THOR - Tübingen Choroideremia Gene Therapy Trial

Plain-language summary

This study examined a gene therapy called rAAV2.REP1 for the inherited eye disease choroideremia. It enrolled men aged 18 and older with a genetically confirmed diagnosis of choroideremia (or meeting specific clinical criteria). It was conducted in Phase 2 and has been completed.

The summary above is a plain-language rendering of the official record. The original English title is shown for reference.

Trial details

Phase

Phase 2

Status

Completed

Sponsor

STZ eyetrial

Intervention

rAAV2.REP1

Start date

1/1/2016

Estimated completion

2/1/2018

Countries

Germany

Related genes

Locations

• Tübingen, Germany

Eligibility criteria

Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.

Inclusion Criteria:

1. Participant is willing and able to give informed consent for participation in the study.
2. Male aged 18 years or above.
3. 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.
4. Active disease visible clinically within the macula region
5. 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.

Exclusion Criteria:

1. Female and child participants (under the age of 18)
2. Participants with a history of amblyopia in the study eye
3. Men unwilling to use barrier contraception methods, if relevant
4. 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.
5. 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.
6. 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.
7. Patients with amblyopic eyes should be excluded in general, since the evaluation of the primary endpoint presupposes the ability to fixate both eyes
8. Prior intraocular surgery within six months
9. Intolerance to local anesthesia and/or contraindication to IVT surgery (anemia Hb\<8g/dl, severe cardiovascular disease, severe coagulopathy, etc.)
10. 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)
11. Patients suffering from other genetic mutations leading to pathological retinal conditions
12. Patients treated by oral corticoids within 14 days prior inclusion at the study entry