Concomitant Longitudinal Evaluation of Adalimumab With Methotrexate in the Real World: the CLEAR Study

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and efficacy of the use of the combination therapy adalimumab (ADA) every other week (EOW) with methotrexate (MTX) in suboptimal responders to ADA monotherapy.

Official Title
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Concomitant Longitudinal Evaluation of Adalimumab With Methotrexate in the Real World: the CLEAR Study

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: Adalimumab
* Drug: Methotrexate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who have been on ADA monotherapy (40 mg eow or greater) for at least 16 weeks but who in the opinion of the Investigator have shown a sub-optimal response to treatment and have a Physician's Global Assessment (PGA) of ≥ 3 and a Psoriasis Area Severity Index (PASI) of ≥ 5; or Subjects who after an initial positive response to ADA monotherapy (40 mg eow or greater) have failed to maintain an optimal level of response, based on the opinion of the Investigator, and have a PGA of ≥ 3 and a PASI of ≥ 5; Subjects who are receiving 40 mg ADA once weekly must be on ADA 40 mg eow for 8 weeks prior to screening; Subjects with at least a 6 month history of chronic plaque psoriasis; Subjects greater than or equal to 18 years of age; If female, subject is either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile or is of childbearing potential and is practicing birth control; The results of the serum pregnancy test performed during the Screening Period and urine pregnancy test performed at the Baseline Visit must be negative; Subject is judged to be in good general health as determined by the Principal Investigator; Subjects must be evaluated for latent tuberculosis (TB) infection; Subjects must be able and willing to provide written informed consent and comply with the requirements of the study protocol; Subjects must be willing and able to self-administer subcutaneous (SC) injections or have a qualified person available to administer SC injections. Exclusion Criteria: Subject has any contraindications to MTX or ADA; Subject has a previous failed response or poor tolerance to ADA; Subject has a poorly controlled medical condition which, in the opinion of the Investigator, would put the subject at risk by participation in the study; Subject has a history of clinically significant hematologic, renal or liver disease; Subject has a history of neurologic symptoms suggestive of central nervous system (CNS) demyelinating disease and/or diagnosis of central demyelinating disease; Subject has evidence of dysplasia or history of malignancy (including lymphoma and leukemia) other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma or localized carcinoma in situ of the cervix; Subject has a history of listeriosis, histoplasmosis, untreated TB, persistent chronic infections, or recent active infections requiring hospitalization or treatment with intravenous (iv) anti-infectives within 30 days or oral anti-infectives within 14 days prior to the Baseline visit; Subject is known to have immune deficiency, history of human immunodeficiency virus (HIV) or is immunocompromised; Subject currently uses or plans to use anti-retroviral therapy at any time during the study; Female subject who is pregnant or breast-feeding or considering becoming pregnant during the study or for 150 days after the last dose of study medication; Subject has a history of clinically significant drug or alcohol usage in the last year or cannot maintain an alcohol intake of 30 g a day or less throughout the study (one standard drink is defined as 180 mL/6 oz (approx. 10 g) of wine, 360 mL/12 oz (approx. 15 g) of regular beer, or 45 mL/1.5 oz (approx. 10 g) of spirits; Screening clinical laboratory analyses show any of the following abnormal laboratory results: Aspartate transaminase (AST) or alanine transaminase (ALT) > 2x the upper limit of normal (ULN); Serum total bilirubin > 1.5 mg/dL (> 26 micromol/L), except for subjects with Gilbert's Syndrome; Creatinine > 1.5 mg/dL (133 micromol/L) in subjects ≤ 65 years old and > upper limit of normal range in subjects > 65; Positive Hepatitis B or C serology indicative of previous or current infection. Subject is considered by the Investigator, for any reason, to be an unsuitable candidate for the study; The following treatments are prohibited for all subjects during the study: Phototherapy (ultraviolet A with psoralen [PUVA] within 4 weeks of the Baseline Visit and/or ultraviolet B (UVB) within 2 weeks of the Baseline Visit); Other biologic therapies (including any other anti-tumor necrosis factor [TNF]) within 4 weeks of the Baseline Visit; Any investigational agents of chemical or biologic nature within a minimum of 30 days or 5 half-lives (whichever is longer) of the drug prior to the Baseline visit ; Any other systemic drug therapies for psoriasis within 4 weeks of the Baseline Visit; Oral or injectable corticosteroids, new prescription topical therapies, or changes in the concentration of current prescription topical therapies (including corticosteroids) that are being used, within 2 weeks of the Baseline Visit. Subjects may continue using previously prescribed topical therapies (including corticosteroids) during the study. Prior exposure to biologics that have a potential or known association with progressive multifocal leukoencephalopathy (PML), i.e., natalizumab (Tysabri®) or rituximab (Rituxan®); Subjects with any active viral infection that based on the investigator's clinical assessment makes the subject an unsuitable candidate for the study;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adalimumab Plus Methotrexate<br>Participants received 40 mg adalimumab every other week and methotrexate, between 7.5 and 25 mg/week at the discretion of the Investigator, for 24 weeks. | Drug: Adalimumab<br>* Administered by subcutaneous injection every other week.<br>* Other names: Humira;Drug: Methotrexate<br>* Methotrexate was provided as 2.5 mg tablets for oral administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving a Satisfactory Response at Week 16 Based on Investigator Assessment | Study investigators were asked to complete the following questionnaire at week 16: Overall, at this point in time, how satisfied are you with the psoriasis control provided by the subject's current treatment regimen? The response choices provided were: Completely dissatisfied Moderately dissatisfied Slightly satisfied Highly satisfied Completely satisfied Satisfaction with therapy was defined by the combination of highly or completely satisfied responses. | Week 16 | 
| Percentage of Participants Achieving a Satisfactory Response at Week 16 Based on Patient Self-assessment | Participants were asked to complete the following questionnaire at week 16: Overall, at this point in time, how satisfied are you with your current treatment for psoriasis? The response choices provided were: Completely dissatisfied Moderately dissatisfied Slightly satisfied Highly satisfied Completely satisfied Satisfaction with therapy was defined by the combination of highly or completely satisfied responses. | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving a Satisfactory Response Based on Investigator Assessment Over Time | Study investigators were asked to complete the following questionnaire at each scheduled visit: Overall, at this point in time, how satisfied are you with the psoriasis control provided by the subject's current treatment regimen? The response choices provided were: Completely dissatisfied Moderately dissatisfied Slightly satisfied Highly satisfied Completely satisfied Satisfaction with therapy was defined by the combination of highly or completely satisfied responses. | Baseline, week 8 and week 24 | 
| Percentage of Participants Achieving a Satisfactory Response Based on Patient Self-assessment Over Time | Participants were asked to complete the following questionnaire at each scheduled visit: Overall, at this point in time, how satisfied are you with your current treatment for psoriasis? The response choices provided were: Completely dissatisfied Moderately dissatisfied Slightly satisfied Highly satisfied Completely satisfied Satisfaction with therapy was defined by the combination of highly or completely satisfied responses. | Baseline, week 8 and week 24 | 
| Number of Participants Achieving Each Satisfactory Category Based on Investigator Assessment Over Time | Study investigators were asked to complete the following questionnaire at each scheduled visit: Overall, at this point in time, how satisfied are you with the psoriasis control provided by the subject's current treatment regimen? The response choices provided were: Completely dissatisfied Moderately dissatisfied Slightly satisfied Highly satisfied Completely satisfied | Baseline, weeks 8, 16, and 24 | 
| Number of Participants Achieving Each Satisfactory Category Based on Patient Self-assessment Over Time | Participants were asked to complete the following questionnaire at each scheduled visit: Overall, at this point in time, how satisfied are you with your current treatment for psoriasis? The response choices provided were: Completely dissatisfied Moderately dissatisfied Slightly satisfied Highly satisfied Completely satisfied | Baseline, weeks 8, 16, and 24 | 
| Percentage of Participants Who Achieved a Psoriasis Area and Severity Index (PASI) 50 Response Over Time | PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The PASI score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI 50 response is defined as at least a 50% reduction (improvement) from baseline in PASI score. | Baseline and Weeks 8, 16, and 24 | 
| Percentage of Participants Who Achieved a PASI 75 Response Over Time | PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The PASI score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI 75 response is defined as at least a 75% reduction (improvement) from baseline in PASI score. | Baseline and Weeks 8, 16, and 24 | 
| Percentage of Participants Who Achieved a PASI 90 Response Over Time | PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The PASI score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI 90 response is defined as at least a 90% reduction (improvement) from baseline in PASI score. | Baseline and Weeks 8, 16, and 24 | 
| Percentage of Participants Who Achieved a PASI 100 Response Over Time | PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The PASI score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI 100 response is defined as a 100% reduction (improvement) from baseline in PASI score. | Baseline and Weeks 8, 16, and 24 | 
| Change From Baseline in PASI Score Over Time | PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The PASI score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). | Baseline and weeks 8, 16, and 24 | 
| Percent Change From Baseline in PASI Score | PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The PASI score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). | Baseline and weeks 8, 16, and 24 | 
| Percentage of Participants Achieving a Physician's Global Assessment of Disease Activity (PGA) of Cleared or Minimal Over Time | The PGA is a 6-point scale used to measure the severity of disease at the time of the evaluation. The degree of overall lesion severity was evaluated using the following categories: 0 (Cleared): No evidence of scaling, erythema, or plaque elevation; 1 (Minimal): Occasional fine scale over <5% of lesions, faint erythema, minimal plaque elevation; 2 (Mild): Fine scale dominates, light red coloration, mild plaque elevation; 3 (Moderate): Course scale dominates, moderate red coloration, moderate plaque elevation; 4 (Marked): Thick non-tenacious scale dominates, bright red coloration, marked plaque elevation; 5 (Severe): Very thick tenacious scale predominates, dusky to deep red coloration, severe plaque elevation. The percentage of participants achieving a score of clear (0) or minimal (1) is reported. | Weeks 8, 16, and 24 | 
| Change From Baseline in Body Surface Area (BSA) Affected by Psoriasis | The total body surface area affected by psoriasis (expressed as a percentage) was measured by the investigator using the palm method, where the participant's hand represents 1% of body surface area. A decrease in BSA affected by psoriasis indicates improvement. | Baseline and weeks 8, 16, and 24 | 
| Percent Change From Baseline in Body Surface Area (BSA) Affected by Psoriasis | The total body surface area affected by psoriasis (expressed as a percentage) was measured by the investigator using the palm method, where the participant's hand represents 1% of body surface area. A decrease in BSA affected by psoriasis indicates improvement. | Baseline and weeks 8, 16, and 24 | 
| Change From Baseline in Dermatology Life Quality Index (DLQI) Score Over Time | The DLQI questionnaire asks participants to evaluate the degree that psoriasis has affected their quality of life in the last week, and includes the following parameters: symptoms and feelings, daily activities, leisure activities, work or school activities, personal relationships and treatment related feelings. Participants answer 10 questions on a scale from 0 (not at all) to 3 (very much); the range of the total score is 0 to 30. A score of 21 to 30 means an extremely large effect on the participant's life whereas 0-1 means that the disease has no effect at all. A negative change from Baseline indicates improvement. | Baseline, weeks 8, 16, and 24 | 
| Percent Change From Baseline in Dermatology Life Quality Index (DLQI) Score Over Time | The DLQI questionnaire asks participants to evaluate the degree that psoriasis has affected their quality of life in the last week, and includes the following parameters: symptoms and feelings, daily activities, leisure activities, work or school activities, personal relationships and treatment related feelings. Participants answer 10 questions on a scale from 0 (not at all) to 3 (very much); the range of the total score is 0 to 30. A score of 21 to 30 means an extremely large effect on the participant's life whereas 0-1 means that the disease has no effect at all. A negative change from Baseline indicates improvement. | Baseline, weeks 8, 16, and 24 | 
| Percentage of Participants Who Achieved a DLQI Score of 0 or 1 Over Time | The DLQI questionnaire asks participants to evaluate the degree that psoriasis has affected their quality of life in the last week, and includes the following parameters: symptoms and feelings, daily activities, leisure activities, work or school activities, personal relationships and treatment related feelings. Participants answer 10 questions on a scale from 0 (not at all) to 3 (very much); the range of the total score is 0 to 30. A score of 21 to 30 means an extremely large effect on the participant's life whereas 0-1 means that the disease has no effect at all. | Baseline and Weeks 8, 16, and 24 | 
| Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) at Week 24 |  | Baseline and week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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methotrexate, adalimumab, biologic, psoriasis, Tumor necrosis factor (TNF)-α inhibitor