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

Novartis Pharmaceuticals211 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Eligibility

Sex: ALLMin age: 36 Years

Medical Language ↔ Plain English

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

Locations (38)

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

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: Core study baseline, weeks 52, 78, 104, and >=117

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: up to 1 year, up to 2 years

Number of Patients With Anti-BYM338 Antibodies

Investigated the development of immunogenicity against BYM338.

Time frame: end of double-blind treatment (up to 8 months)

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

Overview

Conditions

Interventions

Eligibility

Locations (38)

Outcomes

Primary Outcomes

Secondary Outcomes