Back to resultsA Study of PTR-01 in Recessive Dystrophic Epidermolysis Bullosa
Primary Purpose
Recessive Dystrophic Epidermolysis Bullosa
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
PTR-01
Sponsored by
About this trial
This is an interventional treatment trial for Recessive Dystrophic Epidermolysis Bullosa focused on measuring RDEB
Eligibility 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:
- 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
Sites / Locations
- Stanford University
- Children's Hospital Colorado
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
PTR-01 3 mg/kg
Arm Description
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.
Outcomes
Primary Outcome Measures
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)
Incidence of treatment-emergent adverse events
Safety and tolerability, as assessed by treatment-emergent adverse events
Incidence of infusion-associated reactions
Safety and tolerability, as assessed by infusion-associated reactions (IAR)
Incidence of anti-drug antibodies (ADA)
Safety and tolerability, as assessed by immunogenicity through anti-drug antibody (ADA) testing
Secondary Outcome Measures
Delivery of PTR-01 to skin
PTR-01 incorporation by immunofluorescence using NC1 & NC2 staining, by dose frequency period
Formation of anchoring fibrils
Formation of new anchoring fibrils as measured by electron microscopy
Change in wound surface area, as assessed by wound imaging
Wound area of target lesions, as assessed by wound imaging
Change in wound surface area, as assessed by Investigator Global Impression of Change (IGIC)
Wound area of target lesions, as assessed by IGIC
Change in total body wound surface area
Change in total body wound surface area, using Rule of Nines
Change in skin integrity, as assessed by suction blister time
Change in skin integrity, as assessed by suction blister time
Change in skin integrity, as assessed by time to re-blistering
Change in skin integrity, as assessed by time to re-blistering
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
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)
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)
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
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)
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)
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)
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)
Stabilization of dysphagia, as assessed using the Brief Esophageal Dysphagia Scale
Stabilization of dysphagia, as assessed using the Brief Esophageal Dysphagia Scale
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
Change in corneal symptoms
Change of corneal symptoms (eye symptoms), as assessed by the Epidermolysis Bullosa Eye Disease Index (EB-EDI)
Stabilization of corneal symptoms
Stabilization of corneal symptoms (eye symptoms), as assessed by the Epidermolysis Bullosa Eye Disease Index (EB-EDI)
Rate of change in nutritional markers (hemoglobin/hematocrit)
Change of nutritional markers, as assessed by hemoglobin/hematocrit
Rate of change in nutritional markers (total protein/albumin)
Change of nutritional markers, as assessed by total protein/albumin
Rate of change in nutritional markers (iron/TIBC)
Change of nutritional markers, as assessed by iron/TIBC
Rate of change in nutritional markers (C-reactive protein)
Change of nutritional markers, as assessed by C-reactive protein
Rate of stabilization of nutritional markers (hemoglobin/hematocrit)
Stabilization of nutritional markers, as assessed by hemoglobin/hematocrit
Rate of stabilization of nutritional markers (total protein/albumin)
Stabilization of nutritional markers, as assessed by total protein/albumin
Rate of stabilization of nutritional markers (iron/TIBC)
Stabilization of nutritional markers, as assessed by iron/TIBC
Rate of stabilization of nutritional markers (C-reactive protein)
Stabilization of nutritional markers, as assessed by C-reactive protein
Change in Investigator Global Impressions of Change (IGIC)
Global impressions of change, as assessed through IGIC (1-7), 7 being worst
Change in Investigator Patient Impressions of Change (PGIC)
Global impressions of change, as assessed through PGIC (1-7), 7 being worst
Change in disease activity and scarring
Change in disease activity and scarring, as assessed by the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI)
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
Change in overall health
Change in overall disability, as assessed by the Health Assessment Questionnaire or Children's Health Assessment Questionnaire (HAQ/CHAQ)
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
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
Change in amount of wound care
Change in amount of wound care, as assessed by patient interviews
Change in time for wound care
Change in time for wound care, as assessed by patient interviews
Change in cost of wound care
Change in cost of wound care, as assessed by patient interviews
Change in overall patient impression of quality of life
Change in overall quality of life, as assessed by patient interviews
Change in overall patient impression of disability
Change in overall disability, as assessed by patient interviews
Full Information
NCT ID
NCT04599881
First Posted
October 8, 2020
Last Updated
September 14, 2021
Sponsor
Phoenix Tissue Repair, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04599881
Brief Title
A Study of PTR-01 in Recessive Dystrophic Epidermolysis Bullosa
Official Title
A Phase 2 Open-Label Study of PTR-01 in Patients With Recessive Dystrophic Epidermolysis Bullosa (RDEB)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
October 15, 2020 (Actual)
Primary Completion Date
August 28, 2021 (Actual)
Study Completion Date
September 1, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Phoenix Tissue Repair, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recessive Dystrophic Epidermolysis Bullosa
Keywords
RDEB
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Open-label study
Masking
None (Open Label)
Masking Description
Open-label
Allocation
N/A
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PTR-01 3 mg/kg
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
PTR-01
Other Intervention Name(s)
Recombinant collagen 7, rC7
Intervention Description
IV recombinant collagen 7 at 3 mg/kg given weekly for 4 doses, followed by bi-weekly for 7 doses
Primary Outcome Measure Information:
Title
Wound healing
Description
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)
Time Frame
Up to 162 days
Title
Incidence of treatment-emergent adverse events
Description
Safety and tolerability, as assessed by treatment-emergent adverse events
Time Frame
Up to 162 days
Title
Incidence of infusion-associated reactions
Description
Safety and tolerability, as assessed by infusion-associated reactions (IAR)
Time Frame
Up to 162 days
Title
Incidence of anti-drug antibodies (ADA)
Description
Safety and tolerability, as assessed by immunogenicity through anti-drug antibody (ADA) testing
Time Frame
Up to 162 days
Secondary Outcome Measure Information:
Title
Delivery of PTR-01 to skin
Description
PTR-01 incorporation by immunofluorescence using NC1 & NC2 staining, by dose frequency period
Time Frame
Up to 162 days
Title
Formation of anchoring fibrils
Description
Formation of new anchoring fibrils as measured by electron microscopy
Time Frame
Up to 162 days
Title
Change in wound surface area, as assessed by wound imaging
Description
Wound area of target lesions, as assessed by wound imaging
Time Frame
Up to 162 days
Title
Change in wound surface area, as assessed by Investigator Global Impression of Change (IGIC)
Description
Wound area of target lesions, as assessed by IGIC
Time Frame
Up to 162 days
Title
Change in total body wound surface area
Description
Change in total body wound surface area, using Rule of Nines
Time Frame
Up to 162 days
Title
Change in skin integrity, as assessed by suction blister time
Description
Change in skin integrity, as assessed by suction blister time
Time Frame
Up to 162 days
Title
Change in skin integrity, as assessed by time to re-blistering
Description
Change in skin integrity, as assessed by time to re-blistering
Time Frame
Up to 162 days
Title
Change in itch severity, as assessed by modified Patient-Reported Outcome Measurement Information System (PROMIS) itch domains
Description
Severity of itch, as assessed by modified Patient-Reported Outcome Measurement Information System (PROMIS) itch domains
Time Frame
Up to 162 days
Title
Change in itch severity, as assessed by the Instrument for Scoring Clinical Outcomes for Research of Epidermolysis Bullosa (iscorEB)
Description
Severity of itch, as assessed by Instrument for Scoring Clinical Outcomes for Research of Epidermolysis Bullosa (iscorEB), maximum score of 234 (worst)
Time Frame
Up to 162 days
Title
Change in the impact of itch on quality of life
Description
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)
Time Frame
Up to 162 days
Title
Change in pain severity, as assessed by modified Patient-Reported Outcome Measurement Information System (PROMIS) pain domains
Description
Change in pain severity, as assessed by Patient-Reported Outcome Measurement Information System (PROMIS) pain domains
Time Frame
Up to 162 days
Title
Change in pain severity, as assessed by the Instrument for Scoring Clinical Outcomes for Research of Epidermolysis Bullosa (iscorEB)
Description
Change in pain severity, as assessed by the Instrument for Scoring Clinical, maximum score of 234 (worst)
Time Frame
Up to 162 days
Title
Change in the impact of pain on quality of life
Description
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)
Time Frame
Up to 162 days
Title
Change of dysphagia, as assessed using the Brief Esophageal Dysphagia Questionnaire
Description
Change of dysphagia, as assessed using the Brief Esophageal Dysphagia Questionnaire, maximum score is 40 (worst)
Time Frame
Up to 162 days
Title
Change in dysphagia, as assessed by volume of oral nutritional intake
Description
Change of dysphagia, as assessed by volume of oral nutritional intake, using patient interview and diary, maximum score is 40 (worst)
Time Frame
Up to 162 days
Title
Stabilization of dysphagia, as assessed using the Brief Esophageal Dysphagia Scale
Description
Stabilization of dysphagia, as assessed using the Brief Esophageal Dysphagia Scale
Time Frame
Up to 162 days
Title
Stabilization of dysphagia, as assessed by volume oral nutritional intake
Description
Stabilization of dysphagia, as assessed by volume oral nutritional intake, using patient interview and diary
Time Frame
Up to 162 days
Title
Change in corneal symptoms
Description
Change of corneal symptoms (eye symptoms), as assessed by the Epidermolysis Bullosa Eye Disease Index (EB-EDI)
Time Frame
Up to 162 days
Title
Stabilization of corneal symptoms
Description
Stabilization of corneal symptoms (eye symptoms), as assessed by the Epidermolysis Bullosa Eye Disease Index (EB-EDI)
Time Frame
Up to 162 days
Title
Rate of change in nutritional markers (hemoglobin/hematocrit)
Description
Change of nutritional markers, as assessed by hemoglobin/hematocrit
Time Frame
Up to 162 days
Title
Rate of change in nutritional markers (total protein/albumin)
Description
Change of nutritional markers, as assessed by total protein/albumin
Time Frame
Up to 162 days
Title
Rate of change in nutritional markers (iron/TIBC)
Description
Change of nutritional markers, as assessed by iron/TIBC
Time Frame
Up to 162 days
Title
Rate of change in nutritional markers (C-reactive protein)
Description
Change of nutritional markers, as assessed by C-reactive protein
Time Frame
Up to 162 days
Title
Rate of stabilization of nutritional markers (hemoglobin/hematocrit)
Description
Stabilization of nutritional markers, as assessed by hemoglobin/hematocrit
Time Frame
Up to 162 days
Title
Rate of stabilization of nutritional markers (total protein/albumin)
Description
Stabilization of nutritional markers, as assessed by total protein/albumin
Time Frame
Up to 162 days
Title
Rate of stabilization of nutritional markers (iron/TIBC)
Description
Stabilization of nutritional markers, as assessed by iron/TIBC
Time Frame
Up to 162 days
Title
Rate of stabilization of nutritional markers (C-reactive protein)
Description
Stabilization of nutritional markers, as assessed by C-reactive protein
Time Frame
Up to 162 days
Title
Change in Investigator Global Impressions of Change (IGIC)
Description
Global impressions of change, as assessed through IGIC (1-7), 7 being worst
Time Frame
Up to 162 days
Title
Change in Investigator Patient Impressions of Change (PGIC)
Description
Global impressions of change, as assessed through PGIC (1-7), 7 being worst
Time Frame
Up to 162 days
Title
Change in disease activity and scarring
Description
Change in disease activity and scarring, as assessed by the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI)
Time Frame
Up to 162 days
Title
Change in overall quality of life, as assessed by the Quality of Life in Epidermolysis Bullosa (QOLEB) questionnaire
Description
Change in overall quality of life, as assessed by the Quality of Life in Epidermolysis Bullosa (QOLEB) questionnaire
Time Frame
Up to 162 days
Title
Change in overall health
Description
Change in overall disability, as assessed by the Health Assessment Questionnaire or Children's Health Assessment Questionnaire (HAQ/CHAQ)
Time Frame
Up to 162 days
Title
Change in mental health
Description
Change in mental health and social functioning, as assessed by the Patient-Reported Outcomes Measurement Information System (PROMIS) mental health domains
Time Frame
Up to 162 days
Title
Change in social function
Description
Change in mental health and social functioning, as assessed by the Patient-Reported Outcomes Measurement Information System (PROMIS) social function domains
Time Frame
Up to 162 days
Title
Change in amount of wound care
Description
Change in amount of wound care, as assessed by patient interviews
Time Frame
Up to 162 days
Title
Change in time for wound care
Description
Change in time for wound care, as assessed by patient interviews
Time Frame
Up to 162 daysUp to 162 days
Title
Change in cost of wound care
Description
Change in cost of wound care, as assessed by patient interviews
Time Frame
Up to 162 days
Title
Change in overall patient impression of quality of life
Description
Change in overall quality of life, as assessed by patient interviews
Time Frame
Up to 162 days
Title
Change in overall patient impression of disability
Description
Change in overall disability, as assessed by patient interviews
Time Frame
Up to 162 days
Other Pre-specified Outcome Measures:
Title
Genotype/phenotype relationships
Description
Correlation between genotype (genetic mutation) and severity of disease
Time Frame
Up to 162 days
Title
Impact of pharmacokinetics on safety outcomes
Description
Correlate Cmax and Area Under the Curve (AUC) with treatment emergent adverse events, infusion associated reactions and immune-mediated reactions
Time Frame
Up to 162 days
Title
Impact of pharmacokinetics on efficacy outcomes
Description
Correlate Cmax and AUC with wound healing
Time Frame
Up to 162 days
Title
Impact of pharmacokinetics on pharmacodynamic outcomes
Description
Correlate Cmax and AUC with suction blister time, C7 immunofluorescence on biopsy and formation of anchoring fibrils by electron microscopy
Time Frame
Up to 162 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility 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:
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
Facility Information:
Facility Name
Stanford University
City
Redwood City
State/Province
California
ZIP/Postal Code
94063
Country
United States
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Study of PTR-01 in Recessive Dystrophic Epidermolysis Bullosa
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