A Study Comparing Risankizumab to Placebo in Participants With Active Psoriatic Arthritis (PsA) Who Have a History of Inadequate Response to or Intolerance to at Least One Disease Modifying Anti-Rheumatic Drug (DMARD) Therapy (KEEPsAKE 1)

• ClinicalTrials.gov Identifier: NCT03675308
• Recruitment Status: Active, not recruiting
• First Posted: September 18, 2018
• Results First Posted: February 24, 2022
• Last Update Posted: May 11, 2023
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: September 12, 2018
• First Posted Date: September 18, 2018
• Results First Submitted Date: January 24, 2022
• Results First Posted Date: February 24, 2022
• Last Update Posted Date: May 11, 2023
• Actual Study Start Date: March 25, 2019
• Actual Primary Completion Date: October 8, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 24, 2022)

Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 24 [ Time Frame: Baseline and Week 24 ]

Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR20 response criteria:

1. ≥ 20% improvement in 68-tender joint count;
2. ≥ 20% improvement in 66-swollen joint count; and
3. ≥ 20% improvement in at least 3 of the 5 following parameters:
   • Physician global assessment of disease activity
   • Patient global assessment of disease activity
   • Patient assessment of pain
   • Health Assessment Questionnaire - Disability Index (HAQ-DI)
   • High-sensitivity C-reactive protein (hsCRP).

Original Primary Outcome Measures (submitted: September 15, 2018)

Percentage of Participants Achieving at least 20% Improvement in American College of Rheumatology (ACR20) at Week 24 [ Time Frame: Baseline, Week 24 ]

ACR20 is defined as at least 20% improvement in swollen joint count, tender joint count, and at least 3 out of the following 5 variables: 1) Patient's Assessment of psoriatic arthritis (PsA) Pain Intensity visual analog scale (VAS), 2) Patient's Global Assessment of Disease VAS, 3) Physician's Global Assessment of Disease Activity VAS, 4) Patient's Assessment of Disability on Health Assessment Questionnaire Disability Index (HAQ-DI), and 5) Serum high-sensitivity C-reactive protein (serum hs-CRP).

Current Secondary Outcome Measures (submitted: January 24, 2022)

• Change From Baseline In Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 24 [ Time Frame: Baseline and Week 24 ]
  The Health Assessment Questionnaire Disability Index is a patient-reported questionnaire that measures the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Participants assessed their ability to do each task on a scale from 0 (without any difficulty) to 3 (unable to do). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability. A negative change from Baseline in the overall score indicates improvement.
• Percentage of Participants Achieving Psoriasis Area Severity Index (PASI) 90 Response at Week 24 [ Time Frame: Baseline and Week 24 ]
  PASI is a composite score based on the percentage of the body surface area (BSA) affected by psoriasis and the intensity of erythema (reddening), induration (thickening or hardening of the skin), and desquamation (peeling of the skin) of lesions assessed at 4 anatomic sites (head, upper extremities, trunk, and lower extremities). At each location, the percentage of BSA involvement is assigned a score from 0 (no involvement) to 6 (90% to 100% involvement), and erythema, induration, and desquamation are scored on a scale from 0 (no symptoms) to 4 (very marked). The PASI score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI 90 response is the percentage of participants who achieved at least a 90% reduction (improvement) from Baseline in PASI score.
• Percentage of Participants With an ACR20 Response at Week 16 [ Time Frame: Baseline and Week 16 ]
  Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR20 response criteria:

  1. ≥ 20% improvement in 68-tender joint count;
  2. ≥ 20% improvement in 66-swollen joint count; and
  3. ≥ 20% improvement in at least 3 of the 5 following parameters:
     • Physician global assessment of disease activity
     • Patient global assessment of disease activity
     • Patient assessment of pain
     • Health Assessment Questionnaire - Disability Index (HAQ-DI)
     • High-sensitivity C-reactive protein (hsCRP).
• Percentage of Participants Achieving Minimal Disease Activity (MDA) at Week 24 [ Time Frame: Week 24 ]
  A participant was classified as achieving MDA if 5 of the following 7 criteria were met:

  • Tender joint count (out of 68 joints) ≤ 1
  • Swollen joint count (out of 66 joints) ≤ 1
  • PASI score ≤ 1 (score ranges from 0 - 72) or percent BSA involved with psoriasis ≤ 3%
  • Patient's assessment of pain ≤ 15 (VAS from 0 to 100)
  • Patient's Global Assessment of disease activity ≤ 20 (VAS from 0 to 100)
  • HAQ-DI score ≤ 0.5 (index score ranges from 0 to 3)
  • Leeds Enthesitis Index ≤ 1 (assesses the presence or absence of enthesitis at 3 bilateral sites, for an overall score range from 0 to 6)
• Change From Baseline in Modified Nail Psoriasis Severity Index (mNAPSI) Score at Week 24 [ Time Frame: Baseline and Week 24 ]
  The investigator assessed each fingernail for onycholysis (separation of the nail plate from the nail bed) and oil-drop (salmon patch) dyschromia (reddish-brown discoloration under the nail plate) on a scale of 0 (none present) to 3 (>30% of the nail), pitting (small, sharply defined depressions in the nail surface) on a scale of 0 (0 pits present) to 3 (> 50 pits present), and nail plate crumbling on a scale of 0 (no crumbling) to 3 (>50% of nail has crumbling) and presence (1) or absence (0) of leukonychia (white spots), splinter hemorrhages, nail bed hyperkeratosis, and red spots in the lunula. The mNAPSI score is calculated as the sum of all the components for all of the participant's fingernails giving a range of possible scores from 0 (absence of nail psoriasis) to 130 (the most severe nail psoriasis). A negative change from Baseline indicates improvement.
• Change From Baseline in Fingernail-Physician Global Assessment (PGA-F) [ Time Frame: Baseline and Week 24 ]
  The PGA-F is a clinician-rated outcomes assessment used to measure the severity of signs and symptoms associated with fingernail psoriasis. Participant's fingernails were assessed separately for nail bed signs and nail matrix signs of disease on a scale from 0 (clear) to 4 (severe). A participant's overall global score is the worse of the nail bed score and nail matrix score. For example, if a participant had a nail bed score '2' and a nail matrix score of '4,' this participant's overall score was '4.' A negative change from Baseline indicates improvement.
• Percentage of Participants With Resolution of Enthesitis at Week 24 [ Time Frame: Week 24 ]
  Resolution of enthesitis is defined as a Leeds Enthesitis Index (LEI) score = 0. LEI is an enthesitis measure developed specifically for PsA and assesses the presence or absence of tenderness at the following 3 bilateral enthesial sites: medial femoral condyles, lateral epicondyles of the humerus, and Achilles tendon insertions. Tenderness on examination is recorded as either present (coded as 1), absent (coded as 0), or not assessed for each of the 6 sites. The LEI is calculated by taking the sum of the scores from the 6 sites. The LEI ranges from 0 to 6 (worst). To increase the sample size due to the smaller number of participants with enthesitis at Baseline, the pre-specified analysis of the resolution of enthesitis included pooled data from KEEPsAKE 1 (this study) and the companion study KEEPsAKE 2 (M15-998; NCT03671148).
• Percentage of Participants With Resolution of Dactylitis at Week 24 [ Time Frame: Week 24 ]
  Resolution of dactylitis is defined as a Leeds Dactylitis Index (LDI) score = 0. LDI basic is a score based on finger circumference and tenderness, assessed across all digits. The LDI basic measures the ratio of the circumference of the affected digit to the circumference of the digit on the opposite hand or foot, using a minimum difference of 10% to define a dactylitic digit. The ratio of circumference is multiplied by a tenderness score (1 for tender, 0 for non-tender). If both sides of a digit are considered involved, or the circumference of the contralateral digit cannot be obtained, a standard reference table is used. Scores from each digit are summed to provide the final LDI. A higher LDI indicates worse dactylitis. To increase sample size due to the smaller number of participants with dactylitis at Baseline, the pre-specified analysis of the resolution of dactylitis included pooled data from KEEPsAKE 1 (this study) and the companion study KEEPsAKE 2 (M15-998; NCT03671148).
• Change From Baseline in PsA Modified Total Sharp Score (mTSS) at Week 24 [ Time Frame: Baseline and Week 24 ]
  The Sharp-van der Heijde modified scoring method for PsA measures the level of joint damage from radiographs of the hands and feet, and was assessed by 2 independent, blinded readers. Joint erosion severity was assessed in 20 joints in each hand and wrist and 6 joints in each foot. Each joint was scored from 0 (no erosion) to 5 for hands/wrists or to 10 for feet (complete collapse). The total erosion score ranges from 0 to 320 (worst). Joint space narrowing (JSN) was assessed in 20 joints of each hand and wrist, and 6 joints of each foot, from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation). The total JSN score ranges from 0 to 208 (worst). Joints with gross osteolysis or pencil in cup were assigned the maximum score for both erosions and JSN. The total mTSS score is the sum of the joint erosion and JSN scores and ranges from 0 (normal) to 528 (worst).
• Change From Baseline In 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score at Week 24 [ Time Frame: Baseline and Week 24 ]
  The Short Form 36-Item Health Survey (SF-36) Version 2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The physical component summary is a weighted combination of the 8 subscales with positive weighting for physical functioning, role-physical, bodily pain, and general health. The SF-36 PCS ranges from 0 to 100. A linear algorithm was applied to the calculation of the PCS which has a normative mean value of 50. Higher scores are associated with less disability; a score of 100 is equivalent to no disability and a score of 0 is equivalent to maximum disability. A positive change from Baseline score indicates improvement.
• Change From Baseline In Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24 [ Time Frame: Baseline and Week 24 ]
  The FACIT-Fatigue questionnaire is a self-administered patient questionnaire that consists of 13 questions designed to measure the degree of fatigue experienced by participants in the previous 7 days, including physical fatigue (e.g., I feel tired), functional fatigue (e.g., trouble finishing things), emotional fatigue (e.g., frustration), and social consequences of fatigue (e.g., limits social activity). Participants respond to the questions on a scale from 0 (not at all) to 4 (very much). The FACIT-Fatigue score is computed by summing the item scores, after reversing those items that are worded in the negative direction. The FACIT-Fatigue score ranges from 0 to 52, where higher scores represent less fatigue. A positive change from Baseline indicates improvement.
• Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 24 [ Time Frame: Baseline and Week 24 ]
  Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR50 response criteria:

  1. ≥ 50% improvement in 68-tender joint count;
  2. ≥ 50% improvement in 66-swollen joint count; and
  3. ≥ 50% improvement in at least 3 of the 5 following parameters:
     • Physician global assessment of disease activity
     • Patient global assessment of disease activity
     • Patient assessment of pain
     • Health Assessment Questionnaire - Disability Index (HAQ-DI)
     • High-sensitivity C-reactive protein (hsCRP).
• Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 24 [ Time Frame: Baseline and Week 24 ]
  Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR70 response criteria:

  1. ≥ 70% improvement in 68-tender joint count;
  2. ≥ 70% improvement in 66-swollen joint count; and
  3. ≥ 70% improvement in at least 3 of the 5 following parameters:
     • Physician global assessment of disease activity
     • Patient global assessment of disease activity
     • Patient assessment of pain
     • Health Assessment Questionnaire - Disability Index (HAQ-DI)
     • High-sensitivity C-reactive protein (hsCRP).

Original Secondary Outcome Measures (submitted: September 15, 2018)

• Change from Baseline to Week 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI) [ Time Frame: Baseline, Week 24 ]
  The HAQ-DI is a self-reported questionnaire of how the patient's illness affects their ability to function in their daily life over the past week.
• Percentage of Participants With ≥ 90% Reduction from Baseline Psoriasis Area and Severity Index (PASI 90) at Week 24 in Participants With ≥ 3% Body Surface Area (BSA) Involving Psoriasis at Baseline [ Time Frame: Baseline, Week 24 ]
  PASI90 denotes greater than or equal to 90% improvement in PASI score. PASI provides a quantitative assessment of psoriasis disease state based on the amount of body surface area that is affected and the degree of severity.
• Change from Baseline to Week 24 in modified Total Sharp Score (PsA-mTSS) at Week 24 [ Time Frame: Baseline, Week 24 ]
  The modified PsA-mTSS method is used to evaluate radiographic evidence of damage.
• Percentage of Participants Achieving Minimal Disease Activity (MDA) at Week 24 [ Time Frame: Baseline, Week 24 ]
  The percentage of participants who achieve MDA.
• Change from Baseline to Week 24 in Fingernail Psoriasis [ Time Frame: Baseline, Week 24 ]
  Fingernail psoriasis will be evaluated using either the Physician Global Assessment - Fingernails (PGA-F) or the modified Nail Psoriasis Severity Index (mNAPSI), depending on location.
• Change from Baseline to Week 24 in Leeds Enthesitis Index (LEI) in Participants with Enthesitis at Baseline [ Time Frame: Baseline, Week 24 ]
  The LEI will be used to assess the presence or absence of enthesitis.
• Change from Baseline to Week 24 in Leeds Dactylitis Index (LDI) in Participants With Dactylitis at Baseline [ Time Frame: Baseline, Week 24 ]
  The LDI will be used to assess the presence or absence of dactylitis.
• Change from Baseline to Week 24 in the 36-Item Short Form Health Questionnaire (SF-36) Physical Component Summary (PCS) Score [ Time Frame: Baseline, Week 24 ]
  The SF-36 is a 36-item, general health, self-administered questionnaire.
• Change from Baseline to Week 24 in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaire Score [ Time Frame: Baseline, Week 24 ]
  The FACIT-Fatigue is a 13-item questionnaire that evaluates fatigue/tiredness and its impact on daily activities and functioning in chronic diseases.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study Comparing Risankizumab to Placebo in Participants With Active Psoriatic Arthritis (PsA) Who Have a History of Inadequate Response to or Intolerance to at Least One Disease Modifying Anti-Rheumatic Drug (DMARD) Therapy
• Official Title: A Phase 3, Randomized, Double-Blind, Study Comparing Risankizumab to Placebo in Subjects With Active Psoriatic Arthritis (PsA) Who Have a History of Inadequate Response to or Intolerance to at Least One Disease Modifying Anti-Rheumatic Drug (DMARD) Therapy (KEEPsAKE 1)
• Brief Summary: The purpose of this study is to compare the safety and efficacy of risankizumab versus placebo in participants with moderately to severely active psoriatic arthritis (PsA).
• Detailed Description: The study consists of a Screening Period (approximately 35 days), Period 1, Period 2, and a 20-week Follow-up Period. Period 1 is a 24-week randomized, double-blind, placebo-controlled, parallel-group treatment period. Period 2 is the long-term treatment period and starts at Week 24. To maintain the blind to the original treatment allocation, treatment at the Week 24 Visit is blinded: participants randomized to placebo receive blinded risankizumab 150 mg, and participants randomized to risankizumab receive blinded placebo. At Week 28 and for the remaining dosing visits (to Week 316), all participants are to receive open-label risankizumab 150 mg every 12 weeks. Participants will remain blinded to the original randomization allocation for the duration of the study. The total study duration is 336 weeks including a telephone call 140 days (20 weeks) after last dose of study drug.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Psoriatic Arthritis

Intervention

• Biological: Placebo
  Placebo for risankizumab administered by subcutaneous injection
• Biological: Risankizumab
  Risankizumab administered by subcutaneous injection
  Other Names:

  • ABBV-066
  • BI 655066
  • SKYRIZI

Study Arms

• Placebo Comparator: Placebo
  Participants randomized to receive double-blind placebo at Week 0, Week 4, and Week 16 in Period 1. At Week 24 participants will receive 150 mg risankizumab followed by open-label 150 mg risankizumab at Week 28, and every 12 weeks thereafter in Period 2 until the final dosing time point at Week 316.
  Interventions:

  • Biological: Placebo
  • Biological: Risankizumab
• Experimental: Risankizumab
  Participants randomized to receive 150 mg risankizumab administered by subcutaneous injection at Week 0, Week 4, and Week 16 in Period 1. At Week 24 participants will receive blinded placebo followed by open-label 150 mg risankizumab at Week 28, and every 12 weeks thereafter in Period 2 until the final dosing time point at Week 316.
  Interventions:

  • Biological: Placebo
  • Biological: Risankizumab

Publications *

• Kristensen LE, Keiserman M, Papp K, McCasland L, White D, Lu W, Wang Z, Soliman AM, Eldred A, Barcomb L, Behrens F. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 1 trial. Ann Rheum Dis. 2022 Feb;81(2):225-231. doi: 10.1136/annrheumdis-2021-221019. Epub 2021 Dec 15.
• Kristensen LE, Keiserman M, Papp K, McCasland L, White D, Lu W, Soliman AM, Eldred A, Barcomb L, Behrens F. Efficacy and safety of risankizumab for active psoriatic arthritis: 52-week results from the KEEPsAKE 1 study. Rheumatology (Oxford). 2022 Oct 25:keac607. doi: 10.1093/rheumatology/keac607. Online ahead of print.
• Thakre N, D'Cunha R, Goebel A, Liu W, Pang Y, Suleiman AA. Population Pharmacokinetics and Exposure-Response Analyses for Risankizumab in Patients with Active Psoriatic Arthritis. Rheumatol Ther. 2022 Dec;9(6):1587-1603. doi: 10.1007/s40744-022-00495-0. Epub 2022 Sep 30.
• Kristensen LE, Soliman AM, Papp K, White D, Barcomb L, Lu W, Eldred A, Behrens F. Risankizumab improved health-related quality of life, fatigue, pain and work productivity in psoriatic arthritis: results of KEEPsAKE 1. Rheumatology (Oxford). 2023 Feb 1;62(2):629-637. doi: 10.1093/rheumatology/keac342.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 24, 2022): 964
• Original Estimated Enrollment (submitted: September 15, 2018): 880
• Estimated Study Completion Date: September 28, 2026
• Actual Primary Completion Date: October 8, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Clinical diagnosis of PsA with symptom onset at least 6 months prior to the Screening Visit and fulfillment of the Classification Criteria for PsA (CASPAR) at the Screening Visit.
• Participant has active disease at Baseline defined as ≥ 5 tender joints (based on 68 joint counts) and ≥ 5 swollen joints (based on 66 joint counts)
• Diagnosis of active plaque psoriasis with at least one psoriatic plaque of ≥ 2 cm diameter or nail changes consistent with psoriasis at Screening Visit.
• Participant has demonstrated an inadequate response or intolerance to or contraindication for conventional synthetic disease modifying anti-rheumatic drugs (csDMARD) therapy(ies).

• Presence of either at Screening:

  • ≥ 1 erosion on radiograph as determined by central imaging review or;
  • High sensitivity C-reactive protein (hsCRP) ≥ 3.0 mg/L.

Exclusion Criteria:

• Participant is considered by investigator, for any reason, to be an unsuitable candidate for the study.
• Participant has a known hypersensitivity to risankizumab.
• Participant has previous treatment with biologic agent.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Belgium, Bosnia and Herzegovina, Brazil, Bulgaria, Canada, Chile, Croatia, Czechia, Denmark, Estonia, Finland, Germany, Greece, Israel, Italy, Korea, Republic of, Latvia, Lithuania, Malaysia, Mexico, Netherlands, New Zealand, Poland, Portugal, Puerto Rico, Romania, Russian Federation, Serbia, Singapore, Slovakia, South Africa, Spain, Sweden, Taiwan, Ukraine, United Kingdom, United States
• Removed Location Countries: Slovenia

Administrative Information

• NCT Number: NCT03675308
• Other Study ID Numbers: M16-011; 2017-002465-22 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: For details on when studies are available for sharing, please refer to the link below.
• Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Use Agreement (DUA). For more information on the process, or to submit a request, visit the following link.
• URL: https://vivli.org/ourmember/abbvie/

• Current Responsible Party: AbbVie
• Original Responsible Party: Same as current
• Current Study Sponsor: AbbVie
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: ABBVIE INC.; AbbVie

• PRS Account: AbbVie
• Verification Date: April 2023