Extension Study to PTR-01-002 (A Study in Recessive Dystrophic Epidermolysis Bullosa (RDEB) Patients Previously Treated With PTR-01)

Study Overview
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Brief Summary
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A sub-set of patients who participated in PTR-01-002 will be enrolled in an open-label study, if they meet the study eligibility criteria.

Detailed Description
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Protocol PTR-01-003 is a 4-part Phase 2, open-label study of PTR-01 in patients who satisfactorily completed study PTR-01-002 and meet current enrollment criteria. In Part 1, patients will be monitored monthly for up to 2 months with patient-reported and Investigator assessments. In Part 2, patients will receive a dose of 3.0 mg/kg every week for a total of 4 doses. This will be followed by Part 3 in which patients will receive a dose of 3.0 mg/kg monthly for a total of 5 additional doses. At the end of each dosing period, efficacy assessments will be performed. During Part 4, patients will be evaluated at Months 1 and 3 after completion of dosing to assess the durability of wound healing and other efficacy parameters. Safety will be assessed continuously throughout the study.

Official Title
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A Phase 2b Open-Label Study of PTR-01 in Recessive Dystrophic Epidermolysis Bullosa (RDEB) Patients Previously Treated With PTR-01 in Study PTR-01-002

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: 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 satisfactorily completed participation in PTR-01-002. 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: 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 (other than PTR-01). 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

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: Phase 2 open-label
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PTR-01<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 once monthly for a total of 5 doses. | Drug: PTR-01<br>* Intravenous recombinant collagen 7<br>* Other names: Recombinant collagen 7 (rC7);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained 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 246 days | 
| Incidence of treatment-emergent adverse events | Safety and tolerability, as assessed by treatment-emergent adverse events | Up to 246 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delivery of recombinant collagen 7 (PTR-01) to skin | Amount of recombinant collagen 7 (PTR-01) incorporation to skin as compared to normal human skin assessed by immunofluorescence using NC1 & NC2 antibody staining | Up to 246 days | 
| Formation of anchoring fibrils | Formation of new anchoring fibrils as measured by electron microscopy | Up to 246 days | 
| Change in wound surface area | Wound surface area of lesions as assessed by medical photography using the Canfield RUBI 3D imaging system | Up to 246 days | 
| Change in skin integrity, as assessed by suction blister time | Change in skin integrity, as assessed by suction blister time | Up to 246 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 246 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, maximum score of 5 (worst) | Up to 246 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 246 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, maximum score of 5 (worst) | Up to 246 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 246 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 246 days | 
| Stabilization of dysphagia, as assessed using the Brief Esophageal Dysphagia Instrument | Stabilization of dysphagia, as assessed using the Brief Esophageal Dysphagia Instrument, maximum score of 40 (worst) | Up to 246 days | 
| Change in corneal symptoms | Change of corneal symptoms (eye symptoms), as assessed by the Epidermolysis Bullosa Eye Disease Index (EB-EDI), maximum score of 100 (worst) | Up to 246 days | 
| Stabilization of corneal symptoms | Stabilization of corneal symptoms (eye symptoms), as assessed by the Epidermolysis Bullosa Eye Disease Index (EB-EDI), maximum score of 100 (worst) | Up to 246 days | 
| Rate of change in nutritional markers (hemoglobin) | Change of nutritional markers, as assessed by hemoglobin | Up to 246 days | 
| Rate of change in nutritional markers (hematocrit) | Change of nutritional markers, as assessed by hematocrit | Up to 246 days | 
| Rate of change in nutritional markers (total protein/albumin) | Change of nutritional markers, as assessed by total protein/albumin | Up to 246 days | 
| Rate of change in nutritional markers (Fe/TIBC) | Change of nutritional markers, as assessed by total Fe/TIBC | Up to 246 days | 
| Rate of change in nutritional markers (C-reactive protein) | Change of nutritional markers, as assessed by total C-reactive protein | Up to 246 days | 
| Change in Investigator Global Impressions of Change (IGIC) | Global impressions of change, as assessed through IGIC (1-7), 7 being worst | Up to 246 days | 
| Change in Investigator Patient Impressions of Change (PGIC) | Global impressions of change, as assessed through PGIC (1-7), 7 being worst | Up to 246 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 maximum score is 67 (worst) | Up to 246 days | 
| Change in overall health | Change in overall disability, as assessed by the Health Assessment Questionnaire or Children's Health Assessment Questionnaire (HAQ/CHAQ) maximum score is 3 (worst) | Up to 246 days | 
| Change in mental health | Change in mental health, as assessed by the Patient-Reported Outcomes Measurement Information System (PROMIS) mental health domains, maximum score is 5 (worst) | Up to 246 days | 
| Change in social function | Change in social functioning, as assessed by the Patient-Reported Outcomes Measurement Information System (PROMIS) social function domains, maximum score is 4 (worst) | Up to 246 days | 
| Change in amount of wound care | Change in amount of wound care, as assessed by patient interviews | Up to 246 days | 
| Change in time for wound care | Change in time for wound care, as assessed by patient interviews | Up to 246 days | 
| Change in cost of wound care | Change in cost of wound care, as assessed by patient interviews | Up to 246 days | 
| Change in overall patient impression of quality of life | Change in overall anecdotal quality of life, as assessed by one-on-one patient interviews | Up to 246 days | 
| Change in overall patient impression of disability | Change in overall anecdotal disability, as assessed by one-on-one patient interviews | Up to 246 days | 
| Effect of anti-drug antibodies (ADA) on pharmacokinetics parameter Cmax | Correlate ADA with Cmax | Up to 246 days | 
| Effect of anti-drug antibodies (ADA) on pharmacokinetics parameter Tmax | Correlate ADA with Tmax | Up to 246 days | 
| Effect of anti-drug antibodies (ADA) on pharmacokinetics parameter Area Under the Curve (AUC) | Correlate ADA with Area Under the Curve (AUC) | Up to 246 days | 
| Effect of anti-drug antibodies (ADA) on pharmacokinetics parameter of clearance of PTR-01 | Correlate ADA with clearance of PTR-01 | Up to 246 days | 
| Effect of anti-drug antibodies (ADA) on pharmacokinetics parameter of PTR-01 half-life | Correlate ADA with PTR-01 half-life | Up to 246 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dystrophic Epidermolysis Bullosa, Epidermolysis Bullosa, RDEB, EB