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

Sporadic Inclusion Body Myositis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02573467
• Other study ID #: CBYM338B2203E1
• Secondary ID: 2015-001411-12
• Status: Completed
• Phase: Phase 3
• First received: July 9, 2015
• Last updated: February 12, 2018
• Start date: November 2, 2015
• Est. completion date: February 13, 2017

Study information

• Verified date: February 2018
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 211
• Est. completion date: February 13, 2017
• Est. primary completion date: August 17, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 36 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Myositis
• Myositis, Inclusion Body
• Sporadic Inclusion Body Myositis

Intervention

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

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Cauldfield	Victoria
Australia	Novartis Investigative Site	Nedlands	Western Australia
Australia	Novartis Investigative Site	St. Leonards	New South Wales
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Edegem	Antwerpen
Belgium	Novartis Investigative Site	Gent
Denmark	Novartis Investigative Site	Copenhagen
France	Novartis Investigative Site	Paris
Italy	Novartis Investigative Site	Brescia	BS
Italy	Novartis Investigative Site	Messina	ME
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Padova	PD
Italy	Novartis Investigative Site	Roma	Lazio
Japan	Novartis Investigative Site	Kodaira	Tokyo
Japan	Novartis Investigative Site	Kumamoto City	Kumamoto
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Osaka-city	Osaka
Japan	Novartis Investigative Site	Sendai-city	Miyagi
Japan	Novartis Investigative Site	Tokushima
Japan	Novartis Investigative Site	Wakayama-city	Wakayama
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Leiden
Switzerland	Novartis Investigative Site	Zuerich
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Newcastle upon Tyne
United Kingdom	Novartis Investigative Site	Salford	Manchester
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	Dallas	Texas
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Kansas City	Kansas
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Orange	California
United States	Novartis Investigative Site	Phoenix	Arizona
United States	Novartis Investigative Site	Portland	Oregon
United States	Novartis Investigative Site	Sacramento	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	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
Secondary	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
Secondary	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)
Secondary	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
Secondary	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
Secondary	Number of Patients With Anti-BYM338 Antibodies	Investigated the development of immunogenicity against BYM338.	end of double-blind treatment (up to 8 months)