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A Study of Ixekizumab (LY2439821) Versus Adalimumab in Participants With Psoriatic Arthritis (SPIRIT-H2H)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03151551
Recruitment Status : Active, not recruiting
First Posted : May 12, 2017
Results First Posted : April 2, 2019
Last Update Posted : April 2, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Brief Summary:
The main purpose of this study is to evaluate the effectiveness and safety of ixekizumab versus adalimumab in participants with psoriatic arthritis (PsA) who are biologic disease-modifying anti-rheumatic drugs (DMARD) naive.

Condition or disease Intervention/treatment Phase
Psoriatic Arthritis Drug: Ixekizumab Drug: Adalimumab Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 566 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 52-Week Multicenter, Randomized, Open-Label, Parallel- Group Study Evaluating the Efficacy and Safety of Ixekizumab Versus Adalimumab in Patients With Psoriatic Arthritis Who Are Biologic Disease-Modifying Anti-Rheumatic Drug Naive
Actual Study Start Date : August 24, 2017
Actual Primary Completion Date : November 15, 2018
Estimated Study Completion Date : August 15, 2019


Arm Intervention/treatment
Experimental: Ixekizumab

160 milligrams (mg) ixekizumab given subcutaneously (SC) at baseline for all participants.

80 mg ixekizumab given once every 2 weeks (Q2W) SC from week 2 to week 12 and once every 4 weeks (Q4W) thereafter for participants with moderate-to-severe plaque Ps.

80 mg ixekizumab given SC Q4W starting week 4 for participants not meeting criteria for moderate-to-severe plaque Ps.

Drug: Ixekizumab
Administered SC
Other Name: LY2439821

Active Comparator: Adalimumab

80 mg adalimumab given SC at baseline followed by 40 mg Q2W given SC starting week 1 for participants with moderate-to-severe plaque Ps.

40 mg adalimumab given Q2W SC at baseline followed by 40 mg Q2W starting at Week 2 given SC for participants not meeting criteria for moderate-to-severe plaque Ps.

Drug: Adalimumab
Administered SC




Primary Outcome Measures :
  1. Percentage of Participants Simultaneously Achieving American College of Rheumatology 50 (ACR50) and Psoriasis Area and Severity Index 100 (PASI100) [ Time Frame: Week 24 ]
    ACR50 response is a ≥50% improvement from baseline for tender joint count(TJC)& swollen joint count (SJC)& in at least 3 of the following 5 criteria: Participant's(pts) assessment of joint pain Visual Analog Scale (VAS),Pts Global Assessment of Disease Activity (PatGA)VAS, Physician's Global Assessment of Disease Activity (PGA)VAS, Pts assessment of physical function using the Health Assessment Questionnaire-Disability Index(HAQ-DI), or High Sensitivity(assay)C-Reactive Protein (hs-CRP). PASI is an index combining assessments of the extent of body-surface involvement in head, trunk, arms, legs, and severity of desquamation, erythema and plaque thickness in each region, yielding overall score of 0-no involvement, to 72-most severe involvement. Pts achieving PASI100 were defined as having 100% improvement in the PASI score compared to baseline. Pts with active plaque PsO with a BSA≥3% & PASI=0 at baseline were considered PASI100 responders if they had achieved PASI=0 & BSA=0 at week 24.


Secondary Outcome Measures :
  1. Percentage of Participants Achieving ACR50 [ Time Frame: Week 24 ]
    ACR50 response is defined as a ≥50% improvement from baseline for tender joint count (TJC) and swollen joint count (SJC) and in at least 3 of the following 5 criteria: Participant's assessment of joint pain Visual Analog Scale (VAS), Participant's Global Assessment of Disease Activity (PatGA) VAS, Physician's Global Assessment of Disease Activity (PGA) VAS, participant's assessment of physical function using the Health Assessment Questionnaire-Disability Index (HAQ-DI), or High Sensitivity (assay) C-Reactive Protein (hs-CRP).

  2. Percentage of Participants Achieving PASI100 [ Time Frame: Week 24 ]
    PASI is an index combining assessments of the extent of body-surface involvement in head, trunk, arms, legs, and severity of desquamation, erythema and plaque thickness in each region, yielding overall score of 0-no involvement, to 72-most severe involvement. Participants achieving PASI100 were defined as having 100% improvement in the PASI score compared to baseline. Any participants with active plaque psoriasis (PsO) with a BSA ≥3% and PASI = 0 at baseline were considered PASI100 responders if & only if they had achieved PASI=0 & BSA=0 at week 24.

  3. Change From Baseline in TJC [ Time Frame: Baseline, Week 52 ]
    TJC is determined by examination of 68 joint counts that are assessed for tenderness by pressure and joint manipulation on physical examination.

  4. Change From Baseline in SJC [ Time Frame: Baseline, Week 52 ]
    SJC is determined by examination of 66 joint counts that are classified as either swollen or not swollen. Swelling is defined as palpable fluctuating synovitis of the joint.

  5. Change From Baseline in Participant's Assessment of Pain VAS [ Time Frame: Baseline, Week 52 ]
    Participants are asked to assess his/her current level of arthritis pain by marking a vertical tick on a horizontal VAS with the left end marked as "no pain" and the right end marked "worst possible pain."

  6. Change From Baseline in Participant's Global Assessment of Disease Activity [ Time Frame: Baseline, Week 52 ]
    The participant's overall assessment of his or her PsA activity is recorded using a horizontal VAS.

  7. Change From Baseline in Physician's Global Assessment of Disease Activity [ Time Frame: Baseline, Week 52 ]
    The investigator, who must be a physician, is asked to give an overall assessment of the severity of the participant's current PsA activity using a horizontal VAS.

  8. Change From Baseline in C-Reactive Protein (CRP) [ Time Frame: Baseline, Week 52 ]
    CRP is the ACR Core Set laboratory measure of acute-phase reactant.

  9. Change From Baseline in HAQ-DI [ Time Frame: Baseline, Week 52 ]
    HAQ-DI is a participant reported questionnaire that measures disease-associated disability (physical function). It consists of 24 questions with 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other daily activities. The disability section scores the participant's self-perception on the degree of difficulty (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do), covering the 8 domains. The reported use of special aids or devices and/or the need for assistance of another person to perform these activities is assessed. The HAQ-DI is a composite ranging from 0-3 with lower scores indicating less functional disability.

  10. Percentage of Participants Simultaneously Achieving ACR50 and PASI100 [ Time Frame: Week 52 ]
    Proportion of participants simultaneously achieving ACR50 and PASI100 will be derived from the number of participants who have achieved PASI100 and achieved ACR50 divided by the total number of participants.

  11. Change From Baseline in Disease Activity Score-CRP (DAS28-CRP) [ Time Frame: Baseline, Week 52 ]
    The DAS28-CRP is a measure of disease activity in 28 joints that consists of a composite numerical score with the following variables: TJC28, SJC28, hs-CRP (measured in milligrams per liter), and Participant's Global Assessment of Disease Activity recorded by participants on a 0 to 100 VAS. For DAS28-CRP, the Tender Joint Count 28 (TJC28) and Swollen Joint Count (SJC28) are a subset of TJC and SJC, and include 14 joints on each side of the body: 2 shoulders, 2 elbows, 2 wrists, 10 metacarpophalangeal joints, the 2 interphalangeal joints of the thumb, the 8 proximal interphalangeal joints, and the 2 knees.

  12. Percentage of Participants Achieving Minimal Disease Activity (MDA) [ Time Frame: Week 52 ]
    MDA is achieved if 5 of 7 outcome measures are fulfilled: TJC ≤1; SJC ≤1; psoriasis activity and severity index (PASI total score) ≤1 or BSA ≤3; participant pain VAS score of ≤15; participant global disease activity VAS score of ≤20; HAQ-DI score ≤0.5; and tender entheseal points ≤1.

  13. Percentage of Participants Achieving Psoriatic Arthritis Response Criteria (PsARC) [ Time Frame: Week 52 ]
    The PsARC is a composite criteria reported in terms of the percentage of participants achieving response according to the following criterion: TJC, SJC, PGA, and PatGA. Overall response is defined by improvement from baseline assessment in 2 of 4 criteria, 1 of which must be a joint count; there must not be worsening in any of the 4 criteria: at least 30% reduction in TJC, at least 30% reduction in SJC, at least a 20 millimeter (mm) reduction in PGA and at least a 20 mm reduction in PatGA.

  14. Change From Baseline in Modified Composite Psoriatic Disease Activity Index (CPDAI) Score (Modified) [ Time Frame: Baseline, Week 52 ]
    The CPDAI is a validated instrument intended to assess composite psoriatic disease activity and response to therapy. Domains include peripheral arthritis as assessed by the number of tender and swollen joints and the HAQ-DI, skin as assessed by the PASI and the Dermatology Life Quality Index (DLQI), enthesitis as assessed by the number of sites with enthesitis and the HAQ-DI, and dactylitis as assessed by the number of digits affected.

  15. Change From Baseline in the Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index in Participants With Enthesitis at Baseline [ Time Frame: Baseline, Week 52 ]
    The SPARCC enthesitis index evaluates tenderness in a total of 16 entheseal sites: the greater trochanter (right/left [R/L]), quadriceps tendon insertion into the patella (R/L), patellar ligament insertion into the patella and tibial tuberosity (R/L), Achilles tendon insertion (R/L), plantar fascia insertion (R/L), medial epicondyles of humerus (R/L),Lateral epicondyle humerus (R/L) and the supraspinatus insertion (R/L).

  16. Change From Baseline in the Leeds Enthesitis Index (LEI) in Participants With Enthesitis at Baseline [ Time Frame: Baseline, Week 52 ]
    The LEI was developed specifically for use in PsA. It measures enthesitis at 6 sites (lateral epicondyle of humerus, right/left (R/L); medial femoral condyle,(R/L); Achilles tendon insertion, (R/L)).

  17. Change From Baseline in the Leeds Dactylitis Index-Basic (LDI-B) in Participants With Dactylitis at Baseline [ Time Frame: Baseline, Week 52 ]
    The LDI-B measures the severity of dactylitis. In each digit, the ratio of the circumference of the affected digit to the circumference of the digit on the opposite hand or foot measured in mm. Each dactylitic digit is defined by a minimum increase of 10% in circumference over the contra-lateral digit.

  18. Change From Baseline in Psoriasis Body Surface Area (BSA) [ Time Frame: Baseline, Week 52 ]
    The investigator evaluates the percentage involvement of psoriasis on each participant's BSA on a continuous scale from 0% = no involvement to 100% = full involvement, where 1% corresponded to the size of the participant's handprint including the palm, fingers, and thumb.

  19. Change From Baseline in the Nail Psoriasis Severity Index (NAPSI) Fingernails Score in the Subgroup of Participants With Fingernail Involvement at Baseline [ Time Frame: Baseline, Week 52 ]
    The NAPSI scale is used to evaluate the severity of fingernail bed Ps and fingernail matrix Ps by area of involvement. The fingernail is divided into quadrants. Each fingernail is given a score for fingernail bed Ps 0 (none) to 4 (Ps in 4 quadrants of the fingernail) and fingernail matrix Ps 0 (none) to 4 (Ps in 4 quadrants of the matrix), depending on the presence (score of 1) or absence (score of 0) of any of the features of fingernail bed or matrix Ps in each quadrant. The sum of all fingernails equals the total NAPSI score range is from 0 (no effect) to 80 (more severe psoriasis).

  20. Change From Baseline in the Itch NRS [ Time Frame: Baseline, Week 52 ]
    The Itch NRS is a participant-administered, 11-point horizontal scale anchored at 0 and 10, with 0 representing "no itch" and 10 representing "worst itch imaginable." Overall severity of a participant's itching from psoriasis is indicated by circling the number that best described the worst level of itching in the past 24 hours.

  21. Change From Baseline in Fatigue Severity NRS (Fatigue NRS) Score [ Time Frame: Baseline, Week 52 ]
    The Fatigue Severity NRS is a participant-administered single-item 11-point horizontal scale anchored at 0 and 10, with 0 representing "no fatigue" and 10 representing "as bad as you can imagine." Participants rate their fatigue (weariness, tiredness) by circling the 1 number that described their worst level of fatigue during the past 24 hours.

  22. Change From Baseline in Medical Outcomes Study 36-item Short Form Health Survey (SF-36): Physical Component Summary (PCS) [ Time Frame: Baseline, Week 52 ]
    SF-36 is a standardized participant-administered measure designed to evaluate 8 domains of functional health and well-being.

  23. Change From Baseline in SF-36: Mental Component Summary (MCS) [ Time Frame: Baseline, Week 52 ]
    SF-36 is a standardized participant-administered measure designed to evaluate 8 domains of functional health and well-being.

  24. Change From Baseline in Measures of Health Utility (EuroQol-5 Dimensions 5 Level [EQ-5D 5L]) [ Time Frame: Baseline, Week 52 ]
    The EQ-5D-5L is a standardized measure of health status used to provide a simple, generic measure of health for clinical and economic appraisal. The EQ-5D-5L consists of 2 components: a descriptive system of the respondent's health and a rating of his/her current health state using a VAS. The descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.

  25. Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score [ Time Frame: Baseline, Week 52 ]
    DLQI is a participant-administered, 10-question, validated, quality-of-life questionnaire that covers 6 domains, including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment.

  26. Change From Baseline on the Treatment Satisfaction Questionnaire [ Time Frame: Baseline, Week 52 ]
    The Treatment Satisfaction Questionnaire is a clinician-administered questionnaire which provides an assessment of the participant's opinion of the effectiveness, safety, and overall satisfaction of the study medication.

  27. Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Baseline, Week 52 ]
    The C-SSRS is a scale that captures the occurrence, severity, and frequency of suicide-related ideations and behaviors during the assessment period.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Presents with established diagnosis of active psoriatic arthritis for at least 6 months, and currently meets Classification for Psoriatic Arthritis (CASPAR) criteria
  • Active PsA defined as the presence of at least 3 (out of 68) tender and at least 3 (out of 66) swollen joints
  • Presence of active plaque psoriasis with a BSA ≥3%
  • Men must agree to use a reliable method of birth control or remain abstinent during the study
  • Women must agree to use reliable birth control or remain abstinent during the study and for at least 12 weeks after stopping treatment
  • Have had an inadequate response when treated with 1 or more conventional synthetic disease-modifying antirheumatic drugs (csDMARDs)

Exclusion Criteria:

  • Current or prior use of biologic agents for treatment of Ps or PsA
  • Evidence of active inflammatory arthritic syndromes or spondyloarthropathies other than PsA
  • Have participated in any study with interleukin 17 (IL-17) antagonists, including ixekizumab
  • Serious disorder or illness other than psoriatic arthritis
  • Serious infection within the last 3 months
  • Active Crohn's disease or active ulcerative colitis
  • Active vasculitis or uveitis
  • Diagnosis of or history of malignant disease <5 years prior to randomization
  • Women who are breastfeeding

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03151551


  Show 131 Study Locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
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Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
  Study Documents (Full-Text)

Documents provided by Eli Lilly and Company:
Study Protocol  [PDF] May 26, 2017
Statistical Analysis Plan  [PDF] December 3, 2018


Additional Information:
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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT03151551     History of Changes
Other Study ID Numbers: 16687
I1F-MC-RHCF ( Other Identifier: Eli Lilly and Company )
2016-004585-25 ( EudraCT Number )
First Posted: May 12, 2017    Key Record Dates
Results First Posted: April 2, 2019
Last Update Posted: April 2, 2019
Last Verified: March 1, 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
URL: https://www.clinicalstudydatarequest.com/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Arthritis
Arthritis, Psoriatic
Joint Diseases
Musculoskeletal Diseases
Spondylarthropathies
Spondylarthritis
Spondylitis
Spinal Diseases
Bone Diseases
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
Adalimumab
Ixekizumab
Antirheumatic Agents
Anti-Inflammatory Agents
Dermatologic Agents