4D-125 for Retinitis Pigmentosa

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called 4D-125 for X-linked retinitis pigmentosa, a genetic eye condition affecting retinal function. The study consists of two parts: one observes the natural progression of the condition, and the other tests the 4D-125 treatment through eye injections. The trial targets males with a confirmed genetic mutation linked to this condition and vision issues that might benefit from the treatment. Participants should not have received previous treatments using AAV (a type of gene therapy) and should not have other significant eye conditions. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to be among the first to benefit from this innovative therapy.

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.

Is there any evidence suggesting that 4D-125 IVT Injection is likely to be safe for humans?

Previous studies have shown that 4D-125 is well-tolerated by participants. Research indicates that eight patients with X-linked retinitis pigmentosa (XLRP) did not experience serious side effects after receiving the treatment. This included five patients who received the highest dose of 1 trillion viral particles per eye. Furthermore, these trials reported no serious side effects related to the treatment. Ongoing patient monitoring continues to support these findings. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for retinitis pigmentosa, which often involve vitamin A supplements or vision aids, 4D-125 offers a novel gene therapy approach. This treatment is unique because it uses an AAV (adeno-associated virus) vector to deliver a therapeutic gene directly into the retina via an intravitreal (IVT) injection. This method targets the underlying genetic causes of the disease, potentially providing a more effective and long-lasting solution. Researchers are excited about 4D-125 because it represents a significant step forward in addressing the root cause of vision loss in retinitis pigmentosa, offering hope for improved vision and quality of life for patients.

What evidence suggests that 4D-125 might be an effective treatment for retinitis pigmentosa?

Research has shown that 4D-125, an eye injection, may help treat X-linked retinitis pigmentosa (XLRP). This gene therapy replaces a faulty gene with a healthy one, potentially slowing the loss of vision-critical cells in the eye. Early results from previous studies indicated that 4D-125 is safe for patients and may slow disease progression. Although more research is needed, these initial findings suggest that 4D-125 could be a promising treatment for this genetic eye condition. Participants in this trial will receive 4D-125 as part of either the Dose Exploration or Dose Expansion arms, where it will be administered as a single-dose IVT injection. ^{2 3 6 7 8}

Who Is on the Research Team?

Schonmei Lee, MD

Principal Investigator

4D Molecular Therapeutics

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. ir.4dmoleculartherapeutics.com ir.4dmoleculartherapeutics.com/node/7056/pdf

4D Molecular Therapeutics Presents Interim Results from ... “These data support our belief that 4D-125 is well tolerated, and has the potential to both slow the progressive loss of photoreceptors in.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04517149

NCT04517149 | 4D-125 in Patients With X-Linked Retinitis ... 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 ...

3. withpower.com withpower.com/trial/phase-2-retinitis-5-2020-f4842

4D-125 for Retinitis Pigmentosa · Info for Participants 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 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11349810/

Gene Therapies in Clinical Development to Treat Retinal ... In the low-dose cohort (2 × 1011 vg/eye), there was a 53% reduction in the requirement of supplemental injections 2 years after receiving ADVM-022 and in the ...

5. globenewswire.com globenewswire.com/news-release/2021/10/10/2311484/0/en/4D-Molecular-Therapeutics-Presents-Interim-Results-from-the-Ongoing-4D-125-Phase-1-2-Clinical-Trial-in-Patients-with-Advanced-X-linked-Retinitis-Pigmentosa-at-the-ASRS-Annual-Meeti.html

4D Molecular Therapeutics Presents Interim Results from the Interim Safety Data Summary​​ 4D-125 was well-tolerated in all eight XLRP patients, including in five patients at the top dose level of 1E12 vg/ ...

6. 4dmt.gcs-web.com 4dmt.gcs-web.com/news-releases/news-release-details/4d-molecular-therapeutics-presents-interim-results-ongoing-4d

Release Details - 4D Molecular Therapeutics Interim Safety Data Summary​​ 4D-125 was well-tolerated in all eight XLRP patients, including in five patients at the top dose level of 1E12 vg/ ...

7. clinicaltrialsarena.com clinicaltrialsarena.com/news/4d-molecular-xlrp-trial/

4D Molecular's therapy shows improvements in Phase I/II ... In the trial, 4D-125 was well-tolerated with no treatment-associated serious adverse events reported. ... The ongoing Phase I/II trial is ...

8. ir.4dmoleculartherapeutics.com ir.4dmoleculartherapeutics.com/node/6916/html

SEC Filing | 4D Molecular Therapeutics Initial Phase 1 Dose Escalation Safety and Tolerability Data Summary: 4D-110 for choroideremia and 4D-125 for X-linked retinitis pigmentosa. Clinical trial ...