Safety and efficacy of a bilateral single subretinal injection of rAAV.hCNGA3 in adult and minor patients with CNGA3-linked achromatopsia investigated in a randomized, wait list controlled, observer-masked trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaetsklinikum Tuebingen AöR

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

11 Mar 2021 → ongoing

Decision date (initial)

2024-07-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515553-17-00

EudraCT number

2014-001874-32

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To proof the safety and efficacy of rAAV.hCNGA3 in patients with achromatopsia if applied bilaterally in adults and minors.

Conditions and MedDRA coding

CNGA3-linked achromatopsia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. clinical diagnosis of achromatopsia
2. 6-12 years of age
3. ≥ 18 years of age
4. bi-allelic pathogenic or likely pathogenic mutation in CNGA3
5. BCVA ≥ 20/400
6. a minimal outer nuclear layer thickness of 10μm at 3° eccentricity (normal =38±6μm)
7. ability to understand and willingness to consent to study protocol
8. no infection with Human Immundeficiency Virus (HIV)
9. Male patients must agree to use condoms during the first 6 months post treatment.
10. Female patients of childbearing potential must agree to use an effective method ofbirth control during the first 6 months post treatment.
11. negative pregnancy test in women with childbearing potential (a woman who istwo years post-menopausal or surgically sterile is not considered to be ofchildbearing potential)

Exclusion criteria 21

1. any other retinopathy due to other diseases e.g. (but not limited to) arterialhypertension, trauma or acquired inflammatory diseases (uveitis serology) ,retinopathy of the premature
2. systemic conditions (e.g. coronary heart disease, congenital/genetic conditions,autoimmune disorders) which may affect study participation or outcome measures
3. current or recent participation in other study or administration of biologic agentwithin the last three months
4. recent (within the last 6 months) ocular surgery, intravitreal or subretinalimplantation of a medical device
5. known sensitivity to any compound used in the study
6. contraindications to systemic immunosuppression
7. subject/partner of childbearing potential unwilling to use adequate contraceptionfor six months after dosing
8. nursing or pregnant female subject
9. any other cause that, in the investigator‘s opinion, renders potential subjects notsuitable for the study
10. causal mutations in other genes for hereditary retinal diseases
11. contraindications in view of the planned surgery (e.g. anaemia Hb<8g/dl, severecoagulopathy, severe blood pressure fluctuations) including intolerance andcontraindications to general anaesthesia
12. ocular opacity and mature cataract
13. ocular infection with herpes simplex virus in medical history
14. history of ocular malignancies
15. disorders of the inner retina (e.g. retinal vascular occlusions in the patients history)
16. glaucoma defined as damage of the optic nerve
17. history of poorly controlled (HbA1c > 7%) Diabetes Mellitus type 1 or type 2
18. patients treated with systemic corticoids within 14 days prior inclusion
19. systemic illness or medically significant abnormal laboratory values >3 UNL in bloodanalysis including renal and hepatic functions at inclusion
20. absence of vision on the contralateral eye
21. contraindication to pharmacological mydriasis (e.g. history of angle blockglaucoma)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Contrast sensitivity (Pelli Robson 3 m) 6 months after treatment

Secondary endpoints 8

1. Contrast sensitivity (Pelli Robson 3 m)
2. BCVA assessed using the ETDRS visual acuity protocol
3. FrACT (Freiburg Visual Acuity & Contrast Test)
4. Roth FM28 sat
5. VA-CAL (Visual acuity under different conditions of contrast and ambient light)
6. Patient reported outcomes (VFQ25/CVFQ, A3-PRO)
7. Electroretinography
8. Chromatic pupil campimetry (CPC) cone protocol – exploratory - functional

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsklinikum Tuebingen AöR

Sponsor organisation

Universitaetsklinikum Tuebingen AöR

Address

Geissweg 3, Innenstadt Innenstadt

City

Tuebingen

Postcode

72076

Country

Germany

Scientific contact point

Organisation

Universitaetsklinikum Tuebingen AöR

Contact name

Dr. med Tobias Peters

Public contact point

Organisation

Universitaetsklinikum Tuebingen AöR

Contact name

Dr. med Tobias Peters

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