NCT02346422

A Phase 1/2 Study of High-dose Genetically Targeted Enzyme Replacement Therapy for Advanced Heart Failure

A Phase 1/2 Study of the Safety and Preliminary Activity of MYDICAR® at a Dose of 2.5 x 10^13 DNase Resistant Particles (DRP) in Subjects With Advanced Heart Failure Divided Into 2 Phases: Phase 1 Open-label and Phase 2 Randomized, Double-blind, Placebo-controlled

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 9 (actual)
• Sponsor: Celladon Corporation · Industry
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this trial is to characterize the safety profile and preliminary activity of high-dose MYDICAR® in persons with advanced heart failure when added to their maximal and optimized therapy.

Detailed description

Heart failure (HF) is a disabling chronic disease and the most frequent discharge diagnosis for hospitalization among older adults.The American Heart Association (AHA) 2006 update on heart disease reported that 5 million Americans are believed to have symptomatic HF, and 550,000 patients are newly diagnosed each year. The estimated direct and indirect cost of HF in the United States (U.S.) for 2006 was \~$29.6 billion. Despite the significant resources expended on the treatment of this disease, outcomes remain poor. The five-year survival for individuals diagnosed with HF is less than 50%, and in end-stage HF, the one-year survival may be as low as 25% regardless of medical therapy. Recent studies suggest that the failing heart is not refractory to treatment, as was previously believed. For example, the observation that a small percentage of subjects with left ventricular assist devices can be permanently weaned from their device strongly suggests that damaged hearts are capable of recovering lost function. Celladon Corporation (Celladon) is investigating gene transfer as a method to restore calcium ion (Ca++) cycling in HF patients. The gene therapy vehicle uses a recombinant adeno-associated viral vector (AAV), which consists of an AAV serotype 1 capsid and contains the human sarcoplasmic reticulum Ca++ ATPAse (SERCA2a) complementary DNA (cDNA) flanked by inverted terminal repeats derived from AAV serotype 2 (AAV1/SERCA2a). MYDICAR® refers to AAV1/SERCA2a drug product intended for administration by percutaneous delivery. Phase 1/2 clinical trials have demonstrated initial safety and evidence of improvement in clinical outcomes at MYDICAR doses of up to 1 x 10\^13 DNase-resistant particles (DRP). The trial described here is designed to investigate the safety profile and preliminary activity of MYDICAR at a dose of 2.5 x 10\^13 DRP; this dose is 2.5-fold higher than previously investigated doses.

Conditions

• Ischemic Cardiomyopathy
• Non-ischemic Cardiomyopathy
• Heart Failure
• Cardiomyopathies

Interventions

Type	Name	Description
GENETIC	MYDICAR Phase 1	Single dose of MYDICAR
GENETIC	MYDICAR Phase 2	Single dose of MYDICAR
GENETIC	Placebo Phase 2 only	Single dose of placebo

Timeline

• Start date: 2015-04-01
• Primary completion: 2015-06-26
• First posted: 2015-01-27
• Last updated: 2017-01-31

Locations

4 sites across 1 country: United States