Gene Therapy with 4D-110 for Choroideremia

Recruiting at 1 trial location

Overseen By Xuan Tran

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: 4D Molecular Therapeutics

Disqualifiers: Ocular infection, AAV treatment, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

13 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will evaluate safety, tolerability, and preliminary efficacy of a single intravitreal (IVT) injection of a recombinant adeno-associated virus (AAV) gene therapy, 4D-110, in male patients with genetically-confirmed Choroideremia (CHM).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment 4D-110 for choroideremia?

Research shows that gene therapy using a viral vector to deliver the REP1 protein can improve vision in patients with choroideremia. In a clinical trial, patients treated with this approach experienced a median gain of 4.5 letters in visual acuity, suggesting that this type of gene therapy can help sustain and improve vision. ^{1 2 3 4 5}

Is gene therapy with 4D-110 for choroideremia safe?

Gene therapy using adeno-associated viral vectors for choroideremia has shown encouraging safety results in clinical trials. Most side effects were mild or moderate, and no serious toxicity was identified in preclinical studies. These findings suggest that the treatment is generally safe for humans. ^{1 2 3 6 7}

How is the treatment 4D-110 for choroideremia different from other treatments?

The treatment 4D-110 is a gene therapy that uses an adeno-associated viral vector to deliver a functional copy of the gene responsible for producing Rab Escort Protein 1 (REP1), which is missing or defective in choroideremia patients. This approach is unique because it directly addresses the genetic cause of the disease, potentially restoring vision by improving REP1 function, unlike other treatments that may only manage symptoms. ^{1 2 3 4 5}

Research Team

Schonmei Lee, MD

Principal Investigator

4D Molecular Therapeutics

Eligibility Criteria

This trial is for male patients with a confirmed genetic condition called Choroideremia. Participants must have a certain level of vision, roughly around 20/200 or better in both eyes. They can't join if they've had previous AAV treatments, active eye infections/inflammation, or other eye conditions that could affect the treatment's success.

Inclusion Criteria

Both eyes must have ≥ 34 ETDRS letters (~20/200)

I have a confirmed CHM gene mutation.

Exclusion Criteria

My eyes are healthy enough for the treatment and won't affect the study's results.

I have received AAV treatment before.

I have an active eye infection or inflammation.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intravitreal injection of 4D-110 at one of three dose levels

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Regular visits as per study protocol

Treatment Details

Interventions

• 4D-110

Trial Overview The study is testing a single injection into the eye of gene therapy called 4D-110 to see how safe and effective it is for treating Choroideremia. This involves using a virus (AAV) to deliver genetic material into cells.

Participant Groups

Group I: 4D-110 Dose 3 Experimental Treatment 1 Intervention

4D-110 IVT injection

Group II: 4D-110 Dose 2 Experimental Treatment 1 Intervention

4D-110 IVT injection

Group III: 4D-110 Dose 1 Experimental Treatment 1 Intervention

4D-110 IVT injection

Who Is Running the Clinical Trial?

4D Molecular Therapeutics

Lead Sponsor

Trials

9

Recruited

850+

Findings from Research

The long-term safety of AAV2-REP1 in choroideremia patients showed some adverse effects, including localized intraretinal immune responses and permanent retinal damage, raising concerns about its effectiveness in late-stage disease.

Antisense oligonucleotide (ASO) therapy demonstrated potential benefits, recovering significant amounts of normal RNA and protein in fibroblasts from trial patients, suggesting it may be a promising alternative treatment for certain subgroups of choroideremia patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AAV2-Mediated Gene Therapy for Choroideremia: 5-Year Results and Alternate Anti-sense Oligonucleotide Therapy. Zhai, Y., Xu, M., Radziwon, A., et al.[2023]

References

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

AAV-mediated gene therapy for choroideremia: preclinical studies in personalized models. [2022]

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

Beneficial effects on vision in patients undergoing retinal gene therapy for choroideremia. [2023]

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

Choroideremia Gene Therapy Phase 2 Clinical Trial: 24-Month Results. [2022]

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

AAV2-Mediated Gene Therapy for Choroideremia: 5-Year Results and Alternate Anti-sense Oligonucleotide Therapy. [2023]

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

Choroideremia: towards a therapy. [2018]

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

Two-Year Results After AAV2-Mediated Gene Therapy for Choroideremia: The Alberta Experience. [2022]

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

Subretinal timrepigene emparvovec in adult men with choroideremia: a randomized phase 3 trial. [2023]