A Phase I/II Study of KB103, a Topical HSV1-COL7, on DEB Patients

NCT03536143 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: KB103-001
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This study was conducted to assess the safety and efficacy of topical Beremagene Geperpavec (KB103, HSV1-COL7) on DEB patients.

Conditions

Dystrophic Epidermolysis Bullosa

Keywords

bullosa; DEB; RDEB; Krystal; epidermolysis; Beremagene; Geperpavec; KB103; HSV-COL7A1

Outcome Measures

Primary Outcomes (5)

• Number of Subjects Reported at Least One Adverse Event, Safety Population

  Safety assessments included evaluation of medical and medication history, physical / skin examination, vital signs, adverse events, and laboratory evaluations. Due to the 'split-person' intrasubject design, the safety assessments were reported at subject level, but not per intervention.

  baseline to 12 weeks

• Number of Adverse Events Reported, Safety Population

  Safety assessments included evaluation of medical and medication history, physical / skin examination, vital signs, adverse events, and laboratory evaluations. Due to the 'split-person' intrasubject design, the safety assessments were reported at subject level, but not per intervention.

  baseline to 12 weeks

• Complete Wound Closure Responder, ITT Population

  One wound is a responder if the reduction from baseline in wound surface is ≥90%.

  from baseline at Weeks 8, 10, and 12

• Time to Wound Closure Analysis, ITT Population

  Time to wound closure was defined as the time from the first treatment to Complete Wound Closure (≥90% reduction in wound surface area from baseline)

  baseline to complete wound closure

• Duration of Wound Closure, ITT Population

  Duration of wound closure

  Time from the complete closure to the first reopening of the same wound

Study Arms (2)

Topical beremagene geperpavec

EXPERIMENTAL

HSV1-COL7A1 vector (KB103)

Biological: Topical beremagene geperpavec

Placebo

PLACEBO COMPARATOR

Placebo

Biological: Placebo gel

Interventions

Topical beremagene geperpavec BIOLOGICAL

Topical gel of non-integrating, replication-incompetent HSV-1 expressing the human collagen VII protein

Also known as: HSV1-COL7A1, KB103

Topical beremagene geperpavec

Placebo gel BIOLOGICAL

Placebo gel

Placebo

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical diagnosis of the recessive form of dystrophic epidermolysis bullosa (RDEB).
• Age
• Phase 1: 18 years old or older,
• Phase 2a: 5 years old or older,
• Phase 2b: 2 years old or older,
• Phase 2c: 2 years old or older.
• Willing and able to give consent/assent
• Confirmation of RDEB diagnosis by genetic testing, IF, and IEM
• LH24 antibody negative (non-collagenous \[NC\] 2domain \[NC2-\]) and NC1 domain \[NC1+\]). (This criterion is applicable to the first 2 adults on the study (Phase 1). Subsequent subjects can be NC1+ or NC1-)
• Confirmed RDEB COL7A1 mutations in subject
• Wound that meets the wound size/surface area entry criteria:
• Phase 1: Two wounds up to 10 cm2; 1 randomized to B-VEC and 1 randomized to placebo
• Phase 2a and 2b: At least 3 wounds up to 20 cm2; 2 wounds randomized to B-VEC and 1 randomized to placebo
• Phase 2c: At least 2 wounds up to 50 cm2; at least 1 randomized to B-VEC and 1 randomized to placebo
• Subjects, who are, in the opinion of the investigator, able to understand the study, cooperate with the study procedures, and are willing to return to the clinic for all the required follow-up visits.

You may not qualify if:

• Medical instability limiting ability to travel to the investigative center
• The presence of medical illness expected to complicate participation and/or compromise the safety of this technique, such as active infection with human immunodeficiency virus (HIV), hepatitis B (as determined by hepatitis B surface antigen screening), or hepatitis C (as determined by detection of hepatitis C antibodies, or positive result of hepatitis C polymerase chain reaction \[PCR\] analysis)
• Serum antibodies to COL7 demonstrated on enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence microscopy, Western blot, or cell-mediated immunity to enzyme-lined ImmunoSpot® (subjects with negative results within 12 months of screening are eligible)
• Active infection in the area that will undergo administration
• Evidence of systemic infection
• Known allergy to any of the constituents of the product
• Current evidence or a history of squamous cell carcinoma in the area that will undergo treatment
• Active drug or alcohol addiction
• Hypersensitivity to local anesthesia (lidocaine/prilocaine cream)
• Receipt of chemical or biological study product for the specific treatment of RDEB in the past 3 months
• Specific wounds that have previously been administered investigational gene or cell therapy
• Subjects who have taken systemic antibiotics within 7 days
• Positive pregnancy test or breast-feeding
• Clinically significant abnormalities as determined by the investigator

Sponsors & Collaborators

• Krystal Biotech, Inc.: lead

Study Sites (1)

Stanford University

Stanford, California, 94305, United States

Location

Related Publications (1)

• Gurevich I, Agarwal P, Zhang P, Dolorito JA, Oliver S, Liu H, Reitze N, Sarma N, Bagci IS, Sridhar K, Kakarla V, Yenamandra VK, O'Malley M, Prisco M, Tufa SF, Keene DR, South AP, Krishnan SM, Marinkovich MP. In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial. Nat Med. 2022 Apr;28(4):780-788. doi: 10.1038/s41591-022-01737-y. Epub 2022 Mar 28.

  PMID: 35347281 RESULT

MeSH Terms

Conditions

Epidermolysis Bullosa Dystrophica

Condition Hierarchy (Ancestors)

Epidermolysis Bullosa; Skin Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Collagen Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Skin Diseases, Vesiculobullous

Results Point of Contact

• Title: Dr. Hubert Chen, MD, Senior Vice President of Clinical Development
• Organization: Krystal Biotech

inquiries@krystalbio.com

(412) 586-5830

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Intrasubject treatment assignment/randomization

Study Record Dates

• First Submitted: April 20, 2018
• First Posted: May 24, 2018
• Study Start: May 6, 2018
• Primary Completion: November 1, 2019
• Study Completion: November 1, 2019
• Last Updated: January 31, 2023
• Results First Posted: January 31, 2023

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)