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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

Primary Purpose

Sporadic Inclusion Body Myositis

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Bimagrumab
Placebo
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sporadic Inclusion Body Myositis focused on measuring sporadic inclusion body myositis,, muscle wasting,, extension study,, BYM338,, bimagrumab,

Eligibility Criteria

36 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

BYM338/bimagrumab 10 mg/kg

BYM338/bimagrumab 3 mg/kg

BYM338/bimagrumab 1 mg/kg

Placebo

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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.
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.
Estimated Annual Number of Falls Per Participant Within Treatment Group
Participants documented any fall occurrences in a paper diary during the study.
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.
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.
Number of Patients With Anti-BYM338 Antibodies
Investigated the development of immunogenicity against BYM338.

Full Information

First Posted
July 9, 2015
Last Updated
February 12, 2018
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02573467
Brief Title
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
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2018
Overall Recruitment Status
Completed
Study Start Date
November 2, 2015 (Actual)
Primary Completion Date
August 17, 2016 (Actual)
Study Completion Date
February 13, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sporadic Inclusion Body Myositis
Keywords
sporadic inclusion body myositis,, muscle wasting,, extension study,, BYM338,, bimagrumab,

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Non-Randomized
Enrollment
211 (Actual)

8. Arms, Groups, and Interventions

Arm Title
BYM338/bimagrumab 10 mg/kg
Arm Type
Experimental
Arm Description
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.
Arm Title
BYM338/bimagrumab 3 mg/kg
Arm Type
Experimental
Arm Description
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.
Arm Title
BYM338/bimagrumab 1 mg/kg
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Bimagrumab
Other Intervention Name(s)
BYM338
Intervention Description
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
Intervention Name(s)
Placebo
Intervention Description
Matching placebo to BYM338 was provided in colorless glass vials with a rubber stopper and aluminum flip-off caps.
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths.
Description
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)
Title
Change From Core Study Baseline in 6 Minute Walking Distance Test (6MWD)
Description
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 Outcome Measure Information:
Title
Change From Core Study Baseline in Quadriceps Quantitative Muscle Testing (QMT) on the Right Side
Description
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
Title
Change From Core Study Baseline in Sporadic Inclusion Body Myositis (sIBM) Functional Assessment (sIFA) Score
Description
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
Title
Estimated Annual Number of Falls Per Participant Within Treatment Group
Description
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)
Title
Change From Core Study Baseline in Short Physical Performance Battery (SPPB) Score
Description
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
Title
Change in Muscles of the Thigh
Description
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
Title
Number of Patients With Anti-BYM338 Antibodies
Description
Investigated the development of immunogenicity against BYM338.
Time Frame
end of double-blind treatment (up to 8 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
36 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85028
Country
United States
Facility Name
Novartis Investigative Site
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Novartis Investigative Site
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Novartis Investigative Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33101
Country
United States
Facility Name
Novartis Investigative Site
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Novartis Investigative Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Novartis Investigative Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Novartis Investigative Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Novartis Investigative Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43221
Country
United States
Facility Name
Novartis Investigative Site
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Novartis Investigative Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Facility Name
Novartis Investigative Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Novartis Investigative Site
City
St. Leonards
State/Province
New South Wales
ZIP/Postal Code
2065
Country
Australia
Facility Name
Novartis Investigative Site
City
Cauldfield
State/Province
Victoria
ZIP/Postal Code
3162
Country
Australia
Facility Name
Novartis Investigative Site
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
Novartis Investigative Site
City
Edegem
State/Province
Antwerpen
ZIP/Postal Code
2650
Country
Belgium
Facility Name
Novartis Investigative Site
City
Bruxelles
ZIP/Postal Code
1200
Country
Belgium
Facility Name
Novartis Investigative Site
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Facility Name
Novartis Investigative Site
City
Paris
ZIP/Postal Code
75013
Country
France
Facility Name
Novartis Investigative Site
City
Brescia
State/Province
BS
ZIP/Postal Code
25123
Country
Italy
Facility Name
Novartis Investigative Site
City
Roma
State/Province
Lazio
ZIP/Postal Code
00168
Country
Italy
Facility Name
Novartis Investigative Site
City
Messina
State/Province
ME
ZIP/Postal Code
98125
Country
Italy
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20133
Country
Italy
Facility Name
Novartis Investigative Site
City
Padova
State/Province
PD
ZIP/Postal Code
35128
Country
Italy
Facility Name
Novartis Investigative Site
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
466-8560
Country
Japan
Facility Name
Novartis Investigative Site
City
Kumamoto City
State/Province
Kumamoto
ZIP/Postal Code
860-8556
Country
Japan
Facility Name
Novartis Investigative Site
City
Sendai-city
State/Province
Miyagi
ZIP/Postal Code
980-8574
Country
Japan
Facility Name
Novartis Investigative Site
City
Osaka-city
State/Province
Osaka
ZIP/Postal Code
534-0021
Country
Japan
Facility Name
Novartis Investigative Site
City
Kodaira
State/Province
Tokyo
ZIP/Postal Code
187-8551
Country
Japan
Facility Name
Novartis Investigative Site
City
Wakayama-city
State/Province
Wakayama
ZIP/Postal Code
641-8510
Country
Japan
Facility Name
Novartis Investigative Site
City
Tokushima
ZIP/Postal Code
770-8503
Country
Japan
Facility Name
Novartis Investigative Site
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Leiden
ZIP/Postal Code
2333 ZA
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Zuerich
ZIP/Postal Code
8091
Country
Switzerland
Facility Name
Novartis Investigative Site
City
Salford
State/Province
Manchester
ZIP/Postal Code
M6 8HD
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
London
ZIP/Postal Code
NW1 2BU
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Newcastle upon Tyne
ZIP/Postal Code
NE4 5PL
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
33597289
Citation
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.
Results Reference
derived

Learn more about this trial

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

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