This study is an open-label, long-term study for those patients who participated in the prior proof-of-concept protocol, in which the preliminary efficacy for BYM338 in patients with sIBM was demonstrated after a single 30 mg/kg i.v. dose of BYM338. This study is designed to confirm the efficacy, safety and tolerability of BYM338 in sIBM with long-term dosing. However due to lack of efficacy in patients with sIBM, the study was terminated early.
This is a non-confirmatory, multicenter, open-label, non-randomized trial which will extend active treatment to those patients that participated in the preceding proof-of-concept study (CBYM338X2205) in order to collect long-term safety and tolerability data. Up to 14 patients with sIBM will be invited to enroll into the study to receive BYM338 open-label for a period of approximately 3 years or until BYM338 is commercially available, whichever comes first. The study consists of a maximum 28-day screening period, a 5-day baseline period, and a treatment period consisting of the site visits at 4-week intervals for treatment administration, safety and pharmacokinetic follow-up. All patients will be administered a medium level i.v. BYM338 dose regardless of their treatment allocation in the prior study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
Novartis Investigative Site
Phoenix, Arizona, United States
Novartis Investigative Site
Boston, Massachusetts, United States
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Any Adverse Event was defined as occurrence of any symptom regardless of intensity grade, Serious Adverse Event (SAEs) assessed as medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in persistent or significant disability/incapacity
Time frame: Up to 29 month
Changes From Baseline in Lean Body Mass (LBM) by Dual-Energy X-ray Absorptiometery (DXA)
To assess the effect of multiple doses of BYM338 on lean body mass as measured by DXA in terms of change from baseline.
Time frame: Baseline, Day 1, 57, 113, 169, 365, 533, and day 729
Pharmacokinetics (PK) Parameter of Cmin From Multiple i.v. Dosing
To obtain pharmacokinetic data from multiple i.v. dosing of BYM338 in this patient population. Pre-dose, 30 mins \& 4 hours post-dose on Day 1. Pre-dose only on each subsequent administration
Time frame: Day 29, 85, 169, 253, 337, 421, 505, 589, 673, 757, 1177
Changes From Baseline in Physical Function Reported by Patients
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. Due to the no-signal this analysis was cancelled.
Time frame: Baseline, Week 104
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Changes From Baseline in Muscle Strength.
Quadriceps muscle strength was measured, Quadriceps Quantitative Muscle Testing (QMT) by portable fixed dynamometry (PFD). A negative change from baseline indicates deterioration
Time frame: Baseline, Day 1, 113, 169, 365, 533, 729
Changes From Baseline in Muscle Function (Hand-grip and Pinch-grip Dynamometry)
The effect of BYM338 on additional muscle function measures (hand-grip and pinch-grip dynamometry).
Time frame: Baseline,Day 1, 113, 169, 365, 533, 729
Changes From Baseline in Muscle Function 6 Minute Walking Distance
The effect of BYM338 on additional muscle function measures (6 minute walking distance). The 6MWD test measured the distance (in meters) that a participant walked in a 6 minute timeframe. A positive change from baseline indicates improvement.
Time frame: Baseline,Day 1, 113, 169, 365, 533, 729
Change From Baseline of Thigh Muscle Volume (TMV) by MRI Scan
Thigh Muscle Volume (TMV) change was evaluated by a responder analysis. Patients whose loss of muscle TMV by MRI was equal or more than 2% at Week 8 and 16 were considered responders
Time frame: Baseline, Day 1, 57, 113
Pharmacokinetics (PK) Parameter of Cmax
To obtain pharmacokinetic data from multiple i.v. dosing of BYM338 in this patient population. Pre-dose, 30 mins \& 4 hours post-dose on Day 1.
Time frame: Day 1
Time to Reach the Maximum Concentration After Drug Administration (Tmax)
The time to reach the maximum concentration after drug administration
Time frame: Day 1