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 )

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Sporadic Inclusion Body Myositis	Drug: BYM338/bimagrumab; Drug: Placebo	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 251 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: September 26, 2013
• Actual Primary Completion Date: January 6, 2016
• Actual Study Completion Date: January 6, 2016

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.

Eligibility Criteria

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

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.);

Contacts and Locations

Locations

United States, Arizona

Novartis Investigative Site

Phoenix, Arizona, United States, 85028

United States, California

Novartis Investigative Site

Orange, California, United States, 92868

Novartis Investigative Site

Sacramento, California, United States, 95817

United States, Florida

Novartis Investigative Site

Miami, Florida, United States, 33101

United States, Kansas

Novartis Investigative Site

Kansas City, Kansas, United States, 66160

United States, Maryland

Novartis Investigative Site

Baltimore, Maryland, United States, 21287

United States, Massachusetts

Novartis Investigative Site

Boston, Massachusetts, United States, 02114

Novartis Investigative Site

Boston, Massachusetts, United States, 02115

United States, Ohio

Novartis Investigative Site

Columbus, Ohio, United States, 43221

United States, Oregon

Novartis Investigative Site

Portland, Oregon, United States, 97239

United States, Texas

Novartis Investigative Site

Dallas, Texas, United States, 75235

Novartis Investigative Site

Houston, Texas, United States, 77030

Australia, New South Wales

Novartis Investigative Site

St. Leonards, New South Wales, Australia, 2065

Australia, Victoria

Novartis Investigative Site

Cauldfield, Victoria, Australia, 3162

Australia, Western Australia

Novartis Investigative Site

Nedlands, Western Australia, Australia, 6009

Belgium

Novartis Investigative Site

Bruxelles, Belgium, 1200

Novartis Investigative Site

Edegem, Belgium, 2650

Novartis Investigative Site

Gent, Belgium, 9000

Denmark

Novartis Investigative Site

Copenhagen, Denmark, 2100

France

Novartis Investigative Site

Paris, France, 75013

Italy

Novartis Investigative Site

Brescia, BS, Italy, 25123

Novartis Investigative Site

Roma, Lazio, Italy, 00168

Novartis Investigative Site

Messina, ME, Italy, 98125

Novartis Investigative Site

Milano, MI, Italy, 20133

Novartis Investigative Site

Padova, PD, Italy, 35128

Japan

Novartis Investigative Site

Nagoya-city, Aichi, Japan, 466-8560

Novartis Investigative Site

Kumamoto City, Kumamoto, Japan, 860-8556

Novartis Investigative Site

Sendai-city, Miyagi, Japan, 980-8574

Novartis Investigative Site

Osaka-city, Osaka, Japan, 534-0021

Novartis Investigative Site

Tokushima-city, Tokushima, Japan, 770-8503

Novartis Investigative Site

Kodaira-city, Tokyo, Japan, 187-8551

Novartis Investigative Site

Wakayama-city, Wakayama, Japan, 641-8510

Netherlands

Novartis Investigative Site

Amsterdam, Netherlands

Novartis Investigative Site

Leiden, Netherlands, 2333 ZA

Switzerland

Novartis Investigative Site

Zuerich, Switzerland, 8091

United Kingdom

Novartis Investigative Site

Salford, Manchester, United Kingdom, M6 8HD

Novartis Investigative Site

London, United Kingdom, NW1 2BU

Novartis Investigative Site

Newcastle upon Tyne, United Kingdom, NE4 5PL

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01925209
• Other Study ID Numbers: CBYM338B2203
• First Posted: August 19, 2013
• Results First Posted: May 12, 2017
• Last Update Posted: August 11, 2017
• Last Verified: August 2017

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

sporadic inclusion body myositis,; myositis,; muscle wasting,; controlled clinical trial,; randomized,; body mass,; muscle function,; strength,; performance,; physical function

Additional relevant MeSH terms:

Myositis; Myositis, Inclusion Body; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases