4D-125 for Retinitis Pigmentosa

Recruiting at 6 trial locations

Overseen By Sabrina Pol

Age: Any Age

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: 4D Molecular Therapeutics

Disqualifiers: AAV treatment, Eye conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

21 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new eye injection treatment for males with a genetic eye disease. The treatment replaces a faulty gene with a healthy one to help stop or slow down the disease. Gene therapy has been extensively studied and shows promise for treating genetic eye diseases by delivering functional genes to replace faulty ones.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug 4D-125 IVT Injection for Retinitis Pigmentosa?

Research shows that similar treatments, like intravitreal dexamethasone implants, have been effective in improving vision and reducing macular edema (swelling in the central part of the retina) in patients with retinitis pigmentosa, suggesting potential benefits for 4D-125 as well. ^{1 2 3 4 5}

Is 4D-125 IVT Injection safe for humans?

Intravitreous (IVT) injections, like 4D-125, are generally considered safe, but there is a rare risk of a serious eye infection called endophthalmitis, which can lead to vision loss. ^{6 7 8 9 10}

What makes the drug 4D-125 IVT Injection unique for treating Retinitis Pigmentosa?

The 4D-125 IVT Injection is unique because it is administered directly into the eye, allowing for higher concentrations of the drug to reach the affected area compared to other methods like oral or intravenous routes. This direct approach is particularly beneficial for treating conditions in the back of the eye, such as Retinitis Pigmentosa. ^{5 11 12 13 14}

Research Team

Schonmei Lee, MD

Principal Investigator

4D Molecular Therapeutics

Eligibility Criteria

This trial is for males aged 12 and older with X-linked retinitis pigmentosa (XLRP) due to RPGR gene mutations. Participants must have at least one eye suitable for injection and a certain level of vision measured by ETDRS letters. Those under phase 1 need vision between ~20/32 and ~20/200, while phase 2 requires both eyes to see at least ~20/200.

Inclusion Criteria

I have at least one eye that can be treated with an injection and my vision is between 20/32 and 20/200.

I have at least one eye suitable for injection and both eyes can see well enough (about 20/200 vision).

I am a male and at least 6 years old.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Observational Natural History Cohort

Gather data to characterize and evaluate natural disease progression in male patients with XLRP

Varies

Treatment

Single intravitreal injection of 4D-125 at two dose levels in one or both eyes

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Long-term Follow-up

Continued safety follow-up and assessment of preliminary efficacy measures

36 months

Treatment Details

Interventions

• 4D-125 IVT Injection

Trial Overview The study is testing the safety and effects of a new treatment called '4D-125 IVT Injection' in two parts: observing the natural progression of XLRP in some participants, while others receive the experimental injection directly into their eyes to assess its impact on their condition.

Participant Groups

Group I: Observational Experimental Treatment 1 Intervention

Natural History

Group II: 4D-125 Dose Exploration Experimental Treatment 1 Intervention

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.

Group III: 4D-125 Dose Expansion Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

4D Molecular Therapeutics

Lead Sponsor

Trials

9

Recruited

850+

Findings from Research

In a systematic review of 10 studies involving 295 patients and 1287 intravitreal injections for retinoblastoma, significant ocular side effects were rare, occurring in only 8 out of 261 patients receiving standard melphalan doses (0.031 proportion).

The study suggests that careful injection techniques and adherence to standard dosing regimens can further reduce the risk of serious ocular complications, which include conditions like iris atrophy and retinal detachment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocular side effects following intravitreal injection therapy for retinoblastoma: a systematic review. Smith, SJ., Smith, BD., Mohney, BG.[2022]

A systematic review of 14,866 intravitreous injections showed that the risk of serious adverse events, particularly endophthalmitis, is low, with a prevalence of 0.3% per injection and 0.9% per eye.

Despite the low overall risk, careful injection technique and post-injection monitoring are crucial, as rare complications can lead to permanent vision loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risks of intravitreous injection: a comprehensive review. Jager, RD., Aiello, LP., Patel, SC., et al.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Intravitreal dexamethasone implant (Ozurdex) for macular edema secondary to retinitis pigmentosa. [2021]

2. Denmark pubmed.ncbi.nlm.nih.gov

Intravitreal triamcinolone acetonide for treatment of cystoid macular oedema in patients with retinitis pigmentosa. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Prospective pilot study: efficacy of intravitreal dexamethasone and bevacizumab injections in the treatment of macular oedema associated with branch retinal vein occlusion. [2015]

4. Turkey pubmed.ncbi.nlm.nih.gov

Intravitreal Dexamethasone Implant (Ozurdex) for Refractory Macular Edema Secondary to Retinitis Pigmentosa. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Optical coherence tomography and focal electroretinogram evaluation of cystoid macular edema secondary to retinitis pigmentosa treated with intravitreal triamcinolone: case report. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Adverse events after intravitreal triamcinolone in patients with and without uveitis. [2013]

7. England pubmed.ncbi.nlm.nih.gov

Ocular side effects following intravitreal injection therapy for retinoblastoma: a systematic review. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Risks of intravitreous injection: a comprehensive review. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Antibiotic resistance of ocular surface flora with repeated use of a topical antibiotic after intravitreal injection. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

A RANDOMIZED PAIRED-EYE TRIAL OF INTRAVITREAL DEXAMETHASONE IMPLANT FOR CYSTOID MACULAR EDEMA IN RETINITIS PIGMENTOSA. [2021]

11. Germany pubmed.ncbi.nlm.nih.gov

Intravitreal injection associated rhegmatogenous retinal detachment: outcomes of a European analysis. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Quantifying burden of intravitreal injections: questionnaire assessment of life impact of treatment by intravitreal injections (QUALITII). [2023]

13. France pubmed.ncbi.nlm.nih.gov

[Interest of optical coherence tomography performed immediately before intravitreal injection of anti-VEGF in exudative AMD]. [2015]

14. France pubmed.ncbi.nlm.nih.gov

[Intravitreal injection at IOTA-teaching hospital about 201 patients]. [2023]