A phase 1/2, open-label, safety, tolerability and preliminary efficacy study of implantation into one eye of an ATMP in patients with retinitis pigmentosa due to monogenic mutation


ATMP intervention clinical Study in Ophthalmology (phase I/II)


Retinitis Pigmentosa (RP), also known as Rod-cone dystrophy, is a group of rare inherited disorders. RP is associated with progressive peripheral vision loss and night vision difficulties that can lead to central vision loss, most patients are legally blind by the age of 40. RP inheritance can be autosomal dominant, autosomal recessive, simplex case or X-linked. Until recently, there was no effective treatment available in Europe that can prevent or reverse vision loss in RP. A first gene therapy aiming at restoring gene defects in the RPE (RPE65 mutation) had been marketed approved in the US in 2017 but the restoration of the vision is not complete. The use of human Embryonic Stem Cell (hESC) has been proposed for the treatment of a wide range of disorders, including myocardial regeneration after myocardial infarction, islet cell replacement in patients with diabetes. In preclinical disease models of RP, functional Retinal Pigment Epithelium derived from hESC can be transplanted in the subretinal space potential to prevent photoreceptor cell death and restore vision. The use of hESC-RPE is an innovative and promising new therapy for the treatment of RP.


This was an open-label, phase 1/2, non-randomized, single group assignment, in 2 sequential cohorts. A first cohort of 2 patients with very advanced loss of visual acuity and a second cohort of 10 patients with less advanced loss of visual acuity.



  • Assess safety and tolerability of the ATMP for 56 weeks after implantation
  • Curative study: Instant pain relief


  • Evaluation of photoreceptor survival
  • Change in visual function (by diagnosys-Full-field stimulus, D-FST)


  • Evaluate placement and position of the patch
  • Assess preliminary efficacy based on :
    • Evaluation of visual function
    • Eye fundus
    • Evaluation of photoreceptor survival
  • Assess long-term safety, tolerability and efficacy up to 5 years after ATMP implantation


  • Scientific article (ongoing)
  • Intermediary analysis (ongoing)

Key factors of success

  • ICTA’s rigorousness
  • ICTA’s capability to propose innovative solutions for unusual projects

LESSONS LEARNED to speed up the start-up phase of the next study

  • Importance of close collaboration between ICTA and Sponsor and active involvement of Sponsor during the course of the study
  • Optimal project coordination: Safety management, logistics, sub-contractors management.


Recruitment / number of center

Rare disease and low patient potential.
Only one surgeon trained to the procedure in France.
Communication to patient association
Communication with other ophthalmology centers to reach patients.
7 out of 12 planned patients were implanted.
AE/SAE notification

Timelines for SUSARs notification, all AEs related to ATMP are considered as SUSARs.
Very close contact with the sites
Monitoring visit after the treatment of each patient.
1 audit performed by an independent third party => 0 Critical finding and 0 observation on safety.
ATMP handling

ATMP production was 30 days with a 48-hour stability.
Strict schedule and communication plan were validated and implemented early in the study.
Regular reminders to the site and the laboratory.
All patients were implanted at the scheduled date.