The Efficacy and Safety of 3% Cannabidiol (CBD) Cream in Patients With Epidermolysis Bullosa: A Phase II/III Trial

NCT04613102 | Withdrawn Phase 2 DMC

• 1 other identifier: 1000062062
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Epidermolysis bullosa (EB) is rare, devastating, and currently incurable genetic blistering disorders characterized by fragility of skin and mucosal membranes. Therapeutic options for EB are limited. Acute and chronic wounds cause pain, itching and infection, altering quality of life and impair wound healing. In absence of a cure, wound care is paramount to alleviate suffering. Anecdotal experience suggest that CBD application alleviates the pain and itching and improves wound healing by controlling the inflammatory process. We propose to undertake a phase II/III study exploring the safety, tolerability and efficacy of topical application of 3% Cannabidiol cream (CBD) on acute and chronic wounds affecting patients with EB. We are doing this trial to determine safety and tolerability of topical CBD cream in a cohort of RDEB patients with chronic wounds (phase II trial), and to evaluate the efficacy and safety of CBD cream in EB with acute and chronic wounds in promoting wound healing, decrease blister formation, pain, itching and improve overall quality of life (phase III trial)

Conditions

Epidermolysis Bullosa; Pain; Itch

Outcome Measures

Primary Outcomes (9)

• Group A (patients with acute wounds). Difference in the total wound count (blister, open and closed wounds) compared to baseline

  Difference in the total wound count (blister, open and closed wounds) compared to baseline

  8 weeks

• Group B (patients with chronic wounds). Percent change in the surface area of patients treated vs patients on placebo compared to baseline

  Percent change in the surface area of patients treated with CBD vs patients on placebo compared to baseline

  8 weeks

• Group B (patients with chronic wounds). Proportion of treated patients that had more than 75% wound shrinkage

  Proportion of patients that had more than 75% wound shrinkage (on the side of the body treated with CBD - in phase 3), compared to baseline.

  8 weeks

• Group B. Proportion of treated patients that had more than 50% wound shrinkage

  Proportion of patients that had more than 50% wound shrinkage (on the side of the body treated with CBD - in phase 3), compared to baseline.

  8 weeks

• Percent changes in pain scores compared to baseline

  Visual Analog Scale (VAS) is a 10 cm line with anchor statements on the left (0 -no pain) and on the right (10- worst pain ever). The patient is asked to mark their pain level on the line at each study visit. The pain is scored using the VAS by measuring the distance in centimeters (0-10) from the "no pain" anchoring point. Difference in the pain score assessed using VAS, reported by the patient, between baseline and week 4, and week 8 visits will be calculated and multiplied by 10 to get result in percents(%).

  8 weeks

• Percent changes in itch scores compared to baseline

  The intensity of itch is measured using the Visual Analog Scale for itch (VAS).It is a 10 cm line with anchor statements on the left (0- no itching) and on the right (10 -worst possible itching). The patient is asked to mark the intensity of itch on the line at each study visit. The itch is scored using the VAS by measuring the distance in centimeters (0-10) from the "no itch" anchoring point. the difference in the itch score as assessed using VAS( reported by the patient) between the first and visits Week 4 and Week 8, will be multiplied by 10 to get result in percents.

  8 weeks

• Percent changes in iscorEB (instrument for scoring clinical outcomes for research of EB), patient and clinician scores compared to baseline

  iscorEB is a measurement tool for evaluating the disease severity in EB patient. It evaluates the cutaneous, mucosal and other organ impact of EB and includes clinician and patient reported outcomes in a single instrument. Score ranges between 0-120 for both reported outcomes. Patient portion of this instrument contains 15 questions. Each question has a score range from 0-8.Total score range for iscorEB patient portion is between 0 and 120. Reduction in iscorEB scores indicates improvement. An increase in score indicates deterioration. The difference in total patient and clinician scores between baseline and Week 4 ,8 visits will be divided by 120 ( max score for each portion)and multiplied by 100, to get the results in percents.

  8 weeks

• Percent changes in Quality of Life in Epidermolysis Bullosa Questionnaire score (QOLEB) EBQOL scores compared to baseline

  QOLEB is a measurement tool containing 17 questions. Each question has a score range from 0-3.Total score range is between 0 and 51. Difference in the total scores between baseline and the study visits week 4, 8, will be divided by 51 and multiplied by 100 to get the result in percents.

  8 weeks

• correlation between patient's impression of improvement (VAS) and objective tools

  Patient's impression of improvement is measured using the Visual Analog Scale (VAS). It is a 10 cm line with 3 anchor statements: on the left -"worsening", mid- "no changes", and on the right - "improvement". The patient is asked to mark his/her impression of improvement on the line at the final study visit. It will be scored by measuring the distance in centimeters (0-5) from the "no changes" anchoring point. The difference in this score as assessed using VAS( reported by the patient) between the baseline and EOS visit ,will be multiplied by 20 to get result in percents.

  8 weeks

Secondary Outcomes (4)

• • Percentage of patients that needed to stop the medication as a result of an adverse event

  8 weeks

• Percentage of patients who experienced a serious adverse event

  8 weeks

• Percentage of patients who had detectable levels of CBD in the blood

  8 weeks

• • Percentage of patients who had clinical and laboratory evidence of infection in the wounds

  8 weeks

Study Arms (2)

interventional arm, phase 2

EXPERIMENTAL

All participant of phase 2 will receive CBD cream for their chronic wound treatment. This is an open-label part of the study.

Drug: AVCN583601 (3% Cannabidiol cream)

Interventional arm, phase 3

EXPERIMENTAL

Each participants of the phase 3 will receive the active study medication (AVCN583601) during the entire study treatment period on the one of his body sides, and placebo cream - on the other body side simultaneously (left/right). So, each participant will be his own control. The research support pharmacy will randomize, which side of the body participant should apply CBD cream on, and provide two jars with the study medications, labeled accordingly ( Left /Right).

Drug: AVCN583601 (3% Cannabidiol cream)

Interventions

AVCN583601 (3% Cannabidiol cream) DRUG

Topical application twice daily for 4 weeks (phase 2) and for 8 weeks (phase 3).

Also known as: Cannabidiol cream

Interventional arm, phase 3; interventional arm, phase 2

Eligibility Criteria

• Age: 4 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis of RDEB (clinically and/or molecular diagnosis)-
• Wounds that have not been healing for over 4 weeks
• Patients 4-50 years of age
• Diagnosis of EB (clinically and/or molecular diagnosis)
• Evidence of either acute or chronic wounds on both extremities
• Patients enrolled in phase II are also eligible for participation in this phase, if they meet the current criteria and are interested in participation \* Signed consent/assent form

You may not qualify if:

• Previous known allergy or intolerance to CBD cream
• Topical and systemic use of cannabinoids in the past 2 weeks
• Topical use of antibiotics, corticosteroids for the past 2 weeks
• Other systemic medications that will interfere with the wound healing (corticosteroids, immunosuppressives, antibiotics) in the past 4 weeks
• Surgery of the selected area in the past 8 weeks
• Patients received medications metabolized via CYP3A4 enzyme (ketoconazole, itraconazole, ritonavir, clarithromycin, phenobarbital, rifampicin, carbamazepine, hexobarbital) for the past 2 weeks
• Pregnancy

Sponsors & Collaborators

• Elena Pope: lead
• Avicanna Inc: collaborator

Study Sites (1)

The Hospital for Sick Children

Toronto, Ontario, M5G1X8, Canada

Location

MeSH Terms

Conditions

Epidermolysis Bullosa; Pain; Pruritus

Condition Hierarchy (Ancestors)

Skin Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Vesiculobullous; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Skin Manifestations

Study Officials

• Elena Pope, MD

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Only phase 3 of the clinical trial is going to be double-blinded.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Dermatology section head

Model Details: Phase 2 of the study is open label . Phase 3 study participants will be his own control: they will be treated by the active medication ( AVCN583601) and placebo simultaneously during full study treatment period, applying thestudy cream from two different jars to two different body sides ( left/right).

Study Record Dates

• First Submitted: October 27, 2020
• First Posted: November 3, 2020
• Study Start: August 1, 2020
• Primary Completion: September 1, 2022
• Study Completion: December 30, 2022
• Last Updated: June 18, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)