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THOR - Tübingen Choroideremia Gene Therapy Trial (THOR)

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ClinicalTrials.gov Identifier: NCT02671539
Recruitment Status : Active, not recruiting
First Posted : February 2, 2016
Last Update Posted : September 26, 2018
Sponsor:
Collaborator:
University Hospital Tuebingen
Information provided by (Responsible Party):
STZ eyetrial

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.

Condition or disease Intervention/treatment Phase
Choroideremia Genetic: rAAV2.REP1 Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: THOR - Tübingen Choroideremia Gene Therapy Trial Open Label Phase 2 Clinical Trial Using an Adeno-associated Viral Vector (AAV2) Encoding Rab-escort Protein 1 (REP1)
Study Start Date : January 2016
Actual Primary Completion Date : March 2018
Estimated Study Completion Date : March 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: open label injection of rAAV2.REP1
This is an open label, single arm interventional trial with subretinal injection of rAAV2.REP1 and fellow eye comparison
Genetic: rAAV2.REP1
single subretinal injection




Primary Outcome Measures :
  1. best corrected visual acuity in treated eye [ Time Frame: up to 24 months after vector administration ]
    Change from baseline in best corrected visual acuity in treated eye, compared to untreated control eye up to 24 months after vector administration


Secondary Outcome Measures :
  1. Absence of vector-related adverse reactions [ Time Frame: 24 months after vector administration ]
  2. fundus autofluorescence analysis [ Time Frame: 24 months after vector administration ]
    improved retinal anatomy in treated eye compared to the untreated control eye 24 months after vector administration

  3. central visual field using microperimetry readings [ Time Frame: 24 months after vector administration ]
    improved visual function in treated eye compared to the untreated control eye 24 months after vector administration

  4. contrast sensitivity [ Time Frame: 24 months after vector administration ]
    improved visual function other than best corrected visual acuity in treated eye compared to the untreated control eye 24 months after vector administration (scale)

  5. colour vision [ Time Frame: 24 months after vector administration ]
    improved visual function other than best corrected visual acuity in treated eye compared to the untreated control eye 24 months after vector administration (physiological parameter)



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02671539


Locations
Germany
University Hospital Tuebingen, Center for Ophthalmology
Tuebingen, Germany, 72076
Sponsors and Collaborators
STZ eyetrial
University Hospital Tuebingen
Investigators
Principal Investigator: Manuel D Fischer, MD, PhD Centre for Ophthalmology, University Hospital Tübingen, Germany

Responsible Party: STZ eyetrial
ClinicalTrials.gov Identifier: NCT02671539     History of Changes
Other Study ID Numbers: THOR-TUE-01
First Posted: February 2, 2016    Key Record Dates
Last Update Posted: September 26, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by STZ eyetrial:
gene therapy
hereditary retinal degeneration
rAAV2.REP1

Additional relevant MeSH terms:
Choroideremia
Eye Diseases, Hereditary
Eye Diseases
Choroid Diseases
Uveal Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked