Gene Therapy for Fanconi Anemia

Not currently recruiting at 1 trial location

Overseen By Clinical Information

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Rocket Pharmaceuticals Inc.

Must not be taking: Androgens, Investigational therapy

Disqualifiers: HLA-identical donor, Myelodysplastic syndrome, Leukemia, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy, RP-L102, for treating Fanconi anemia, subtype A (FA-A), a condition that can lead to bone marrow failure. The treatment uses the patient's own stem cells, corrected outside the body with a special virus carrying the FANCA gene, and then reintroduced to prevent bone marrow issues. Ideal participants are those diagnosed with FA-A, experiencing frequent symptoms affecting blood cell counts, and lacking a matching sibling donor. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop taking androgens (like danazol or oxymetholone) and any other investigational therapy for treating or preventing Fanconi anemia-related bone marrow failure.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that RP-L102, a gene therapy for Fanconi anemia, is generally safe for patients. So far, no major safety concerns have emerged. Earlier studies found no serious safety issues, suggesting the treatment does not cause severe side effects. Researchers use a lentiviral vector to correct faulty genes in stem cells, which are then returned to the patient's body. This approach aims to prevent bone marrow failure without causing harm. While potential risks should always be considered, current data indicates that RP-L102 is safe for humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Fanconi Anemia, which often include bone marrow transplants and supportive therapies, RP-L102 offers a groundbreaking approach by using gene therapy. RP-L102 involves taking a patient's own stem cells, enriching them, and then introducing a healthy version of the FANCA gene using a lentiviral vector, effectively correcting the genetic defect at its source. This method not only addresses the underlying cause of Fanconi Anemia but also minimizes the risks associated with donor stem cells, such as rejection. Researchers are excited because this has the potential to provide a long-term solution with fewer complications compared to current options.

What evidence suggests that this gene therapy could be an effective treatment for Fanconi anemia?

Research has shown that a type of gene therapy using blood-forming cells, such as RP-L102, could help treat Fanconi Anemia subtype A (FA-A). In earlier studies, this therapy successfully integrated new cells into the body and addressed bone marrow failure, a major issue in FA-A. Participants in this trial will receive stem cells with corrected genes, which improved blood cell production without requiring harsh pre-treatments. This method aims to correct the genetic defect, offering hope for lasting benefits. Early results are promising, suggesting this therapy could effectively address the root cause of FA-A. ^{1 2 3 5 6}

Who Is on the Research Team?

Margaret MacMillan, MD

Principal Investigator

University of Minnesota

Rajni Agarwal, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for patients with Fanconi anemia subtype A, confirmed by a specific blood test. Participants must be at least 1 year old and weigh over 8 kg, have certain levels of blood cells, and women who can bear children must use effective contraception. People with stable or improving blood counts due to mosaicism, other serious health issues, pregnant or breastfeeding women, those with suitable sibling donors or current cancer are excluded.

Inclusion Criteria

At least 30 CD34+ cells/μL are determined in one bone marrow (BM) aspiration within 3 months prior to CD34+ cell collection

I belong to the FA-A complementation group.

Provide informed consent in accordance with current legislation

Exclusion Criteria

I need dialysis for my kidney condition.

Any concomitant disease or condition that, in the opinion of the Principal Investigator, renders the subject unfit to participate in the study

Pregnant or breastfeeding women

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Hematopoietic stem cells from mobilized peripheral blood are transduced ex vivo with a lentiviral vector carrying the FANCA gene and infused intravenously back to the patient

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including hematologic stability and genetic correction

24 months

Long-term follow-up

Participants are monitored for overall survival and bone marrow failure free survival

3 years

What Are the Treatments Tested in This Trial?

Interventions

• RP-L102

Trial Overview The study tests RP-L102 gene therapy in Fanconi anemia subtype A patients. It involves taking the patient's own stem cells from their blood, adding a correct version of the FANCA gene outside the body using a virus as a carrier, then infusing these corrected cells back into the patient to help prevent bone marrow failure.

How Is the Trial Designed?

Group I: RP-L102 Experimental Treatment 1 Intervention

RP-L102 is CD34+ enriched cells from subjects with Fanconi anemia subtype A transduced ex vivo with a lentiviral vector carrying the FANCA gene

Who Is Running the Clinical Trial?

Rocket Pharmaceuticals Inc.

Lead Sponsor

Trials

17

Recruited

430+

Published Research Related to This Trial

Gene therapy (GT) appears to be a safe procedure for improving bone marrow function in patients with Fanconi anemia, as shown in a systematic review of three clinical trials involving nine patients, with no serious adverse effects reported after one year.

While GT led to stabilization in blood lineages, the limited number of studies and short follow-up duration highlight the need for further research to understand the long-term clinical outcomes and potential of GT as a standard treatment for Fanconi anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of gene therapy in Fanconi anemia: A systematic and literature review with future directions. Shafqat, S., Tariq, E., Parnes, AD., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03814408

A Clinical Trial to Evaluate the Safety of RP-L102 in ... The objective of this study is to assess the therapeutic safety and preliminary efficacy of a hematopoietic cell-based gene therapy.

2. rocketpharma.com rocketpharma.com/clinical-trials/fanconi-anemia/

Fanconi Anemia (FA) - Clinical Trials RP-L102 is being developed for Fanconi Anemia (FA), complementation group A (FA-A), a rare genetic disorder caused by mutations in the FANCA gene affecting ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0140673624018804

results from open-label phase 1/2 (FANCOLEN-1) and long ... These results show for the first time that haematopoietic gene therapy without genotoxic conditioning enables sustained engraftment and reversal of BMF ...

4. scge.mcw.edu scge.mcw.edu/platform/data/clinicalTrials/report/NCT04248439

Gene Therapy for Fanconi Anemia, Complementation ... The objective of this study is to assess the therapeutic efficacy of a hematopoietic cell-based gene therapy for patients with Fanconi anemia, subtype A ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04069533?cond=Fanconi%20anemia,%20complementation%20group%20A&viewType=Table&rank=3

Lentiviral-mediated Gene Therapy for Pediatric Patients ... This is an open-label Phase II clinical trial to evaluate the efficacy of a hematopoietic cell-based gene therapy for pediatric patients with Fanconi Anemia, ...

6. cgtlive.com cgtlive.com/view/rocket-pharmaceuticals-bla-fanconi-anemia-gene-therapy-rp-l102

Rocket Pharmaceuticals Pulls BLA for Fanconi Anemia ... “Data generated to date continue to support that RP-L102 has been generally well tolerated, with no significant safety signals observed, and a ...