Michael I Polkey1, Jens Praestgaard2, Amy Berwick3, Frits M E Franssen4, Dave Singh5, Michael C Steiner6, Richard Casaburi7, Hanns-Christian Tillmann8, Estelle Lach-Trifilieff8, Ronenn Roubenoff8, Daniel S Rooks3. 1. 1 National Institute for Health Research Respiratory Biomedical Research Unit, Royal Brompton and Harefield National Health Service Foundation Trust and Imperial College London, London, United Kingdom. 2. 2 Novartis Pharmaceuticals Corporation, East Hanover, New Jersey. 3. 3 Novartis Institutes for BioMedical Research, Cambridge, Massachusetts. 4. 4 Department of Research and Education, CIRO, Center of Expertise for Chronic Organ Failure, Horn, the Netherlands. 5. 5 Centre for Respiratory Medicine and Allergy, University of Manchester and the Medicines Evaluation Unit, University Hospital of South Manchester National Health Service Foundation Trust, Manchester, United Kingdom. 6. 6 Centre for Exercise and Rehabilitation Science, National Institute for Health Research Leicester Biomedical Research Centre, Respiratory, Glenfield Hospital, Leicester, United Kingdom. 7. 7 Rehabilitation Clinical Trials Center, Los Angeles Biomedical Research Institute, Harbor-University of California Los Angeles Medical Center, Torrance, California; and. 8. 8 Novartis Institutes for BioMedical Research, Basel, Switzerland.
Abstract
RATIONALE: Bimagrumab is a fully human monoclonal antibody that blocks the activin type II receptors, preventing the activity of myostatin and other negative skeletal muscle regulators. OBJECTIVES: To assess the effects of bimagrumab on skeletal muscle mass and function in patients with chronic obstructive pulmonary disease (COPD) and reduced skeletal muscle mass. METHODS:Sixty-seven patients with COPD (mean FEV1, 1.05 L [41.6% predicted]; aged 40-80 yr; body mass index < 20 kg/m2 or appendicular skeletal muscle mass index ≤ 7.25 [men] and ≤ 5.67 [women] kg/m2), received two doses of either bimagrumab 30 mg/kg intravenously (n = 33) or placebo (n = 34) (Weeks 0 and 8) over 24 weeks. MEASUREMENTS AND MAIN RESULTS: We assessed changes in thigh muscle volume (cubic centimeters) as the primary endpoint along with 6-minute-walk distance (meters), safety, and tolerability. Fifty-five (82.1%) patients completed the study. Thigh muscle volume increased by Week 4 and remained increased at Week 24 in bimagrumab-treated patients, whereas no changes were observed with placebo (Week 4: +5.9% [SD, 3.4%] vs. 0.0% [3.3%], P < 0.001; Week 8: +7.0% [3.7%] vs. -0.7% [2.8%], P < 0.001; Week 16: +7.8% [5.1%] vs. -0.9% [4.5%], P < 0.001; Week 24: +5.0% [4.9%] vs. -1.3% [4.3%], P < 0.001). Over 24 weeks, 6-minute-walk distance did not increase significantly in either group. Adverse events in the bimagrumab group included muscle-related symptoms, diarrhea, and acne, most of which were mild in severity. CONCLUSIONS: Blocking the action of negative muscle regulators through the activin type II receptors with bimagrumab treatment safely increased skeletal muscle mass but did not improve functional capacity in patients with COPD and low muscle mass. Clinical trial registered with www.clinicaltrials.gov (NCT01669174).
RCT Entities:
RATIONALE: Bimagrumab is a fully human monoclonal antibody that blocks the activin type II receptors, preventing the activity of myostatin and other negative skeletal muscle regulators. OBJECTIVES: To assess the effects of bimagrumab on skeletal muscle mass and function in patients with chronic obstructive pulmonary disease (COPD) and reduced skeletal muscle mass. METHODS: Sixty-seven patients with COPD (mean FEV1, 1.05 L [41.6% predicted]; aged 40-80 yr; body mass index < 20 kg/m2 or appendicular skeletal muscle mass index ≤ 7.25 [men] and ≤ 5.67 [women] kg/m2), received two doses of either bimagrumab 30 mg/kg intravenously (n = 33) or placebo (n = 34) (Weeks 0 and 8) over 24 weeks. MEASUREMENTS AND MAIN RESULTS: We assessed changes in thigh muscle volume (cubic centimeters) as the primary endpoint along with 6-minute-walk distance (meters), safety, and tolerability. Fifty-five (82.1%) patients completed the study. Thigh muscle volume increased by Week 4 and remained increased at Week 24 in bimagrumab-treated patients, whereas no changes were observed with placebo (Week 4: +5.9% [SD, 3.4%] vs. 0.0% [3.3%], P < 0.001; Week 8: +7.0% [3.7%] vs. -0.7% [2.8%], P < 0.001; Week 16: +7.8% [5.1%] vs. -0.9% [4.5%], P < 0.001; Week 24: +5.0% [4.9%] vs. -1.3% [4.3%], P < 0.001). Over 24 weeks, 6-minute-walk distance did not increase significantly in either group. Adverse events in the bimagrumab group included muscle-related symptoms, diarrhea, and acne, most of which were mild in severity. CONCLUSIONS: Blocking the action of negative muscle regulators through the activin type II receptors with bimagrumab treatment safely increased skeletal muscle mass but did not improve functional capacity in patients with COPD and low muscle mass. Clinical trial registered with www.clinicaltrials.gov (NCT01669174).
Entities:
Keywords:
6-minute-walk distance; bimagrumab; lean body mass; thigh muscle volume
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