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 COPD and reduced skeletal muscle mass. METHODS: Sixty-seven COPD patients (mean FEV1 1.05 L [41.6% predicted]; aged 40-80 years; 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 (TMV, cm3) as the primary endpoint along with 6-minute walk distance (6MWD, m), safety, and tolerability. Fifty-five (82.1%) patients completed the study. TMV 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% [3.4%, SD] 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, 6MWD did not increase significantly in either group. Adverse events in 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 registration available at www.clinicaltrials.gov, ID NCT01669174.