The Efficacy and Safety of Adding Methotrexate to Etanercept in Psoriasis

NCT01001208 | Completed Phase 3 Results

• 1 other identifier: 20070559
• Study Type: interventional
• Target: 478
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the efficacy of adding methotrexate to etanercept compared with etanercept monotherapy as measured by the percentage of participants achieving a 75% improvement from baseline in the Psoriasis Area and Severity Index (PASI 75) at Week 24.

Conditions

Psoriasis

Keywords

Etanercept; Methotrexate; Psoriasis

Outcome Measures

Primary Outcomes (1)

• PASI 75 Response at Week 24

  Percentage of participants achieving at least a 75% decrease (improvement) from Baseline in the Psoriasis Area and Severity Index (PASI) at Week 24. PASI Score incorporates measures of erythema, desquamation, infiltration, and affected body surface area. Involvement and severity of psoriasis was scored by a blinded assessor using a scale of 0 to 72, where 0 = no psoriasis and 72 = severe disease.

  Baseline and 24 Weeks

Secondary Outcomes (9)

• PASI 50 Response at Week 24

  Baseline and 24 Weeks

• Static Physician Global Assessment (sPGA) Response at Week 24

  Week 24

• PASI 50 Response at Week 12

  Baseline and 12 Weeks

• PASI 75 Response at Week 12

  Baseline and 12 Weeks

• Static Physician Global Assessment (sPGA) Response at Week 12

  Week 12

Study Arms (2)

Etanercept Plus Methotrexate

EXPERIMENTAL

Participants received 50 mg etanercept twice weekly (BIW) for the first 12 weeks and then 50 mg etanercept once weekly (QW) for the second 12 weeks. Participants also received active methotrexate titrated as follows: 7.5 mg per week (3 capsules) for weeks 1 and 2, 10 mg per week (4 capsules) for weeks 3 and 4, and then up to 15 mg per week (6 capsules) or the maximum tolerated dose for the remainder of the 24-week treatment period.

Drug: Methotrexate; Drug: Etanercept

Etanercept Plus Placebo

ACTIVE COMPARATOR

Participants received 50 mg etanercept twice weekly (BIW) for the first 12 weeks and then 50 mg etanercept once weekly (QW) for the second 12 weeks. Participants also received oral placebo that was the same number of capsules per week as the methotrexate dosing regimen.

Drug: Etanercept; Drug: Placebo

Interventions

Methotrexate DRUG

Methotrexate tablets over-encapsulated for blinding

Etanercept Plus Methotrexate

Etanercept DRUG

1 mL for subcutaneous injection

Also known as: Enbrel

Etanercept Plus Methotrexate; Etanercept Plus Placebo

Placebo DRUG

Matching placebo to methotrexate capsules

Etanercept Plus Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Is capable of understanding and giving written, voluntary informed consent before study screening
• Male or female ≥18 years of age at time of screening
• Has had stable moderate to severe plaque psoriasis for at least 6 months (eg, no morphology changes or significant flares of disease activity)
• Has involved body surface area (BSA) ≥ 10% and Psoriasis Area and Severity Index (PASI) ≥ 10 at screening and at baseline
• Is a candidate for systemic therapy or phototherapy in the opinion of the investigator
• Has a negative test for hepatitis B surface antigen and hepatitis C antibody
• Has a negative purified protein derivative test within 30 days prior to the first IP dose. Tuberculin skin tests should be considered positive when they have greater than or equal to 5 mm of induration at 48-72 hours after test is placed. Patients with a positive tuberculin skin test (if less than or equal to 14 mm of induration) are allowed if they have a history of Bacillus Calmette-Guerin vaccination with a negative Quantiferon test in the past year, no symptoms per tuberculosis worksheet, and a negative chest X ray.
• Has a negative serum pregnancy test within 28 days before initiating Investigational Product (IP) and negative urine pregnancy test at baseline for females (except those at least 3 years post menopausal or surgically sterile)
• Females are willing to use highly effective form of birth control (decided upon with the investigator) during the study and for 3 months after the end of treatment (except women at least 3 years post menopausal or surgically sterile)
• Males are willing to use highly effective form of birth control (decided upon with the investigator) during the study and for 5 months after the end of treatment (except for men who are surgically sterile or whose female partners are at least 3 years post menopausal, surgically sterile, or are using a highly effective form of birth control)
• Men with a pregnant female partner are willing to use effective methods (decided upon with the investigator) to ensure that an unborn child is not exposed to IP via semen
• Patient or designee must have the ability to inject etanercept subcutaneously

You may not qualify if:

• Skin-disease related
• Has active guttate, erythrodermic, or pustular psoriasis at the time of the screening visit.
• Has evidence of skin conditions at the time of the screening visit (eg, eczema) that would interfere with evaluations of the effect of IP on psoriasis.
• Medical conditions
• Has significant concurrent medical conditions, including:
• Type 1 diabetes
• Poorly controlled type 2 diabetes (hemoglobin A1c \> 8.5)
• Symptomatic heart failure (New York Heart Association \[NYHA\] class II, III, or IV)
• Myocardial infarction within the last year
• Current or history of unstable angina pectoris within the last year
• Uncontrolled hypertension as defined by a resting blood pressure ≥ 160/95 mmHg prior to randomization (confirmed by a repeat assessment)
• Severe chronic pulmonary disease (eg, requiring oxygen therapy)
• No major chronic inflammatory disease or connective tissue disease other than psoriasis and/or psoriatic arthritis
• Multiple sclerosis or any other demyelinating disease
• Active malignancy, including evidence of cutaneous basal or squamous cell carcinoma or melanoma, or history of cancer (other than fully resected and surgically cured cutaneous basal cell and squamous cell carcinoma) within 5 years before the first IP dose. If malignancy occurred more than 5 years ago, documentation of disease-free state since treatment is required.

Sponsors & Collaborators

• Amgen: lead
• Immunex Corporation: collaborator

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Psoriasis

Interventions

Methotrexate; Etanercept

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2009
• First Posted: October 26, 2009
• Study Start: November 1, 2009
• Primary Completion: December 1, 2010
• Study Completion: February 1, 2011
• Last Updated: August 12, 2013
• Results First Posted: August 12, 2013

Record last verified: 2013-07