Efficacy and Safety of Bimagrumab/BYM338 at 52 Weeks on Physical Function, Muscle Strength, Mobility in sIBM Patients (RESILIENT)

A Randomized, Double-blind, Placebo-controlled, Multicenter, Parallel Group, Dose-finding, Pivotal, Phase 2b/3 Study to Evaluate the Efficacy, Safety, and Tolerability of Intravenous BYM338 at 52 Weeks on Physical Function, Muscle Strength, and Mobility and Additional Long Term Safety up to 2 Years in Patients With Sporadic Inclusion Body Myositis

This study evaluated the efficacy, safety and tolerability of multiple doses of bimagrumab/BYM338 vs placebo, when administered intravenously (i.v.), on physical function, muscle strength, and mobility in patients with sporadic inclusion body myositis (sIBM).

Study Overview

• Status: Completed
• Conditions: Sporadic Inclusion Body Myositis
• Intervention / Treatment: Drug: BYM338/bimagrumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 251
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • St. Leonards, New South Wales, Australia, 2065
      • Novartis Investigative Site
  • Victoria
    • Cauldfield, Victoria, Australia, 3162
      • Novartis Investigative Site
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Novartis Investigative Site
• Belgium
  • Bruxelles, Belgium, 1200
    • Novartis Investigative Site
  • Edegem, Belgium, 2650
    • Novartis Investigative Site
  • Gent, Belgium, 9000
    • Novartis Investigative Site
• Denmark
  • Copenhagen, Denmark, 2100
    • Novartis Investigative Site
• France
  • Paris, France, 75013
    • Novartis Investigative Site
• Italy
  • BS
    • Brescia, BS, Italy, 25123
      • Novartis Investigative Site
  • Lazio
    • Roma, Lazio, Italy, 00168
      • Novartis Investigative Site
  • ME
    • Messina, ME, Italy, 98125
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20133
      • Novartis Investigative Site
  • PD
    • Padova, PD, Italy, 35128
      • Novartis Investigative Site
• Japan
  • Aichi
    • Nagoya-city, Aichi, Japan, 466-8560
      • Novartis Investigative Site
  • Kumamoto
    • Kumamoto City, Kumamoto, Japan, 860-8556
      • Novartis Investigative Site
  • Miyagi
    • Sendai-city, Miyagi, Japan, 980-8574
      • Novartis Investigative Site
  • Osaka
    • Osaka-city, Osaka, Japan, 534-0021
      • Novartis Investigative Site
  • Tokushima
    • Tokushima-city, Tokushima, Japan, 770-8503
      • Novartis Investigative Site
  • Tokyo
    • Kodaira-city, Tokyo, Japan, 187-8551
      • Novartis Investigative Site
  • Wakayama
    • Wakayama-city, Wakayama, Japan, 641-8510
      • Novartis Investigative Site
• Netherlands
  • Amsterdam, Netherlands
    • Novartis Investigative Site
  • Leiden, Netherlands, 2333 ZA
    • Novartis Investigative Site
• Switzerland
  • Zuerich, Switzerland, 8091
    • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom, NW1 2BU
    • Novartis Investigative Site
  • Newcastle upon Tyne, United Kingdom, NE4 5PL
    • Novartis Investigative Site
  • Manchester
    • Salford, Manchester, United Kingdom, M6 8HD
      • Novartis Investigative Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85028
      • Novartis Investigative Site
  • California
    • Orange, California, United States, 92868
      • Novartis Investigative Site
    • Sacramento, California, United States, 95817
      • Novartis Investigative Site
  • Florida
    • Miami, Florida, United States, 33101
      • Novartis Investigative Site
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Novartis Investigative Site
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Novartis Investigative Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Novartis Investigative Site
    • Boston, Massachusetts, United States, 02115
      • Novartis Investigative Site
  • Ohio
    • Columbus, Ohio, United States, 43221
      • Novartis Investigative Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Novartis Investigative Site
  • Texas
    • Dallas, Texas, United States, 75235
      • Novartis Investigative Site
    • Houston, Texas, United States, 77030
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Diagnosed with sporadic inclusion body myositis;
• Must be able to walk (assistive aids allowed, including intermittent use of wheelchair);

Key Exclusion Criteria:

• Must not have other conditions that significantly limit ability to move around;
• Must not be using corticosteroids. Must not have used systemic corticosteroid (at daily dose >=10mg prednisone) for the past 3 months;
• Must meet cardiovascular requirements;
• Must not be pregnant or nursing;
• Must not have a chronic active infection (e.g., HIV, hepatitis B or C, tuberculosis, etc.);

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BYM338/bimagrumab 10 mg/kg; Participants received study medication with BYM338 at 10 mg/kg from Day 1 to Week 52 and up to Week 104, administered by intravenous (i.v.) infusion every 4 weeks.	Drug: BYM338/bimagrumab; 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.
Experimental: BYM338/bimagrumab 3 mg/kg; Participants received study medication with BYM338 at 3 mg/kg from Day 1 to Week 52 and up to Week 104, administered by i.v. infusion every 4 weeks.	Drug: BYM338/bimagrumab; 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.
Experimental: BYM338/bimagrumab 1 mg/kg; Participants received study medication with BYM338 at 1 mg/kg from Day 1 to Week 52 and up to Week 104, administered by i.v. infusion every 4 weeks.	Drug: BYM338/bimagrumab; 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.
Placebo Comparator: Placebo; Participants received matching placebo to BYM338 from Day 1 to Week 52 and up to Week 104, administered by i.v. infusion every 4 weeks.	Drug: Placebo; Matching placebo to BYM338 was provided in colorless glass vials with a rubber stopper and aluminum flip-off caps.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in 6 Minute Walking Distance (6MWD) Test at Week 52	The 6MWD test measured the distance (in meters) that a participant walked in a 6 minute timeframe. A positive change from baseline indicates improvement.	Baseline, Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimated Within Treatment Group Lean Body Mass (LBM) Ratio at Week 52	LBM was measured via dual energy x-ray absorptiometry (DXA) and calculated as (LBM at Week 52/LBM at baseline)*100 . A positive change from baseline indicates improvement.	Baseline, Week 52
Change From Baseline in Quadriceps Quantitative Muscle Testing (QMT) on the Right Side at Week 52	Quadriceps muscle strength was measured by portable fixed dynamometry (PFD) on the right side. A negative change from baseline indicates deterioration.	Baseline, Week 52
Change From Baseline in Sporadic Inclusion Body Myositis (sIBM) Functional Assessment (sIFA) Score at Week 52	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.	Baseline, Week 52
Estimated Annual Number of Falls Per Patient Within Treatment Group	Participants documented any fall occurrences in a paper diary during the study.	Week 52
Change From Baseline in Short Physical Performance Battery (SPPB) Score at Week 52	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.	Baseline, Week 52

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Hanna MG, Badrising UA, Benveniste O, Lloyd TE, Needham M, Chinoy H, Aoki M, Machado PM, 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, Katsuno M, Murata K, Nodera H, Nishino I, Romano CD, Williams VSL, Vissing J, Auberson LZ, Wu M, de Vera A, Papanicolaou DA, Amato AA; RESILIENT Study Group. Safety and efficacy of intravenous bimagrumab in inclusion body myositis (RESILIENT): a randomised, double-blind, placebo-controlled phase 2b trial. Lancet Neurol. 2019 Sep;18(9):834-844. doi: 10.1016/S1474-4422(19)30200-5.

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2013
• Primary Completion (Actual): January 6, 2016
• Study Completion (Actual): January 6, 2016

Study Registration Dates

• First Submitted: August 15, 2013
• First Submitted That Met QC Criteria: August 15, 2013
• First Posted (Estimate): August 19, 2013

Study Record Updates

• Last Update Posted (Actual): August 11, 2017
• Last Update Submitted That Met QC Criteria: August 7, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: physical function; sporadic inclusion body myositis,; myositis,; muscle wasting,; controlled clinical trial,; randomized,; body mass,; muscle function,; strength,; performance,
• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Myositis; Myositis, Inclusion Body
• Other Study ID Numbers: CBYM338B2203