Prademagene zamikeracel for recessive dystrophic epidermolysis bullosa wounds (VIITAL): a two-centre, randomised, open-label, intrapatient-controlled phase 3 trial

Abstract

Background: Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic skin disease caused by mutations in the COL7A1 gene encoding type VII collagen. Individuals with RDEB have fragile skin and most develop large, chronic wounds. The aim of the VIITAL study was to evaluate the efficacy and safety of a one-time surgical application of prademagene zamikeracel in wound healing.

Methods: This randomised, open-label, intrapatient-controlled, phase 3 trial was conducted at two institutions in the USA. Eligible patients were aged 6 years or older, had a confirmed clinical and genetic diagnosis of RDEB, at least two chronic wounds (>20 cm²), had no evidence of an immune response to type VII collagen, and expressed the amino-terminal NC1 fragment of type VII collagen. Large, chronic wounds on the participants were matched in pairs by size, chronicity, and anatomical region and computer randomised (1:1) to treatment (prademagene zamikeracel) or control (standard of care). There was no masking. Prademagene zamikeracel is an autologous COL7A1 gene-modified cellular sheet that is sutured onto to a large, chronic RDEB wound. A maximum of six wounds could be treated with prademagene zamikeracel per patient. The coprimary endpoints were the proportion of wounds with at least 50% healing and pain reduction from baseline at week 24 in the intention-to-treat population of all patients and their randomised wounds. The safety analysis population included all patients and evaluated wounds, randomised and non-randomised. This completed trial was registered with ClinicalTrials.gov (NCT04227106).

Findings: Between Jan 1, 2020, and March 31, 2022, 15 patients were screened and 11 were enrolled (43 randomised wound pairs). Four (36%) of 11 participants were male and seven (64%) of 11 participants were female, with a median age of 21 years (IQR 17-30). 86 wounds were matched and randomised: 43 (50%) to prademagene zamikeracel and 43 (50%) to control. At week 24, 35 (81%) of 43 treated wounds were at least 50% healed from baseline for prademagene zamikeracel compared with seven (16%) of 43 control wounds (mean difference 67% [95% CI 50 to 89]; p<0·0001). The mean change from baseline to week 24 in wound pain was -3·07 with prademagene zamikeracel and -0·90 in controls (mean pairwise difference -2·23 [-3·45 to -0·66]; p=0·0002). No serious treatment-related adverse events were observed.

Interpretation: Prademagene zamikeracel improved wound healing and pain versus control and was well tolerated, supporting its potential to reduce wound burden in patients with large, chronic RDEB wounds.

Funding: Abeona Therapeutics.