X-Linked Retinitis PigmentosaPhase 1/2NCT04517149
4D-125 in Patients With X-Linked Retinitis Pigmentosa (XLRP)
A Phase 1/2 study testing 4D-125 IVT Injection and Observational in people with X-Linked Retinitis Pigmentosa, run by 4D Molecular Therapeutics at 8 sites in United States.
Trial summary
This is a Phase 1/2 multicenter study with two parallel parts: an observational natural history cohort and an open-label, prospective interventional trial in males with non-syndromic X-linked retinitis pigmentosa (XLRP) due to mutations in the gene encoding retinitis pigmentosa GTPase regulator (RPGR). Read more about this study
- Who is it for?
- Ages 12 years and older, men only
- Conditions the study is for
- X-Linked Retinitis Pigmentosa
- What is being tested?
- 4D-125 IVT Injection and Observational
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 8 sitesUnited States
- Study dates
- 9 Jun 2020to May 2029
- 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 12 years and older
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Patient has previously received any AAV treatment
- Pre-existing eye conditions or surgical complications that would preclude participation in an interventional clinical trial or interfere with the interpretation of study endpoints
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
University of Michigan Kellogg Eye Center
Ann Arbor, Michigan, 48105
University of Colorado
Aurora, Colorado, 80045
Retina Foundation of the Southwest
Dallas, Texas, 75231
Duke University Eye Center/Dept. of Ophthalmology
Durham, North Carolina, 27710
Vitreo Retinal Associates
Gainesville, Florida, 32607
Columbia University Medical Center/Edward Harkness Eye Institute
New York, New York, 10032
Casey Eye Institute, Oregon Health and Science University
Portland, Oregon, 97239
University of Utah John A. Moran Eye Center
Salt Lake City, Utah, 84132
About this study
Official title: An Open-label, Phase 1/2 Trial of Gene Therapy 4D-125 in Males With X-linked Retinitis Pigmentosa (XLRP) Caused by Mutations in the RPGR Gene
This is a Phase 1/2 multicenter study with two parallel parts: an observational natural history cohort and an open-label, prospective interventional trial in males with non-syndromic X-linked retinitis pigmentosa (XLRP) due to mutations in the gene encoding retinitis pigmentosa GTPase regulator (RPGR).
Read the detailed description
This Phase 1/2 study will gather data in an observational phase Natural History Cohort to further characterize and evaluate natural disease progression in male patients with genetically-confirmed X-linked retinitis pigmentosa (XLRP) caused by mutations in the gene encoding retinitis pigmentosa GTPase regulator (RPGR). The study will also evaluate the safety and tolerability, as assessed by frequency and severity of ocular and systemic adverse events, as well as preliminary clinical efficacy of a single intravitreal (IVT) injection of 4D-125 at two dose levels in this patient population in one or both eyes (the contralateral eye dose provided the subject is eligible and provides consent).
4D-125 has been developed as a gene replacement therapy for XLRP. After receiving 4D-125, patients will be followed for 24 months with continued safety follow-up and 36 additional months of long-term follow-up. Secondary endpoints will assess preliminary efficacy measures over time after 4D-125 administration.
- Conditions
- X-Linked Retinitis Pigmentosa
- Being tested
- 4D-125 IVT Injection, Observational
- Keywords
- XLRP, Gene therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
4D-125 IVT InjectionBiological
4D-125 drug product developed for gene therapy, which comprises an AAV capsid variant (4D-R100) carrying a codon-optimized human Retinitis Pigmentosa GTPase Regulator transgene.
ObservationalOther
Natural History
| Study group | Role | What they receive |
|---|---|---|
| 4D-125 Dose Exploration | Experimental | Dose 1 and Dose 2
4D-125 will be administered at the assigned dose level as a single dose, IVT injection on Day 1. The contralateral eye may also be dosed with 4D-125 as a single dose, IVT injection provided the subject is eligible and provides consent. Receives: Biological: 4D-125 IVT Injection |
| 4D-125 Dose Expansion | Experimental | 4D-125 will be administered at the assigned dose level as a single dose, IVT injection on Day 1 in both adults and pediatric participants. For adult participants only, the contralateral eye may also be dosed with 4D-125 as a single dose, IVT injection provided the subject is eligible and provides consent. Receives: Biological: 4D-125 IVT Injection |
| Observational | Other | Natural History Receives: Other: Observational |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and severity of TEAEs and serious adverse events (SAEs), including clinically significant changes in safety parameters
Measured: 24 months to 60 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2020
- Study start9 Jun 2020
- Primary completionJun 2026 (estimated)
- Study completionMay 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for X-Linked Retinitis PigmentosaStudies of the same condition, open and under way.
- More trials run by 4D Molecular TherapeuticsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Non-randomised
- Intervention model
- Sequential
- Model description
- In Phase 1, up to 2 dose exploration cohorts will be enrolled; each cohort will initially recruit up to 3 patients to receive a single uniocular IVT injection of 4D-125 in a standard 3+3 design. The cohort will be expanded in the event of a dose limiting toxicity (DLT). Any cohort may be expanded by an additional 3 subjects (to a maximum of 12 patients) to provide additional safety information and/or to confirm the selected dose for expansion. Once the dose level has been selected, the Phase 2 Dose Expansion Cohort will be opened to dose an additional 6-12 adult patients, and includes a pediatric sub-population of up to 6 patients. For adult participants only, the contralateral eye may also be dosed with 4D-125 as a single dose, IVT injection provided the subject is eligible and provides consent.
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- 4D Molecular Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Schonmei Lee, MD, Study director, 4D Molecular Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04517149
- Sponsor's protocol ID
- 4D-125-C001
- Status last verified
- Mar 2025
- First submitted
- 14 Aug 2020
- Last updated
- 21 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Phase 1/2 Trial of Gene Therapy 4D-125 in Males With X-linked Retinitis Pigmentosa (XLRP) Caused by Mutations in the RPGR Gene
- ClinicalTrials.gov ID
- NCT04517149
- Acronym / sponsor ID
- 4D-125-C001
- Conditions
- X-Linked Retinitis Pigmentosa
- Keywords
- XLRP, Gene therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 21 participants (actual)
- Lead sponsor
- 4D Molecular TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 9 Jun 2020 (actual)
- Primary completion
- Jun 2026 (estimated)
- Study completion
- May 2029 (estimated)
- First posted
- 18 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 1/2 multicenter study with two parallel parts: an observational natural history cohort and an open-label, prospective interventional trial in males with non-syndromic X-linked retinitis pigmentosa (XLRP) due to mutations in the gene encoding retinitis pigmentosa GTPase regulator (RPGR).
Detailed description
This Phase 1/2 study will gather data in an observational phase Natural History Cohort to further characterize and evaluate natural disease progression in male patients with genetically-confirmed X-linked retinitis pigmentosa (XLRP) caused by mutations in the gene encoding retinitis pigmentosa GTPase regulator (RPGR). The study will also evaluate the safety and tolerability, as assessed by frequency and severity of ocular and systemic adverse events, as well as preliminary clinical efficacy of a single intravitreal (IVT) injection of 4D-125 at two dose levels in this patient population in one or both eyes (the contralateral eye dose provided the subject is eligible and provides consent).
4D-125 has been developed as a gene replacement therapy for XLRP. After receiving 4D-125, patients will be followed for 24 months with continued safety follow-up and 36 additional months of long-term follow-up. Secondary endpoints will assess preliminary efficacy measures over time after 4D-125 administration.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- In Phase 1, up to 2 dose exploration cohorts will be enrolled; each cohort will initially recruit up to 3 patients to receive a single uniocular IVT injection of 4D-125 in a standard 3+3 design. The cohort will be expanded in the event of a dose limiting toxicity (DLT). Any cohort may be expanded by an additional 3 subjects (to a maximum of 12 patients) to provide additional safety information and/or to confirm the selected dose for expansion. Once the dose level has been selected, the Phase 2 Dose Expansion Cohort will be opened to dose an additional 6-12 adult patients, and includes a pediatric sub-population of up to 6 patients. For adult participants only, the contralateral eye may also be dosed with 4D-125 as a single dose, IVT injection provided the subject is eligible and provides consent.
| Arm | Type | Receives |
|---|---|---|
| 4D-125 Dose Exploration | Experimental | Biological: 4D-125 IVT InjectionDose 1 and Dose 2 4D-125 will be administered at the assigned dose level as a single dose, IVT injection on Day 1. The contralateral eye may also be dosed with 4D-125 as a single dose, IVT injection provided the subject is eligible and provides consent. |
| 4D-125 Dose Expansion | Experimental | Biological: 4D-125 IVT Injection4D-125 will be administered at the assigned dose level as a single dose, IVT injection on Day 1 in both adults and pediatric participants. For adult participants only, the contralateral eye may also be dosed with 4D-125 as a single dose, IVT injection provided the subject is eligible and provides consent. |
| Observational | Other | Other: ObservationalNatural History |
Who may qualify
- Ages
- 12 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (2 listed)
- Patient has previously received any AAV treatment
- Pre-existing eye conditions or surgical complications that would preclude participation in an interventional clinical trial or interfere with the interpretation of study endpoints
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 4D-125 IVT Injection4D-125 drug product developed for gene therapy, which comprises an AAV capsid variant (4D-R100) carrying a codon-optimized human Retinitis Pigmentosa GTPase Regulator transgene. | Biological | 4D-125 Dose Expansion, 4D-125 Dose Exploration |
| ObservationalNatural History | Other | Observational |
Primary outcome
Incidence and severity of TEAEs and serious adverse events (SAEs), including clinically significant changes in safety parameters
Time frame: 24 months to 60 Months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Schonmei Lee, MD study director
4D Molecular Therapeutics
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing 4D-125 IVT Injection and Observational in people with X-Linked Retinitis Pigmentosa, run by 4D Molecular Therapeutics at 8 sites in United States.
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 0 inclusion and 2 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 21 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. 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?
Incidence and severity of TEAEs and serious adverse events (SAEs), including clinically significant changes in safety parameters (time frame: 24 months to 60 Months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 21 Mar 2025.