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

NCT ID: NCT02573467

Last Updated: 2018-03-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 211 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-02
• Study Completion Date: 2017-02-13

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Bimagrumab

Intervention Type: 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.

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.

Group Type: EXPERIMENTAL

Bimagrumab

Intervention Type: 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.

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.

Group Type: EXPERIMENTAL

Bimagrumab

Intervention Type: 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.

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Other Intervention Names

BYM338

Eligibility Criteria

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

• Minimum Eligible Age: 36 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Phoenix, Arizona, United States

Novartis Investigative Site

Orange, California, United States

Novartis Investigative Site

Sacramento, California, United States

Novartis Investigative Site

Miami, Florida, United States

Novartis Investigative Site

Kansas City, Kansas, United States

Novartis Investigative Site

Baltimore, Maryland, United States

Novartis Investigative Site

Boston, Massachusetts, United States

Novartis Investigative Site

Boston, Massachusetts, United States

Novartis Investigative Site

Columbus, Ohio, United States

Novartis Investigative Site

Portland, Oregon, United States

Novartis Investigative Site

Dallas, Texas, United States

Novartis Investigative Site

Houston, Texas, United States

Novartis Investigative Site

St Leonards, New South Wales, Australia

Novartis Investigative Site

Cauldfield, Victoria, Australia

Novartis Investigative Site

Nedlands, Western Australia, Australia

Novartis Investigative Site

Edegem, Antwerpen, Belgium

Novartis Investigative Site

Brussels, , Belgium

Novartis Investigative Site

Ghent, , Belgium

Novartis Investigative Site

Copenhagen, , Denmark

Novartis Investigative Site

Paris, , France

Novartis Investigative Site

Brescia, BS, Italy

Novartis Investigative Site

Rome, Lazio, Italy

Novartis Investigative Site

Messina, ME, Italy

Novartis Investigative Site

Milan, MI, Italy

Novartis Investigative Site

Padua, PD, Italy

Novartis Investigative Site

Nagoya, Aichi-ken, Japan

Novartis Investigative Site

Kumamoto, Kumamoto, Japan

Novartis Investigative Site

Sendai, Miyagi, Japan

Novartis Investigative Site

Osaka, Osaka, Japan

Novartis Investigative Site

Kodaira, Tokyo, Japan

Novartis Investigative Site

Wakayama, Wakayama, Japan

Novartis Investigative Site

Tokushima, , Japan

Novartis Investigative Site

Amsterdam, , Netherlands

Novartis Investigative Site

Leiden, , Netherlands

Novartis Investigative Site

Zurich, , Switzerland

Novartis Investigative Site

Salford, Manchester, United Kingdom

Novartis Investigative Site

London, , United Kingdom

Novartis Investigative Site

Newcastle upon Tyne, , United Kingdom

Countries

United States; Australia; Belgium; Denmark; France; Italy; Japan; Netherlands; Switzerland; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 33597289 (View on PubMed)

Other Identifiers

2015-001411-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CBYM338B2203E1

Identifier Type: -

Identifier Source: org_study_id