Lamellar IchthyosisPhase 2NCT03738800
A Safety, Efficacy and Systemic Exposure Study of CD5789 Cream in Adults and Adolescents With Lamellar Ichthyosis
A Phase 2 study testing CD5789 Cream 200 µg/g and CD5789 Cream 100 µg/g in people with Lamellar Ichthyosis, run by Mayne Pharma International Pty Ltd at 36 sites in 9 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Lamellar Ichthyosis
- What is being tested?
- CD5789 Cream 200 µg/g and CD5789 Cream 100 µg/g
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 65 participants
- Where
- 36 sitesin 9 countries
- Study dates
- 1 May 2019to 3 Sep 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Subject has any variant of ichthyosis other than LI or another disorder of keratinization, including syndromic ichthyoses.
- Subject has current moderate or severe stinging/burning at Screening.
- 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.
- 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.
- Subject was previously treated with trifarotene/CD5789 in an acne or ichthyosis study.
- 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.
Show all 25Show fewer
- 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
- 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.
- Subject with positive serology for hepatitis B surface antigen, hepatitis C, or are known to be HIV positive or to have AIDS at Screening.
- Subject with any of the following laboratory values at Screening:
- Aspartate aminotransferase or alanine aminotransferase >1.5 × upper limit of normal defined by the laboratory
- Total bilirubin >1.25 × ULN at Screening. Subjects with known Gilbert's syndrome may be included with total bilirubin >1.25 × ULN
- Hemoglobin <12.5 g/dL for men and <11.5 g/dL for women
- Platelets <150 × 109/L or >400 × 109/L.
- 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.
- 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.
- 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.
- Subject has a known allergy or sensitivity to any of the components of the investigational products.
- 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.).
- Subject is inherently sensitive to sunlight.
- Subject is unable or unwilling to stop use of topical or systemic retinoids.
- Subject is presumed to be abusing drug or alcohol at Screening or Baseline Visits based on medical history or current clinical symptoms.
- Subject is participating in another interventional clinical trial.
- Subject is institutionalized.
- Subject is in any way related to the sponsor, investigator, or site personnel.
Trial locations and contacts
36 sites in 9 countries.
36 sites in 9 countries
United States10 sites
Children's Hospital Colorado
Aurora, Colorado, 80045
Massachusetts General Hospital
Boston, Massachusetts, 02114
Medical University of South Carolina
Charleston, South Carolina, 29425
Dawes Fretzin Clinical Research Group, LLC
Indianapolis, Indiana, 46250
Yale University
New Haven, Connecticut, 06519
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
DermAssociates, PC
Rockville, Maryland, 20850
Texas Dermatology and Laser Specialists
San Antonio, Texas, 78218
TCR Medical Corporation
San Diego, California, 92123
NorthShore University HealthSystem
Skokie, Illinois, 60077
Ukraine6 sites
Medical Center of Private Enterprise "Dzerkalo"
Dnipro, 49000
Dnipropetrovsk State Hospital of Dermatovenerology
Dnipro, 49074
Medical Center "Family Medicine Clinic"
Dnipro, 49600
Ternopil Regional Clinical Dermatovenereological Dispensary
Ternopil, 46006
TDC PE "Asclepius"
Uzhhorod, 88000
Community Institution "Zaporizhzhya Regional Dermatovenereology Clinical Hospital"
Zaporizhzhya, 69063
Germany5 sites
Charite - Universitaetsmedizin Berlin
Berlin
Universitätsklinkum Frankfurt
Frankfurt
Kath. Kinderkrankenhaus Wilhelmstift
Hamburg
Ludwig-Maximilians University
Munich
Universitatsmedizin Rostock
Rostock
Spain5 sites
Hospital Clinic de Barcelona
Barcelona
Hospital Nino Jesus
Madrid, 28009
Clinica Universidad de Navarra (Madrid)
Madrid
Hospital Niño Jesús
Madrid
Clinica Universidad de Navarra
Pamplona
Australia4 sites
Eastern Health Monash University
Box Hill
Veracity Clinical Research
Brisbane
Royal Children's Hospital
Parkville
Premier Specialists Ptd Ltd
Sydney
France3 sites
Dermatologie pédiatrique
Paris
CHU Charles Nicolle
Rouen
CHU de Toulouse- Hospital Larrey
Toulouse
United Kingdom1 site
Royal London Hospital Barts Health Nhs Trust
London
About this study
Official title: A Phase 2 Randomized, Multicenter, Double-blind, Vehicle Controlled, 90-Day, Safety, Efficacy & Systemic Exposure Study of Trifarotene (CD5789) Cream HE1 in Adults and Adolescents With Autosomal Recessive Ichthyosis With Lamellar Scale
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.
Read the 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
- Being tested
- CD5789 Cream 200 µg/g, CD5789 Cream 100 µg/g, CD5789 Cream Vehicle
- Medical subject headings
- Ichthyosis, Lamellar
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD5789 Cream 200 µg/gDrug
A fixed dose (determined at Visit 1) of 200 µg/g applied topically twice weekly to up to 90% BSA
CD5789 Cream 100 µg/gDrug
A fixed dose (determined at Visit 1) of 100 µg/g applied topically twice weekly to up to 90% BSA
CD5789 Cream VehicleDrug
A fixed dose (determined at Visit 1) applied topically twice weekly, up to 36 g per dose up to 90% BSA
| Study group | Role | What they receive |
|---|---|---|
| CD5789 Cream 200 µg/g | Experimental | CD5789 200 µg/g, topical, 50g Receives: Drug: CD5789 Cream 200 µg/g |
| CD5789 Cream 100 µg/g | Experimental | CD5789 100 µg/g, topical, 50g Receives: Drug: CD5789 Cream 100 µg/g |
| CD5789 Cream Vehicle | Placebo comparator | CD5789 Cream Vehicle, topical, 50g Receives: Drug: CD5789 Cream Vehicle |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Percentage of Subjects in Each Treatment Group Who Experienced Successful Resolution of LI.
The percentage of subjects in each treatment group who experienced successful resolution of LI where "success" is defined as clear/almost clear on treated areas and at least a 2-grade change from Baseline at Day 90/end-of-treatment (EOT) in the Double-blind Period on the 5-point IGA full body scale.
Measured: 90 Days
Secondary outcomes (6)
Total 16-point Visual Index for Ichthyosis Severity (VIIS)
5-point Visual Index for Ichthyosis Severity (VIIS) for scaling (overall 16 points) for scaling, i.e. 0-4 points for 4 body areas: chest/abdomen, back, arms and legs) where minimum is 0 and maximum is 16 (e.g. 4 points for each of the four body parts).
0 (Clear) No scaling
- (Almost Clear) Very fine, non-coalescent scales
- (Mild) Small and thin, non-coalescent scales
- (Moderate) Large and rather thick scales starting to coalesce
- (Severe) Very large, adherent, coalescent and very thick scales
Measured: 90 Days
The Difference in Mean Scores Using Individual Score for Roughness
The amount of roughness of the skin will be measured on a 5-point scale. 0 (Clear) Smooth skin
- (Almost Clear) Hardly palpably roughness
- (Mild) Mild roughness (fine sand paper-like)
- (Moderate) Moderate, coarse roughness (coarse sand paper-like)
- (Severe) Very coarse skin (broken cornflakes-like)
Measured: 90 Days
The Difference in Mean Scores Using Palm Sole Assessment
Thickening of the skin on the palms and soles will be measured on a 5-point scale:
0 (Clear) No thickening, no roughness, no fissure
- (Almost Clear) Only slight thickening, minimal to no roughness, no fissures
- (Mild) Some thickening, mild roughness on palpation, few fissures may be present
- (Moderate) Substantial and diffuse thickening, coarse roughness on palpation may be present, fissures may be present
- (Severe) Very thickened and rough skin, numerous fissures
Measured: 90 Days
The Difference in Proportion of Subjects With Presence of Fissures on Palms Between the Active and Vehicle Groups
Fissuring will be assessed by recording the presence or absence of fissures, the number of fissures present, and the pain associated with each fissure. The subject will assess pain associated with fissures as ranging from 0-3 (none, mild, moderate, severe) at day 90 between the active trifarotene cream HE1 and vehicle groups
Measured: 90 Days
Quality of Life Measurement Per Dermatology Life Quality Index (DLQI)
The DLQI, or the Dermatology Quality of Life Index, is a dermatology-specific Quality of Life instrument. It is a simple 10-question validated questionnaire with 6 domains (symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment); higher scores indicate poorer quality of life. Responses collected are on a scale of 0-3 depending on the question relevance to the subject.
Response (Score) Very much (scored 3) A lot (scored 2) A little (scored 1) Not at all (scored 0) Not relevant (scored 0) A minimum score of 0 and maximum score of 30 is obtained by summing the score of each question. The higher the score, the more quality of life is impaired.
0-1 = no effect at all on patient's life 2-5 = small effect on patient's life 6-10 = moderate effect on patient's life 11-20 = very large effect on patient's life 21-30 = extremely large effect on patient's life
Measured: 90 Days
The Difference in Proportion of Subjects With Presence of Fissures on Soles Between the Active and Vehicle Groups
Fissuring will be assessed by recording the presence or absence of fissures, the number of fissures present, and the pain associated with each fissure. The subject will assess pain associated with fissures as ranging from 0-3 (none, mild, moderate, severe) at day 90 between the active trifarotene cream HE1 and vehicle groups
Measured: 90 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2018
- Study start1 May 2019
- Primary completion3 Sep 2021
- Study completion3 Sep 2021
Why it stopped: Futility
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Lamellar IchthyosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayne Pharma International Pty Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Keith A. Choate, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03738800
- Sponsor's protocol ID
- 18-ICH-001
- Status last verified
- Feb 2023
- First submitted
- 24 Oct 2018
- Last updated
- 14 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Randomized, Multicenter, Double-blind, Vehicle Controlled, 90-Day, Safety, Efficacy & Systemic Exposure Study of Trifarotene (CD5789) Cream HE1 in Adults and Adolescents With Autosomal Recessive Ichthyosis With Lamellar Scale
- ClinicalTrials.gov ID
- NCT03738800
- Acronym / sponsor ID
- 18-ICH-001
- Conditions
- Lamellar Ichthyosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Futility
- Enrolment
- 65 participants (actual)
- Lead sponsor
- Mayne Pharma International Pty LtdIndustry (pharma, biotech, devices)
- Study start
- 1 May 2019 (actual)
- Primary completion
- 3 Sep 2021 (actual)
- Study completion
- 3 Sep 2021 (actual)
- First posted
- 13 Nov 2018 (actual)
- Results
- Posted 14 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| CD5789 Cream 200 µg/g | Experimental | Drug: CD5789 Cream 200 µg/gCD5789 200 µg/g, topical, 50g |
| CD5789 Cream 100 µg/g | Experimental | Drug: CD5789 Cream 100 µg/gCD5789 100 µg/g, topical, 50g |
| CD5789 Cream Vehicle | Placebo comparator | Drug: CD5789 Cream VehicleCD5789 Cream Vehicle, topical, 50g |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (25 listed)
- Subject has any variant of ichthyosis other than LI or another disorder of keratinization, including syndromic ichthyoses.
- Subject has current moderate or severe stinging/burning at Screening.
- 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.
- 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.
- Subject was previously treated with trifarotene/CD5789 in an acne or ichthyosis study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CD5789 Cream 200 µg/gA fixed dose (determined at Visit 1) of 200 µg/g applied topically twice weekly to up to 90% BSA | Drug | CD5789 Cream 200 µg/g |
| CD5789 Cream 100 µg/gA fixed dose (determined at Visit 1) of 100 µg/g applied topically twice weekly to up to 90% BSA | Drug | CD5789 Cream 100 µg/g |
| CD5789 Cream VehicleA fixed dose (determined at Visit 1) applied topically twice weekly, up to 36 g per dose up to 90% BSA | Drug | CD5789 Cream Vehicle |
Primary outcome
The Percentage of Subjects in Each Treatment Group Who Experienced Successful Resolution of LI.
Time frame: 90 Days
The percentage of subjects in each treatment group who experienced successful resolution of LI where "success" is defined as clear/almost clear on treated areas and at least a 2-grade change from Baseline at Day 90/end-of-treatment (EOT) in the Double-blind Period on the 5-point IGA full body scale.
6 secondary outcomes
Total 16-point Visual Index for Ichthyosis Severity (VIIS)
Time frame: 90 Days
The Difference in Mean Scores Using Individual Score for Roughness
Time frame: 90 Days
The Difference in Mean Scores Using Palm Sole Assessment
Time frame: 90 Days
The Difference in Proportion of Subjects With Presence of Fissures on Palms Between the Active and Vehicle Groups
Time frame: 90 Days
Quality of Life Measurement Per Dermatology Life Quality Index (DLQI)
Time frame: 90 Days
The Difference in Proportion of Subjects With Presence of Fissures on Soles Between the Active and Vehicle Groups
Time frame: 90 Days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Lamellar Ichthyosis
Not yet recruitingObservational study
Lymphocyte Phenotype of Autosomal Recessive Congenital Ichthyoses Mutated NIPAL4 (Nipal4-nEDD)
Sezary Syndrome, Ichthyosis, Lamellar
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Keith A. Choate, MD principal investigator
Yale University
36 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CD5789 Cream 200 µg/g and CD5789 Cream 100 µg/g in people with Lamellar Ichthyosis, run by Mayne Pharma International Pty Ltd at 36 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 36 sites in United States, Ukraine, Germany, Spain, Australia and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Percentage of Subjects in Each Treatment Group Who Experienced Successful Resolution of LI. (time frame: 90 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2023.