THOR - Tübingen Choroideremia Gene Therapy Trial

NCT02671539 | Completed Phase 2 DMC

• 1 other identifier: THOR-TUE-01
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

An open label monocentric phase II trial in adult males with a clinical phenotype of choroideremia and a confirmed molecular diagnosis of a null mutation in the gene encoding REP1 to assess the anatomical and functional outcomes, as well as the safety of a single subretinal injection of rAAV2.REP1 in 6 subjects with genetically confirmed choroideremia for up to 24 months.

Conditions

Choroideremia

Keywords

gene therapy; hereditary retinal degeneration; rAAV2.REP1

Outcome Measures

Primary Outcomes (1)

• best corrected visual acuity in treated eye

  Change from baseline in best corrected visual acuity in treated eye, compared to untreated control eye up to 24 months after vector administration

  up to 24 months after vector administration

Secondary Outcomes (5)

• Absence of vector-related adverse reactions

  24 months after vector administration

• fundus autofluorescence analysis

  24 months after vector administration

• central visual field using microperimetry readings

  24 months after vector administration

• contrast sensitivity

  24 months after vector administration

• colour vision

  24 months after vector administration

Study Arms (1)

open label injection of rAAV2.REP1

EXPERIMENTAL

This is an open label, single arm interventional trial with subretinal injection of rAAV2.REP1 and fellow eye comparison

Genetic: rAAV2.REP1

Interventions

rAAV2.REP1 GENETIC

single subretinal injection

open label injection of rAAV2.REP1

Eligibility Criteria

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

You may qualify if:

• Participant is willing and able to give informed consent for participation in the study.
• Male aged 18 years or above.
• Genetically confirmed diagnosis of choroideremia. Patients without a confirmed mutation in the CHM gene, but who have the clinical phenotype typical of choroideremia can only be enrolled if they meet all the following three criteria: (i) family history consistent with X-linked inheritance, (ii) absent REP1 protein on Western blot of a blood sample and, (iii) normal RPE65 gene on sequencing.
• Active disease visible clinically within the macula region
• Best-corrected visual acuity equal to or worse than 6/9 (20/32; Decimal 0.63; LogMAR 0.2) but better than or equal to 6/60 (20/200; Decimal 0.1; LogMAR 1.0) in the study eye.

You may not qualify if:

• Female and child participants (under the age of 18)
• Participants with a history of amblyopia in the study eye
• Men unwilling to use barrier contraception methods, if relevant
• Absence of quantifiable visual function in the fellow eye or other ocular morbidity which might confound use of the fellow eye as a long-term control.
• Any other significant ocular and non-ocular disease/disorder or retinal surgery which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the results of the study, or the participant's ability to participate in the study. This would include not taking or having a contraindication to oral prednisolone, such as a history of gastric ulcer or significant side effects.
• Participants who have participated in another research study involving an investigational product in the past 12 weeks, or having had gene or cellular therapy at any time prior to this study.
• Patients with amblyopic eyes should be excluded in general, since the evaluation of the primary endpoint presupposes the ability to fixate both eyes
• Prior intraocular surgery within six months
• Intolerance to local anesthesia and/or contraindication to IVT surgery (anemia Hb\<8g/dl, severe cardiovascular disease, severe coagulopathy, etc.)
• High fever or high fever disease, patients with a history of autoimmune conditions/ other systemic diseases that may have ocular manifestations (e.g. sarcoidosis) or neurodegenerative conditions (e.g. multiple sclerosis, neuromyelitis optica, Parkinson's disease)
• Patients suffering from other genetic mutations leading to pathological retinal conditions

Sponsors & Collaborators

• STZ eyetrial: lead
• University Hospital Tuebingen: collaborator

Study Sites (1)

University Hospital Tuebingen, Center for Ophthalmology

Tübingen, 72076, Germany

Location

Related Publications (1)

• Fischer MD, Ochakovski GA, Beier B, Seitz IP, Vaheb Y, Kortuem C, Reichel FFL, Kuehlewein L, Kahle NA, Peters T, Girach A, Zrenner E, Ueffing M, MacLaren RE, Bartz-Schmidt KU, Wilhelm B. Efficacy and Safety of Retinal Gene Therapy Using Adeno-Associated Virus Vector for Patients With Choroideremia: A Randomized Clinical Trial. JAMA Ophthalmol. 2019 Nov 1;137(11):1247-1254. doi: 10.1001/jamaophthalmol.2019.3278.

  PMID: 31465092 DERIVED

MeSH Terms

Conditions

Choroideremia

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Choroid Diseases; Uveal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked

Study Officials

• Manuel D Fischer, MD, PhD

  Centre for Ophthalmology, University Hospital Tübingen, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2016
• First Posted: February 2, 2016
• Study Start: January 1, 2016
• Primary Completion: February 1, 2018
• Study Completion: February 1, 2018
• Last Updated: October 27, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)