A Phase 1/2 Trial of PTR-01 in Adult Patients With Recessive Dystrophic Epidermolysis Bullosa (RDEB) (PTR-01-001)

A Phase 1/2 Randomized, Saline-Controlled, Single-Blind, Multiple Ascending Dose, Dose-Escalation, Multi-Center Trial of PTR-01 in Adult Patients With Recessive Dystrophic Epidermolysis Bullosa (RDEB)

Protocol PTR-01-001 is a Phase 1/2 study of PTR-01.

The study is divided into an up to 4-week Screening Period, a 10-week Treatment Period and an 8-week Follow-up Period.

Cohorts 1, 2, 3 and 4 will consist of 2, 4, 3 and 3 patients respectively. Each cohort will consist of patients divided into two groups (Group 1 and Group 2) randomized in a 1:1 ratio. Patients in Group 1 will receive three doses of active drug followed by 3 doses of saline control. Patients in Group 2 will receive three doses of saline control followed by 3 doses of active drug.

Cohort 1 patients randomized to Group 1 will receive 3 doses of active treatment (PTR-01) at a dose of 0.1 mg/kg followed by 3 doses of saline control for a total of 6 doses. Cohort 1 patients randomized to Group 2 will receive 3 doses of saline control followed by 3 doses of active treatment (PTR-01) at a dose of 0.1 mg/kg for a total of 6 doses.

Study Overview

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

Detailed Description

Protocol PTR-01-001 is a saline-controlled, single and repeat dose, dose-escalation, crossover study designed to determine the safety, tolerability, tissue kinetics, pharmacodynamics and preliminary efficacy of PTR 01.

The study is divided into three periods: an up to 4-week Screening Period, a 10-week Treatment Period and an 8-week Follow-up Period. During the Screening Period and Follow-up Period there will be no study drug treatment.

During the Treatment Period a total of 3 doses of PTR-01 and 3 doses of saline control will be administered to patients for a total of 6 doses over a 10-week period in three cohorts dosed at 0.1, 0.3, 1.0 and 3.0 mg/kg (active drug). Twelve patients with a diagnosis of RDEB and a history of at least one chronic wound will be enrolled. Those patients who do not have documentation of genetic analysis and IF staining will have blood for genetic analysis and a biopsy for IF staining prior to enrollment (both required).

Cohorts 1, 2, 3 and 4 will consist of 2, 4, 3 and 3 patients respectively. Each cohort will consist of patients divided into two groups (Group 1 and Group 2) randomized in a 1:1 ratio. Patients will receive doses 2 weeks apart. Patients in Group 1 will receive three doses of active drug followed by 3 doses of saline control. Patients in Group 2 will receive three doses of saline control followed by 3 doses of active drug. This cross-over design will yield a total of 14 patients all of whom will receive active drug and saline control.

Prior to randomization, patients will complete a Screening Period to assess the extent and impact of skin disease involvement and the chronicity of at least one wound. Only patients who meet all of the eligibility criteria will be randomized for treatment.

Cohort 1 patients randomized to Group 1 will receive 3 doses of active treatment (PTR-01) at a dose of 0.1 mg/kg followed by 3 doses of saline control for a total of 6 doses. Cohort 1 patients randomized to Group 2 will receive 3 doses of saline control followed by 3 doses of active treatment (PTR-01) at a dose of 0.1 mg/kg for a total of 6 doses. After the last patient in Cohort 1 has received their third dose and safety labs for all patients have been reviewed by the Data Safety Monitoring Board (DSMB), the next cohort may be enrolled. This same schedule and safety review process will be followed for all subsequent dosing cohorts, with Cohort 2, Cohort 3 and Cohort 4 receiving 0.3, 1.0 and 3.0 mg/kg respectively.

Efficacy assessments will be performed prior to first dose of therapy (at the end of the Screening Period), after the last dose of study drug in Period 1, after the last dose of study drug in Period 2 of the Treatment Period and 2 weeks (Day 85) after the last dose of study drug (at the end of the Follow-up Period).

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2; Phase 1

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
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson Univeristiy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Be at least 16 years of age.
2. Has signed the current approved informed consent form.
3. Has a diagnosis of RDEB based on genetic analysis and consistent with a recessive inheritance pattern.
4. Has deficient C7 staining at the dermal-epidermal junction (DEJ) by IF.
5. Has at least 1 unhealed wound 10-200 cm2 for at least 6 weeks at the Screening Visit.

6. 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 (see Section 7.4.1.2 for details on the definition of non-childbearing potential).
   • 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.
7. Be willing and able to comply with this protocol.

Exclusion Criteria:

1. Has known systemic hypersensitivity to any of the inactive ingredients in PTR-01.
2. Is pregnant or nursing.
3. Has received in the last six months any investigational gene therapy product or in the last three months any non-gene therapy investigational products.
4. Is anticipated to receive new regimens of antibiotics or other anti-infectives during the trial.
5. 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 successful completion of the clinical study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PTR-01 0.1 mg/kg; Three intravenous infusions of PTR-01 at 0.1 mg/kg with doses 2 weeks apart.	Drug: PTR-01; Recombinant human collagen 7 (rC7); Other Names: Recombinant human collagen 7 (rC7)
Experimental: PTR-01 0.3 mg/kg; Three intravenous infusions of PTR-01 at 0.3 mg/kg with doses 2 weeks apart.	Drug: PTR-01; Recombinant human collagen 7 (rC7); Other Names: Recombinant human collagen 7 (rC7)
Experimental: PTR-01 1.0 mg/kg; Three intravenous infusions of PTR-01 at 1.0 mg/kg with doses 2 weeks apart.	Drug: PTR-01; Recombinant human collagen 7 (rC7); Other Names: Recombinant human collagen 7 (rC7)
Placebo Comparator: Normal Saline; Saline control to mimic PTR-01.	Drug: Normal saline; Saline control
Experimental: PTR-01 3.0 mg/kg; Three intravenous infusions of PTR-01 at 3.0 mg/kg with doses 2 weeks apart.	Drug: PTR-01; Recombinant human collagen 7 (rC7); Other Names: Recombinant human collagen 7 (rC7)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent adverse events	The primary endpoint of this study is safety and tolerability, as assessed by treatment-emergent adverse events, infusion-associated reactions (IAR) and immunogenicity	Up to Day 127

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To measure the peak serum concentration (Cmax) of PTR-01	Pharmacokinetic parameter estimates of Cmax	Pre-dose, 15 minutes, 60 minutes, 2 hours, 4 hours, 8 hours and 24 hours post-dose
To measure the time to peak concentration (Tmax) of PTR-01	Pharmacokinetic parameter estimates of Tmax	Pre-dose, 15 minutes, 60 minutes, 2 hours, 4 hours, 8 hours and 24 hours post-dose
To measure the area under the curve (AUC) of PTR-01	Pharmacokinetic parameter estimates of AUC	Pre-dose, 15 minutes, 60 minutes, 2 hours, 4 hours, 8 hours and 24 hours post-dose
To measure the clearance of PTR-01	Pharmacokinetic parameter estimates of clearance	Pre-dose, 15 minutes, 60 minutes, 2 hours, 4 hours, 8 hours and 24 hours post-dose
To measure the half-life (t1/2) of PTR-01	Pharmacokinetic parameter estimates of t1/2	Pre-dose, 15 minutes, 60 minutes, 2 hours, 4 hours, 8 hours and 24 hours post-dose
Change from Baseline in rC7	Change in rC7 on skin biopsy by immunofluorescence (IF)	Screening and Day 127
Change from Baseline in anchoring fibrils	Change in anchoring fibrils on skin biopsy by electron microscopy (EM)	Screening and Day 127
Duration of rC7 residence in tissue	Duration of rC7 residence in tissue by skin biopsy	Screening and Day 127

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in suction blister time	Change from Baseline in suction blister time (as compared to placebo and historical controls)	Baseline and Day 127
Change from Baseline in target wound size	Change from Baseline in target wound size (percent healing from Baseline)	Baseline and Day 127
Change from Baseline in healing of up to 5 chronic wounds	Change in healing of up to 5 wounds that chronically heal and reopen	Baseline and Day 127
Change from Baseline in wound surface area	Change from Baseline in wound surface area	Screening and Day 127
Change from Baseline in patient reported outcomes as assessed by the Leuven Itch Scale (LIS)	Change from Baseline in patient reported outcomes	Baseline and Day 127
Change from Baseline in patient reported outcomes as assessed by the pruritus-specific quality-of-life instrument ("ItchyQoL")	Change from Baseline in patient reported outcomes	Baseline and Day 127
Change from Baseline in patient reported outcomes as assessed by the Quality of Life in Epidermolysis Bullosa (QOLEB) Questionnaire	Change from Baseline in patient reported outcomes	Baseline and Day 127
Change from Baseline in patient reported outcomes as assessed by the full Health Assessment Questionnaire (HAQ)	Change from Baseline in patient reported outcomes	Baseline and Day 127
Change from Baseline in the Investigator Global Assessment	Change from Baseline in the Investigator Global Assessment (IGA)	Screening and Day 127
Change from Baseline in the biochemical marker albumin	Change from Baseline in biochemical markers of disease (albumin)	Screening and Day 127
Change from Baseline in the biochemical marker iron	Change from Baseline in biochemical markers of disease (iron)	Screening and Day 127
Change from Baseline in the biochemical marker total iron binding capacity	Change from Baseline in biochemical markers of disease (total iron binding capacity)	Screening and Day 127
Change from Baseline in the biochemical marker hemoglobin	Change from Baseline in biochemical markers of disease (hemoglobin)	Screening and Day 127
Change from Baseline in the biochemical marker hematocrit	Change from Baseline in biochemical markers of disease (hematocrit)	Screening and Day 127
Change from Baseline in the biochemical marker total protein	Change from Baseline in biochemical markers of disease (total protein)	Screening and Day 127

Collaborators and Investigators

• Sponsor: Phoenix Tissue Repair, Inc.
• Investigators: Study Director: Theresa Podrebarac, MD, Phoenix Tissue Repair

Publications and helpful links

Helpful Links

• Sponsor website

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2019
• Primary Completion (Actual): November 30, 2020
• Study Completion (Actual): November 30, 2020

Study Registration Dates

• First Submitted: November 19, 2018
• First Submitted That Met QC Criteria: November 21, 2018
• First Posted (Actual): November 26, 2018

Study Record Updates

• Last Update Posted (Actual): March 9, 2021
• Last Update Submitted That Met QC Criteria: March 8, 2021
• Last Verified: March 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-01-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: There are currently no plans to share individual participant data with other researchers.

Drug and device information, study documents

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