TY - JOUR
T1 - Cardiac and skeletal muscle effects in the randomized HOPE-Duchenne trial
AU - Taylor, Michael
AU - Jefferies, John
AU - Byrne, Barry
AU - Lima, Joao
AU - Ambale-Venkatesh, Bharath
AU - Ostovaneh, Mohammad R.
AU - Makkar, Raj
AU - Goldstein, Bryan
AU - Smith, Rachel Ruckdeschel
AU - Fudge, James
AU - Malliaras, Konstantinos
AU - Fedor, Brian
AU - Rudy, Jeff
AU - Pogoda, Janice M.
AU - Marbán, Linda
AU - Ascheim, Deborah D.
AU - Marbán, Eduardo
AU - Victor, Ronald G.
N1 - Publisher Copyright:
© 2019 American Academy of Neurology.
PY - 2019/2/19
Y1 - 2019/2/19
N2 - ObjectiveTo assess the feasibility, safety, and efficacy of intracoronary allogeneic cardiosphere-derived cells (CAP-1002) in patients with Duchenne muscular dystrophy (DMD).MethodsThe Halt Cardiomyopathy Progression (HOPE)-Duchenne trial is a phase I/II, randomized, controlled, open-label trial (NCT02485938). Patients with DMD >12 years old, with substantial myocardial fibrosis, were randomized (1:1) to usual care (control) or global intracoronary infusion of CAP-1002 (75 million cells). Participants were enrolled at 3 US medical centers between January and August 2016 and followed for 12 months. An independent Data and Safety Monitoring Board provided safety oversight. Cardiac function and structure were assessed by MRI, and analyzed by a blinded core laboratory. Skeletal muscle function was assessed by performance of the upper limb (PUL).ResultsTwenty-five eligible patients (mean age 17.8 years; 68% wheelchair-dependent) were randomized to CAP-1002 (n = 13) or control (n = 12). Incidence of treatment-emergent adverse events was similar between groups. Compared to baseline, MRI at 12 months revealed significant scar size reduction and improvement in inferior wall systolic thickening in CAP-1002 but not control patients. Mid-distal PUL improved at 12 months in 8 of 9 lower functioning CAP-1002 patients, and no controls (p = 0.007).ConclusionsIntracoronary CAP-1002 in DMD appears safe and demonstrates signals of efficacy on both cardiac and upper limb function for up to 12 months. Thus, future clinical research on CAP-1002 treatment of DMD cardiac and skeletal myopathies is warranted.Classification of evidenceThis phase I/II study provides Class II evidence that for patients with DMD, intracoronary CAP-1002 is feasible and appears safe and potentially effective.
AB - ObjectiveTo assess the feasibility, safety, and efficacy of intracoronary allogeneic cardiosphere-derived cells (CAP-1002) in patients with Duchenne muscular dystrophy (DMD).MethodsThe Halt Cardiomyopathy Progression (HOPE)-Duchenne trial is a phase I/II, randomized, controlled, open-label trial (NCT02485938). Patients with DMD >12 years old, with substantial myocardial fibrosis, were randomized (1:1) to usual care (control) or global intracoronary infusion of CAP-1002 (75 million cells). Participants were enrolled at 3 US medical centers between January and August 2016 and followed for 12 months. An independent Data and Safety Monitoring Board provided safety oversight. Cardiac function and structure were assessed by MRI, and analyzed by a blinded core laboratory. Skeletal muscle function was assessed by performance of the upper limb (PUL).ResultsTwenty-five eligible patients (mean age 17.8 years; 68% wheelchair-dependent) were randomized to CAP-1002 (n = 13) or control (n = 12). Incidence of treatment-emergent adverse events was similar between groups. Compared to baseline, MRI at 12 months revealed significant scar size reduction and improvement in inferior wall systolic thickening in CAP-1002 but not control patients. Mid-distal PUL improved at 12 months in 8 of 9 lower functioning CAP-1002 patients, and no controls (p = 0.007).ConclusionsIntracoronary CAP-1002 in DMD appears safe and demonstrates signals of efficacy on both cardiac and upper limb function for up to 12 months. Thus, future clinical research on CAP-1002 treatment of DMD cardiac and skeletal myopathies is warranted.Classification of evidenceThis phase I/II study provides Class II evidence that for patients with DMD, intracoronary CAP-1002 is feasible and appears safe and potentially effective.
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U2 - 10.1212/WNL.0000000000006950
DO - 10.1212/WNL.0000000000006950
M3 - Article
C2 - 30674601
AN - SCOPUS:85061849120
SN - 0028-3878
VL - 92
SP - E866-E878
JO - Neurology
JF - Neurology
IS - 8
ER -