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Retinitis PigmentosaPhase 1/2PigmentNCT04611503

PDE6A Gene Therapy for Retinitis Pigmentosa

A Phase 1/2 study testing subretinal injection of rAAV.hPDE6A in people with Retinitis Pigmentosa, run by STZ eyetrial at 1 site in Germany.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The PDE6A gene encodes a subunit of the rod phosphodiesterase. The loss of this enzyme function leads to a chronically elevated cGMP level which causes an increased calcium inflow into the cell and thereby the hyperactivation of cell death pathways. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Retinitis Pigmentosa
What is being tested?
subretinal injection of rAAV.hPDE6A
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteGermany
Study dates
24 Sep 2019to Jul 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Universitätsklinikum Tübingen, Department für Augenheilkunde

    Tübingen, 72076

Other trials in Germany

About this study

Official title: PIGMENT - PDE6A Gene Therapy for Retinitis Pigmentosa

The PDE6A gene encodes a subunit of the rod phosphodiesterase. The loss of this enzyme function leads to a chronically elevated cGMP level which causes an increased calcium inflow into the cell and thereby the hyperactivation of cell death pathways. The goal of the PIGMENT study is to develop, produce and investigate a recombinant adeno-associated viral (AAV) gene transfer vector for the curative therapy of PDE6A-linked retinitis pigmentosa in patients, in order to counteract their disease progression and to stop further impairment of visual function. The vector is given with a single subretinal injection.

Read the 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).

Being tested
subretinal injection of rAAV.hPDE6A
Medical subject headings
Retinitis Pigmentosa

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • subretinal injection of rAAV.hPDE6ADrug

    Also called Gene therapy

    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).

Study groups in NCT04611503
Study groupRoleWhat they receive
Subretinal injection of rAAV.hPDE6AExperimentalSingle subretinal injection of rAAV.hPDE6A
Receives: Drug: subretinal injection of rAAV.hPDE6A

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Slit lamp examination

    to determine possibly occurring ocular inflammation and to observe if there are any treatment effects

    Measured: 1 year + 4 years follow-up

  2. Fundus biomicroscopy to determine possibly occurring ocular inflammation and to observe if there are any treatment effects

    To determine possibly occurring ocular inflammation and to observe if there are any treatment effects

    Measured: 1 year + 4 years follow-up

  3. Angiography

    To determine possibly occurring ocular inflammation and to observe if there are any treatment effects

    Measured: 1 year + 4 years follow-up

Secondary outcomes (6)

  1. Visual acuity

    To determine any therapy effects concerning visual acuity

    Measured: 1 year + 4 years follow-up

  2. Contrast sensitivity

    To determine any therapy effects concerning the contrast sensitivity

    Measured: 1 year + 4 years follow-up

  3. Visual field

    To determine any therapy effects concerning the visual field

    Measured: 1 year + 4 years follow-up

  4. Colour vision

    To determine any therapy effects concerning colour vision

    Measured: 1 year + 4 years follow-up

  5. Pupillography

    To determine any therapy effects concerning pupil reaction

    Measured: 1 year + 4 years follow-up

  6. Electrophysiology

    To determine any therapy effects concerning the electrophysiology

    Measured: 1 year + 4 years follow-up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Nov 2020
  2. Study start24 Sep 2019
  3. Primary completionJul 2027 (estimated)
  4. Study completionJul 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04611503
Sponsor's protocol ID
RDC-PDE6A-01
Acronym
Pigment
Status last verified
Apr 2024
First submitted
20 May 2020
Last updated
18 Apr 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Seitz IP, Wozar F, Ochakovski GA, Reichel FF, Korte S, Korbmacher B, Wilhelm B, Susskind D, Bartz-Schmidt KU, Fischer MD, Peters T; RD Cure Consortium. Ocular Safety and Toxicology of Subretinal Gene Therapy With rAAV.hPDE6A in Nonhuman Primates. Transl Vis Sci Technol. 2025 Jan 2;14(1):29. doi: 10.1167/tvst.14.1.29.

    PubMed 39878701

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing subretinal injection of rAAV.hPDE6A in people with Retinitis Pigmentosa, run by STZ eyetrial at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 18 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Slit lamp examination (time frame: 1 year + 4 years follow-up). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04611503, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2024.

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