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

• ClinicalTrials.gov Identifier: NCT01925209
• Recruitment Status: Completed
• First Posted: August 19, 2013
• Results First Posted: May 12, 2017
• Last Update Posted: August 11, 2017
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: August 15, 2013
• First Posted Date: August 19, 2013
• Results First Submitted Date: January 5, 2017
• Results First Posted Date: May 12, 2017
• Last Update Posted Date: August 11, 2017
• Actual Study Start Date: September 26, 2013
• Actual Primary Completion Date: January 6, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 5, 2017)

Change From Baseline in 6 Minute Walking Distance (6MWD) Test at Week 52 [ Time Frame: Baseline, 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.

Original Primary Outcome Measures (submitted: August 15, 2013)

Change from Baseline in 6 Minute Walking Distance Test (6MWD) meters to Week 52 [ Time Frame: Baseline, Week 52 ]

Change from baseline to Week 52 in the distance a patient can walk in a set timeframe. 6 Minute Walking Distance Test measures the distance (in meters) that a patient can walk in a 6 minute timeframe.

Current Secondary Outcome Measures (submitted: April 5, 2017)

• Estimated Within Treatment Group Lean Body Mass (LBM) Ratio at Week 52 [ Time Frame: Baseline, 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.
• Change From Baseline in Quadriceps Quantitative Muscle Testing (QMT) on the Right Side at Week 52 [ Time Frame: Baseline, Week 52 ]
  Quadriceps muscle strength was measured by portable fixed dynamometry (PFD) on the right side. A negative change from baseline indicates deterioration.
• Change From Baseline in Sporadic Inclusion Body Myositis (sIBM) Functional Assessment (sIFA) Score at Week 52 [ Time Frame: Baseline, 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.
• Estimated Annual Number of Falls Per Patient Within Treatment Group [ Time Frame: Week 52 ]
  Participants documented any fall occurrences in a paper diary during the study.
• Change From Baseline in Short Physical Performance Battery (SPPB) Score at Week 52 [ Time Frame: Baseline, 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.

Original Secondary Outcome Measures (submitted: August 15, 2013)

• Change from Baseline in lean body mass (LBM) at Week 52 [ Time Frame: Baseline, Week 52 ]
  Change from baseline to Week 52 in the total and appendicular lean body mass
• Change from Baseline in quadriceps Quantitative Muscle Testing (QMT) at Week 52 [ Time Frame: Baseline, Week 52 ]
  Change from baseline to Week 52 in quadriceps QMT.
• Change from Baseline in Patient-Reported Physical Function at Week 52 [ Time Frame: Baseline, Week 52 ]
  Change from baseline to Week 52 in a patient reported outcome instrument.
• Rate of Fall Events [ Time Frame: Baseline, Day 1, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108 ]
  Number of falls
• Change from Baseline in Short Physical Performance Battery score at Week 52 [ Time Frame: Baseline, Week 52 ]
  Change from baseline to Week 52 in physical performance as measured by the Short Physical Performance Battery (SPPB).
• Safety and Tolerability of different i.v. BYM338 doses [ Time Frame: Baseline, Day 1, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, 104, 108 ]
  Safety and tolerability
• Change from Baseline in 6MWD meters to Week 52 [ Time Frame: Baseline, Week 52 ]
  Dose-response relationship

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy and Safety of Bimagrumab/BYM338 at 52 Weeks on Physical Function, Muscle Strength, Mobility in sIBM Patients
• Official Title: 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
• Brief Summary: 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Sporadic Inclusion Body Myositis

Intervention

• 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.
• Drug: Placebo
  Matching placebo to BYM338 was provided in colorless glass vials with a rubber stopper and aluminum flip-off caps.

Study Arms

• 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.
  Intervention: Drug: BYM338/bimagrumab
• 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.
  Intervention: Drug: BYM338/bimagrumab
• 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.
  Intervention: Drug: BYM338/bimagrumab
• 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.
  Intervention: Drug: Placebo

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 21, 2016): 251
• Original Estimated Enrollment (submitted: August 15, 2013): 240
• Actual Study Completion Date: January 6, 2016
• Actual Primary Completion Date: January 6, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.);

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 36 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Denmark, France, Italy, Japan, Netherlands, Switzerland, United Kingdom, United States
• Removed Location Countries: Germany, Poland

Administrative Information

• NCT Number: NCT01925209
• Other Study ID Numbers: CBYM338B2203
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: Same as current
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

• PRS Account: Novartis
• Verification Date: August 2017