Recessive Dystrophic Epidermolysis Bullosa
Conditions
Keywords
RDEB
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.
Interventions
DRUGPTR-01
IV recombinant collagen 7 at 3 mg/kg given weekly for 4 doses, followed by bi-weekly for 7 doses
Sponsors
Phoenix Tissue Repair, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open-label
Intervention model description
Open-label study
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-emergent adverse events | Up to 162 days | Safety and tolerability, as assessed by treatment-emergent adverse events |
| Incidence of anti-drug antibodies (ADA) | Up to 162 days | Safety and tolerability, as assessed by immunogenicity through anti-drug antibody (ADA) testing |
| Wound healing | 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) |
| Incidence of infusion-associated reactions | Up to 162 days | Safety and tolerability, as assessed by infusion-associated reactions (IAR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in wound surface area, as assessed by Investigator Global Impression of Change (IGIC) | Up to 162 days | Wound area of target lesions, as assessed by IGIC |
| Change in total body wound surface area | Up to 162 days | Change in total body wound surface area, using Rule of Nines |
| Change in skin integrity, as assessed by suction blister time | Up to 162 days | Change in skin integrity, as assessed by suction blister time |
| Change in skin integrity, as assessed by time to re-blistering | Up to 162 days | 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 | Up to 162 days | Severity of itch, as assessed by modified Patient-Reported Outcome Measurement Information System (PROMIS) itch domains |
| 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 quality of life, as assessed by the Quality of Life in Epidermolysis Bullosa (QOLEB) questionnaire |
| Change in itch severity, as assessed by the Instrument for Scoring Clinical Outcomes for Research of Epidermolysis Bullosa (iscorEB) | 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) |
| Change in the impact of itch on quality of life | 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) |
| Change in pain severity, as assessed by modified Patient-Reported Outcome Measurement Information System (PROMIS) pain domains | Up to 162 days | 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) | Up to 162 days | 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 | 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) |
| Change of dysphagia, as assessed using the Brief Esophageal Dysphagia Questionnaire | Up to 162 days | 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 | 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) |
| Stabilization of dysphagia, as assessed using the Brief Esophageal Dysphagia Scale | Up to 162 days | Stabilization of dysphagia, as assessed using the Brief Esophageal Dysphagia Scale |
| Stabilization of dysphagia, as assessed by volume oral nutritional intake | Up to 162 days | Stabilization of dysphagia, as assessed by volume oral nutritional intake, using patient interview and diary |
| Change in corneal symptoms | Up to 162 days | Change of corneal symptoms (eye symptoms), as assessed by the Epidermolysis Bullosa Eye Disease Index (EB-EDI) |
| Stabilization of corneal symptoms | Up to 162 days | 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) | Up to 162 days | Change of nutritional markers, as assessed by hemoglobin/hematocrit |
| Rate of change in nutritional markers (total protein/albumin) | Up to 162 days | Change of nutritional markers, as assessed by total protein/albumin |
| Rate of change in nutritional markers (iron/TIBC) | Up to 162 days | Change of nutritional markers, as assessed by iron/TIBC |
| Rate of change in nutritional markers (C-reactive protein) | Up to 162 days | Change of nutritional markers, as assessed by C-reactive protein |
| Rate of stabilization of nutritional markers (hemoglobin/hematocrit) | Up to 162 days | Stabilization of nutritional markers, as assessed by hemoglobin/hematocrit |
| Rate of stabilization of nutritional markers (total protein/albumin) | Up to 162 days | Stabilization of nutritional markers, as assessed by total protein/albumin |
| Rate of stabilization of nutritional markers (iron/TIBC) | Up to 162 days | Stabilization of nutritional markers, as assessed by iron/TIBC |
| Rate of stabilization of nutritional markers (C-reactive protein) | Up to 162 days | Stabilization of nutritional markers, as assessed by C-reactive protein |
| Change in Investigator Global Impressions of Change (IGIC) | Up to 162 days | Global impressions of change, as assessed through IGIC (1-7), 7 being worst |
| Change in Investigator Patient Impressions of Change (PGIC) | Up to 162 days | Global impressions of change, as assessed through PGIC (1-7), 7 being worst |
| Change in disease activity and scarring | Up to 162 days | Change in disease activity and scarring, as assessed by the Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) |
| Change in overall health | Up to 162 days | Change in overall disability, as assessed by the Health Assessment Questionnaire or Children's Health Assessment Questionnaire (HAQ/CHAQ) |
| Change in mental health | 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 |
| Change in social function | 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 |
| Change in amount of wound care | Up to 162 days | Change in amount of wound care, as assessed by patient interviews |
| Change in time for wound care | Up to 162 daysUp to 162 days | Change in time for wound care, as assessed by patient interviews |
| Change in cost of wound care | Up to 162 days | Change in cost of wound care, as assessed by patient interviews |
| Change in overall patient impression of disability | Up to 162 days | Change in overall disability, as assessed by patient interviews |
| Change in overall patient impression of quality of life | Up to 162 days | Change in overall quality of life, as assessed by patient interviews |
| Delivery of PTR-01 to skin | Up to 162 days | PTR-01 incorporation by immunofluorescence using NC1 & NC2 staining, by dose frequency period |
| Formation of anchoring fibrils | Up to 162 days | Formation of new anchoring fibrils as measured by electron microscopy |
| Change in wound surface area, as assessed by wound imaging | Up to 162 days | Wound area of target lesions, as assessed by wound imaging |
Other
| Measure | Time frame | Description |
|---|---|---|
| Genotype/phenotype relationships | Up to 162 days | Correlation between genotype (genetic mutation) and severity of disease |
| Impact of pharmacokinetics on pharmacodynamic outcomes | Up to 162 days | Correlate Cmax and AUC with suction blister time, C7 immunofluorescence on biopsy and formation of anchoring fibrils by electron microscopy |
| Impact of pharmacokinetics on efficacy outcomes | Up to 162 days | Correlate Cmax and AUC with wound healing |
| Impact of pharmacokinetics on safety outcomes | Up to 162 days | Correlate Cmax and Area Under the Curve (AUC) with treatment emergent adverse events, infusion associated reactions and immune-mediated reactions |
Countries
United States
Outcome results
None listed