A Study to Evaluate the Safety and Efficacy of Adalimumab in Subjects With Chronic Plaque Psoriasis and Nail Psoriasis

Study Overview
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Brief Summary
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This study is being conducted to assess the safety and efficacy of adalimumab in participants with nail psoriasis.

Official Title
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A Phase 3, Multicenter, Double-Blind, Randomized, Parallel-Arm, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Adalimumab for Treatment of Nail Psoriasis in Patients With Chronic Plaque Psoriasis

Conditions
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Nail Psoriasis, Plaque Psoriasis

Intervention / Treatment
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* Biological: Adalimumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must have body surface area (BSA) ≥ 10% and a target fingernail Modified Nail Psoriasis Severity Index (mNAPSI) ≥ 8 at Week 0, OR BSA ≥ 5%, a target fingernail mNAPSI ≥ 8 and a total mNAPSI score of ≥ 20 at Week 0. Subject must have a Nail Psoriasis Physical Functioning Severity score of > 3, OR a Nail Psoriasis Pain Numeric Rating Scale (NRS) score of >3. Subjects must have a Physician's Global Assessment (PGA) of Fingernail Psoriasis and a PGA of Skin Psoriasis of at least moderate. Subject must have discontinued use of all systemic therapies for the treatment of psoriasis, or systemic therapies known to improve psoriasis for at least 4 weeks prior to Week 0, ustekinumab must have been discontinued at least 12 weeks prior to Week 0. Target fingernail must have mNAPSI score of ≥ 8. Adult subjects with clinical diagnosis of chronic plaque psoriasis (with disease duration of at least 6 months). Exclusion Criteria: Prior adalimumab therapy. Diagnosis of other active skin diseases or skin infections (bacterial, fungal, or viral) that may interfere with evaluation of skin or fingernail psoriasis. Recent infection requiring treatment. Significant medical events or conditions that may put patients at risk for participation, including recent history of drug or alcohol abuse. Female subjects who are pregnant or breast-feeding or considering becoming pregnant during the study. History of cancer, except successfully treated skin cancer.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Adalimumab (ADA)<br>Period A: ADA 40 mg subcutaneous every other week (sc eow) for 25 weeks starting 1 week after initial loading dose of 80 mg. Period B: Placebo at Week 26 followed by ADA 40 mg sc eow from Week 27 through Week 51. | Biological: Adalimumab<br> <br> * Other names: Humira;Other: Placebo<br> <br> |
| Placebo Comparator: Placebo<br>Period A: Placebo sc eow for 25 weeks. Period B: ADA 80 mg sc at Week 26 followed by ADA 40 mg sc eow from Week 27 through Week 51. | Biological: Adalimumab<br> <br> * Other names: Humira;Other: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving a Total Fingernail Modified Nail Psoriasis Severity Index (mNAPSI) 75 Response at Week 26 | Each fingernail was assessed for psoriasis with mNAPSI, and the scores of all 10 fingernails were combined. Investigators assessed each nail abnormality for each of a participant's nails by grading 3 features or groups of features (pitting, onycholysis and oil-drop dyschromia, and crumbling) and noting the presence or absence of 4 features (leukonychia, splinter hemorrhages, hyperkeratosis, and red spots in the lunula). The range of possible scores was 0 to 130, with a score of 0 indicating absence of nail psoriasis and a score of 130 indicating the most severe nail psoriasis. A decrease in mNAPSI score indicates improvement. The mNAPSI 75 response is defined as at least 75% reduction from baseline in mNAPSI. | Week 26 | 
| For United States (US) Regulatory Purposes: Percentage of Participants With a Physician's Global Assessment of Fingernails (PGA-F) of Clear or Minimal at Week 26 | The PGA-F is a 5-point scale used to assess fingernails separately for nail bed signs and nail matrix signs of disease. A global score of between 0 indicating clear, and 4 indicating severe, was separately assigned for nail bed involvement and nail matrix involvement. A participant's overall global score was the worse of the nail bed and nail matrix score. Data presents the percentage of participants with a PGA-F overall global score that met the definition of clear (0) or minimal (1) with at least a 2-grade improvement relative to Baseline at Week 26. | Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Total Fingernail Nail Psoriasis Severity Index (NAPSI) Score at Week 26 | Each fingernail was assessed for nail matrix psoriasis and nail bed psoriasis with NAPSI and the scores of all 10 fingernails were combined. The range of possible scores was 0 to 80, with a score of 0 indicating absence of nail psoriasis and 80 indicating most severe nail psoriasis. A decrease in NAPSI score indicates improvement. | Baseline, Week 26 | 
| Percentage of Participants Achieving Total Fingernail mNAPSI Score of 0 at Week 26 | Each fingernail was assessed for psoriasis with mNAPSI, and the scores of all 10 fingernails were combined. The range of possible scores was 0 to 130, with a score of 0 indicating absence of nail psoriasis and a score of 130 indicating the most severe nail psoriasis. A decrease in mNAPSI score indicates improvement. | Week 26 | 
| Percent Change From Baseline in Nail Psoriasis Pain Numeric Rating Scale (NRS) at Week 26 | An NRS was used to capture a participant's self-reporting of her/his worst fingernail pain and average fingernail pain due to fingernail psoriasis. The participant rated the severity of fingernail pain over the past 7 days on a scale from 0 indicating no pain, to 10 indicating severe pain. A negative change from Baseline indicates improvement. | Baseline, Week 26 | 
| Change From Baseline in Nail Psoriasis Physical Functioning Severity Score at Week 26 | Participants were asked to rate the impact of their fingernail psoriasis on their ability to perform physical tasks (eg, typing, housework, buttoning a shirt or blouse, picking up coins from a table, tying shoes, yard work, etc.) over the past 7 days on a scale of 0 indicating no impact on ability to perform physical tasks, to 10 indicating severe impact on ability to perform physical tasks. A negative change from Baseline indicates improvement. | Baseline, Week 26 | 
| Percentage of Participants With at Least 50% Improvement in the Scalp Component of the Brigham Scalp Nail Inverse Palmo-Plantar Psoriasis Index (B-SNIPI) at Week 26 | The range of possible scores was 0 to 20 for scalp psoriasis, with a score of 0 indicating absence of psoriasis. A decrease in B-SNIPI score indicates improvement. Data presents the percentage of participants achieving 50% improvement in the scalp component of the B-SNIPI among participants with Baseline scalp score of ≥ 6. | Baseline, Week 26 | 
| Percentage of Participants Achieving Clear or Minimal in Nail Bed Component of the PGA-F at Week 26 | The PGA-F is a 5-point scale used to assess fingernails separately for nail bed signs and nail matrix signs of disease. A global score of between 0 indicating clear, and 4 indicating severe, was separately assigned for nail bed involvement and nail matrix involvement. A participant's overall global score was the worse of the nail bed and nail matrix score. Data presents the percentage of participants with a nail bed component of the PGA-F that met definition of clear (0) or minimal (1) among those with a Baseline nail bed component of moderate or worse. | Week 26 | 
| Percentage of Participants Achieving Clear or Minimal in Nail Matrix Component of the PGA-F At Week 26 | The PGA-F is a 5-point scale used to assess fingernails separately for nail bed signs and nail matrix signs of disease. A global score of between 0 indicating clear, and 4 indicating severe, was separately assigned for nail bed involvement and nail matrix involvement. A participant's overall global score was the worse of the nail bed and nail matrix score. Data presents the percentage of participants with a nail matrix component of the PGA-F that met definition of clear (0) or minimal (1) among those with a Baseline nail matrix component of moderate or worse. | Week 26 | 
| Percentage of Participants Achieving Target Fingernail mNAPSI Score of 0 at Week 26 | The target fingernail was assessed for psoriasis with mNAPSI. The range of possible scores was 0 to 13, with a score of 0 indicating absence of nail psoriasis and a score of 13 indicating the most severe nail psoriasis. A decrease in mNAPSI score indicates improvement. | Week 26 | 
| Percentage of Participants Achieving Target Fingernail mNAPSI Score of ≤ 2 at Week 26 | The target fingernail was assessed for psoriasis with mNAPSI. The range of possible scores was 0 to 13, with a score of 0 indicating absence of nail psoriasis and a score of 13 indicating the most severe nail psoriasis. A decrease in mNAPSI score indicates improvement. | Week 26 | 
| Percentage of Participants Achieving Total Fingernail mNAPSI Score of ≤ 2 at Week 26 | Each fingernail was assessed for psoriasis with mNAPSI, and the scores of all 10 fingernails were combined. The range of possible scores was 0 to 130, with a score of 0 indicating absence of nail psoriasis and a score of 130 indicating the most severe nail psoriasis. A decrease in mNAPSI score indicates improvement. | Week 26 | 
| Change From Baseline in Target Fingernail mNAPSI Score at Week 26 | The target fingernail was assessed for psoriasis with mNAPSI. The range of possible scores was 0 to 13, with a score of 0 indicating absence of nail psoriasis and a score of 13 indicating the most severe nail psoriasis. A decrease in mNAPSI score indicates improvement. | Baseline, Week 26 | 
| Percent Change From Baseline in Target Fingernail mNAPSI Score at Week 26 | The target fingernail was assessed for psoriasis with mNAPSI. The range of possible scores was 0 to 13, with a score of 0 indicating absence of nail psoriasis and a score of 13 indicating the most severe nail psoriasis. A decrease in mNAPSI score indicates improvement. | Baseline, Week 26 | 
| Change From Baseline in Total Fingernail mNAPSI Score at Week 26 | Each fingernail was assessed for psoriasis with mNAPSI, and the scores of all 10 fingernails were combined. The range of possible scores was 0 to 130, with a score of 0 indicating absence of nail psoriasis and a score of 130 indicating the most severe nail psoriasis. A decrease in mNAPSI score indicates improvement. | Baseline, Week 26 | 
| Percent Change From Baseline in Total Fingernail mNAPSI Score at Week 26 | Each fingernail was assessed for psoriasis with mNAPSI, and the scores of all 10 fingernails were combined. The range of possible scores was 0 to 130, with a score of 0 indicating absence of nail psoriasis and a score of 130 indicating the most severe nail psoriasis. A decrease in mNAPSI score indicates improvement. | Baseline, Week 26 | 
| Percentage of Participants Achieving Total Fingernail NAPSI Score of 0 at Week 26 | Each fingernail was assessed for nail matrix psoriasis and nail bed psoriasis with NAPSI and the scores of all 10 fingernails were combined. The range of possible scores was 0 to 80, with a score of 0 indicating absence of nail psoriasis and 80 indicating most severe nail psoriasis. A decrease in NAPSI score indicates improvement. | Week 26 | 
| Percentage of Participants Achieving Target Fingernail NAPSI Score of 0 at Week 26 | The target fingernail was assessed for nail matrix psoriasis and nail bed psoriasis with NAPSI. The range of possible scores was 0 to 8, with a score of 0 indicating absence of nail psoriasis and 8 indicating most severe nail psoriasis. A decrease in NAPSI score indicates improvement. | Week 26 | 
| Change From Baseline in Target Fingernail NAPSI Score at Week 26 | The target fingernail was assessed for nail matrix psoriasis and nail bed psoriasis with NAPSI. The range of possible scores was 0 to 8, with a score of 0 indicating absence of nail psoriasis and 8 indicating most severe nail psoriasis. A decrease in NAPSI score indicates improvement. | Baseline, Week 26 | 
| Percent Change From Baseline in Target Fingernail NAPSI Score at Week 26 | The target fingernail was assessed for nail matrix psoriasis and nail bed psoriasis with NAPSI. The range of possible scores was 0 to 8, with a score of 0 indicating absence of nail psoriasis and 8 indicating most severe nail psoriasis. A decrease in NAPSI score indicates improvement. | Baseline, Week 26 | 
| Change From Baseline in Total Fingernail NAPSI Score at Week 26 | Each fingernail was assessed for nail matrix psoriasis and nail bed psoriasis with NAPSI and the scores of all 10 fingernails were combined. The range of possible scores was 0 to 80, with a score of 0 indicating absence of nail psoriasis and 80 indicating most severe nail psoriasis. A decrease in NAPSI score indicates improvement. | Baseline, Week 26 | 
| Change From Baseline in Psoriasis Area Severity Index (PASI) Score at Week 26 | 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 score ranges from 0 to 72, with 0 indicating no psoriasis and 72 indicating very severe psoriasis. A decrease in PASI score indicates improvement. | Baseline, Week 26 | 
| Percent Change From Baseline in PASI Score at Week 26 | 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 score ranges from 0 to 72, with 0 indicating no psoriasis and 72 indicating very severe psoriasis. A decrease in PASI score indicates improvement. | Baseline, Week 26 | 
| Percentage of Participants Achieving PASI 75/50/90/100 Responses at Week 26 | 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 score ranges from 0 to 72, with 0 indicating no psoriasis and 72 indicating very severe psoriasis. PASI-75, 50, 90, and 100 responses are the percentage of participants with a Baseline PASI score ≥ 5 who achieved at least a 75%, 50%, 90%, or 100% reduction (improvement), respectively, from Baseline in PASI score at Week 26. A 100% reduction was considered complete clearance of psoriasis. Data presents the percentage of participants achieving PASI 75/50/90/100 responses at Week 26 among participants with a Baseline PASI score ≥ 5. | Week 26 | 
| Percentage of Participants Achieving Physician's Global Assessment of Skin Psoriasis (PGA-S) Clear or Minimal at Week 26 | The PGA-S is a 6-point scale used to measure the severity of skin disease at the time of the qualified investigator's evaluation of the participant. The degree of overall lesion severity was assessed, with 0 indicating cleared and 5 indicating severe. A decrease in PGA-S score indicates improvement. Data present the percentage of participants achieving a PGA-S of clear (0) or minimal (1) with at least a 2-grade improvement relative to Baseline at Week 26. | Week 26 | 
| Percentage of Participants Achieving PGA-S of Clear at Week 26 | The PGA-S is a 6-point scale used to measure the severity of skin disease at the time of the qualified investigator's evaluation of the participant. The degree of overall lesion severity was assessed, with 0 indicating cleared and 5 indicating severe. A decrease in PGA-S score indicates improvement. Data present the percentage of participants achieving a PGA-S of clear (0) with at least a 2-grade improvement relative to Baseline at Week 26. | Week 26 | 
| Percentage of Participants Achieving 50% Improvement in the Inverse Psoriasis Component of the B-SNIPI at Week 26 | The range of possible B-SNIPI scores was 0 to 20 for inverse psoriasis, with a score of 0 indicating absence of psoriasis and a score of 20 indicating most severe psoriasis. A decrease in B-SNIPI score indicates improvement. Data presents the percentage of participants achieving 50% improvement in the inverse component of the B-SNIPI among participants with a Baseline inverse psoriasis score of ≥ 6. | Week 26 | 
| Change From Baseline in Total Body Surface Area (BSA) at Week 26 | BSA affected by psoriasis was measured by the physician selecting the participant's right or left hand as the measuring device. For purposes of clinical estimation, the total surface of the palm plus 5 digits was to be assumed to be approximately equivalent to 1% BSA. Measurement of the total area of involvement by the physician was aided by imagining if scattered plaques were moved so that they were next to each other and then estimated the total area involved. A decrease in BSA affected by psoriasis indicates improvement. | Baseline, Week 26 | 
| Percent Change From Baseline in Total BSA at Week 26 | BSA affected by psoriasis was measured by the physician selecting the participant's right or left hand as the measuring device. For purposes of clinical estimation, the total surface of the palm plus 5 digits was to be assumed to be approximately equivalent to 1% BSA. Measurement of the total area of involvement by the physician was aided by imagining if scattered plaques were moved so that they were next to each other and then estimated the total area involved. A decrease in BSA affected by psoriasis indicates improvement. | Baseline, Week 26 | 
| Percent Change From Baseline in Nail Psoriasis Pain NRS at Week 26 | An NRS was used to capture a participant's self-reporting of her/his worst fingernail pain and average fingernail pain due to fingernail psoriasis. The participant rated the severity of fingernail pain over the past 7 days on a scale from 0 indicating no pain, to 10 indicating severe pain. A negative change from Baseline indicates improvement. | Baseline, Week 26 | 
| Percent Change From Baseline in Nail Psoriasis Physical Functioning Severity Score at Week 26 | Participants were asked to rate the impact of their fingernail psoriasis on their ability to perform physical tasks (eg, typing, housework, buttoning a shirt or blouse, picking up coins from a table, tying shoes, yard work, etc.) over the past 7 days on a scale of 0 indicating no impact on ability to perform physical tasks, to 10 indicating severe impact on ability to perform physical tasks. A negative change from Baseline indicates improvement. | Baseline, Week 26 | 
| Change From Baseline in Nail Assessment in Psoriasis and Psoriatic Arthritis Quality of Life (NAPPA QoL) at Week 26 | Participants rated specific impacts of fingernail psoriasis on various aspects of their QoL over the past 7 days on a 5-point scale, with 0 indicating not at all, and 4 indicating very impactful. A participant's overall global score was the mean of all items and could range from 0 to 4, with 0 indicating no impact and 4 indicating most impact. A decrease in NAPPA QoL score indicates improvement. | Baseline, Week 26 | 
| Percent Change From Baseline in Nail Assessment in NAPPA QoL at Week 26 | Participants rated specific impacts of fingernail psoriasis on various aspects of their QoL over the past 7 days on a 5-point scale, with 0 indicating not at all, and 4 indicating very impactful. A participant's overall global score was the mean of all items and could range from 0 to 4, with 0 indicating no impact and 4 indicating most impact. A decrease in NAPPA QoL score indicates improvement. | Baseline, Week 26 | 
| Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Week 26 | Participants assessed symptoms and impacts of dermatologic diseases on their QoL over the past 7 days, with 0 indicating not at all, and 3 indicating very much. The range of possible DLQI scores was 0 to 30, with a score of 0 indicating no effect at all on a participant's life and a score of 30 indicating extremely large effect on participant's life. A decrease in DLQI score indicates improvement. | Baseline, Week 26 | 
| Percentage of Participants Achieving DLQI of 0 and 0/1 at Week 26 | Participants assessed symptoms and impacts of dermatologic diseases on their QoL over the past 7 days, with 0 indicating not at all, and 3 indicating very much. The range of possible DLQI scores was 0 to 30, with a score of 0 indicating no effect at all on a participant's life and a score of 30 indicating extremely large effect on participant's life. A decrease in DLQI score indicates improvement. Data presents the percentage of participants with a score of 0 (no effect) or 1 (little effect) at Week 26. | Week 26 | 
| Change From Baseline in Work Productivity and Activity Impairment Nail Psoriasis (WPAI:NPSO) at Week 26 | The WPAI: NPSO assessed impact of fingernail psoriasis on work productivity and non-work activity limitation. Participants were asked during the past 7 days, how many hours did you miss from work because of problems associated with your fingernail psoriasis (absenteeism), during the past seven days, how many hours did you miss from work because of any other reason, such as vacation, holidays, time off to participate in this study (presenteeism), how much did your fingernail psoriasis affect your productivity while you were working (overall work impairment), and much did your fingernail psoriasis affect your ability to do your regular daily activities, other than work at a job (activity impairment). Answers were rated on an 11-point scale, with 0 indicating fingernail psoriasis had no effect on this and 10 indicating fingernail psoriasis completely prevented me from this. A decrease in the WPAI:NPSO score indicates improvement. | Baseline, Week 26 | 
| Change From Baseline in EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Health State Assessment at Week 26 | The EQ-5D-5L descriptive system comprises 5 dimensions of health (mobility, self -care, usual activities, pain/discomfort, and anxiety/depression) to describe the subject's current health state. Each dimension comprises 5 levels with corresponding numeric scores, where 1 indicates no problems, and 5 indicates extreme problems. A unique EQ-5D-5L health state is defined by combining the numeric level scores for each of the 5 dimensions and the total score is normalized from -0.594 to 1.000, with higher scores representing a better health state. An increase in the EQ-5D-5L total score indicates improvement. | Baseline, Week 26 | 
| Change From Baseline in EQ-5D Visual Analogue Scale (VAS) at Week 26 | The EQ-5D VAS records the participant's self-rated health status on a vertical graduated scale from 0 to 100, with 0 indicating the worst imaginable health state and 100 indicating the best imaginable health state. An increase in EQ-5D-5L VAS score indicates improvement. | Baseline, Week 26 | 
| Change From Baseline in Hospital Anxiety Depression Scale (HADS) at Week 26 | Participants rated their anxiety and depression over the past 7 days at Week 26. The range of possible scores was 0 to 21, with a score of 0 indicating absence of anxiety and depression and 21 indicating the most severe anxiety and depression. A decrease in HADS score indicates improvement. | Baseline, Week 26 | 
| Percentage of Participants With a New Diagnosis of Psoriatic Arthritis (PsA) During the Study | The percentage of participants with a new diagnosis of PsA (ie, with an adverse event of PsA) during the study, among participants without PsA at Baseline. | up to Week 26 | 
| Change From Baseline in Nail Psoriasis Quality of Life (Nail PsQoL) Score at Week 26 | Participants were asked how their fingernail psoriasis impacted their overall quality of life over the past 7 days on an 11-point scale, with 0 indicating no impact, and 10 indicating severe impact. A negative change from Baseline indicates improvement. | Baseline, Week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nail Psoriasis, Plaque Psoriasis