Tissue replacement in RPE related dystrophies

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre D'Etude Des Cellules Souches

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

19 Aug 2019 → ongoing

Decision date (initial)

2024-06-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

CECS / I-STEM

External identifiers

EU CT number

2024-513662-18-00

EudraCT number

2018-000457-53

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To assess safety and tolerability of implantation of the IMP (ISTEM-01) in patients with retinitis pigmentosa over 56 weeks after IMP implantation.

Secondary objectives 3

1. To evaluate the placement and position of the patch
2. To assess preliminary efficacy for 2nd cohort only based on: Evaluation of visual function, Eye fundus, Evaluation of photoreceptor survival
3. To assess long-term safety, tolerability and efficacy (for 2nd cohort) up to 5 years after IMP implantation.

Conditions and MedDRA coding

Patients with retinitis pigmentosa due to monogenic mutation

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Documented diagnosis of retinis pigmentosa based on a genetic test confirming the presence of a monogenic mutation that affects a gene involved in the visual signalling process specifically at the level of RPEs, namely RPE65 or LRAT, or MerTK
2. 18 years old ≤ Age ≤ 65 years old
3. During the SARS-Cov-2 pandemic period, patient negative to SARS-CoV-2 (PCR or any new test validated)
4. For patient of the first cohort: Visual acuity ≤ 20/200 in the best eye (legally blind). For patient of the second cohort: 20/63 > Visual acuity > 20/800 in the worst eye And Visual field exceeding 10° central to the V4 test in the worst eye And Visible photoreceptor outer nuclear layer (ONL) on a spectral domain optical coherence tomography (OCT) scan

Exclusion criteria 6

1. History of allergy or sensitivity to one of the products used during the study
2. Prior treatment with a gene or cell therapy product
3. Patients with preformed anti-HLA antibodies against the human Embryonic Stem Cell (hESC) line RC9 with MFI > 2000 or patients with intermediate MFI values (between 500 and 2000) at screening associated to medical history of clinical significance, according to expert’s opinion
4. Presence of any ocular disease or ocular media opacity which in the opinion of the investigator precludes accurate evaluation
5. Patients treated with Luxturna®
6. Systemic corticosteroid therapy or other immunosuppressive/ immunomodulating or anti-retroviral drugs within 2 months prior to baseline

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Safety and tolerability measured by the incidence of adverse events (AE) or serious adverse events (SAE) evaluated by changes in ophthalmologic exams, laboratory parameters, vital signs and in the physical examination from baseline to each visit, will be evaluated for each patient over 56 weeks.

Secondary endpoints 8

1. Placement and position of the therapeutic patch by serial spectral domain Ocular Coherence Tomography (OCT) scan at Baseline, and by study visit
2. Change in leakage or perfusion in normal fundal vasculature and presence of abnormal vasculature by fundus fluorescein angiography at Baseline, weeks 24 and 56 and yearly during the long-term follow-up study.
3. Change in thickness of RPE layer by B-mode orbital ultrasound at Baseline, weeks 24, and 56 and yearly during the long-term follow-up study.
4. Change in eye exam and IntraOcular Pressure (IOP) from baseline, and by study visit
5. Change in ETDRS/ best corrected visual acuity (BCVA) from baseline and by study visit
6. Change in kinetic perimetry from baseline, at weeks 4, 8, 12, 24, 36, 48 and 56 and yearly during the long-term follow-up study.
7. Evidence of retinal and RPE functionnality by global, pattern and multifocal ERG at baseline and week 56 and yearly during the long term follow-up period
8. Functional survival of retinal photoreceptors by microperimetry over hESC-derived RPE at weeks 4, 8, 12, 24, 36, 48 and 56 and yearly during the long term follow-up period

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre D'Etude Des Cellules Souches

Sponsor organisation

Centre D'Etude Des Cellules Souches

Address

28 Rue Henri Desbrueres

City

Corbeil Essonnes

Postcode

91100

Country

France

Scientific contact point

Organisation

Centre D'Etude Des Cellules Souches

Contact name

General Manager

Public contact point

Organisation

Centre D'Etude Des Cellules Souches

Contact name

General Manager

Third parties 2

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

2 submissions — initial application plus substantial / non-substantial modifications