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

NCT02573467 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: CBYM338B2203E12015-001411-12
• Study Type: interventional
• Target: 211
• Locations: 10 countries
• Sites: 38

Brief Summary

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.

Conditions

Sporadic Inclusion Body Myositis

Keywords

sporadic inclusion body myositis,; muscle wasting,; extension study,; BYM338,; bimagrumab,

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• Change From Core Study Baseline in Quadriceps Quantitative Muscle Testing (QMT) on the Right Side

  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

  Core study baseline, week 52, week 78, week 104, and >=week 117

• Estimated Annual Number of Falls Per Participant Within Treatment Group

  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

  Core study baseline, week 52, week 78, week 104 and >=week 117

• Change in Muscles of the Thigh

  up to 1 year, up to 2 years

Study Arms (4)

BYM338/bimagrumab 10 mg/kg

EXPERIMENTAL

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/bimagrumab 3 mg/kg

EXPERIMENTAL

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/bimagrumab 1 mg/kg

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Bimagrumab DRUG

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.

Also known as: BYM338

BYM338/bimagrumab 1 mg/kg; BYM338/bimagrumab 10 mg/kg; BYM338/bimagrumab 3 mg/kg

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 36 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (38)

Novartis Investigative Site

Phoenix, Arizona, 85028, United States

Location

Novartis Investigative Site

Orange, California, 92868, United States

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Novartis Investigative Site

Sacramento, California, 95817, United States

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Novartis Investigative Site

Miami, Florida, 33101, United States

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Novartis Investigative Site

Kansas City, Kansas, 66160, United States

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Novartis Investigative Site

Baltimore, Maryland, 21287, United States

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Novartis Investigative Site

Boston, Massachusetts, 02114, United States

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Novartis Investigative Site

Boston, Massachusetts, 02115, United States

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Novartis Investigative Site

Columbus, Ohio, 43221, United States

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Novartis Investigative Site

Portland, Oregon, 97239, United States

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Novartis Investigative Site

Dallas, Texas, 75235, United States

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Novartis Investigative Site

Houston, Texas, 77030, United States

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Novartis Investigative Site

St Leonards, New South Wales, 2065, Australia

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Novartis Investigative Site

Cauldfield, Victoria, 3162, Australia

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Novartis Investigative Site

Nedlands, Western Australia, 6009, Australia

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Novartis Investigative Site

Edegem, Antwerpen, 2650, Belgium

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Novartis Investigative Site

Brussels, 1200, Belgium

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Novartis Investigative Site

Ghent, 9000, Belgium

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Novartis Investigative Site

Copenhagen, 2100, Denmark

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Novartis Investigative Site

Paris, 75013, France

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Novartis Investigative Site

Brescia, BS, 25123, Italy

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Novartis Investigative Site

Rome, Lazio, 00168, Italy

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Novartis Investigative Site

Messina, ME, 98125, Italy

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Novartis Investigative Site

Milan, MI, 20133, Italy

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Novartis Investigative Site

Padua, PD, 35128, Italy

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Novartis Investigative Site

Nagoya, Aichi-ken, 466-8560, Japan

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Novartis Investigative Site

Kumamoto, Kumamoto, 860-8556, Japan

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Novartis Investigative Site

Sendai, Miyagi, 980-8574, Japan

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Novartis Investigative Site

Osaka, Osaka, 534-0021, Japan

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Novartis Investigative Site

Kodaira, Tokyo, 187-8551, Japan

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Novartis Investigative Site

Wakayama, Wakayama, 641-8510, Japan

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Novartis Investigative Site

Tokushima, 770-8503, Japan

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Novartis Investigative Site

Amsterdam, 1105 AZ, Netherlands

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Novartis Investigative Site

Leiden, 2333 ZA, Netherlands

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Novartis Investigative Site

Zurich, 8091, Switzerland

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Novartis Investigative Site

Salford, Manchester, M6 8HD, United Kingdom

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Novartis Investigative Site

London, NW1 2BU, United Kingdom

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Novartis Investigative Site

Newcastle upon Tyne, NE4 5PL, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 33597289 DERIVED

MeSH Terms

Conditions

Myositis, Inclusion Body; Muscular Atrophy

Interventions

bimagrumab

Condition Hierarchy (Ancestors)

Myositis; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2015
• First Posted: October 9, 2015
• Study Start: November 2, 2015
• Primary Completion: August 17, 2016
• Study Completion: February 13, 2017
• Last Updated: March 13, 2018
• Results First Posted: March 13, 2018

Record last verified: 2018-02

Locations

JP (7); FR (1); DK (1); CH (1); IT (5); GB (3); BE (3); US (12); AU (3); NL (2)