A Study of PTR-01 in Recessive Dystrophic Epidermolysis Bullosa

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Recessive Dystrophic Epidermolysis Bullosa

Intervention / Treatment
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* Drug: PTR-01


Participation Criteria
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Eligibility Criteria
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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: 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. Has a diagnosis of RDEB based on genetic analysis and consistent with a recessive inheritance pattern. Has deficient C7 staining at the dermal-epidermal junction (DEJ) by IF. 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. 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: Has known systemic hypersensitivity to any of the inactive ingredients in PTR-01. Has previously had an anaphylactic reaction to PTR-01. Is pregnant or nursing. Has received in the last six months any investigational gene therapy product or in the last three months any non-gene therapy investigational products. Is anticipated to receive new regimens of antibiotics or other anti-infectives during the trial. 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

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open-label study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PTR-01 3 mg/kg<br>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<br>* IV recombinant collagen 7 at 3 mg/kg given weekly for 4 doses, followed by bi-weekly for 7 doses<br>* Other names: rC7;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RDEB