Exclusion criterion #10 was removed and text added as a new expanded section, “Section 4.3 Contraindications for Infusion of Investigational Medicinal Product”. Exclusion criterion #15 was added to exclude subjects with current history of malignancy except for basal cell carcinoma. The collection of biopsies or specimens of myocardial tissue was added, if a subject received a left ventricular assist device or transplant, for qPCR analysis to determine presence of the vector transgene. “Section 7.15 Clinical Events” was added.

Inclusion Criterion #2 was changed to exclude hypertrophic cardiomyopathy and include toxic and alcoholic myopathies if sufficient time had elapsed to rule out spontaneous recovery. Inclusion Criterion #5 was changed to include New York Heart Association Class II. Inclusion Criterion #6 was changed to specify that optimized HF therapy was to also be ‘individualized’ and ‘appropriate to the individual subject’. Inclusion Criterion #9 was added, which required all subjects to have a risk factor of either hospitalization within 6 months of Screening or elevated N-terminal prohormone brain natriuretic peptide/B-Type natriuretic peptide within 30 days of Screening. Inclusion Criterion #10 was added regarding angiography. Exclusion Criterion #2 was changed to include acute myocarditis. Exclusion Criterion #13 was changed to define anemia as hemoglobin ≤9g/dL provided there was no evidence of bleeding. Exclusion Criterion #15 was changed to specify “Diagnosis of, or treatment for, any cancer other than basal cell carcinoma within the last 5 years.” The end of study and Primary Analysis Date Cutoff definitions were changed. “Discontinuation of the Study” was changed to “Discontinuation of Enrollment” and the reasons for discontinuing enrollment were restricted to the recommendation of the Data Monitoring Committee or in the event of bankruptcy. Study medication storage conditions were updated for unopened vials to include 2-8°C for up to 3 months. The table of “Commercially Available MYDICAR Device Delivery Products” was expanded.

The number of subjects was increased from 200 to 250 (from 100 to 125 per treatment group) and the number of required primary endpoints was increased from 180 to 186 in order to declare the Primary Analysis Date Cutoff. Appendix L was added to describe hospitalization and biohazard handling procedures in Hungary.

The duration of follow-up of subjects was extended from 2 to 5 years with the addition of the Extended Long-Term Follow-Up Period which encompassed quarterly telephonic visits.

The modified intention-to-treat (mITT) population (randomized subjects who received study medication) was defined as the analysis population for the primary efficacy analysis. The mITTx analysis population was added, which excluded subjects who were adeno-associated virus serotype 1 neutralizing antibody positive or equivocal 1:2 at Baseline.

The extended long-term follow-up (LT-FUP) was eliminated. LT-FUP quarterly visits were changed to telephone calls and collection of health status only. Tissue collection was eliminated. The collection of clinical events in the LT-FUP was eliminated.