A Phase 1/2a gene therapy clinical trial in Retinitis Pigmentosa subjects.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Gensight Biologics

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

22 Dec 2017 → ongoing

Decision date (initial)

2024-08-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

GENSIGHT-BIOLOGICS

External identifiers

EU CT number

2024-516059-42-00

EudraCT number

2017-002204-27

ClinicalTrials.gov

NCT03326336

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Dose response

To evaluate the safety and tolerability of escalating doses of GS030-DP administered via a single intravitreal injection (IVT) and repeated light stimulation using GS030-MD in subjects with non-syndromic retinitis pigmentosa.

Secondary objectives 3

1. Evaluate the treatment effect of GS030 as assessed by vision and ocular measures, including visual acuity, visual function, orientation and mobility, and quality of life.
2. Compare visual acuity, visual function, orientation and mobility before and after gene transfer, with and without GS030-MD
3. Evaluate immune response (humoral and cellular) to recombinant adeno-associated viral vector derived from serotype 2 (rAAV2.7m8), and to ChrimsonR-tdTomato (ChR-tdT) protein.

Conditions and MedDRA coding

Retinitis Pigmentosa

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. Signed informed consent form.
2. Age ≥18 years to ≤75 years at the time of ICF signature.
3. Diagnosis of non-syndromic RP defined as: Clinical diagnosis of nonsyndromic RP based on history, mid-peripheral visual dysfunction, and fundoscopic appearance, or diagnosis of non-syndromic RP is confirmed on full-field ERG.
4. Visual acuity: Visual acuity in the dose-escalation cohorts of no better than LP, or Visual acuity in the extension cohort of no better than CF pending review of dose-escalation cohort data by the DSMB.
5. Relatively preserved ganglion cell layer volume and retinal nerve fiber layer thickness, as measured with spectral domain optical coherence tomography (SD-OCT).
6. Retains memory of former useful vision.
7. Ability to obtain adequate pupillary dilation to permit thorough ocular examination and testing.
8. Negative serum pregnancy test for women of childbearing age only.
9. Female subjects (if of childbearing potential) must agree to use highly effective methods of birth control up to 12 months after GS030-DP IVT, and male subjects must agree to use condoms for up to 12 months after GS030-DP IVT. (Highly effective methods of birth control include: combined (estrogen and progesterone containing) hormonal contraception (oral, injectable or transdermal) associated with inhibition of ovulation; progesterone-only hormonal contraception (oral, injectable or transdermal) associated with inhibition of ovulation; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomized partner (provided that partner is the sole sexual partner of the woman of childbearing potential and that the vasectomized partner has received medical assessment of the surgical success); true sexual abstinence, when consistent with the preferred and usual lifestyle of the subject (sexual abstinence defined as refraining from heterosexual intercourse during the entire period of risk associated with study treatments).
10. Ability to wear, utilize, and follow all instructions on proper use of the GS030-MD.
11. Interpupillary distance of ≥51 mm and ≤72 mm.
12. Refractive error of the study eye between -9 diopters and +6 diopters.
13. Review of all selection criteria to ensure continued compliance from Visit 2 through Visit 4.
14. Have a negative urine pregnancy test at Visit 4 for women of childbearing potential (women who are 2 years post-menopausal or surgically sterile are not considered to be of childbearing potential).
15. Have a negative test result for infection with HIV (results from test performed at Visit 1).
16. Ability to tolerate repeated light stimuli produced by the GS030-MD, as assessed in the inclusion phase (Visit 2 through Visit 4).

Exclusion criteria 30

1. Prior receipt of any gene therapy.
2. Subjects participating in another clinical trial and receiving an investigational medicinal product within 90 days prior to Visit 1.
3. Subjects with systemic disease or other pathology other than that related to diagnosis of non-syndromic RP whose symptoms or associated treatments may affect vision, for example cancers or pathology of the central nervous system.
4. Subjects with systemic disease or other medical or psychiatric conditions that preclude safe participation in the study.
5. Subjects who are taking photosensitizing drugs used in psoralen plus ultraviolet light (PUVA) therapy for psoriasis, eczema, vitiligo, and other similar diseases, or photosensitizing drugs used for photodynamic therapy in the treatment of cancer or eye diseases.
6. Subjects receiving immunosuppressive therapies, other than the immune modulating regimen described in this protocol.
7. Subjects of reproductive potential unwilling to use effective contraception for the 12 months after administration of GS030-DP.
8. Subjects who are pregnant or breastfeeding.
9. Subjects who are unwilling or unable to comply with the study protocol.
10. Subjects with any condition that would not allow them to complete follow-up examinations during the study and, in the opinion of the investigator, would make them unsuitable for the study.
11. Subjects who are human immunodeficiency virus (HIV) positive.
12. Subjects with known allergy to corticosteroids, or who will be unable to tolerate the corticosteroid regimen, or with an active intercurrent infection contraindicating treatment.
13. Subjects who have undergone significant ocular surgery (per investigator determination) within 3 months prior to Visit 1.
14. Presence of narrow iridocorneal angles contraindicating pupillary dilation.
15. Presence of disorders of the ocular media which interfere with visual acuity and other ocular assessments, including SD-OCT, during the study period.
16. Presence of any systemic or ocular diseases, or pathologies, other than non-syndromic RP, or their associated therapies, that can cause or have the potential to cause vision loss.
17. Prior vitreomacular surgery.
18. Presence of vitreo-macular adhesion or traction, epiretinal membrane macular pucker and macular hole, evident by ophthalmoscopy and/or by SD-OCT examinations and assessed by the investigator to significantly affect central vision.
19. Current evidence of retinal detachment assessed by the investigator to significantly affect central vision.
20. Active ocular inflammation or recurrent history of idiopathic or autoimmune-associated uveitis.
21. Hypersensitivity to GS030-DP or to any of the ingredients.
22. Presence of an Active Implantable Medical Device.
23. Subjects who have undergone thermal laser procedure to the retina within 3 months of trial entry, or any prior thermal laser procedure to the macular region.
24. Any non-selection criteria which become applicable after the selection visit.
25. Presence, at the time of study inclusion, of infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye.
26. Presence of systemic illness, including alcohol and drug abuse (except nicotine), or medically significant abnormal laboratory values that are deemed by the investigator to preclude the subject's safe participation in the study.
27. Presence of illness or disease that, in the opinion of the investigator, include symptoms and/or associated treatments that can alter visual function, for instance cancers or pathology of the central nervous system.
28. Any medical or psychological condition that, in the opinion of the investigator, may compromise the safe participation of the subject in the study or would preclude compliance with the study protocol or ability of the subject to successfully complete the study.
29. The subject is unable or unwilling to comply with the protocol requirements.
30. Failure to demonstrate presence of either ganglion cell layer or recognizable retinal nerve fiber layer.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Safety and tolerability of GS030 treatment at Week 52/Year 1 based on local and systemic safety issues, specifically those related to IVT of GS030-DP and the subsequent repeated use of GS030-MD, as assessed by incidence of adverse events (AEs).

Secondary endpoints 4

1. Assessment of the treatment effect on visual function, functional vision and mobility, with the change from baseline to Week 52 of parameters measured with FrACT, Humphrey visual field 102, full field threshold stimulus test (FST), Grating visual Acuity Test (GAT), square localization test and direction of motion test, door task, and line task, visual shape perception tests.
2. Assessment of the treatment effect on structural changes of the posterior pole of the fundus from baseline to Week 52 with parameters measured with SD-OCT, color fundus photography, and fundus auto fluorescence (FAF).
3. Assessment of the treatment effect on QoL changes from baseline to Week 52 with the Visual Function Questionnaire-25 (VFQ-25) and ShortForm Survey 36 Version 2 (SF-36v2).
4. Humoral and cellular immune responses to rAAV2.7m8 and ChR-tdT protein.

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Gensight Biologics

Sponsor organisation

Gensight Biologics

Address

74 Rue Du Faubourg Saint Antoine

City

Paris

Postcode

75012

Country

France

Scientific contact point

Organisation

Gensight Biologics

Contact name

GENSIGHT-BIOLOGICS

Public contact point

Organisation

Gensight Biologics

Contact name

GENSIGHT-BIOLOGICS

Third parties 6

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

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

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