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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02573467




Registration number
NCT02573467
Ethics application status
Date submitted
9/07/2015
Date registered
9/10/2015
Date last updated
13/03/2018

Titles & IDs
Public 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
Scientific 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
Secondary ID [1] 0 0
2015-001411-12
Secondary ID [2] 0 0
CBYM338B2203E1
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sporadic Inclusion Body Myositis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Bimagrumab
Treatment: Drugs - Placebo

Experimental: 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.

Experimental: 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.

Experimental: 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.

Placebo Comparator: 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.


Treatment: Drugs: 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.

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

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
to end of study (up to 14 months, including the 6-month treatment-free follow-up period)
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
Core study baseline, weeks 52, 78, 104, and >=117
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Core study baseline, week 52, week 78, week 104 and >=week 117
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Core study baseline, week 52, week 78, week 104, and >=week 117
Secondary outcome [3] 0 0
Estimated Annual Number of Falls Per Participant Within Treatment Group - Participants documented any fall occurrences in a paper diary during the study.
Timepoint [3] 0 0
Core baseline to end of extension double-blind treatment (up to a maximum of 32 months)
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
Core study baseline, week 52, week 78, week 104 and >=week 117
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
up to 1 year, up to 2 years
Secondary outcome [6] 0 0
Number of Patients With Anti-BYM338 Antibodies - Investigated the development of immunogenicity against BYM338.
Timepoint [6] 0 0
end of double-blind treatment (up to 8 months)

Eligibility
Key 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.
Minimum age
36 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - St. Leonards
Recruitment hospital [2] 0 0
Novartis Investigative Site - Cauldfield
Recruitment hospital [3] 0 0
Novartis Investigative Site - Nedlands
Recruitment postcode(s) [1] 0 0
2065 - St. Leonards
Recruitment postcode(s) [2] 0 0
3162 - Cauldfield
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Kansas
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Oregon
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
Belgium
State/province [10] 0 0
Antwerpen
Country [11] 0 0
Belgium
State/province [11] 0 0
Bruxelles
Country [12] 0 0
Belgium
State/province [12] 0 0
Gent
Country [13] 0 0
Denmark
State/province [13] 0 0
Copenhagen
Country [14] 0 0
France
State/province [14] 0 0
Paris
Country [15] 0 0
Italy
State/province [15] 0 0
BS
Country [16] 0 0
Italy
State/province [16] 0 0
Lazio
Country [17] 0 0
Italy
State/province [17] 0 0
ME
Country [18] 0 0
Italy
State/province [18] 0 0
MI
Country [19] 0 0
Italy
State/province [19] 0 0
PD
Country [20] 0 0
Japan
State/province [20] 0 0
Aichi
Country [21] 0 0
Japan
State/province [21] 0 0
Kumamoto
Country [22] 0 0
Japan
State/province [22] 0 0
Miyagi
Country [23] 0 0
Japan
State/province [23] 0 0
Osaka
Country [24] 0 0
Japan
State/province [24] 0 0
Tokyo
Country [25] 0 0
Japan
State/province [25] 0 0
Wakayama
Country [26] 0 0
Japan
State/province [26] 0 0
Tokushima
Country [27] 0 0
Netherlands
State/province [27] 0 0
Amsterdam
Country [28] 0 0
Netherlands
State/province [28] 0 0
Leiden
Country [29] 0 0
Switzerland
State/province [29] 0 0
Zuerich
Country [30] 0 0
United Kingdom
State/province [30] 0 0
Manchester
Country [31] 0 0
United Kingdom
State/province [31] 0 0
London
Country [32] 0 0
United Kingdom
State/province [32] 0 0
Newcastle upon Tyne

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02573467
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications