Gene therapy randomised clinical trials in Europe – a review paper of methodology and design

Figures & data

Table 1. Characteristics of randomised, double-blind, parallel-group, placebo-controlled CTs included in the systematic review

Registered number in EudraCT	Study name/Study design	Trade name/INN	Indication	Rare disease	Published papers of the RCT
2012–001700-37	CUPID-2b: phase 2b	AAV1/SERCA2a	Ischemic Cardiomyopathy (heart failure and reduced ejection fraction)	no	Greenberg, B., (2016)^5; Greenberg, B. (2014)^12
2011–004761-33	phase 2b	pGM169/GL67A	Cystic fibrosis	yes	Alton, E. (2016)^14
2006–001246-13	TRIST: phase 3	TroVax (Attenuated recombinant vaccinia virus containing the gene for human 5T4 oncofoetal antigen)	Locally advanced or metastatic renal clear cell adenocarcinoma	EU/3/06/429	TroVax® Protocol TV3/001/06 Synopsis^6; Amato, R. (2010)^11
2004–002508-13	phase 2	Ad2/HIF-1α/VP16	Peripheral Arterial Disease (PAD): Intermittent Claudication (IC)	no	Ad2/HIF-1α/VP16, Abbreviated Clinical Study Report: PADHIF00704^9; Creager, М. (2011)^10
2005–004068-21	phase 2			no	n/a
2016–002761-63	phase 3	VGX-3100	HPV-16 and/or HPV-18 related high grade squamous intraepithelial lesions (HSIL) of the cervix	no	n/a
2015–001265-11	RESCUE: phase 3, Subjects Affected for 6 Months or Less	Recombinant AAV vector serotype 2 containing the human wild type mitochondrial ND4 gene (lenadogene nolparvovec)	Leber Hereditary Optic Neuropathy Due to the G11778A	EU/3/11/860	n/a
2015–001266-26	REVERSE: phase 3, Subjects Affected for more than 6 Months and to 12 months		Mutation in the Mitochondrial NADH Dehydrogenase 4 Gene	EU/3/11/860	n/a
2017–002187-40	REFLECT: phase 3, in Subjects Affected for Up to One Year			EU/3/11/860	n/a

AAV1/SERCA2a: adeno-associated virus serotype 1 (AAV1); Sarcoplasmic/endoplasmic reticulum Ca2+-ATPase gene; pGM169/GL67A: Plasmid expressing the human CFTR gene complexed with cationic lipid 67 and helper lipids; CFTR: cystic fibrosis transmembrane conductance regulator; Ad2/HIF-1alfa/VP16: A recombinant adenovirus expressing a constitutively-active hybrid form of the Hypoxia-inducible factor-1α subunit; HPV-16/HPV-18: Human Papillomavirus Strains 16/18; NADH: Nicotinamide Adenine Dinucleotide – Hydrogen.

Figure 1. PRISMA Study Flow Diagram. EudraCT: European Union Drug Regulating Authorities Clinical Trials; ICTRP: International Clinical Trials Registry Platform; CCRCT: Cochrane Central Register of Controlled Trials; CDSR: Cochrane Database of Systematic Reviews; CT: clinical trial; ATMP: advanced therapy medicinal product; GTMP: gene therapy medicinal product; RCT: randomized clinical trial; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses