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NCT02250443: BYM338

Study of Long-term Safety, Efficacy Tolerability of BYM338 in Patients With Sporadic Inclusion Body Myositis

Completed Phase 2, PHASE3 Results posted Last updated 30 December 2020
What this trial tests

Phase 2, PHASE3 trial testing BYM338 (Bimagrumab) in Sporadic Inclusion Body Myositis (sIBM) in 10 participants. Completed in 23 August 2016.

Timeline
11 March 2014
Primary endpoint
23 August 2016
23 August 2016

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 2, PHASE3
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment10
Start date11 March 2014
Primary completion23 August 2016
Estimated completion23 August 2016
Sites2 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

Adults 40 to 75, any sex, with Sporadic Inclusion Body Myositis (sIBM). 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 as a Measure of Safety and Tolerability Primary · Up to 29 month

Any Adverse Event was defined as occurrence of any symptom regardless of intensity grade, Serious Adverse Event (SAEs) assessed as medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in persistent or significant disability/incapacity

Death
GroupValue95% CI
BYM3380
Serious adverse events (SAE)
GroupValue95% CI
BYM3382
Adverse Events (AE)
GroupValue95% CI
BYM33810
Changes From Baseline in Lean Body Mass (LBM) by Dual-Energy X-ray Absorptiometery (DXA) Secondary · Baseline, Day 1, 57, 113, 169, 365, 533, and day 729

To assess the effect of multiple doses of BYM338 on lean body mass as measured by DXA in terms of change from baseline.

Day 1
GroupValue95% CI
BYM3380± 0
Day 57
GroupValue95% CI
BYM3384.292± 2.7480
Day 113
GroupValue95% CI
BYM3385.552± 3.6066
Day 169
GroupValue95% CI
BYM3387.463± 4.5687
Day 365
GroupValue95% CI
BYM3386.919± 2.9669
Day 533
GroupValue95% CI
BYM3386.885± 3.7894
Day 729
GroupValue95% CI
BYM3380.727± NA
Pharmacokinetics (PK) Parameter of Cmin From Multiple i.v. Dosing Secondary · Day 29, 85, 169, 253, 337, 421, 505, 589, 673, 757, 1177

To obtain pharmacokinetic data from multiple i.v. dosing of BYM338 in this patient population. Pre-dose, 30 mins \& 4 hours post-dose on Day 1. Pre-dose only on each subsequent administration

Day 29 (n=10)
GroupValue95% CI
BYM33813.4± 5.01
Day 85 (n=10)
GroupValue95% CI
BYM33824.1± 13.1
Day 169 (n=10)
GroupValue95% CI
BYM33826.3± 15.9
Day 253 (n=9)
GroupValue95% CI
BYM33828.8± 12.1
Day 337 (n=10)
GroupValue95% CI
BYM33824.4± 14.6
Day 421 (n=9)
GroupValue95% CI
BYM33824.5± 11.5
Day 505 (n=8)
GroupValue95% CI
BYM33828.3± 10.6
Day 589 (n=6)
GroupValue95% CI
BYM33839.8± 30.2
Changes From Baseline in Muscle Strength. Secondary · Baseline, Day 1, 113, 169, 365, 533, 729

Quadriceps muscle strength was measured, Quadriceps Quantitative Muscle Testing (QMT) by portable fixed dynamometry (PFD). A negative change from baseline indicates deterioration

Quadriceps score left side Day 1
GroupValue95% CI
BYM3380± 0
left side Day 113
GroupValue95% CI
BYM338-5.80± 28.160
left side Day 169
GroupValue95% CI
BYM338-5.95± 26.587
left side Day 365
GroupValue95% CI
BYM338-9.51± 28.149
left side Day 533
GroupValue95% CI
BYM338-25.77± 21.321
left side Day 729
GroupValue95% CI
BYM338178.26± NA
Quadriceps score Right side Day 1
GroupValue95% CI
BYM3380± 0
Right side Day 113
GroupValue95% CI
BYM338-4.83± 29.904
Changes From Baseline in Muscle Function (Hand-grip and Pinch-grip Dynamometry) Secondary · Baseline,Day 1, 113, 169, 365, 533, 729

The effect of BYM338 on additional muscle function measures (hand-grip and pinch-grip dynamometry).

Left hand-grip day 1
GroupValue95% CI
BYM3380± 0
Left hand-grip day 113
GroupValue95% CI
BYM33825.58± 37.544
Left hand-grip day 169
GroupValue95% CI
BYM33821.36± 43.815
Left hand-grip day 365
GroupValue95% CI
BYM338-1.42± 47.973
Left hand-grip day 533
GroupValue95% CI
BYM3382.78± 16.934
Left hand-grip day 729
GroupValue95% CI
BYM3388.95± 24.034
Right hand-grip day 1
GroupValue95% CI
BYM3380± 0
Right hand-grip day 113
GroupValue95% CI
BYM33899.59± 184.472
Changes From Baseline in Muscle Function 6 Minute Walking Distance Secondary · Baseline,Day 1, 113, 169, 365, 533, 729

The effect of BYM338 on additional muscle function measures (6 minute walking distance). The 6MWD test measured the distance (in meters) that a participant walked in a 6 minute timeframe. A positive change from baseline indicates improvement.

Day 1
GroupValue95% CI
BYM3380± 0
Day 113
GroupValue95% CI
BYM338-1.56± 13.685
Day 169
GroupValue95% CI
BYM338-7.41± 12.463
Day 365
GroupValue95% CI
BYM338-8.97± 15.763
Day 533
GroupValue95% CI
BYM338-16.99± 22.382
Day 729
GroupValue95% CI
BYM338-17.86± NA
Change From Baseline of Thigh Muscle Volume (TMV) by MRI Scan Secondary · Baseline, Day 1, 57, 113

Thigh Muscle Volume (TMV) change was evaluated by a responder analysis. Patients whose loss of muscle TMV by MRI was equal or more than 2% at Week 8 and 16 were considered responders

Day 1
GroupValue95% CI
BYM3380± 0
Day 57
GroupValue95% CI
BYM3384.14± 4.250
Day 113
GroupValue95% CI
BYM3384.51± 6.300
Pharmacokinetics (PK) Parameter of Cmax Secondary · Day 1

To obtain pharmacokinetic data from multiple i.v. dosing of BYM338 in this patient population. Pre-dose, 30 mins \& 4 hours post-dose on Day 1.

GroupValue95% CI
BYM338278± 62.6
Time to Reach the Maximum Concentration After Drug Administration (Tmax) Secondary · Day 1

The time to reach the maximum concentration after drug administration

GroupValue95% CI
BYM3380.7440.648 – 4.73

Adverse events — posted to ClinicalTrials.gov

Time frame: period up to 104 weeks. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

BYM338 10mg/kg i.v.
Serious: 2/10 (20%)
Deaths:

Serious adverse events (9 terms)

ReactionSystemBYM338 10mg/kg i.v.
AnaemiaBlood and lymphatic system disorders
Myocardial infarctionCardiac disorders
TachyarrhythmiaCardiac disorders
Gastrointestinal haemorrhageGastrointestinal disorders
Haemorrhoidal haemorrhageGastrointestinal disorders
DehydrationMetabolism and nutrition disorders
Iron deficiencyMetabolism and nutrition disorders
Lung adenocarcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Oesophageal carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Other adverse events (73 terms — click to expand)

ReactionSystemBYM338 10mg/kg i.v.
FallInjury, poisoning and procedural complications
Muscle spasmsMusculoskeletal and connective tissue disorders
DiarrhoeaGastrointestinal disorders
Skin abrasionInjury, poisoning and procedural complications
AcneSkin and subcutaneous tissue disorders
Oedema peripheralGeneral disorders
Urinary tract infectionInfections and infestations
Ligament sprainInjury, poisoning and procedural complications
ArthralgiaMusculoskeletal and connective tissue disorders
RashSkin and subcutaneous tissue disorders
NauseaGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
GoutMetabolism and nutrition disorders
Musculoskeletal painMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
LymphadenopathyBlood and lymphatic system disorders
Atrial fibrillationCardiac disorders
Myocardial infarctionCardiac disorders
TinnitusEar and labyrinth disorders
Abdominal painGastrointestinal disorders
Frequent bowel movementsGastrointestinal disorders
Haemorrhoidal haemorrhageGastrointestinal disorders
Inguinal herniaGastrointestinal disorders
VomitingGastrointestinal disorders
Peripheral swellingGeneral disorders
CellulitisInfections and infestations
Fungal skin infectionInfections and infestations
InfluenzaInfections and infestations
NasopharyngitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
Avulsion fractureInjury, poisoning and procedural complications
Bone contusionInjury, poisoning and procedural complications
ConcussionInjury, poisoning and procedural complications
ContusionInjury, poisoning and procedural complications
Corneal abrasionInjury, poisoning and procedural complications
LacerationInjury, poisoning and procedural complications
Limb injuryInjury, poisoning and procedural complications
ScratchInjury, poisoning and procedural complications
Tibia fractureInjury, poisoning and procedural complications
Mammogram abnormalInvestigations

Most-reported serious reactions: Anaemia, Myocardial infarction, Tachyarrhythmia, Gastrointestinal haemorrhage, Haemorrhoidal haemorrhage, Dehydration, Iron deficiency, Lung adenocarcinoma.

Data from ClinicalTrials.gov NCT02250443 adverse events section.

Sponsor's own description

This study is an open-label, long-term study for those patients who participated in the prior proof-of-concept protocol, in which the preliminary efficacy for BYM338 in patients with sIBM was demonstrated after a single 30 mg/kg i.v. dose of BYM338. This study is designed to confirm the efficacy, safety and tolerability of BYM338 in sIBM with long-term dosing. However due to lack of efficacy in patients with sIBM, the study was terminated early.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Myostatin/Activin Receptor Ligands in Muscle and the Development Status of Attenuating Drugs.
    Rodgers BD, Ward CW. · · 2022 · cited 68× · PMID 34520530 · DOI 10.1210/endrev/bnab030
  2. Inhibition of myostatin and related signaling pathways for the treatment of muscle atrophy in motor neuron diseases.
    Abati E, Manini A, Comi GP, Corti S. · · 2022 · cited 53× · PMID 35727341 · DOI 10.1007/s00018-022-04408-w
  3. Therapeutic applications and challenges in myostatin inhibition for enhanced skeletal muscle mass and functions.
    Wetzlich B, Nyakundi BB, Yang J. · · 2025 · cited 37× · PMID 39340593 · DOI 10.1007/s11010-024-05120-y
  4. Pathogenesis, Intervention, and Current Status of Drug Development for Sarcopenia: A Review.
    Jang JY, Kim D, Kim ND. · · 2023 · cited 36× · PMID 37371730 · DOI 10.3390/biomedicines11061635
  5. Follistatin Gene Therapy Improves Ambulation in Becker Muscular Dystrophy.
    Al-Zaidy SA, Sahenk Z, Rodino-Klapac LR, Kaspar B, et al · · 2015 · cited 34× · PMID 27858738 · DOI 10.3233/jnd-150083
  6. Long-term safety and tolerability of bimagrumab (BYM338) in sporadic inclusion body myositis.
    Sivakumar K, Cochrane TI, Sloth B, Ashar H, et al · · 2020 · cited 21× · PMID 32690797 · DOI 10.1212/wnl.0000000000010417

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Other recruiting trials for Sporadic Inclusion Body Myositis (sIBM)

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing