E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with severe atopic dermatitis, defined as a score of 8-9 on the Rajka and Langeland criteria who are unresponsive, intolerant or contra-indicated to cyclisporin treatment. |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003639 |
E.1.2 | Term | Atopic dermatitis |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the efficacy of methotrexate versus azathiorpine treatment in adult patients with chronic severe AD. |
|
E.2.2 | Secondary objectives of the trial |
• Safety and tolerability • The effect of therapy on quality of life.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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, intolerant or contra-indicated to cyclosporin 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: - sponge, foams, jellies, diaphragm or 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)).
|
|
E.4 | Principal 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 azathioprine 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. A history of lymphoproliferative disease, including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy and/or splenomegaly. 14. Subject has any known malignancy or had a history of malignancy. 15. Subject has undergone allergy immunotherapy previously for prevention of anaphylactic reactions. 16. Subject participates in another trial using an investigational agent or procedure during participation in the trial. 17. Subject is dependant of a concomitant medication that has interaction with the study medication and thereby should be avoided.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variables are the SCORAD and Investigators Global Assessment response at week 12. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The endpoint of the trial is 24 weeks after starting with therapy. Further details provided in protocol. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |