYM338/Bimagrumab 3 mg/kg	-9.73	± 68.302
BYM338/Bimagrumab 1 mg/kg	-18.66	± 81.536
Placebo	-32.78	± 96.494

Week 104

Group	Value	95% CI
BYM338/Bimagrumab 10 mg/kg	-22.68	± 102.549
BYM338/Bimagrumab 3 mg/kg	-50.58	± 118.012
BYM338/Bimagrumab 1 mg/kg	-25.08	± 95.737
Placebo	-61.30	± 107.399

>=Week 117

Group	Value	95% CI
BYM338/Bimagrumab 10 mg/kg	-206.65	± 281.923
BYM338/Bimagrumab 3 mg/kg	-5.0	± NA
BYM338/Bimagrumab 1 mg/kg	-53.65	± 114.322
Placebo	31.60	± NA

Change From Core Study Baseline in Quadriceps Quantitative Muscle Testing (QMT) on the Right Side Secondary · Core study baseline, week 52, week 78, week 104 and >=week 117

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.

Week 52

Group	Value	95% CI
BYM338/Bimagrumab 10 mg/kg	-6.29	± 31.121
BYM338/Bimagrumab 3 mg/kg	-19.70	± 77.820
BYM338/Bimagrumab 1 mg/kg	-5.62	± 32.245
Placebo	-14.22	± 27.577

Week 78

Group	Value	95% CI
BYM338/Bimagrumab 10 mg/kg	-9.43	± 41.285
BYM338/Bimagrumab 3 mg/kg	-23.76	± 73.729
BYM338/Bimagrumab 1 mg/kg	-17.04	± 25.696
Placebo	-21.02	± 31.391

Week 104

Group	Value	95% CI
BYM338/Bimagrumab 10 mg/kg	-11.92	± 35.243
BYM338/Bimagrumab 3 mg/kg	-16.99	± 34.379
BYM338/Bimagrumab 1 mg/kg	-18.63	± 37.968
Placebo	-21.91	± 39.985

>=Week 117

Group	Value	95% CI
BYM338/Bimagrumab 10 mg/kg	67.64	± NA
BYM338/Bimagrumab 3 mg/kg	33.38	± NA
BYM338/Bimagrumab 1 mg/kg	-19.36	± 18.475
Placebo	-18.24	± NA

Change From Core Study Baseline in Sporadic Inclusion Body Myositis (sIBM) Functional Assessment (sIFA) Score Secondary · Core study baseline, week 52, week 78, week 104, and >=week 117

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 value

Week 52

Group	Value	95% CI
BYM338/Bimagrumab 10 mg/kg	-1.34	± 15.249
BYM338/Bimagrumab 3 mg/kg	1.80	± 11.910
BYM338/Bimagrumab 1 mg/kg	3.17	± 11.380
Placebo	5.16	± 13.889

Week 78

Group	Value	95% CI
BYM338/Bimagrumab 10 mg/kg	-0.27	± 13.745
BYM338/Bimagrumab 3 mg/kg	5.33	± 13.099
BYM338/Bimagrumab 1 mg/kg	6.52	± 12.918
Placebo	7.41	± 14.410

Week 104

Group	Value	95% CI
BYM338/Bimagrumab 10 mg/kg	3.54	± 14.998
BYM338/Bimagrumab 3 mg/kg	8.04	± 16.861
BYM338/Bimagrumab 1 mg/kg	5.97	± 12.849
Placebo	7.39	± 15.580

>=Week 117

Group	Value	95% CI
BYM338/Bimagrumab 10 mg/kg	-16.37	± 21.857
BYM338/Bimagrumab 3 mg/kg	10.91	± NA
BYM338/Bimagrumab 1 mg/kg	1.37	± 17.655
Placebo	6.36	± NA

Estimated Annual Number of Falls Per Participant Within Treatment Group Secondary · Core baseline to end of extension double-blind treatment (up to a maximum of 32 months)

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

Group	Value	95% CI
BYM338/Bimagrumab 10 mg/kg	4.164
BYM338/Bimagrumab 3 mg/kg	3.879
BYM338/Bimagrumab 1 mg/kg	3.480
Placebo	3.835

Change From Core Study Baseline in Short Physical Performance Battery (SPPB) Score Secondary · Core study baseline, week 52, week 78, week 104 and >=week 117

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.

Week 52

Group	Value	95% CI
BYM338/Bimagrumab 10 mg/kg	0.3	± 1.73
BYM338/Bimagrumab 3 mg/kg	0.2	± 1.61
BYM338/Bimagrumab 1 mg/kg	-0.4	± 1.74
Placebo	-0.3	± 1.31

Week 78

Group	Value	95% CI
BYM338/Bimagrumab 10 mg/kg	-0.5	± 2.58
BYM338/Bimagrumab 3 mg/kg	-0.1	± 1.54
BYM338/Bimagrumab 1 mg/kg	-0.4	± 1.69
Placebo	-0.9	± 1.92

Week 104

Group	Value	95% CI
BYM338/Bimagrumab 10 mg/kg	-1.4	± 3.29
BYM338/Bimagrumab 3 mg/kg	-0.9	± 2.77
BYM338/Bimagrumab 1 mg/kg	-1.1	± 2.56
Placebo	-1.3	± 2.35

>=Week 117

Group	Value	95% CI
BYM338/Bimagrumab 10 mg/kg	-3.0	± 4.24
BYM338/Bimagrumab 3 mg/kg	0.0	± NA
BYM338/Bimagrumab 1 mg/kg	0.3	± 2.06
Placebo	0.0	± NA

Number of Patients With Anti-BYM338 Antibodies Secondary · end of double-blind treatment (up to 8 months)

Investigated the development of immunogenicity against BYM338.

Group	Value	95% CI
BYM338/Bimagrumab 10 mg/kg	0
BYM338/Bimagrumab 3 mg/kg	1
BYM338/Bimagrumab 1 mg/kg	0
Placebo	2

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, up to 14 months.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

BYM338/Bimagrumab 10 mg/kg

Serious: 12/53 (23%)

Deaths: 1/53

BYM338/Bimagrumab 3 mg/kg

Serious: 10/52 (19%)

Deaths: 1/52

BYM338/Bimagrumab 1 mg/kg

Serious: 7/51 (14%)

Deaths: 1/51

Placebo

Serious: 8/55 (15%)

Deaths: 2/55

Pooled Active Treatment Groups

Serious: 29/156 (19%)

Deaths: 3/156

Serious adverse events (43 terms)

Reaction	System	BYM338/Bimagrumab 10 mg/kg	BYM338/Bimagrumab 3 mg/kg	BYM338/Bimagrumab 1 mg/kg	Placebo	Pooled Active Treatment Gr…
Pneumonia	Infections and infestations	—	—	—	—	—
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Sepsis	Infections and infestations	—	—	—	—	—
Ankle fracture	Injury, poisoning and procedural complications	—	—	—	—	—
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—
Colitis	Gastrointestinal disorders	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—
Dysphagia	Gastrointestinal disorders	—	—	—	—	—
Oesophageal achalasia	Gastrointestinal disorders	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—
Cellulitis	Infections and infestations	—	—	—	—	—
Urosepsis	Infections and infestations	—	—	—	—	—
Avulsion fracture	Injury, poisoning and procedural complications	—	—	—	—	—
Fall	Injury, poisoning and procedural complications	—	—	—	—	—
Head injury	Injury, poisoning and procedural complications	—	—	—	—	—
Hip fracture	Injury, poisoning and procedural complications	—	—	—	—	—
Lower limb fracture	Injury, poisoning and procedural complications	—	—	—	—	—
Patella fracture	Injury, poisoning and procedural complications	—	—	—	—	—
Pelvic fracture	Injury, poisoning and procedural complications	—	—	—	—	—
Subarachnoid haemorrhage	Injury, poisoning and procedural complications	—	—	—	—	—
Subdural haemorrhage	Injury, poisoning and procedural complications	—	—	—	—	—
Ulna fracture	Injury, poisoning and procedural complications	—	—	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—	—	—

Other adverse events (31 terms — click to expand)

Reaction	System	BYM338/Bimagrumab 10 mg/kg	BYM338/Bimagrumab 3 mg/kg	BYM338/Bimagrumab 1 mg/kg	Placebo	Pooled Active Treatment Gr…
Fall	Injury, poisoning and procedural complications	—	—	—	—	—
Contusion	Injury, poisoning and procedural complications	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—
Skin abrasion	Injury, poisoning and procedural complications	—	—	—	—	—
Muscle spasms	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Laceration	Injury, poisoning and procedural complications	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—	—
Ligament sprain	Injury, poisoning and procedural complications	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Hypertension	Vascular disorders	—	—	—	—	—
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—
Acne	Skin and subcutaneous tissue disorders	—	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—	—
Limb injury	Injury, poisoning and procedural complications	—	—	—	—	—
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Neck pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—	—	—
Foot fracture	Injury, poisoning and procedural complications	—	—	—	—	—
Injury	Injury, poisoning and procedural complications	—	—	—	—	—
Muscular weakness	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Haematoma	Vascular disorders	—	—	—	—	—
Seasonal allergy	Immune system disorders	—	—	—	—	—
Joint injury	Injury, poisoning and procedural complications	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—
Productive cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—

Most-reported serious reactions: Pneumonia, Pneumonia aspiration, Sepsis, Ankle fracture, Basal cell carcinoma, Squamous cell carcinoma, Anaemia, Colitis.

Data from ClinicalTrials.gov NCT02573467 adverse events section.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.