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

• Register: ISRCTN
• Last refreshed on: 5 May 2019
• Main ID: ISRCTN62315004
• Date of registration: 17/06/2011
• Prospective Registration: No
• Primary sponsor: Orfagen (France)
• Public title: Clinical efficacy and safety of R0002 cream in the initial and maintenance therapies of lamellar ichthyosis (LI)
• Scientific title: Clinical efficacy and safety of R0002 cream in the initial and maintenance therapies of lamellar ichthyosis (LI): a randomised controlled trial
• Date of first enrolment: 31/05/2011
• Target sample size: 80
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN62315004
• Study type: 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 (Treatment)
• Phase: Not Applicable

Countries of recruitment

Algeria, Austria, France, Germany, Italy, Sweden, Tunisia

Contacts

• Name: Ruzicka Thomas

Key inclusion & exclusion criteria

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 patient?s 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)

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

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Lamellar ichthyosis (LI)
Skin and Connective Tissue Diseases
Lamellar ichthyosis (LI)

Intervention(s)

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

Primary Outcome(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

Secondary Outcome(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

Secondary ID(s)

2010-022284-35

R00002 CR 301 (ORF)

Source(s) of Monetary Support

Orfagen (France)

Ethics review

Status:
Approval date:
Contact:

Ethics Committee of Hospital Necker, France approved on 13/12/2010. All other centres will seek ethics approval before recruitment of the first participant.

Results

• Results available: Yes
• Date Completed: 03/12/2013