Clinical efficacy and safety of R0002 cream in the initial and maintenance therapies of lamellar ichthyosis (LI)

ISRCTN	ISRCTN62315004
DOI	https://doi.org/10.1186/ISRCTN62315004
Clinical Trials Information System (CTIS)	2010-022284-35
Protocol serial number	R00002 CR 301 (ORF)
Sponsor	Orfagen (France)
Funder	Orfagen (France)

Submission date: 30/03/2011
Registration date: 17/06/2011
Last edited: 15/04/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Skin and Connective Tissue Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Ruzicka Thomas
Scientific

Department of Dermatology and Allergies
Ludwig-Maximilian-University Munich
Frauenlobstraße 9-11
Munich
80337
Germany

Study information

Primary study design	Interventional
Study design	Period I: randomised double-blind two-parallel group comparative Period II: open-labelled non comparative Period III: randomised double-blind vehicle-controlled
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Clinical efficacy and safety of R0002 cream in the initial and maintenance therapies of lamellar ichthyosis (LI): a randomised controlled trial
Study objectives	1. To demonstrate the long-term clinical efficacy and safety of R0002 cream in LI patients in real-life setting conditions 2. To assess the durability of remission (relapse / prevention) under maintenance treatment 3. To assess the relapse/rebound after the end of the maintenance treatment. 4. To evaluate benefit and life quality outcome of the patients 5. To measure the systemic absorption of the active drug in LI patients in the real life condition of product use at the end of initial therapy and maintenance therapy 6. To monitor laboratory values during normal conditions of product use 7. To evaluate the overall acceptability of the product by the patients On 04/03/2014 the following changes were made to the trial record: 1. The anticipated start date was changed from 01/04/2011 to 31/05/2011 2. The anticipated end date was changed from 31/08/2012 to 03/12/2013 On 10/03/2014 Morocco and Netherlands were removed from the countries of recruitment field.
Ethics approval(s)	Ethics Committee of Hospital Necker, France approved on 13/12/2010. All other centres will seek ethics approval before recruitment of the first participant.
Health condition(s) or problem(s) studied	Lamellar ichthyosis (LI)
Intervention	Wash-out period: (at least 7 days) observational, treatment free. Followed by: 1. Period I (84 days): R0002 cream every other day and its vehicle every other day (=> one arm of 40 patients) or urea cream 10% (for patients < 12 years old) or 5% (for children < 12 years old) every day (=> second arm of 40 patients) 2. Period II (84 days): R0002 cream every other day (=> all 80 patients) 3. Period III (up to 56 days): R0002 cream every other day (=> one arm of 40 patients) or its vehicle every other day (=> one arm of 40 patients) Added 10/03/2014: 4. Period IV: open-labelled non comparative 5. Children follow-up: open-labelled, among children between 9 and 17 years old; follow-up without treatment
Intervention type	Other
Primary outcome measure(s)	Response to test treatment at the end of initial therapy (D84): comparison between treatment groups of severity of the lesions (scaling and roughness), according to a severity scale for all periods, by an independent physician
Key secondary outcome measure(s)	1. Time-course severity of scaling, roughness and erythema on the treated areas, according to the scale used in the primary efficacy parameter for scaling and roughness and to a severity scale for erythema, during all periods, by an independent physician 2. Assessment of the relapse/rebound of the treated areas, according to the scale defined in the primary efficacy parameter, during Period II and Period III 3. Separate assessment of the overall clinical severity of the lesions on palms and soles during all periods, according to a severity scale, by an independent physician 4. Autoevaluation of the overall severity of the lesions by the patients, during all periods 5. Life quality assessment by the patients, using the generic Short-Form 12 questionnaire (SF-12) for patients from 16 years of age and the Dermatologic Life Quality Index (DLQI) for patients over 16 years of age (i.e. from 17 years of age), or the child DLQI (CDLQI) for patients between 9 years and 16 years old, at Baseline, end of Period I, and end of Period II 6. Global local tolerance made on end of Period I and end of Period II according to a scale 7. Overall acceptability by the patients (efficacy, local tolerance, ease of use) at end of Period I and end of Period II 8. Plasma monitoring of tazarotenic acid at baseline, at end of Period I, end of Period II and end of period III 9. Blood laboratory tests at Baseline, end of Period I), end of Period II, and end of period III 10. Measurement of bone metabolism, using plasmatic biochemical markers at Baseline, end of Period I, end of Period II, and end of period III 11. Physical examination at each visit 12. Adverse events - an independent Data Safety Management Board (DSMB) will be set up to review adverse events during the study and take any decision in the interest of the patient safety 13. Compliance Added 10/03/2014: In period IV: all efficacy and safety secondary outcome measures at each visit In children follow-up: safety outcome measures at each visit
Completion date	03/12/2013

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	9 Years
Sex	All
Target sample size at registration	80
Key inclusion criteria	1. Male or female patients of at least 9 years old 2. Patients with a documented diagnosis of LI based on clinical signs, histopathology and/or genotype and, when possible, pedigree analysis 3. Patients requiring topical treatment by keratolytics either as monotherapy or as alternate therapy to oral retinoids 4. Patients with a global score of at least 3 for each parameter scaling and roughness, according to the scale used for primary efficacy parameter 5. Patients or patients parents/guardians able to understand and follow the study procedures 6. Written informed consent (personally signed and dated) from the patients and/or parent(s)/ guardian(s) (according to local legislation) 7. Patients or patients parents/guardians affiliated to a healthcare security system (when applicable in the national regulation)
Key exclusion criteria	1. Patients under 9 years of age 2. Pregnant or lactating women 3. Women of childbearing potential with no reliable medical contraception (oral contraceptive, intra-uterine contraceptive device), and unwilling to use condoms up to 8 weeks after the last test product application 3.1. [For german centers only] Young girls (9-17 years old) who are already of child bearing potential but not already taking a medical contraception (oral contraceptive, intra uterine contraceptive device) beforehand to the clinical trial, and unwilling to use condoms up to 8 weeks after the last test product application 4. Women of childbearing potential with a positive systemic pregnancy test at baseline 5. Patients with congenital ichthyoses other than LI 6. Patients with an erythrodermic component of LI (EARLI) 7. Patients with LI of overall severity < 3 for scaling or roughness, according to the scale used for primary efficacy parameter 8. Patients with lesional superinfection 9. Patients with skin or other disease likely to interfere with the study conduct or the evaluation parameters 10. Patients with excessive pruritus, burning, skin redness or peeling, not fully recovered at baseline 11. Patients with inherent sensitivity to sunlight 12. Patients with a known contact allergy to one of the ingredients contained in the test products 13. Patients treated with topicals (e.g. vitamin A analogues, vitamin D analogues) within 14 days prior to baseline 14. Patients treated with tazarotene gel within 28 days prior to baseline 15. Patients treated with keratolytics (e.g. urea, hydroxy-acids) or moisturisers other than the standard moisturiser within 7 days prior to baseline 16. Patients treated with concomitant dermatologic medications and cosmetics that have a strong drying effect within 7 days prior to baseline 17. Patients treated with oral retinoids during the preceding 28 days, or with oral vitamin A supplementation (more than 3000 IU per day) during the preceding 7 days of baseline 18. Patients treated with drugs known to be photosensitisers (e.g. thiazides, tetracyclines, quinolones, phenothiazines, sulfonamides, hydrochlorates, chlorpromazine, psoralen, amiodarone, tar) within 14 days prior to baseline 19. Patients with a medical condition that potentially alters bone metabolism (e.g. osteoporosis, thyroid dysfuntion, cushing syndrome) or treated with a medication interfering with bone activity (e.g. corticosteroids, thyroid hormones, vitamin D analogues, cytotoxics, biphospbonates, calcitonins, tetracyclines, quinolones, thiazides, salicylates in long-term course, heparin, theophylline, barbiturates, colchicines) within the preceding 56 days prior to baseline 20. Patients treated with ultraviolet (UV) therapy or patients medically exposed to UV within 28 days prior to baseline 21. Patients having significant sun exposure due to their occupation 22. Patients who participated in a study within the 3 months prior to study entry 23. Patients or patients parents/guardians who are unable to understand and/or to follow the study procedures and patient instructions 24. Patients or patients parents/guardians who are unwilling to give personally signed and dated written informed consent
Date of first enrolment	31/05/2011
Date of final enrolment	03/12/2013

Locations

Countries of recruitment

Algeria
Austria
France
Germany
Italy
Sweden
Tunisia

Study participating centre

Department of Dermatology and Allergies

Munich
80337
Germany

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Basic results				No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

15/04/2019: The followong changes have been made:
1. A EudraCT link has been added to the basic results (scientific).
2. The EudraCT number has been added.