Study of Subretinally Injected AAVB-081 in Patients with Usher Syndrome Type IB (USH1B) Retinitis Pigmentosa

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Aavantgarde Bio S.r.l.

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

1 Jul 2024 → ongoing

Decision date (initial)

2024-11-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

European Union

External identifiers

EU CT number

2024-518489-29-00

EudraCT number

2022-001092-14

ClinicalTrials.gov

NCT06591793

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

- To assess the safety and tolerability of subretinal administration of AAVB-081 in participants with USH1B retinitis pigmentosa
- To determine a well-tolerated dose with optimal risk-benefit profile (RBP)

Secondary objectives 1

1. To assess the effect of AAVB-081 on retinal anatomy and function

Conditions and MedDRA coding

Usher Syndrome Type 1B (USH1B) Retinitis Pigmenotsa

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. All participants: Informed consent signed by the participant or participant’s legally authorized representative (if applicable).
2. All participants: Male and female adults diagnosed with USH1B; ≥ 18 to 50 ≤ 60 years of age
3. All participants: Molecular diagnosis of USH1B due to MYO7A mutations (homozygotes or compound heterozygotes) by a Sponsor approved Clinical Laboratory Improvement Amendments (CLIA) laboratory.
4. All participants: Residual central visual function evidenced by LLVA of ≥10 letters
5. All participants: Female participants of childbearing potential must use a highly effective method of contraception (see Appendix 3 for examples) for 1 year after treatment (from Day 0). Male participants who have a partner of childbearing potential must use condoms (barrier contraception) for 1 year after treatment. For the purpose of this protocol, a female participant is considered of childbearing potential (FPOCBP), i.e., fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.

Exclusion criteria 20

1. Unable or unwilling to meet the requirements of the study.
2. History of retinal detachment.
3. Poorly controlled diabetes mellitus (of any type), defined as HbA1c ≥7, in the 6 months prior to subretinal injection.
4. Presence of moderate or severe non-proliferative diabetic retinopathy or worse, diabetic macular edema (DME), retinal tumors, high axial myopia (>-6 Diopters), and micro/nanophthalmos.
5. Known sensitivity to medications planned for use in the peri- operative period.
6. Participants who are pregnant and/or breastfeeding at Screening.
7. Any other condition that would not allow the potential participant to complete follow-up examinations during the course of the study and in the opinion of the investigator, makes the potential participant unsuitable for the study.
8. Unable to communicate with suitable verbal/auditory and/or tactile sign language (in the opinion of the investigator).
9. Participation in a clinical study with an investigational drug in the past six months, or 5 half-lives, whichever is longer.
10. Previous participation in any other gene therapy trial.
11. Pre-existing eye conditions that would preclude the planned surgery or interfere with the interpretation of study endpoints (including but not limited to glaucoma, steroid response, corneal or significant lenticular or media opacities, cystoid macular oedema, macular hole, uveitis, epiretinal membrane).
12. Any systemic condition that would preclude subretinal surgery.
13. Profound vision loss in one eye with visual acuity of counting fingers or worse on semiquantitative scale.
14. Complicating ocular and systemic diseases, medications, or clinically significant abnormal baseline laboratory values.
15. Prior ocular non-macular laser within 3 months, prior cataract surgery within 3 months, use of post-operative anti-inflammatory drops in the past month, presence of inflammatory complications of cataract surgery in the past month, any other non-retinal intra-ocular surgery in the past 6 months prior to Day 0; and prior macular laser or retinal surgery at any time.
16. Use of high dose vitamin A (>7500 retinol equivalent units or >3300 IU per day), tretinoin-containing skin crème (e.g., Retin-A), or isotretinoin within 3 months prior to Day 0, or intended use during the study.
17. Chronic use of Viagra (sildenafil) or any other phosphodiesterase type 5 inhibitors used to treat erectile dysfunction, defined as at least once per month over the 12 months prior to Screening and until completion of study participation.
18. Participants who are positive for hepatitis B, hepatitis C, HIV, tuberculosis (TB), or syphilis infection.
19. Suspected or laboratory confirmed SARS-CoV-2 infection within 14 days prior to Day 0.
20. Has received a live, attenuated vaccine within 30 days prior to Day 0. Examples of live vaccines include, but are not limited, to the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), typhoid vaccine, and covid vaccine.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. The incidence and severity of adverse events (AEs) including serious adverse events (SAEs), treatment emergent adverse events (TEAEs) and dose limiting toxicities (DLTs) at 24 months.
2. The incidence and nature of DLTs at each dose level at 24 months

Investigational products

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

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Aavantgarde Bio S.r.l.

Sponsor organisation

Aavantgarde Bio S.r.l.

Address

Via Uberto Visconti Di Modrone 18

City

Milan

Postcode

20122

Country

Italy

Scientific contact point

Organisation

Aavantgarde Bio S.r.l.

Contact name

-

Public contact point

Organisation

Aavantgarde Bio S.r.l.

Contact name

-

Third parties 3

Sponsor responsibilities

Article 77 compliance

Aavantgarde Bio S.r.l.

Contact point sponsor

Aavantgarde Bio S.r.l.

Article 77 implementation

Aavantgarde Bio S.r.l.

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 9 files

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

Application history

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