OBJECTIVES: The aim of this analysis was to characterise design and status of advanced gene therapies (GTs) clinical trials.

METHODS: The databases of ClinicalTrials.gov have been downloaded on June 2019 and underwent automatized analysis using R algorithms for data mining. The databases were searched for records related to GTs using key words related to gene therapy, gene transfer and adeno-associated vectors. Relevant records related to advanced interventional studies (phase 1/2, 2, 2/3 and 3) were transferred to Excel-based data-extraction table for further descriptive analysis.

RESULTS: A total number of 390 interventional trials were selected including 212, 118, 14 and 46 phase 1/2, 2, 2/3 and 3 trials respectively. The overall proportion of randomised controlled trials (RCTs) was 31% and was relatively constant across different 5-year periods analysed since 1995. Higher study phase was associated with a higher proportion of RCTs: 10%, 50%, 57%, and 72% for phase 1/2, 2, 2/3 and phase 3 trials, respectively. Overall, blinded allocation was reported for 66% or RCTs with no apparent interaction between study phase and masking. The proportion of interventional non-RCT with a parallel assignment was 34% for all trials and 17%, 50%, 43% and 67% for phase 1/2, 2, 2/3 and phase 3 trials, respectively. Overall, 28%, 52% and 11% trials were completed, ongoing or terminated, with no apparent interaction between status and study phase. The status was unknown for 8% of studies.

CONCLUSIONS: The overall number of advanced phase GT clinical trials is limited, although available evidence comprise of relatively high proportion of blinded RCTs and comparative non-RCT studies. A deeper assessment of the methodological credibility of advanced GT trials is required, including evaluation of the appropriateness of comparator selections, relevance of primary outcomes and sample sizes.