Clinical trial NCT02573467: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Sporadic Inclusion Body Myositis
Keywords: sporadic inclusion body myositis,
muscle wasting,
extension study,
BYM338,
bimagrumab,
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-10-09
Enrollment: 211
Sex: ALL
Minimum age (years): 36
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths.
timeFrame: to end of study (up to 14 months, including the 6-month treatment-free follow-up period)
measure: Change From Core Study Baseline in 6 Minute Walking Distance Test (6MWD)
timeFrame: Core study baseline, weeks 52, 78, 104, and >=117
Secondary outcomes:
measure: Change From Core Study Baseline in Quadriceps Quantitative Muscle Testing (QMT) on the Right Side
timeFrame: Core study baseline, week 52, week 78, week 104 and >=week 117
measure: Change From Core Study Baseline in Sporadic Inclusion Body Myositis (sIBM) Functional Assessment (sIFA) Score
timeFrame: Core study baseline, week 52, week 78, week 104, and >=week 117
measure: Estimated Annual Number of Falls Per Participant Within Treatment Group
timeFrame: Core baseline to end of extension double-blind treatment (up to a maximum of 32 months)
measure: Change From Core Study Baseline in Short Physical Performance Battery (SPPB) Score
timeFrame: Core study baseline, week 52, week 78, week 104 and >=week 117
measure: Change in Muscles of the Thigh
timeFrame: up to 1 year, up to 2 years
measure: Number of Patients With Anti-BYM338 Antibodies
timeFrame: end of double-blind treatment (up to 8 months)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Orange
country: United States
facility: Novartis Investigative Site
state: California
city: Sacramento
country: United States
facility: Novartis Investigative Site
state: California
city: Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: Kansas City
country: United States
facility: Novartis Investigative Site
state: Kansas
city: Baltimore
country: United States
facility: Novartis Investigative Site
state: Maryland
city: Boston
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Boston
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Columbus
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Portland
country: United States
facility: Novartis Investigative Site
state: Oregon
city: Dallas
country: United States
facility: Novartis Investigative Site
state: Texas
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: St. Leonards
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Cauldfield
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Nedlands
country: Australia
facility: Novartis Investigative Site
state: Western Australia
city: Edegem
country: Belgium
facility: Novartis Investigative Site
state: Antwerpen
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Gent
country: Belgium
facility: Novartis Investigative Site
city: Copenhagen
country: Denmark
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Brescia
country: Italy
facility: Novartis Investigative Site
state: BS
city: Roma
country: Italy
facility: Novartis Investigative Site
state: Lazio
city: Messina
country: Italy
facility: Novartis Investigative Site
state: ME
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Padova
country: Italy
facility: Novartis Investigative Site
state: PD
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Kumamoto City
country: Japan
facility: Novartis Investigative Site
state: Kumamoto
city: Sendai-city
country: Japan
facility: Novartis Investigative Site
state: Miyagi
city: Osaka-city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Kodaira
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Wakayama-city
country: Japan
facility: Novartis Investigative Site
state: Wakayama
city: Tokushima
country: Japan
facility: Novartis Investigative Site
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Leiden
country: Netherlands
facility: Novartis Investigative Site
city: Zuerich
country: Switzerland
facility: Novartis Investigative Site
city: Salford
country: United Kingdom
facility: Novartis Investigative Site
state: Manchester
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Newcastle upon Tyne
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
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.