A Long-Term Efficacy and Safety Study of Ixekizumab (LY2439821) in Participants With Active Psoriatic Arthritis (SPIRIT P3)
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| ClinicalTrials.gov Identifier: NCT02584855 |
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Recruitment Status :
Completed
First Posted : October 23, 2015
Results First Posted : November 15, 2019
Last Update Posted : November 15, 2019
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Psoriatic Arthritis | Drug: Ixekizumab Drug: Placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 394 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 3, Multicenter Study With a 36-Week Open-Label Period Followed by a Randomized Double-Blind Withdrawal Period From Week 36 to Week 104 to Evaluate the Long-Term Efficacy and Safety of Ixekizumab (LY2439821) 80 mg Every 2 Weeks in Biologic Disease-Modifying Antirheumatic Drug-Naive Patients With Active Psoriatic Arthritis |
| Actual Study Start Date : | September 14, 2015 |
| Actual Primary Completion Date : | October 30, 2018 |
| Actual Study Completion Date : | October 30, 2018 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Ixekizumab Open Label
Open-Label Treatment Period: Starting dose of 160 milligrams (mg) ixekizumab given as two subcutaneous (SC) injections at baseline (week 0) followed by 80 mg given as one SC injection every two weeks (Q2W) from week 2 to randomization (week 36 to 64).
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Drug: Ixekizumab
Administered SC
Other Name: LY2439821 |
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Experimental: Ixekizumab
Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: 80 mg ixekizumab given as one SC injection Q2W from randomization to week 104 (or, early termination or relapse). |
Drug: Ixekizumab
Administered SC
Other Name: LY2439821 |
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Placebo Comparator: Placebo
Participants completed open label and met criteria for randomization to the double-blind Withdrawal Period. Double-Blind Withdrawal Period: Placebo given as one SC injection Q2W any time from randomization to week 104 (or, early termination or relapse) |
Drug: Ixekizumab
Administered SC
Other Name: LY2439821 Drug: Placebo Administered SC |
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Experimental: IXE80Q2W Non-randomized
Participants completed open label but did not meet criteria for randomization to the double-blind Withdrawal Period. Participants continued to receive 80 mg given as one SC injection every two weeks during the double-blind withdrawal period. |
Drug: Ixekizumab
Administered SC
Other Name: LY2439821 |
- Double-Blind Withdrawal Period: Time to Relapse (No Longer Meeting Coates Criteria for Minimal Disease Activity [MDA]) [ Time Frame: Double Blind Randomization through Week 104 (or Early Termination or Relapse) ]Relapse is loss of MDA response. MDA is achieved if 5 of 7 outcome measures are fulfilled:TJC ≤1;SJC ≤1;psoriasis activity & severity index(PASI total score) ≤1 or body surface area(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.Participants met the randomization criteria if they had MDA for 3 consecutive months over 4 consecutive visits.Time-to relapse was calculated in weeks as follows:((Date of Relapse) - Date of first injection of randomized study treatment in period 3)+1) divided by 7.If the date of first dose is missing,the date of randomization will be used.Participants completing Period 3 will be censored at date of completion(the date of the last scheduled visit in the period).Participants without a date of completion or discontinuation for Period 3 will be censored at latest non-missing date out of the following dates:date of last dose & date of last attended visit in Period 3.
- Double-Blind Withdrawal Period: Percentage of Participants Who Relapse in MDA [ Time Frame: Double Blind Randomization through Week 104 (or Early Termination or Relapse) ]Relapsed participants are defined as participants no longer meeting Coates criteria for MDA. 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 body surface area (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.
- Double-Blind Withdrawal Period: Time to Loss of Response in Each Individual Component of MDA: Tender Joint Count 68 (TJC) [ Time Frame: Double Blind Randomization through Week 104 (or Early Termination or Relapse) ]
TJC is the number of tender and painful joints determined for each participant by examination of 68 joints.TJC possible values range from 0 to 68. A lower TJC indicated less number of joints with tenderness. A higher TJC indicated more joint tenderness. Joints were assessed by pressure and joint manipulation on physical examination. Participants were asked for pain sensations on these manipulations and watched for spontaneous pain reactions. Any positive response on pressure, movement, or both was translated into a single tender-versus-nontender dichotomy.
Loss of Response = Not Meeting less than or equal to 1 TJC. Time to loss of response (in weeks) = (date of loss of response - date of first injection of randomized dose of study treatment in the Randomized Double-Blind Withdrawal Period + 1)/7.
- Double-Blind Withdrawal Period: Time to Loss of Response in Each Individual Component of MDA: Swollen Joint Count 66 (SJC) [ Time Frame: Double Blind Randomization through Week 104 (or Early Termination or Relapse) ]
SJC is the number of swollen joints determined for each participant by examination of 66 joints. SJC possible values range from 0 to 66. A lower SJC indicated less joints with swelling. A higher SJC indicated more joints with swelling. Swelling was defined as palpable fluctuating synovitis of the joint.
Loss of Response = Not Meeting less than or equal to 1 SJC. Time to loss of response (in weeks) = (date of loss of response - date of first injection of randomized dose of study treatment in the Randomized Double-Blind Withdrawal Period + 1)/7.
- Double-Blind Withdrawal Period: Time to Loss of Response in Each Individual Component of MDA: Psoriasis Area and Severity Index (PASI) [ Time Frame: Double Blind Randomization through Week 104 (or Early Termination or Relapse) ]
The PASI is an index that combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of desquamation, erythema, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 for no psoriasis to 72 for the most severe disease.
Loss of Response = Not Meeting less than or equal to 1 PASI total score. Time to loss of response (in weeks) = (date of loss of response - date of first injection of randomized dose of study treatment in the Randomized Double-Blind Withdrawal Period + 1)/7.
- Double-Blind Withdrawal Period: Time to Loss of Response in Each Individual Component of MDA: BSA [ Time Frame: Double Blind Randomization through Week 104 (or Early Termination or Relapse) ]
BSA is an investigator evaluated measure, where the percentage of involvement of psoriasis on each participant's BSA is assessed. BSA was measured 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. Loss of Response = Not meeting less than or equal to 3% BSA.
Time to loss of response (in weeks) = (date of loss of response - date of first injection of randomized dose of study treatment in the Randomized Double-Blind Withdrawal Period + 1)/7.
- Double-Blind Withdrawal Period: Time to Loss of Response in Each Individual Component of MDA: Pain Visual Analog Scale (VAS) Score [ Time Frame: Double Blind Randomization through Week 104 (or Early Termination or Relapse) ]The pain VAS is an instrument used to measure a person's subjective quantitative evaluation of an item such as pain intensity. The VAS contains a continuous line between two endpoints whereby the respondent places a mark on the line to indicate his or her response The scale ranges from 0 (no pain) to 100 (unbearable pain). The scores were measured to the nearest millimeter from the left. Loss of Response = Not Meeting less than or equal to 15 Pain VAS. Time to loss of response (in weeks) = (date of loss of response - date of first injection of randomized dose of study treatment in the Randomized Double-Blind Withdrawal Period + 1)/7.
- Double-Blind Withdrawal Period: Time to Loss of Response in Each Individual Component of MDA: Patients Global Assessment of Disease Activity (PatGA) Visual Analog Scale (VAS) Score [ Time Frame: Double Blind Randomization through Week 104 (or Early Termination or Relapse) ]
Participants scored their overall assessment of their psoriatic arthritis (PsA) activity on a 0 to 100 mm horizontal VAS. The scale ranged from 0 (no disease activity) to 100 (extremely active disease activity). The scores were measured to the nearest millimeter from the left.
Loss of Response = Not Meeting less than or equal to 20 PatGA. Time to loss of response (in weeks) = (date of loss of response - date of first injection of randomized dose of study treatment in the Randomized Double-Blind Withdrawal Period + 1)/7.
- Double-Blind Withdrawal Period: Time to Loss of Response in Each Individual Component of MDA: Health Assessment Questionnaire-Disability Index (HAQ-DI) [ Time Frame: Double Blind Randomization through Week 104 (or Early Termination or Relapse) ]
The HAQ-DI questionnaire assesses 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)] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (severe disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition.
Loss of Response = Not Meeting less than or equal to 0.5 HAQ-DI. Time to loss of response (in weeks) = (date of loss of response - date of first injection of randomized dose of study treatment in the Randomized Double-Blind Withdrawal Period + 1)/7.
- Double-Blind Withdrawal Period: Time to Loss of Response in Each Individual Component of MDA: Tender Entheseal Points [ Time Frame: Double Blind Randomization through Week 104 (or Early Termination or Relapse) ]Tender entheseal points was based on the assessment of the 18 entheseal points. Loss of Response = Not Meeting less than or equal to 1 Tender Entheseal Point. Time to loss of response (in weeks) = (date of loss of response - date of first injection of randomized dose of study treatment in the Randomized Double-Blind Withdrawal Period + 1)/7.
- Open-Label Treatment Period: Time to Achieve Randomization Criteria (Meeting MDA for 3 Consecutive Months Over 4 Consecutive Visits) [ Time Frame: Open Label Baseline through Double-Blind Randomization (Week 36 to 64) ]
Time to meeting MDA for 3 Consecutive Months Over 4 Consecutive Visits. Time to first response (in weeks) = [(date of first response - date of first injection of study treatment in the Open-Label Treatment Period)+1]/7.
Open-Label Treatment Period ended at the time when a participant was randomized so the end time was not the same for all participants. Participants were randomized only if they met randomization criteria which was at anytime from week 36 to week 64.
- Double-Blind Withdrawal Period: Time to Re-Gain MDA Following Relapse in MDA [ Time Frame: Relapse in MDA After Double Blind Randomization through Week 104 (or Early Termination) ]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. Time to first response (in weeks) = (date of first response - date of first injection of study treatment in the Relapse Period + 1)/7.
- Double-Blind Withdrawal Period: Change From Baseline in Physical Functioning Assessed by the Health Assessment Questionnaire-Disability Index (HAQ-DI) [ Time Frame: Baseline, 40 Weeks from Double Blind Randomization (Week 36 to 64) ]
The HAQ-DI questionnaire assesses 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)] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (severe disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition.Least Square (LS) mean calculated using Mixed Model Repeated Measurements (MMRM) analysis with treatment group, baseline measure, geographic region, cDMARD use, treatment week, baseline measure-by-treatment week interaction term, and treatment week-by-treatment interaction term as fixed factors.
Participants were randomized only if they met randomization criteria which was at anytime from week 36 to week 64.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Presents with established diagnosis of active psoriatic arthritis (PsA) for at least 6 months, and currently meets Classification for Psoriatic Arthritis (CASPAR) criteria
- Active PsA defined as the presence of at least 3 tender and at least 3 swollen joints
- Presence of active psoriatic skin lesion or a history of plaque psoriasis (Ps)
- 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 been treated with 1 or more conventional disease-modifying antirheumatic drugs (cDMARDs)
Exclusion Criteria:
- Current or prior use of biologic agents for treatment of Ps or PsA
- Inadequate response to greater than or equal to 4 conventional disease-modifying antirheumatic drugs (DMARDS)
- Current use of more than one cDMARDs
- Diagnosis of active inflammatory arthritic syndromes or spondyloarthropathies other than PsA
- Have received treatment with interleukin (IL) -17 or IL12/23 targeted monoclonal antibody (MAb) therapy
- Serious disorder or illness other than psoriatic arthritis
- Serious infection within the last 3 months
- Breastfeeding or nursing (lactating) women
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): NCT02584855
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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 |
Documents provided by Eli Lilly and Company:
| Responsible Party: | Eli Lilly and Company |
| ClinicalTrials.gov Identifier: | NCT02584855 |
| Other Study ID Numbers: |
14518 I1F-MC-RHBF ( Other Identifier: Eli Lilly and Company ) 2015-002433-22 ( EudraCT Number ) |
| First Posted: | October 23, 2015 Key Record Dates |
| Results First Posted: | November 15, 2019 |
| Last Update Posted: | November 15, 2019 |
| Last Verified: | November 2018 |
| 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://vivli.org/ |
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Spondyloarthritis Spondylarthropathy |
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Arthritis Arthritis, Psoriatic Joint Diseases Musculoskeletal Diseases Spondylarthropathies Spondylarthritis Spondylitis |
Spinal Diseases Bone Diseases Psoriasis Skin Diseases, Papulosquamous Skin Diseases Ixekizumab Dermatologic Agents |