A Safety, Efficacy and Systemic Exposure Study of CD5789 Cream in Adults and Adolescents With Lamellar Ichthyosis

NCT ID: NCT03738800

Last Updated: 2023-08-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-01
• Study Completion Date: 2021-09-03

Brief Summary

This is a phase 2 randomized, multi-center, double-blind, vehicle controlled, 90 day, safety, efficacy, and systemic exposure study followed by a 90 day open-label extension of trifarotene cream in adults and adolescents with autosomal recessive ichthyosis with lamellar scale.

Detailed Description

This is a 2-cohort, multicenter study in subjects with moderate to severe LI. Adults (Cohort A) and adults and adolescents (Cohort B) will be randomized in a double-blind fashion to 1 of 2 doses of active or vehicle and treated twice weekly for 90 days. Subjects who complete the randomized, double-blind portion of the study will be eligible to enter a 90 day, open-label extension study.

Approximately 15 adults (≥18 years old) will be randomized into the first cohort of subjects (Cohort A) in a 1:1:1 ratio and treated twice weekly for up to 90 days. If no safety issues are identified, both adults and adolescents (ages 12-17 years, inclusive) will be allowed to enroll in Cohort B. Subjects in Cohort B will be randomized 1:1:1 and treated twice weekly for up to 90 days in the same manner as subjects in Cohort A.

All subjects who complete 90 days of double-blind study treatment will be eligible to enroll in a 90 open-label extension. Subjects in the open-label extension will receive active twice weekly for up to 90 days.

Conditions

Lamellar Ichthyosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

CD5789 Cream 200 µg/g

CD5789 200 µg/g, topical, 50g

Group Type: EXPERIMENTAL

CD5789 Cream 200 µg/g

Intervention Type: DRUG

A fixed dose (determined at Visit 1) of 200 µg/g applied topically twice weekly to up to 90% BSA

CD5789 Cream 100 µg/g

CD5789 100 µg/g, topical, 50g

Group Type: EXPERIMENTAL

CD5789 Cream 100 µg/g

Intervention Type: DRUG

A fixed dose (determined at Visit 1) of 100 µg/g applied topically twice weekly to up to 90% BSA

CD5789 Cream Vehicle

CD5789 Cream Vehicle, topical, 50g

Group Type: PLACEBO_COMPARATOR

CD5789 Cream Vehicle

Intervention Type: DRUG

A fixed dose (determined at Visit 1) applied topically twice weekly, up to 36 g per dose up to 90% BSA

Interventions

CD5789 Cream 200 µg/g

A fixed dose (determined at Visit 1) of 200 µg/g applied topically twice weekly to up to 90% BSA

Intervention Type: DRUG

CD5789 Cream 100 µg/g

A fixed dose (determined at Visit 1) of 100 µg/g applied topically twice weekly to up to 90% BSA

Intervention Type: DRUG

CD5789 Cream Vehicle

A fixed dose (determined at Visit 1) applied topically twice weekly, up to 36 g per dose up to 90% BSA

Intervention Type: DRUG

Eligibility Criteria

Exclusion Criteria

1. Subject has any variant of ichthyosis other than LI or another disorder of keratinization, including syndromic ichthyoses.

2. Subject has current moderate or severe stinging/burning at Screening.

3. Subject has an ongoing cutaneous infection or any other significant concomitant skin disease (other than the LI) which, in the investigator's opinion, may interfere with the study assessments.

4. Subject with fasting triglycerides >200 mg/dL or >2.25 mmol/L and/or total cholesterol >250 mg/dL or >6.5 mmol/L. Subjects whose triglycerides and/or total cholesterol are within normal limits with a stable dose of lipid-lowering agents for at least 6 months may be included.

5. Subject was previously treated with trifarotene/CD5789 in an acne or ichthyosis study.

6. Subject has any other significant concomitant disease, or poorly controlled medical condition other than LI that in the investigator's opinion may put him or her at risk if he or she takes part in the study, and/or that may interfere with the study assessments.

7. Subject has a medical condition that potentially alters bone metabolism (e.g., osteoporosis, thyroid dysfunction, Cushing syndrome, Crohn's disease, or ulcerative colitis). Subjects with hypothyroidism who are on a stable dose of thyroid hormone replacement therapy and whose thyroid-stimulating hormone (TSH) is normal may be included

8. Subject is being treated for major depression disorder and/or has a history of major depression or suicide attempt requiring hospitalization, medications, and close psychiatric surveillance to prevent suicide attempts.

9. Subject with positive serology for hepatitis B surface antigen, hepatitis C, or are known to be HIV positive or to have AIDS at Screening.

10. Subject with any of the following laboratory values at Screening:

1. Aspartate aminotransferase or alanine aminotransferase >1.5 × upper limit of normal defined by the laboratory

2. Total bilirubin >1.25 × ULN at Screening. Subjects with known Gilbert's syndrome may be included with total bilirubin >1.25 × ULN

3. Hemoglobin <12.5 g/dL for men and <11.5 g/dL for women

4. Platelets <150 × 109/L or >400 × 109/L.

11. Subject has any clinically other significant abnormal laboratory value (hematology, chemistry, or urinalysis) at Screening that, in the investigator's opinion, may put the subject at risk if he or she takes part in the study, and/or that may interfere with the study assessments.

12. Subject has had recent systemic malignancy (e.g., within 5 years) with exception of nonmelanoma skin cancer or cervical intraepithelial neoplasia of Grade 1 who are >6 months post-treatment.

13. Subject has a history of long QT syndrome or has clinically significant electrocardiogram (ECG) abnormalities, including clinically significant conduction disorders or significant arrhythmias, or QTcF interval >450 ms.

14. Subject has a known allergy or sensitivity to any of the components of the investigational products.

15. Subject has been exposed to excessive UV radiations on the treated zones within 1 month before Baseline visit or is planning intensive UV exposure during the study (e.g., occupational exposure to the sun, sunbathing, phototherapy, etc.).

16. Subject is inherently sensitive to sunlight.

17. Subject is unable or unwilling to stop use of topical or systemic retinoids.

18. Subject is presumed to be abusing drug or alcohol at Screening or Baseline Visits based on medical history or current clinical symptoms.

19. Subject is participating in another interventional clinical trial.

20. Subject is institutionalized.

21. Subject is in any way related to the sponsor, investigator, or site personnel.

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mayne Pharma International Pty Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Keith A. Choate, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

TCR Medical Corporation

San Diego, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

Yale University

New Haven, Connecticut, United States

NorthShore University HealthSystem

Skokie, Illinois, United States

Dawes Fretzin Clinical Research Group, LLC

Indianapolis, Indiana, United States

DermAssociates, PC

Rockville, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Texas Dermatology and Laser Specialists

San Antonio, Texas, United States

Eastern Health Monash University

Box Hill, , Australia

Veracity Clinical Research

Brisbane, , Australia

Royal Children's Hospital

Parkville, , Australia

Premier Specialists Ptd Ltd

Sydney, , Australia

The Hospital for Sick Children

Toronto, , Canada

Dermatologie pédiatrique

Paris, , France

CHU Charles Nicolle

Rouen, , France

CHU de Toulouse- Hospital Larrey

Toulouse, , France

Charite - Universitaetsmedizin Berlin

Berlin, , Germany

Universitätsklinkum Frankfurt

Frankfurt, , Germany

Kath. Kinderkrankenhaus Wilhelmstift

Hamburg, , Germany

Ludwig-Maximilians University

Munich, , Germany

Universitatsmedizin Rostock

Rostock, , Germany

Tel Aviv Sourasky Mc

Tel Aviv, , Israel

Hospital Clinic de Barcelona

Barcelona, , Spain

Hospital Nino Jesus

Madrid, , Spain

Clinica Universidad de Navarra (Madrid)

Madrid, , Spain

Hospital Niño Jesús

Madrid, , Spain

Clinica Universidad de Navarra

Pamplona, , Spain

Medical Center of Private Enterprise "Dzerkalo"

Dnipro, , Ukraine

Dnipropetrovsk State Hospital of Dermatovenerology

Dnipro, , Ukraine

Medical Center "Family Medicine Clinic"

Dnipro, , Ukraine

Ternopil Regional Clinical Dermatovenereological Dispensary

Ternopil, , Ukraine

TDC PE "Asclepius"

Uzhhorod, , Ukraine

Community Institution "Zaporizhzhya Regional Dermatovenereology Clinical Hospital"

Zaporizhzhya, , Ukraine

Royal London Hospital Barts Health Nhs Trust

London, , United Kingdom

Countries

United States; Australia; Canada; France; Germany; Israel; Spain; Ukraine; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

18-ICH-001

Identifier Type: -

Identifier Source: org_study_id