To compare the efficacy of Diacerein 1% Ointment to Control Ointment when applied once-daily in subjects with EBS.To compare the effects of Diacerein 1% Ointment to Control Ointment in subjects with EBS in:* Safety and tolerability* Pruritus * Pain…
ID
Source
Brief title
Condition
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy endpoint is based on the ITT population, and is the
proportion of subjects who achieve *40% reduction in BSA of EBS lesions from
Visit 2 (Week 0) to Visit 8 (Week 16).
Secondary outcome
* The proportion of subjects achieving success on the IGA, where success is
defined as at least a 2-point reduction, from Visit 2 (Week 0) to Visit 8 (Week
16).
* The proportion of subjects who achieve * 40% reduction in BSA of EBS lesions
from Visit 2 (Week 0) to Visit 6 (Week 8).
* The proportion of subjects achieving success on the IGA, where success is
defined as at least a 2-point reduction, from Visit 2 (Week 0) to Visit 6 (Week
8).
* The proportion of subjects with a reduction in overall pain intensity from
Visit 2 (Week 0) to Visit 6 (Week 8).
* The proportion of subjects with a reduction in overall pruritus intensity
from Visit 2 (Week 0) to Visit 6 (Week 8).
If the comparison for the primary endpoint is significant (two-sided p-value <
0.05), then testing will continue for the key secondary endpoints. The key
secondary endpoints will be analyzed in a similar manner as the primary
endpoint. To control the type I error rate for testing multiple key secondary
endpoints, a fixed-sequence approach for the key secondary endpoints will be
used.
Background summary
Epidermolysis bullosa simplex (EBS) is a rare, genetic skin disease
characterized by
fragility of the skin and mucous membranes resulting in painful blisters and
erosions
after minor trauma, and is associated with significant morbidity and mortality.
EBS is both a pediatric and an adult disease that tends to affect younger
patients most severely.
Diacerein 1% Ointment is a topical ointment containing diacerein
(4,5-bis[acetyloxy]-9,10-
dihydro-9,10-dioxo-2-anthracene carboxylic acid, also known as diacetyl-rhein),
a highly
purified anthraquinone derivative, and is being developed for the treatment of
EBS.
Diacerein in the topical formulation is hydrolyzed to rhein in the epidermis
and dermis following
administration. Diacerein and rhein have been shown to inhibit the in vitro and
in vivo
production and activity of interleukin-1* (IL-1*) and other pro-inflammatory
cytokines.
IL-1* is a pro-inflammatory cytokine that has been linked to a number of
inflammatory
and autoimmune diseases, including rheumatoid arthritis (RA), OA, hemophilic
arthropathy, gouty arthritis, type 2 diabetes mellitus (T2DM), diabetic
nephropathy
(DN), and EBS. In vitro and in vivo animal studies have shown that both
diacerein and its
active metabolite rhein inhibit the production and activity of pro-inflammatory
and procatabolic
cytokines such as IL-1 and IL-6, and the expression of inducible nitric oxide
synthase
(iNOS) and tumor necrosis factor-* (TNF-*).
Study objective
To compare the efficacy of Diacerein 1% Ointment to Control Ointment when
applied
once-daily in subjects with EBS.
To compare the effects of Diacerein 1% Ointment to Control Ointment in subjects
with
EBS in:
* Safety and tolerability
* Pruritus
* Pain
* Mobility
* Reduction in BSA of EBS lesions
* Reduction in Lesion Surface Area of the reference lesion.
Study design
This is an international, multicenter, randomized, double-blind,
vehicle-controlled,
parallel group study to evaluate the safety and efficacy of topical Diacerein 1%
Ointment for the treatment of subjects with EBS. Subject randomization will
bestratified by genotype (KRT5 and/or KRT14 or other genotype) and age group
(<8 and *8 years old).
Intervention
Subjects who are enrolled with either apply diacerein 1% ointment or placebo on
EBS lesions
Study burden and risks
Risks: possible side effects of the study medication Burden: blood draws,
filling in questionnaires, instructions on study drug
Century Drive 6
Parsippany NJ 07054
US
Century Drive 6
Parsippany NJ 07054
US
Listed location countries
Age
Inclusion criteria
1. Subject is male or female at least 4 years of age at Visit 1
2. Subject has a documented genetic mutation consistent with EBS. A blood or saliva sample will be collected for genetic confirmation if no documented gene mutation data is available. Gene mutations acceptable for inclusion are as follows: KRT5, KRT14, PLEC1, TGM5, PKP1, DSP, FERMT1, EXPH5, DST, KLHL24.
3. Subject has an Assessment Area of EBS lesions to be treated, that is *2% body surface area (BSA) and the EBS lesions are in one or both of the following body areas:
- Localized: plantar and/or palmar areas (plantar areas where >25% of the area has hyperkeratosis that has been present for greater than 12 weeks cannot be included as part of the Assessment Area)
- Generalized: arms, legs, torso, hands and feet (scalp, groin and areas where, in the investigator*s opinion, the study medication might become occluded cannot be included as part of the Assessment Area
4. Subject*s EBS lesions in the Assessment Area have an Investigator*s Global Assessment (IGA) score of *3
5. Subject/caregiver agrees to not use any topical therapies other than the study medication that, might influence the status of the EBS lesions during the duration of the study (e.g., medicated cleansers, CBD oil, MediHoney, Silvadine cream 1%); the Investigator should consult the Medical Monitor regarding therapies not specified in the protocol
6. Subject/caregiver agrees to follow topical product application instructions during the treatment period
7. If the subject is a woman of childbearing potential, she has a negative urine pregnancy test and agrees to use an approved effective method of birth control, as defined by this protocol (see Section 10.6), for the duration of the study.
8. Subject is non-pregnant, non-lactating and is not planning for pregnancy during the study period
9. Subject is in good general health and free of any known disease state or physical condition which, in the investigator*s opinion, might impair evaluation of the EBS lesions or which exposes the subject to an unacceptable risk by study participation
10. Subject is willing and able to follow all study instructions and to attend all study visits
11. Subject/caregiver is able to comprehend and willing to sign an Informed Consent and/or Assent Form.
Exclusion criteria
1. Subject has EBS lesions to be treated that are infected (i.e., EBS lesions that require therapy to treat an infection)
2. Subject has used any diacerein containing product within 6 months prior to Visit 1
3. Subject has used systemic immunotherapy or cytotoxic chemotherapy within 60 days prior to Visit 1
4. Subject has used systemic steroidal therapy or has used topical steroidal therapy on the EBS lesions to be treated within 30 days prior to Visit 2 (Note: inhaled and ophthalmic products containing steroids are allowed)
5. Subject has evidence of a systemic infection or has used systemic antibiotics within 7 days prior to Visit 1
6. Subject is currently using systemic analgesics and/or anti-histamine therapy for treatment of EBS lesions, unless on a stable regimen (i.e., the same dosing regimen) for at least 4 weeks prior to Visit 1. Note: As needed (PRN) use of acetaminophen/paracetamol or NSAIDs within the 4 weeks prior to Visit 1 are permitted provided the treatment was unrelated to EBS symptom relief.
7. Subject has used any systemic diuretics or cardiac glycosides or any systemic product that, in the opinion of the investigator, might put the subject at undue risk by study participation or interferes with the study medication application or the study assessments within 30 days prior to Visit 1
8. Subject has used any topical product containing allantoin on the EBS lesions to be treated within 30 days prior to Visit 1
9. Subject has a current malignancy, or a history of treatment for a malignancy within 2 years prior to Visit 1 (Note: does not include non-melanoma skin cancer)
10. Subject currently has diabetes mellitus (HbA1c *6.5%). Note: controlled diabetes (HbA1c < 6.5%) is also considered exclusionary
11. Subject has a history of cardiac, hepatic (ALT and or AST >2x ULN, Total bilirubin >1.5x ULN at Visit 1), or renal disease (eGFR<30 ml/min/1.73 m2) that, in the opinion of the investigator, might put the subject at undue risk by study participation or interferes with the study medication application of the study assessments
12. Subject has a non-EBS skin disease (e.g., psoriasis, atopic dermatitis, eczema, sun damage, etc.), or condition (e.g., sunburn) that, in the opinion of the investigator, might put the subject at undue risk by study participation or interferes with the study medication application or the study assessments
13. Subject has a history of sensitivity to any of the ingredients in the study medications.
14. Subject has participated in any investigational drug/device trial in which administration of an investigational study medication occurred within 30 days prior to Visit 1.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-004427-24-NL |
| CCMO | NL61598.042.17 |