FCX-007 for Epidermolysis Bullosa

(DEFI-RDEB Trial)

Recruiting at 4 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Castle Creek Biosciences, LLC.

Disqualifiers: HIV, Hepatitis B/C, Metastatic cancer, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 1

Duration: 12 months

6 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if FCX-007 can improve wound healing in people with RDEB, a condition causing persistent wounds. FCX-007 is injected into the skin to help it heal by providing missing elements. The study observes how treated wounds heal compared to other wounds in the same patients. FCX-007 is a gene therapy designed to deliver COL7A1 to the skin, aiming to restore collagen VII expression and improve wound healing in RDEB patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have received any chemical or biological treatment specifically for RDEB in the past three months before the study.

What data supports the effectiveness of the treatment FCX-007 for Epidermolysis Bullosa?

The research on antisense-mediated exon skipping shows promise for treating genetic skin disorders like recessive dystrophic epidermolysis bullosa by restoring the correct protein production, which is similar to the approach used in FCX-007. Additionally, a related treatment, B-VEC, has shown effectiveness in promoting wound healing in patients with a similar condition, suggesting potential for FCX-007. ^{1 2 3 4 5}

Is FCX-007 safe for humans?

The research does not provide specific safety data for FCX-007 in humans, but a related study on ABCB5+ mesenchymal stem cells for a similar condition reported good tolerability with some manageable adverse events, such as mild lymphadenopathy (swollen lymph nodes) and hypersensitivity reactions. ^{6 7 8 9 10}

How does the treatment FCX-007 differ from other treatments for epidermolysis bullosa?

FCX-007 is unique because it is a gene therapy designed to address the underlying genetic cause of dystrophic epidermolysis bullosa by delivering a functional copy of the COL7A1 gene, which is responsible for producing type VII collagen, a crucial protein for skin stability. This approach aims to restore the production of type VII collagen, unlike traditional treatments that mainly focus on managing symptoms. ^{6 11 12 13 14}

Eligibility Criteria

This trial is for children and adults over 2 years old with Recessive Dystrophic Epidermolysis Bullosa (RDEB) confirmed by a specific genetic mutation. Participants must not have certain infections, antibodies, or cancer history at the treatment site, nor can they be pregnant or breastfeeding. They shouldn't have used other RDEB treatments in the last three months.

Inclusion Criteria

I am at least 2 years old.

I have RDEB confirmed by a COL7A1 genetic test.

Exclusion Criteria

You are allergic to any of the ingredients in the product.

My body has COL7 antibodies.

I have had squamous cell carcinoma where I will get injections.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intradermal injections of FCX-007 in treatment wounds during multiple sessions

12 months

Multiple visits at Day 1, Week 12, Week 24, and Week 36

Follow-up

Participants are monitored for safety and effectiveness after treatment

15 years

Treatment Details

Interventions

• FCX-007

Trial Overview The study tests if FCX-007 (dabocemagene autoficel), alongside usual care, improves wound healing compared to standard care alone in those with RDEB. The FDA's Office of Orphan Products Development funds this research.

Participant Groups

Group I: FCX-007 COL7A1 Genetically-Corrected Autologous Fibroblasts Experimental Treatment 1 Intervention

Intra-subject randomized (paired wounds in each subject receive experimental treatment, FCX-007, or remain untreated). Up to three target wound pairs will be identified for each subject. Following pairing, target wounds will be randomly assigned as the treatment wound (FCX-007 is administered) or control wound. Subjects will receive intradermal injections of FCX-007 in each specified treatment wound in two or more treatment sessions. The first treatment session occurs at Day 1 and the second at Week 12/Month 3. Additional treatment sessions may occur at Week 24/Month 6 and Week 36/Month 9 when unclosed treatment wounds may be re-treated, and unclosed control wounds may be treated.

Who Is Running the Clinical Trial?

Castle Creek Biosciences, LLC.

Lead Sponsor

Trials

12

Recruited

680+

Findings from Research

Beremagene geperpavec (B-VEC) is a promising topical treatment for recessive dystrophic epidermolysis bullosa (RDEB), effectively restoring collagen VII (C7) expression and promoting wound healing in a clinical trial involving nine patients over 12 weeks.

The treatment was found to be safe, with no serious adverse events related to B-VEC, and it successfully met primary and secondary objectives related to wound healing and C7 expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial. Gurevich, I., Agarwal, P., Zhang, P., et al.[2022]

In a phase I/IIa clinical trial involving 16 patients with recessive dystrophic epidermolysis bullosa (RDEB), treatment with ABCB5+ mesenchymal stem cells (MSCs) showed a statistically significant reduction in disease activity scores, indicating potential efficacy as a disease-modifying therapy.

The treatment was well-tolerated, with only three adverse events related to the cell product, all of which were manageable and resolved without lasting effects, suggesting a favorable safety profile for ABCB5+ MSCs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trial of ABCB5+ mesenchymal stem cells for recessive dystrophic epidermolysis bullosa. Kiritsi, D., Dieter, K., Niebergall-Roth, E., et al.[2022]

References

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

Amniotic membrane transplantation for treatment of symblepharon in a patient with recessive dystrophic epidermolysis bullosa. [2008]

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

Antisense-Mediated Splice Modulation to Reframe Transcripts. [2019]

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

Antisense-mediated exon skipping to reframe transcripts. [2012]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Personalized Development of Antisense Oligonucleotides for Exon Skipping Restores Type XVII Collagen Expression in Junctional Epidermolysis Bullosa. [2023]

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

In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Targeted inactivation of the type VII collagen gene (Col7a1) in mice results in severe blistering phenotype: a model for recessive dystrophic epidermolysis bullosa. [2022]

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

Clinical trial of ABCB5+ mesenchymal stem cells for recessive dystrophic epidermolysis bullosa. [2022]

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

Intravenously Administered Recombinant Human Type VII Collagen Derived from Chinese Hamster Ovary Cells Reverses the Disease Phenotype in Recessive Dystrophic Epidermolysis Bullosa Mice. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Immune reactivity to type VII collagen: implications for gene therapy of recessive dystrophic epidermolysis bullosa. [2019]

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

Autoantibodies to Multiple Epitopes on the Non-Collagenous-1 Domain of Type VII Collagen Induce Blisters. [2018]

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

Analysis of the functional consequences of targeted exon deletion in COL7A1 reveals prospects for dystrophic epidermolysis bullosa therapy. [2018]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Case Report: Diagnostic and Therapeutic Challenges in Severe Mechanobullous Epidermolysis Bullosa Acquisita. [2022]

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

Premature termination codons in the type VII collagen gene (COL7A1) underlie severe, mutilating recessive dystrophic epidermolysis bullosa. [2008]

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

Characterization of molecular mechanisms underlying mutations in dystrophic epidermolysis bullosa using site-directed mutagenesis. [2021]