- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04611503
PDE6A Gene Therapy for Retinitis Pigmentosa (Pigment)
PIGMENT - PDE6A Gene Therapy for Retinitis Pigmentosa
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
"PIGMENT - Subretinal PDE6A gene therapy for retinitis pigmentosa" is an open mono-center, phase I/IIa trial with fellow-eye comparison.
The study begins with a detailed preliminary examination (Screening), comprises a total of 13 visits and ends after one year. In between, after the gene therapy injection (injection of the vector under the retina with one of four doses), regular controls are carried out at the Center for Ophthalmology Tübingen. Monitoring will be contimued after the first year, once a year two, three, four and five years after the injection. The study will take place exclusively at the Center for Ophthalmology in Tübingen and involves nine patients.
All patients participating in this study receive treatment, i.e. there is no placebo or sham treatment group. A 30-day safety distance is maintained between each patient and each group. An independent committee will decide, after each injection of three patients, which dose the following three patients will receive.
Patients can benefit from the treatment by slowing or stopping the loss of the rods and allowing them to function to a certain extent. Therefore, a possible benefit for patients may be that the vision problems will be improved by gene therapy. Such improvements could improve the overall quality of life and well-being. However, as no experience with gene therapy for retinitis pigmentosa in humans has yet been gained, we cannot promise any improvement. Within the scope of this study, patients will be given particularly intensive care and psychological support will also be offered in order to do everything for the patient's well-being and health during the study.
Time Schedule: Start of trial Q3/2019 (FPFV), end of recruitment Q3/2020, end of trial Q4/2025 (LPLV), duration of trial per patient: one year with four years of follow-up. The final study report will be prepared after completion of the four year follow-up period (5 years after treatment).
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Tuebingen, Germany, 72076
- Universitätsklinikum Tübingen, Department für Augenheilkunde
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
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
- systemic illness or medically relevant abnormal laboratory values in blood analysis including renal and hepatic functions at inclusion
- patients treated with oral corticoids within 14 days prior inclusion
- current or recent participation in other study/or administration of biologic agent within the last three months
- known sensitivity to any compound used in the study
- contraindications to systemic immunosuppression
- contraindications in view of the planned surgery (e.g. but not limited to anaemia Hb<10g/dl, coagulopathy with PT/PTT >1,5 fold upper limit, hypertension with values above 180 mmHg systolic and 110 mmHg diastolic) including intolerance and contraindications to general anaesthesia
- intolerance to contrast agents used for diagnostic methods like angiography with fluoresceine or indocyanine green (e.g. but not limited to hyperthyroidism, hepatic insufficiency)
- subject/partner of childbearing potential unwilling to use adequate contraception for four months
- nursing or pregnant women
- any other cause that, in the investigator's opinion, renders potential subjects not suitable for the study
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Subretinal injection of rAAV.hPDE6A
Single subretinal injection of rAAV.hPDE6A
|
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).
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Slit lamp examination
Time Frame: 1 year + 4 years follow-up
|
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
Time Frame: 1 year + 4 years follow-up
|
To determine possibly occurring ocular inflammation and to observe if there are any treatment effects
|
1 year + 4 years follow-up
|
Angiography
Time Frame: 1 year + 4 years follow-up
|
To determine possibly occurring ocular inflammation and to observe if there are any treatment effects
|
1 year + 4 years follow-up
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Visual acuity
Time Frame: 1 year + 4 years follow-up
|
To determine any therapy effects concerning visual acuity
|
1 year + 4 years follow-up
|
Contrast sensitivity
Time Frame: 1 year + 4 years follow-up
|
To determine any therapy effects concerning the contrast sensitivity
|
1 year + 4 years follow-up
|
Visual field
Time Frame: 1 year + 4 years follow-up
|
To determine any therapy effects concerning the visual field
|
1 year + 4 years follow-up
|
Colour vision
Time Frame: 1 year + 4 years follow-up
|
To determine any therapy effects concerning colour vision
|
1 year + 4 years follow-up
|
Pupillography
Time Frame: 1 year + 4 years follow-up
|
To determine any therapy effects concerning pupil reaction
|
1 year + 4 years follow-up
|
Electrophysiology
Time Frame: 1 year + 4 years follow-up
|
To determine any therapy effects concerning the electrophysiology
|
1 year + 4 years follow-up
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Dominik Fischer, Prof., University Hospital Tuebingen
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- RDC-PDE6A-01
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Retinitis Pigmentosa
-
MeiraGTx UK II LtdSyne Qua Non Limited; Bionical EmasCompletedGene Therapy for X-linked Retinitis Pigmentosa (XLRP) - Retinitis Pigmentosa GTPase Regulator (RPGR)X-Linked Retinitis PigmentosaUnited Kingdom, United States
-
Oslo University HospitalRecruitingRetinitis Pigmentosa | Retinitis Pigmentosa 11Norway
-
Jinnah Burn and Reconstructive Surgery Centre,...The Layton Rahmatullah Benevolent Trust (LRBT) Free Eye Hospital, Township... and other collaboratorsRecruitingRetinitis Pigmentosa (RP)Pakistan
-
AbbVieActive, not recruitingAdvanced Retinitis PigmentosaUnited States
-
jCyte, IncCalifornia Institute for Regenerative Medicine (CIRM)CompletedRetinitis Pigmentosa (RP)United States
-
Janssen Research & Development, LLCJanssen Research & Development, LLCActive, not recruitingX-Linked Retinitis PigmentosaBelgium, Canada, United States, Israel, United Kingdom, Spain, Denmark, France, Italy, Netherlands, Switzerland
-
Janssen Research & Development, LLCActive, not recruitingX-Linked Retinitis PigmentosaUnited States, United Kingdom
-
GenSight BiologicsRecruitingNon-syndromic Retinitis PigmentosaUnited States, France, United Kingdom
-
Janssen Research & Development, LLCJanssen Research & Development, LLCActive, not recruitingX-Linked Retinitis PigmentosaUnited States, Canada, Israel, United Kingdom, Spain, Denmark, France, Belgium, Italy, Netherlands, Switzerland
-
BiogenCompletedX-Linked Retinitis PigmentosaUnited States, United Kingdom
Clinical Trials on subretinal injection of rAAV.hPDE6A
-
Fondazione Policlinico Universitario Agostino Gemelli...CompletedRetinitis Pigmentosa | Dry Age-related Macular DegenerationItaly
-
Innostellar Biotherapeutics Co.,LtdRecruitingNeovascular Age-Related Macular DegenerationChina
-
Universitaire Ziekenhuizen KU LeuvenDORC Dutch Ophthalmic Research Center International BVRecruitingAge-Related Macular Degeneration | Subretinal HemorrhageBelgium
-
Retina Implant AGCompletedRetinal Degeneration | Retinitis PigmentosaHong Kong
-
Ain Shams UniversityRecruiting
-
Innostellar Biotherapeutics Co.,LtdRecruitingNeovascular Age-Related Macular DegenerationChina
-
Ain Shams UniversityNot yet recruitingRhegmatogenous Retinal Detachment
-
King Khaled Eye Specialist HospitalKing Faisal Specialist Hospital & Research CenterCompletedRetinitis Pigmentosa | Retinal DiseaseSaudi Arabia
-
Retina Implant AGCompletedRetinitis PigmentosaGermany
-
Kyorin UniversityCompletedSubmacular Hemorrhage | Ruptured Retinal Arterial Macro AneurysmsJapan