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

Extension of the CBYM338B2203 Phase IIb/III Study to Evaluate the Long-term Efficacy, Safety and Tolerability of Intravenous BYM338 in Patients With Sporadic Inclusion Body Myositis

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 211
• Phase: 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
  • Gent, Belgium, 9000
    • Novartis Investigative Site
  • Antwerpen
    • Edegem, Antwerpen, Belgium, 2650
      • 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
  • Tokushima, Japan, 770-8503
    • Novartis Investigative Site
  • Aichi
    • Nagoya, 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
  • Tokyo
    • Kodaira, Tokyo, Japan, 187-8551
      • Novartis Investigative Site
  • Wakayama
    • Wakayama-city, Wakayama, Japan, 641-8510
      • Novartis Investigative Site
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • 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: 34 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients who completed the core study
• Written informed consent must be obtained before any extension study assessment is performed.
• Able to communicate well with the investigator.
• Willing to participate for the entire duration of the extension study with commitment to follow study requirements and procedures.

Exclusion Criteria:

• Women who are pregnant
• Women of child-bearing potential unless they are using highly effective methods of contraception during dosing and for 6 months after the last BYM338 dose.
• Current use of prohibited treatments
• History of severe hypersensitivity reaction in the core study
• History of adverse event(s) (including those from the core study) prior to the start of study drug in the extension study that, in the judgment of the investigator, taking into account the subject's overall status, prevent the subject from entering the extension study
• Clinically significant abnormal liver function tests
• Any medical condition or laboratory finding which, in the opinion of the investigator may interfere with participation in the study, might confound the results of the study, or pose an additional safety risk in administering BYM338

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BYM338/bimagrumab 10 mg/kg; Participants received BYM338 10 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period.	Drug: 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.; Other Names: BYM338
Experimental: BYM338/bimagrumab 3 mg/kg; Participants received BYM338 3 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period.	Drug: 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.; Other Names: BYM338
Experimental: BYM338/bimagrumab 1 mg/kg; Participants received BYM338 1 mg/kg administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period.	Drug: 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.; Other Names: BYM338
Placebo Comparator: Placebo; Participants received placebo administered via intravenous infusion every 4 weeks for up to a maximum of 8 months after which they entered a 6-month, treatment-free follow-up period.	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
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths.	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.	to end of study (up to 14 months, including the 6-month treatment-free follow-up period)
Change From Core Study Baseline in 6 Minute Walking Distance Test (6MWD)	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.	Core study baseline, weeks 52, 78, 104, and >=117

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Core Study Baseline in Quadriceps Quantitative Muscle Testing (QMT) on the Right Side	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.	Core study baseline, week 52, week 78, week 104 and >=week 117
Change From Core Study Baseline in Sporadic Inclusion Body Myositis (sIBM) Functional Assessment (sIFA) Score	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. 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.	Core study baseline, week 52, week 78, week 104, and >=week 117
Estimated Annual Number of Falls Per Participant Within Treatment Group	Participants documented any fall occurrences in a paper diary during the study.	Core baseline to end of extension double-blind treatment (up to a maximum of 32 months)
Change From Core Study Baseline in Short Physical Performance Battery (SPPB) Score	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.	Core study baseline, week 52, week 78, week 104 and >=week 117
Change in Muscles of the Thigh	Magnetic resonance imaging (MRI) was planned to be used to characterize changes in muscles of the thigh in a subset of patients.	up to 1 year, up to 2 years
Number of Patients With Anti-BYM338 Antibodies	Investigated the development of immunogenicity against BYM338.	end of double-blind treatment (up to 8 months)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Amato AA, Hanna MG, Machado PM, Badrising UA, Chinoy H, Benveniste O, Karanam AK, Wu M, Tanko LB, Schubert-Tennigkeit AA, Papanicolaou DA, Lloyd TE, Needham M, 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, Aoki M, Katsuno M, Morihata H, Murata K, Nodera H, Nishino I, Romano CD, Williams VSL, Vissing J, Zhang Auberson L; RESILIENT Study Extension Group. Efficacy and Safety of Bimagrumab in Sporadic Inclusion Body Myositis: Long-term Extension of RESILIENT. Neurology. 2021 Mar 23;96(12):e1595-e1607. doi: 10.1212/WNL.0000000000011626. Epub 2021 Feb 17.

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2015
• Primary Completion (Actual): August 17, 2016
• Study Completion (Actual): February 13, 2017

Study Registration Dates

• First Submitted: July 9, 2015
• First Submitted That Met QC Criteria: October 8, 2015
• First Posted (Estimate): October 9, 2015

Study Record Updates

• Last Update Posted (Actual): March 13, 2018
• Last Update Submitted That Met QC Criteria: February 12, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: sporadic inclusion body myositis,; muscle wasting,; extension study,; BYM338,; bimagrumab,
• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Myositis; Myositis, Inclusion Body
• Other Study ID Numbers: CBYM338B2203E1; 2015-001411-12 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No