An Open-Label, Randomized Efficacy and Safety Study of Infliximab Versus Methotrexate in the Treatment of Moderate to Severe Psoriasis

Phase 1

• Conditions: Moderate to severe psoriasis; MedDRA version: 7.1 Level: PT Classification code 10037153

• Registration Number: EUCTR2005-000085-39-BE
• Lead Sponsor: Schering-Plough Research Institute

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2006-02-15
• Study Completion: 2008-06-19
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 800

Inclusion Criteria

The subject must meet ALL of the criteria listed below for entry:
1. Subjects must be =18 to 75 years of age at Screening, of either sex, and of any race.
2. Subjects must have had a diagnosis of moderate to severe plaque-type psoriasis at least 6 months prior to Screening (subjects with concurrent psoriatic arthritis may be enrolled).
3. Subjects must have plaque-type psoriasis covering at least 10% of total BSA at Screening and Baseline.
4. Subjects must have a PASI score of 12 or greater at Screening and Baseline
(see Appendix 7).
5. Subjects must be candidates for phototherapy or systemic treatment of psoriasis (either naïve or history of previous treatment).
6. Subjects must agree to avoid prolonged sun exposure and avoid use of tanning booths or other ultraviolet light sources during the study.
7. Subjects are considered eligible according to tuberculosis (TB) screening criteria:
a) Have no history of latent or active TB prior to screening;
b) Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination;
c)Have had no recent close contact with a person with active TB or, if there has been such contact, will be referred to a physician specialising in TB to undergo additional evaluation and, if warranted, receive appropriate treatment for latent TB rpior to or simultaneously with the first administration of study medication;
d) Within 1 month prior to the first administration of study medication, either have a negative diagnostic TB test results (defined as 2 negative tuberculin skin tests) OR have a newly identified positive diagnostic TB test result (defined as at least 1 positive tuberculin skin test) during screening in which active TB has been ruled out and for which appropriate treatment for latent TB has been initiated either prior to or simultaneously with the first administration of study medication.
8. Subjects must have had a chest x-ray (posterior-anterior and lateral) within 3 months prior to Screening with no evidence of malignancy, infection, or fibrosis, or current or old active TB.
9. Subjects’ Screening and Baseline clinical laboratory tests (CBC, blood chemistry, and urinalysis) must be within the following parameters: (a) Hemoglobin =10 g/dL,
(b) White blood cells =3.5 x 10 9/L, (c) Neutrophils =1.5 x 10 9/L, (d) Platelets =100 x 10 9/L, (e) Serum creatinine <1.5 mg/dL (or <133 µmol/L), (f) Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase =1.5 x upper limit of normal, and (g) Total bilirubin =1 x upper limit of normal.
10. Subjects must be free of any clinically significant disease (other than psoriasis
or psoriatic arthritis) that would interfere with the study evaluations.
11. Subjects must be willing to give written informed consent and be able to adhere to dose and visit schedules.
12. Women of childbearing potential and all men must be using adequate birth control measures (eg, abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, or surgical sterilization) and must continue using such measures until 6 months after receiving the last dose of study medication.

Exclusion Criteria

The subject will be excluded from entry if ANY of the criteria listed below are met:
1. Subjects who have non-plaque forms of psoriasis (eg, erythrodermic, guttate, or pustular).
2. Subjects who have current drug-induced psoriasis (eg, a new onset of psoriasis or an exacerbation of psoriasis from beta blockers, calcium channel blockers, or lithium).
3. Female subjects who are pregnant, nursing, and both men and women who are planning pregnancy during the study period and the 6 months after study completion.
4. Subjects previously treated with infliximab.
5. Subjects previously treated with MTX.
6. Subjects who are currently taking or have taken the following drugs within the
specified time frame prior to baseline: (a) any therapeutic agent targeted at reducing TNF within 3 months, (b) any biologic within 3 months, (c) any live virus or bacterial vaccinations received within 3 months prior to Screening, (d) any systemic medications/treatments that could affect psoriasis or PASI evaluations within 4 weeks, (e) any systemic immunosuppressants within 4 weeks, (f) lithium within 4 weeks, and (g) any topical medications/treatments that could affect psoriasis or PASI
evaluation within 2 weeks. The only allowed topical treatments for psoriasis are shampoos (containing tar or salicylic acid only) and topical moisturisers. Subjects should not use these topical agents during the morning prior to a study visit. Non-medicated shampoos may be used on the morning of a visit.
7. Subjects who have a concomitant diagnosis of congestive heart failure (CHF),
including medically-controlled asymptomatic subjects.
8. Subjects who have a history of chronic or recurrent infectious disease, 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.
9. Subjects who have had or have a serious infection (eg, hepatitis, pneumonia or pyelonephritis), or have been hospitalized or received intravenous (IV) antibiotics for an infection during the 2 months prior to Screening.
10. Subjects who have or have had an opportunistic infection (eg, cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) within 6 months prior to Screening.
11. Subjects who have or have had a Herpes zoster infection within 2 months prior to Screening.
12. Subjects who are known to be infected with human immunodeficiency virus, hepatitis B, or hepatitis C.
13. Subjects who have a history of any clinically significant AEs (including allergic
reactions) to murine or chimeric proteins or human/murine recombinant products.
14. Subjects who have current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, cerebral, or psychiatric disease.
15. Subjects who have a history of demyelinating disease or symptoms suggestive of multiple sclerosis or optic neuritis.
16. Subjects who have current signs and symptoms or history of systemic lupus

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: The secondary objectives of the trial are to assess the safety of infliximab compared with methotrexate and to assess the quality-of-life in subjects with moderate to severe psoriasis.;Primary end point(s): The primary endpoint for the trial is the PASI75 (defined as the proportion of subjects achieving a greater than or equal to 75% improvement in Psoriasis Area and Severity Index) response rate at Week 16.;Main Objective: The primary objective of this trial is to assess the efficacy of infliximab therapy (5mg/kg by body weight) compared with methotrexate in adult subjects (aged 18-75 years) diagnosed with moderate to severe plaque-type psoriasis for at least 6 months prior to study screening (subjects with concurrent psoriatic arthritis may also be enrolled).