A Study of PTR-01 in Recessive Dystrophic Epidermolysis Bullosa

• ClinicalTrials.gov Identifier: NCT04599881
• Recruitment Status: Completed
• First Posted: October 23, 2020
• Last Update Posted: September 16, 2021
• Sponsor: Phoenix Tissue Repair, Inc.
• Information provided by (Responsible Party): Phoenix Tissue Repair, Inc.

Study Description

Brief Summary:

Protocol PTR-01-002 is a 3-part Phase 2, open-label study of PTR-01. While new patients will be enrolled, priority will be given to patients that satisfactorily completed study PTR-01-001.

Condition or disease	Intervention/treatment	Phase
Recessive Dystrophic Epidermolysis Bullosa	Drug: PTR-01	Phase 2

Detailed Description:

Protocol PTR-01-002 is a 3-part Phase 2, open-label study of PTR-01. While new patients will be enrolled, priority will be given to patients that satisfactorily completed study PTR-01-001.

In Part 1, patients will receive a dose of 3.0 mg/kg every week for a total of 4 doses. This will be followed by Part 2 in which patients will receive a dose of 3.0 mg/kg every other week for a total of 7 doses. In Part 3, patients will be followed for 12 weeks. No investigational therapy will be administered during this time. At the end of each dosing period, an efficacy assessment will be performed. Safety will be assessed continuously throughout the study.

Following the end of Part 3, patients may be eligible for a potential long-term extension to further refine the dosing regimen, depending upon study drug availability.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Open-label study
• Masking: None (Open Label)
• Masking Description: Open-label
• Primary Purpose: Treatment
• Official Title: A Phase 2 Open-Label Study of PTR-01 in Patients With Recessive Dystrophic Epidermolysis Bullosa (RDEB)
• Actual Study Start Date: October 15, 2020
• Actual Primary Completion Date: August 28, 2021
• Actual Study Completion Date: September 1, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: PTR-01 3 mg/kg; All patients will receive a PTR-01 dose of 3.0 mg/kg once weekly every week for a total of 4 doses, followed by a dose of 3.0 mg/kg every other week for a total of 7 doses.	Drug: PTR-01; IV recombinant collagen 7 at 3 mg/kg given weekly for 4 doses, followed by bi-weekly for 7 doses; Other Names: Recombinant collagen 7; rC7

Outcome Measures

Primary Outcome Measures :

1. Wound healing [ Time Frame: Up to 162 days ]
   Change in a majority of target lesions of at least 2 levels using a 7-point (1-7) Global Impression of Change instrument (7 being the worst)
2. Incidence of treatment-emergent adverse events [ Time Frame: Up to 162 days ]
   Safety and tolerability, as assessed by treatment-emergent adverse events
3. Incidence of infusion-associated reactions [ Time Frame: Up to 162 days ]
   Safety and tolerability, as assessed by infusion-associated reactions (IAR)
4. Incidence of anti-drug antibodies (ADA) [ Time Frame: Up to 162 days ]
   Safety and tolerability, as assessed by immunogenicity through anti-drug antibody (ADA) testing

Secondary Outcome Measures :

1. Delivery of PTR-01 to skin [ Time Frame: Up to 162 days ]
   PTR-01 incorporation by immunofluorescence using NC1 & NC2 staining, by dose frequency period
2. Formation of anchoring fibrils [ Time Frame: Up to 162 days ]
   Formation of new anchoring fibrils as measured by electron microscopy
3. Change in wound surface area, as assessed by wound imaging [ Time Frame: Up to 162 days ]
   Wound area of target lesions, as assessed by wound imaging
4. Change in wound surface area, as assessed by Investigator Global Impression of Change (IGIC) [ Time Frame: Up to 162 days ]
   Wound area of target lesions, as assessed by IGIC
5. Change in total body wound surface area [ Time Frame: Up to 162 days ]
   Change in total body wound surface area, using Rule of Nines
6. Change in skin integrity, as assessed by suction blister time [ Time Frame: Up to 162 days ]
   Change in skin integrity, as assessed by suction blister time
7. Change in skin integrity, as assessed by time to re-blistering [ Time Frame: Up to 162 days ]
   Change in skin integrity, as assessed by time to re-blistering
8. Change in itch severity, as assessed by modified Patient-Reported Outcome Measurement Information System (PROMIS) itch domains [ Time Frame: Up to 162 days ]
   Severity of itch, as assessed by modified Patient-Reported Outcome Measurement Information System (PROMIS) itch domains
9. Change in itch severity, as assessed by the Instrument for Scoring Clinical Outcomes for Research of Epidermolysis Bullosa (iscorEB) [ Time Frame: Up to 162 days ]
   Severity of itch, as assessed by Instrument for Scoring Clinical Outcomes for Research of Epidermolysis Bullosa (iscorEB), maximum score of 234 (worst)
10. Change in the impact of itch on quality of life [ Time Frame: Up to 162 days ]
    Change in the impact of itch on quality of life, as assessed by the Pruritus-Specific Quality of Life Instrument (ItchyQoL), maximum score of 110 (worst)
11. Change in pain severity, as assessed by modified Patient-Reported Outcome Measurement Information System (PROMIS) pain domains [ Time Frame: Up to 162 days ]
    Change in pain severity, as assessed by Patient-Reported Outcome Measurement Information System (PROMIS) pain domains
12. Change in pain severity, as assessed by the Instrument for Scoring Clinical Outcomes for Research of Epidermolysis Bullosa (iscorEB) [ Time Frame: Up to 162 days ]
    Change in pain severity, as assessed by the Instrument for Scoring Clinical, maximum score of 234 (worst)
13. Change in the impact of pain on quality of life [ Time Frame: Up to 162 days ]
    Change in the impact of pain on quality of life, as assessed by the Instrument for Scoring Clinical Outcomes for Research of Epidermolysis Bullosa (iscorEB) instrument, maximum score of 234 (worst)
14. Change of dysphagia, as assessed using the Brief Esophageal Dysphagia Questionnaire [ Time Frame: Up to 162 days ]
    Change of dysphagia, as assessed using the Brief Esophageal Dysphagia Questionnaire, maximum score is 40 (worst)
15. Change in dysphagia, as assessed by volume of oral nutritional intake [ Time Frame: Up to 162 days ]
    Change of dysphagia, as assessed by volume of oral nutritional intake, using patient interview and diary, maximum score is 40 (worst)
16. Stabilization of dysphagia, as assessed using the Brief Esophageal Dysphagia Scale [ Time Frame: Up to 162 days ]
    Stabilization of dysphagia, as assessed using the Brief Esophageal Dysphagia Scale
17. Stabilization of dysphagia, as assessed by volume oral nutritional intake [ Time Frame: Up to 162 days ]
    Stabilization of dysphagia, as assessed by volume oral nutritional intake, using patient interview and diary
18. Change in corneal symptoms [ Time Frame: Up to 162 days ]
    Change of corneal symptoms (eye symptoms), as assessed by the Epidermolysis Bullosa Eye Disease Index (EB-EDI)
19. Stabilization of corneal symptoms [ Time Frame: Up to 162 days ]
    Stabilization of corneal symptoms (eye symptoms), as assessed by the Epidermolysis Bullosa Eye Disease Index (EB-EDI)
20. Rate of change in nutritional markers (hemoglobin/hematocrit) [ Time Frame: Up to 162 days ]
    Change of nutritional markers, as assessed by hemoglobin/hematocrit
21. Rate of change in nutritional markers (total protein/albumin) [ Time Frame: Up to 162 days ]
    Change of nutritional markers, as assessed by total protein/albumin
22. Rate of change in nutritional markers (iron/TIBC) [ Time Frame: Up to 162 days ]
    Change of nutritional markers, as assessed by iron/TIBC
23. Rate of change in nutritional markers (C-reactive protein) [ Time Frame: Up to 162 days ]
    Change of nutritional markers, as assessed by C-reactive protein
24. Rate of stabilization of nutritional markers (hemoglobin/hematocrit) [ Time Frame: Up to 162 days ]
    Stabilization of nutritional markers, as assessed by hemoglobin/hematocrit
25. Rate of stabilization of nutritional markers (total protein/albumin) [ Time Frame: Up to 162 days ]
    Stabilization of nutritional markers, as assessed by total protein/albumin
26. Rate of stabilization of nutritional markers (iron/TIBC) [ Time Frame: Up to 162 days ]
    Stabilization of nutritional markers, as assessed by iron/TIBC
27. Rate of stabilization of nutritional markers (C-reactive protein) [ Time Frame: Up to 162 days ]
    Stabilization of nutritional markers, as assessed by C-reactive protein
28. Change in Investigator Global Impressions of Change (IGIC) [ Time Frame: Up to 162 days ]
    Global impressions of change, as assessed through IGIC (1-7), 7 being worst
29. Change in Investigator Patient Impressions of Change (PGIC) [ Time Frame: Up to 162 days ]
    Global impressions of change, as assessed through PGIC (1-7), 7 being worst
30. Change in disease activity and scarring [ Time Frame: Up to 162 days ]
    Change in disease activity and scarring, as assessed by the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI)
31. Change in overall quality of life, as assessed by the Quality of Life in Epidermolysis Bullosa (QOLEB) questionnaire [ Time Frame: Up to 162 days ]
    Change in overall quality of life, as assessed by the Quality of Life in Epidermolysis Bullosa (QOLEB) questionnaire
32. Change in overall health [ Time Frame: Up to 162 days ]
    Change in overall disability, as assessed by the Health Assessment Questionnaire or Children's Health Assessment Questionnaire (HAQ/CHAQ)
33. Change in mental health [ Time Frame: Up to 162 days ]
    Change in mental health and social functioning, as assessed by the Patient-Reported Outcomes Measurement Information System (PROMIS) mental health domains
34. Change in social function [ Time Frame: Up to 162 days ]
    Change in mental health and social functioning, as assessed by the Patient-Reported Outcomes Measurement Information System (PROMIS) social function domains
35. Change in amount of wound care [ Time Frame: Up to 162 days ]
    Change in amount of wound care, as assessed by patient interviews
36. Change in time for wound care [ Time Frame: Up to 162 daysUp to 162 days ]
    Change in time for wound care, as assessed by patient interviews
37. Change in cost of wound care [ Time Frame: Up to 162 days ]
    Change in cost of wound care, as assessed by patient interviews
38. Change in overall patient impression of quality of life [ Time Frame: Up to 162 days ]
    Change in overall quality of life, as assessed by patient interviews
39. Change in overall patient impression of disability [ Time Frame: Up to 162 days ]
    Change in overall disability, as assessed by patient interviews

Other Outcome Measures:

1. Genotype/phenotype relationships [ Time Frame: Up to 162 days ]
   Correlation between genotype (genetic mutation) and severity of disease
2. Impact of pharmacokinetics on safety outcomes [ Time Frame: Up to 162 days ]
   Correlate Cmax and Area Under the Curve (AUC) with treatment emergent adverse events, infusion associated reactions and immune-mediated reactions
3. Impact of pharmacokinetics on efficacy outcomes [ Time Frame: Up to 162 days ]
   Correlate Cmax and AUC with wound healing
4. Impact of pharmacokinetics on pharmacodynamic outcomes [ Time Frame: Up to 162 days ]
   Correlate Cmax and AUC with suction blister time, C7 immunofluorescence on biopsy and formation of anchoring fibrils by electron microscopy

Eligibility Criteria

• Ages Eligible for Study: 12 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Patients must meet all of the following criteria to be eligible for study participation in the three month run in period of the study:

1. Willing to provide informed consent form, or if 12 to <18 years of age, legal guardian has provided informed consent form and the minor has signed an assent form acknowledging that they understand and agree to study procedures.
2. Has a diagnosis of RDEB based on genetic analysis and consistent with a recessive inheritance pattern.
3. Has deficient C7 staining at the dermal-epidermal junction (DEJ) by IF.

4. Agrees to use contraception as follows:

   For women of childbearing potential (WOCBP) agrees to use highly effective contraceptive (including abstinence) methods from Screening, through the study, and for at least 10 weeks after the last dose of study drug. Non-childbearing potential is defined as a female who meets either of the following criteria: age ≥50 years and no menses for at least 1 year or documented hysterectomy, bilateral tubal ligation, or bilateral oophorectomy.

   For males, agrees to use a condom with any WOCBP sexual partner from Day 1 of study treatment, through the study, and at least 10 weeks after the last dose of study drug.

5. Be willing and able to comply with this protocol.

Exclusion Criteria:

Patients with any of the following will be excluded from participation in the study:

1. Has known systemic hypersensitivity to any of the inactive ingredients in PTR-01.
2. Has previously had an anaphylactic reaction to PTR-01.
3. Is pregnant or nursing.
4. Has received in the last six months any investigational gene therapy product or in the last three months any non-gene therapy investigational products.
5. Is anticipated to receive new regimens of antibiotics or other anti-infectives during the trial.
6. Has any other medical or personal condition that, in the opinion of the Investigator, may potentially compromise the safety or compliance of the patient, or may preclude the patient's

Contacts and Locations

Locations

United States, California

Stanford University

Redwood City, California, United States, 94063

United States, Colorado

Children's Hospital Colorado

Aurora, Colorado, United States, 80045

Sponsors and Collaborators

Phoenix Tissue Repair, Inc.

More Information

• Responsible Party: Phoenix Tissue Repair, Inc.
• ClinicalTrials.gov Identifier: NCT04599881
• Other Study ID Numbers: PTR-01-002
• First Posted: October 23, 2020
• Last Update Posted: September 16, 2021
• Last Verified: September 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Phoenix Tissue Repair, Inc.:

RDEB

Additional relevant MeSH terms:

Epidermolysis Bullosa; Epidermolysis Bullosa Dystrophica; Skin Abnormalities; Congenital Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Skin Diseases; Skin Diseases, Vesiculobullous; Collagen Diseases; Connective Tissue Diseases