PDE6A Gene Therapy for Retinitis Pigmentosa

NCT04611503 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: RDC-PDE6A-01
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

The PDE6A gene encodes a subunit of the rod phosphodiesterase. The loss of this enzyme function leads to a chronically elevated cGMP level which causes an increased calcium inflow into the cell and thereby the hyperactivation of cell death pathways. The goal of the PIGMENT study is to develop, produce and investigate a recombinant adeno-associated viral (AAV) gene transfer vector for the curative therapy of PDE6A-linked retinitis pigmentosa in patients, in order to counteract their disease progression and to stop further impairment of visual function. The vector is given with a single subretinal injection.

Conditions

Retinitis Pigmentosa

Outcome Measures

Primary Outcomes (3)

• Slit lamp examination

  to determine possibly occurring ocular inflammation and to observe if there are any treatment effects

  1 year + 4 years follow-up

• Fundus biomicroscopy to determine possibly occurring ocular inflammation and to observe if there are any treatment effects

  To determine possibly occurring ocular inflammation and to observe if there are any treatment effects

  1 year + 4 years follow-up

• Angiography

  To determine possibly occurring ocular inflammation and to observe if there are any treatment effects

  1 year + 4 years follow-up

Secondary Outcomes (6)

• Visual acuity

  1 year + 4 years follow-up

• Contrast sensitivity

  1 year + 4 years follow-up

• Visual field

  1 year + 4 years follow-up

• Colour vision

  1 year + 4 years follow-up

• Pupillography

  1 year + 4 years follow-up

Study Arms (1)

Subretinal injection of rAAV.hPDE6A

EXPERIMENTAL

Single subretinal injection of rAAV.hPDE6A

Drug: subretinal injection of rAAV.hPDE6A

Interventions

subretinal injection of rAAV.hPDE6A DRUG

The first 3 patients (C1) will receive the intermediate dose 1x1010 vg. After injection of the 3rd patient of C1, the DMC will give a go/no go decision. If 'nogo', a lower dose (5x109 vg) will be given to the next group of 3 patients (C2). The DMC will give a go/no go decision. In case of a "go" decision, 3 further patients (C3) will be treated with the same dose. In the case of a no-go decision, the next dose will be the minimal dose 1x109 vg. In case of a 'go' decision of the DMC after the third patient, the next 3 patients will receive a subretinal injection of vector at the highest dose 5x1010 vg. The DMC will give a go/no go decision after review of all safety data available at D30 of cohort 2. If safety data is considered favourably by the DMC, then 3further patients (cohort 3) will be treated with the same dose (5x1010 vg). Should any safety concerns arise, the last three patients (cohort 3) will receive the intermediate dose (1x1010 vg).

Also known as: Gene therapy

Subretinal injection of rAAV.hPDE6A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• clinical diagnosis of retinitis pigmentosa
• confirmed mutation in PDE6A gene
• ≥ 18 years of age
• visual acuity ≥ 20/400
• no infection with Human Immundeficiency Virus (HIV)
• negative pregnancy test in women with childbearing potential (a woman who is two years post-menopausal or surgically sterile is not considered to be of childbearing potential)
• Male patients must agree to use condoms during the first 6 months post treatment.
• Female patients of childbearing potential must agree to use an effective method of birth control during the first 6 months post treatment.
• ability to understand and willingness to consent to study protocol

You may not qualify if:

• Ocular (study eye \& fellow eye)
• additional interfering ocular conditions with impact on study results (e.g. ocular opacity and advanced cataract, uveitis, amblyopia)
• recent (6 months) ocular surgery, intravitreal or subretinal implantation of a medical device
• disease causing mutations in another known retinitis pigmentosa gene
• ocular infection with herpes simplex virus in medical history
• history of ocular malignancies
• disorders of the internal retina (e.g. retinal detachment in the patients history)
• glaucoma defined as damage of the optic nerve
• vascular retinal occlusion
• diabetic patients suffering from retinopathy and/or macula edema
• any other retinopathy due to other diseases e.g. (but not limited to) arterial hypertension, trauma or acquired inflammatory diseases (uveitis serology), contraindication to pharmacological mydriasis (e.g. history of angle block glaucoma)
• absence of visual function on the contralateral eye Systemic
• systemic conditions (e.g. coronary heart disease, autoimmune disorders) which may affect study participation or outcome measures
• History of poorly controlled Diabetes Mellitus type 1 or type 2
• current or recent participation in other study/or administration of biologic agent within the last three months

Sponsors & Collaborators

• STZ eyetrial: lead

Study Sites (1)

Universitätsklinikum Tübingen, Department für Augenheilkunde

Tübingen, 72076, Germany

Location

Related Publications (1)

• Seitz IP, Wozar F, Ochakovski GA, Reichel FF, Korte S, Korbmacher B, Wilhelm B, Susskind D, Bartz-Schmidt KU, Fischer MD, Peters T; RD Cure Consortium. Ocular Safety and Toxicology of Subretinal Gene Therapy With rAAV.hPDE6A in Nonhuman Primates. Transl Vis Sci Technol. 2025 Jan 2;14(1):29. doi: 10.1167/tvst.14.1.29.

  PMID: 39878701 DERIVED

MeSH Terms

Conditions

Retinitis Pigmentosa

Interventions

Genetic Therapy

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Retinal Dystrophies; Retinal Degeneration; Retinal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics; Genetic Engineering; Genetic Techniques; Investigative Techniques

Study Officials

• Dominik Fischer, Prof.

  University Hospital Tuebingen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2020
• First Posted: November 2, 2020
• Study Start: September 24, 2019
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: April 18, 2024

Record last verified: 2024-04

Locations

DE (1)