Safety and Efficacy of rAAV.hCNGA3 Gene Therapy in Patients With CNGA3-linked Achromatopsia

NCT02610582 | Active Not Recruiting Phase 1 DMC

• 3 other identifiers: RDC-CNGA3-012014-001874-32096/2015 AMG1
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to proof the safety and efficacy of a single bilateral subretinal injection of rAAV.hCNGA3 in adult and minor patients with CNGA3-linked achromatopsia.

Conditions

Achromatopsia

Keywords

CNGA3-linked

Outcome Measures

Primary Outcomes (1)

• Safety (AE). Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment

  Safety as the primary endpoint will be assessed by clinical examination of ocular inflammation (slit lamp, fundus biomicroscopy, fundus photography. Systemic safety will be assessed by vital signs, routine clinical chemistry testing (including CRP, ESR) and full/differential blood counts. Immunopathology essays will include specific enzyme-linked immunosorbent assays for humoral antibodies against rAAV8 capsid protein. Biodistribution will be monitored by polymerase chain reaction studies on rAAV8 genome in blood, urine, saliva and tear fluid.

  Day 0 - Day 365

Secondary Outcomes (1)

• Efficacy measures. Number of Participants With improved Visual Function.

  Day 14 - Day 365

Study Arms (2)

Treatment arm

OTHER

single subretinal injection of 1x10e11 vector genome particles of rAAV.hCNGA3 in each eye at different time-points

Drug: rAAV.hCNGA3

Waiting group Arm

OTHER

Waiting group will serve as comparator group first and will receive the treatment at a later timepoint.

Drug: rAAV.hCNGA3

Interventions

rAAV.hCNGA3 DRUG

Single subretinal injection of rAAV.hCNGA3

Treatment arm; Waiting group Arm

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• clinical diagnosis of achromatopsia
• years of age
• ≥ 18 years of age
• confirmed mutation in CNGA3
• BCVA ≥ 20/400
• a minimal outer nuclear layer thickness of 10µm at 3° eccentricity (normal = 38±6µm)
• ability to understand and willingness to consent to study protocol
• no infection with Human Immundeficiency Virus (HIV)
• 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.
• 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)

You may not qualify if:

• any other retinopathy due to other diseases e.g. (but not limited to) arterial hypertension, trauma or acquired inflammatory diseases (uveitis serology) , retinopathy of the premature
• systemic conditions (e.g. coronary heart disease, congenital/genetic conditions, autoimmune disorders) which may affect study participation or outcome measures
• current or recent participation in other study or administration of biologic agent within the last three months
• recent (6 months) ocular surgery, intravitreal or subretinal implantation of a medical device
• known sensitivity to any compound used in the study
• contraindications to systemic immunosuppression
• subject/partner of childbearing potential unwilling to use adequate contraception for six months after dosing
• nursing or pregnant female subject women
• any other cause that, in the investigator's opinion, renders potential subjects not suitable for the study
• mutations in another achromatopsia gene
• contraindications in view of the planned surgery (e.g. anaemia Hb\<8g/dl, severe coagulopathy, severe blood pressure fluctuations) including intolerance and contraindications to general anaesthesia
• ocular opacity and mature cataract
• 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)

Sponsors & Collaborators

• STZ eyetrial: lead
• University Hospital Tuebingen: collaborator
• Ludwig-Maximilians - University of Munich: collaborator

Study Sites (1)

University Hospital Tuebingen, Center for Ophthalmology

Tübingen, 72076, Germany

Location

Related Publications (2)

• Reichel FF, Michalakis S, Wilhelm B, Zobor D, Muehlfriedel R, Kohl S, Weisschuh N, Sothilingam V, Kuehlewein L, Kahle N, Seitz I, Paquet-Durand F, Tsang SH, Martus P, Peters T, Seeliger M, Bartz-Schmidt KU, Ueffing M, Zrenner E, Biel M, Wissinger B, Fischer D. Three-year results of phase I retinal gene therapy trial for CNGA3-mutated achromatopsia: results of a non randomised controlled trial. Br J Ophthalmol. 2022 Nov;106(11):1567-1572. doi: 10.1136/bjophthalmol-2021-319067. Epub 2021 May 18.

  PMID: 34006508 DERIVED

• Fischer MD, Michalakis S, Wilhelm B, Zobor D, Muehlfriedel R, Kohl S, Weisschuh N, Ochakovski GA, Klein R, Schoen C, Sothilingam V, Garcia-Garrido M, Kuehlewein L, Kahle N, Werner A, Dauletbekov D, Paquet-Durand F, Tsang S, Martus P, Peters T, Seeliger M, Bartz-Schmidt KU, Ueffing M, Zrenner E, Biel M, Wissinger B. Safety and Vision Outcomes of Subretinal Gene Therapy Targeting Cone Photoreceptors in Achromatopsia: A Nonrandomized Controlled Trial. JAMA Ophthalmol. 2020 Jun 1;138(6):643-651. doi: 10.1001/jamaophthalmol.2020.1032.

  PMID: 32352493 DERIVED

MeSH Terms

Conditions

Color Vision Defects

Condition Hierarchy (Ancestors)

Vision Disorders; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Cone Dystrophy; Eye Diseases, Hereditary; Eye Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Dominik Fischer, Prof.

  University Hospital Tuebingen, Center for Ophthalmology

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 18, 2015
• First Posted: November 20, 2015
• Study Start: November 1, 2015
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: April 18, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)