A Study of PTR-01 in Recessive Dystrophic Epidermolysis Bullosa

A Phase 2 Open-Label Study of PTR-01 in Patients With Recessive Dystrophic Epidermolysis Bullosa (RDEB)

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.

Study Overview

• Status: Completed
• Conditions: Recessive Dystrophic Epidermolysis Bullosa
• Intervention / Treatment: Drug: PTR-01

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 Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Redwood City, California, United States, 94063
      • Stanford University
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wound healing	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)	Up to 162 days
Incidence of treatment-emergent adverse events	Safety and tolerability, as assessed by treatment-emergent adverse events	Up to 162 days
Incidence of infusion-associated reactions	Safety and tolerability, as assessed by infusion-associated reactions (IAR)	Up to 162 days
Incidence of anti-drug antibodies (ADA)	Safety and tolerability, as assessed by immunogenicity through anti-drug antibody (ADA) testing	Up to 162 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delivery of PTR-01 to skin	PTR-01 incorporation by immunofluorescence using NC1 & NC2 staining, by dose frequency period	Up to 162 days
Formation of anchoring fibrils	Formation of new anchoring fibrils as measured by electron microscopy	Up to 162 days
Change in wound surface area, as assessed by wound imaging	Wound area of target lesions, as assessed by wound imaging	Up to 162 days
Change in wound surface area, as assessed by Investigator Global Impression of Change (IGIC)	Wound area of target lesions, as assessed by IGIC	Up to 162 days
Change in total body wound surface area	Change in total body wound surface area, using Rule of Nines	Up to 162 days
Change in skin integrity, as assessed by suction blister time	Change in skin integrity, as assessed by suction blister time	Up to 162 days
Change in skin integrity, as assessed by time to re-blistering	Change in skin integrity, as assessed by time to re-blistering	Up to 162 days
Change in itch severity, as assessed by modified Patient-Reported Outcome Measurement Information System (PROMIS) itch domains	Severity of itch, as assessed by modified Patient-Reported Outcome Measurement Information System (PROMIS) itch domains	Up to 162 days
Change in itch severity, as assessed by the Instrument for Scoring Clinical Outcomes for Research of Epidermolysis Bullosa (iscorEB)	Severity of itch, as assessed by Instrument for Scoring Clinical Outcomes for Research of Epidermolysis Bullosa (iscorEB), maximum score of 234 (worst)	Up to 162 days
Change in the impact of itch on quality of life	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)	Up to 162 days
Change in pain severity, as assessed by modified Patient-Reported Outcome Measurement Information System (PROMIS) pain domains	Change in pain severity, as assessed by Patient-Reported Outcome Measurement Information System (PROMIS) pain domains	Up to 162 days
Change in pain severity, as assessed by the Instrument for Scoring Clinical Outcomes for Research of Epidermolysis Bullosa (iscorEB)	Change in pain severity, as assessed by the Instrument for Scoring Clinical, maximum score of 234 (worst)	Up to 162 days
Change in the impact of pain on quality of life	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)	Up to 162 days
Change of dysphagia, as assessed using the Brief Esophageal Dysphagia Questionnaire	Change of dysphagia, as assessed using the Brief Esophageal Dysphagia Questionnaire, maximum score is 40 (worst)	Up to 162 days
Change in dysphagia, as assessed by volume of oral nutritional intake	Change of dysphagia, as assessed by volume of oral nutritional intake, using patient interview and diary, maximum score is 40 (worst)	Up to 162 days
Stabilization of dysphagia, as assessed using the Brief Esophageal Dysphagia Scale	Stabilization of dysphagia, as assessed using the Brief Esophageal Dysphagia Scale	Up to 162 days
Stabilization of dysphagia, as assessed by volume oral nutritional intake	Stabilization of dysphagia, as assessed by volume oral nutritional intake, using patient interview and diary	Up to 162 days
Change in corneal symptoms	Change of corneal symptoms (eye symptoms), as assessed by the Epidermolysis Bullosa Eye Disease Index (EB-EDI)	Up to 162 days
Stabilization of corneal symptoms	Stabilization of corneal symptoms (eye symptoms), as assessed by the Epidermolysis Bullosa Eye Disease Index (EB-EDI)	Up to 162 days
Rate of change in nutritional markers (hemoglobin/hematocrit)	Change of nutritional markers, as assessed by hemoglobin/hematocrit	Up to 162 days
Rate of change in nutritional markers (total protein/albumin)	Change of nutritional markers, as assessed by total protein/albumin	Up to 162 days
Rate of change in nutritional markers (iron/TIBC)	Change of nutritional markers, as assessed by iron/TIBC	Up to 162 days
Rate of change in nutritional markers (C-reactive protein)	Change of nutritional markers, as assessed by C-reactive protein	Up to 162 days
Rate of stabilization of nutritional markers (hemoglobin/hematocrit)	Stabilization of nutritional markers, as assessed by hemoglobin/hematocrit	Up to 162 days
Rate of stabilization of nutritional markers (total protein/albumin)	Stabilization of nutritional markers, as assessed by total protein/albumin	Up to 162 days
Rate of stabilization of nutritional markers (iron/TIBC)	Stabilization of nutritional markers, as assessed by iron/TIBC	Up to 162 days
Rate of stabilization of nutritional markers (C-reactive protein)	Stabilization of nutritional markers, as assessed by C-reactive protein	Up to 162 days
Change in Investigator Global Impressions of Change (IGIC)	Global impressions of change, as assessed through IGIC (1-7), 7 being worst	Up to 162 days
Change in Investigator Patient Impressions of Change (PGIC)	Global impressions of change, as assessed through PGIC (1-7), 7 being worst	Up to 162 days
Change in disease activity and scarring	Change in disease activity and scarring, as assessed by the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI)	Up to 162 days
Change in overall quality of life, as assessed by the Quality of Life in Epidermolysis Bullosa (QOLEB) questionnaire	Change in overall quality of life, as assessed by the Quality of Life in Epidermolysis Bullosa (QOLEB) questionnaire	Up to 162 days
Change in overall health	Change in overall disability, as assessed by the Health Assessment Questionnaire or Children's Health Assessment Questionnaire (HAQ/CHAQ)	Up to 162 days
Change in mental health	Change in mental health and social functioning, as assessed by the Patient-Reported Outcomes Measurement Information System (PROMIS) mental health domains	Up to 162 days
Change in social function	Change in mental health and social functioning, as assessed by the Patient-Reported Outcomes Measurement Information System (PROMIS) social function domains	Up to 162 days
Change in amount of wound care	Change in amount of wound care, as assessed by patient interviews	Up to 162 days
Change in time for wound care	Change in time for wound care, as assessed by patient interviews	Up to 162 daysUp to 162 days
Change in cost of wound care	Change in cost of wound care, as assessed by patient interviews	Up to 162 days
Change in overall patient impression of quality of life	Change in overall quality of life, as assessed by patient interviews	Up to 162 days
Change in overall patient impression of disability	Change in overall disability, as assessed by patient interviews	Up to 162 days

Other Outcome Measures

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

Collaborators and Investigators

• Sponsor: Phoenix Tissue Repair, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2020
• Primary Completion (Actual): August 28, 2021
• Study Completion (Actual): September 1, 2021

Study Registration Dates

• First Submitted: October 8, 2020
• First Submitted That Met QC Criteria: October 21, 2020
• First Posted (Actual): October 23, 2020

Study Record Updates

• Last Update Posted (Actual): September 16, 2021
• Last Update Submitted That Met QC Criteria: September 14, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: RDEB
• Additional Relevant MeSH Terms: Skin Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Connective Tissue Diseases; Skin Diseases, Genetic; Skin Diseases, Vesiculobullous; Skin Abnormalities; Collagen Diseases; Epidermolysis Bullosa; Epidermolysis Bullosa Dystrophica
• Other Study ID Numbers: PTR-01-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No