To compare the efficacy and safety of methotrexate versus azathioprine treatment in adult patients with chronic severe AD.
ID
Source
Brief title
Condition
- Allergic conditions
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy variables are difference in mean change of the SCORAD and
IGA between groups at week 12.
Also the comparison in the proportion of subjects with a SCORAD reduction of
50% or more and the proportion of subjects with a IGA score of < 3 (clear /
almost clear / mild) at week 12 between methotrexaate an azathioprine (Arm 1
and Arm 2).
Secondary outcome
Secondary efficacy parameters assessed at different time points during the
study are:
• Frequency and severity of Adverse Events
• Frequency of relapses (>SCORAD75 after response (SCORAD50) was met before)
• Absolute and relative change from Baseline up to weeks 12 on the Eczema area
and severity index (EASI), Investigator*s global assessment (IGA), Patient*s
global assessment (PGA), Skindex-17, Patient oriented eczema measurement
(POEM), Pruritus visual analogue scale (VAS), Sleeplessness visual analogue
scale (VAS).
Background summary
Atopic dermatitis is a chronic inflammatory skin disorder secondary to the
activation of allergen specific T-cells in the skin. Most patients with AD can
be treated effectively with emollients and topical anti-inflammatory agents
such as topical steroids and topical calcineurin inhibitors. A subgroup of the
AD patients, the more severe cases, require more than topical treatment to
control their skin disease.
Cyclosporin (AZA) is considered gold standard for systemic treatment of severe
AD and is highly effective. Many patients, however, are contra-indicated for
AZA or have to discontinue treatment due to ineffectiveness or side effects
such as hypertension and nephrotoxicity. It can be concluded that there is a
very limited therapeutic armamentarium for the treatment of severe AD currently.
Recent studies showed potential new systematic treatment options for severe AD.
Two of which will be investigated in this study.
Methotrexate (MTX) targets several key T-cell activities essential for
immunologic responses and inflammation. Recent studies have shown that MTX
selectively depletes activated T cells by an apoptosis-dependant mechanism
without effect on naïve and memory T-cells. Reported clinical improvement of AD
due to MTX treatment in pilot studies suggests a role for MTX in the management
of this T-helper 2 mediated skin disease. This study is needed to determine if
MTX has a genuine role in the therapy of AD.
Azathioprine (AZA) is a purine synthesis inhibitor, inhibiting the
proliferation of cells, especially leukocytes. Two randomized controlled trials
(RCTs) have been conducted comparing AZA with placebo. Both showed promising
results.
Study objective
To compare the efficacy and safety of methotrexate versus azathioprine
treatment in adult patients with chronic severe AD.
Study design
A 24 week multinational multi-center study consisting of a 12-week single blind
study to evaluate the efficacy and safety of methotrexate versus azathioprine
treatment in adult patients with chronic severe AD and a 12-week follow up
period.
Intervention
During 12 weeks patients will be randomized to weekly oral methotrexaat
treatment (Arm 1) or daily oral azathioprine (Arm 2).
Study burden and risks
Patients will visit the clinic one to four-weekly, in total 7 visits including
screening-visit. Visits include evaluation of the severity of AD (SCORAD, IGA,
PGA, EASI, POEM, SKINDEX-17 and VAS), evaluation of the use of concomitant
medications, collection of safety and efficacy data and physical examinations
including vital signs. Routine haematology and urine-analysis will be performed
at screening, baseline, week 2, 4, 8 and 12. Patients will be provided with
diaries detailing intake of MTX or AZA, concomitant medications and AD
symptoms. Additional visits may be required between the scheduled visits to
assess any AD exacerbations reported or if adverse events require close
monitoring.
Participants will be treated with either MTX or AZA. MTX an AZA are medicines
in which a lot of knowledge is collected in other treatment indications over
the years.
Meibergdreef 9
1105 AZ Amsterdam
NL
Meibergdreef 9
1105 AZ Amsterdam
NL
Listed location countries
Age
Inclusion criteria
1. Subject is 18 years of age or older at inclusion (Day 0); both genders.
2. Subject has a diagnosis of AD based on millennium criteria (with or without IgE)
and UK-criteria.
3. Subject has a score of 8-9 on the Rajka and Langeland Criteria which corresponds with a severity of *severe*.
4. Subject is unresponsive, contra-indicated or intolerant to CsA treatment.
5. Female subject is either not of childbearing potential, defined as postmenopausal or surgically sterile or is of childbearing potential and practicing one of the following methods of birth control throughout the study until 3 months after receiving the last study agent:
- Intrauterine device (IUD)
- Contraceptives (oral, parenteral, patch) for three months prior to study drug administration.
- A vasectomized partner
6. Female subjects of childbearing potential must have a negative serum pregnancy test at the Screening visit and a negative urine pregnancy test at Baseline.
7. Sexually active male subjects are able to participate in the study if they use effective contraception during the study and 3 months after discontinuation of the study drug.
8. Have screening laboratory test results within reference values or results without clinical relevance as assessed by the local investigator.
9. Subjects has voluntarily signed and dated an informed consent prior to any study related procedure and is willing to comply with the requirements of this study protocol which has been approved by an Institutional Review Board (IRB/Independent Ethics Committee (IEC)).
Exclusion criteria
1. Subjects is pregnant, nursing, or planning pregnancy (men and women) while enrolled in the study.
2. Subjects has used any investigational drug within the previous 4 weeks or 5 times the half-life of the investigational agent prior to the first administration of study agent, whichever is longer.
3. Subject has ever used azathioprin or methotrexate before
4. Subject has received phototherapy or any systemic medications/treatments that could affect AD evaluation (including, but not limited to, oral or injectable corticosteroids) within the last 4 weeks of the first administration of study agent.
5. Subject has used very potent topical medications/treatments that could affect AD evaluation within 2 weeks of the first administration of study agent.
6. A history of chronic or recurrent infectious diseases, including but not limited to chronic renal infection, chronic chest infection (eg, bronchiectasis), recurrent urinary tract infection (recurrent pyelonephritis or chronic nonremitting cystitis), or open, draining, or infected skin wounds or ulcers.
7. A history of alcohol abuse
8. A history of latent or active granulomatous infection, including TB, histoplasmosis, or coccodioidomycosis, prior to screening.
9. Subject has or had had herpes zoster infection within 2 months of study day 0.
10. Subject is known to be infected with HIV, hepatitis B, or hepatitis C.
11. A history or current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, cerebral, or psychiatric disease.
12. Subject has a transplanted organ (with exception of a corneal transplant > 3 months prior to the first administration of study agent).
13. Subject has any known malignancy or had a history of malignancy
14. Subject is dependant of a concomitant medication that has interaction with the study medication and thereby should be avoided
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 | EUCTR2009-011132-34-NL |
| CCMO | NL27312.018.09 |