An Open-label Extension Study Evaluating the Safety and Efficacy of Upadacitinib (ABT-494) in Rheumatoid Arthritis Subjects

• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Tracking Information

• First Submitted Date: January 28, 2014
• First Posted Date: January 30, 2014
• Last Update Posted Date: February 25, 2019
• Actual Study Start Date: January 24, 2014
• Estimated Primary Completion Date: February 20, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 21, 2019)

• Change in Work Instability Scale - Rheumatoid Arthritis (RA-WIS) [ Time Frame: From Week 0 to Week 312 ]
  Using RA-WIS scale
• Change in EQ-5D [ Time Frame: From Week 0 to Week 312 ]
  Using the EuroQol-5D scale
• ACR 70 Response Rate [ Time Frame: Up to Week 312 ]
  ACR criteria measures improvement in tender or swollen joint counts.
• Change in Health Assessment Questionnaire Disability Index [ Time Frame: From Week 0 to Week 312 ]
  Determined by the Health Assessment Questionnaire (HAQ-DI)
• Change in High-Sensitivity C-Reactive Protein (hsCRP) [ Time Frame: From Week 0 to Week 312 ]
  Determined by hsCRP lab test
• Change in Patient's Global Assessment of Disease Activity [ Time Frame: From Week 0 to Week 312 ]
  Determined by VAS
• Change in DAS28 [CRP] [ Time Frame: From Week 0 to Week 312 ]
  DAS28 [CRP] calculation
• Change in Patient's Assessment of Pain [ Time Frame: From Week 0 to Week 312 ]
  Determined by the Joint Evaluation, Visual Analog Scale (VAS), EuroQoL-5D (EQ-5D)
• Change in Swollen Joint Count [ Time Frame: From Week 0 to Week 312 ]
  Swollen Joint Count will be assessed by a qualified Independent Joint Assessor or Principal Investigator using the Joint Evaluation Worksheet.
• Change in CDAI [ Time Frame: From Week 0 to Week 312 ]
  The sum of tender and swollen joint counts [28 joints] and patient and physician global assessments
• ACR 50 Response Rate [ Time Frame: Up to Week 312 ]
  ACR criteria measures improvement in tender or swollen joint counts.
• Proportion of subjects achieving Low Disease Activity [ Time Frame: Up to Week 312 ]
  Determined by disease activity score using 28 joint counts (DAS28) [CRP] or clinical disease activity index (CDAI) criteria
• Change in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Scale [ Time Frame: From Week 0 to Week 312 ]
  Using the FACIT Fatigue Scale
• American College Rheumatology (ACR) 20 Response Rate [ Time Frame: Up to Week 312 ]
  ACR criteria measures improvement in tender or swollen joint counts.
• Proportion of subjects achieving Clinical Remission [ Time Frame: Up to Week 312 ]
  Determined by DAS28 [CRP] and CDAI criteria
• Change in Tender Joint Count [ Time Frame: From Week 0 to Week 312 ]
  Tender Joint Count will be assessed by a qualified Independent Joint Assessor or Principal Investigator using the Joint Evaluation Worksheet.
• Change in Clinical Laboratory Data [ Time Frame: From Week 0 through 30 day follow-up visit (30 days after last dose of study drug) ]
  Clinical Laboratory Data include hematology, clinical chemistry and urinalysis
• Proportion of subjects with satisfactory humoral response to Prevnar 13 [ Time Frame: Week 4 of the sub-study (approximately 136 weeks) ]
  Satisfactory response is defined as greater than or equal to 2-fold increase in antibody concentration from the vaccination baseline in at least 6 out of the 12 pneumococcal antigens.

Original Primary Outcome Measures (submitted: January 28, 2014)

• American College Rheumatology (ACR) 20 Response Rate [ Time Frame: Up to Week 96 ]
  ACR criteria measures improvement in tender or swollen joint counts.
• ACR 50 Response Rate [ Time Frame: Up to Week 96 ]
  ACR criteria measures improvement in tender or swollen joint counts.
• ACR 70 Response Rate [ Time Frame: Up to Week 96 ]
  ACR criteria measures improvement in tender or swollen joint counts.
• Change in Tender Joint Count [ Time Frame: From Week 0 to Week 96 ]
  Tender Joint Count will be assessed by a qualified Independent Joint Assessor or Principal Investigator using the Joint Evaluation Worksheet.
• Change in Swollen Joint Count [ Time Frame: From Week 0 to Week 96 ]
  Swollen Joint Count will be assessed by a qualified Independent Joint Assessor or Principal Investigator using the Joint Evaluation Worksheet.
• Change in Patient's Assessment of Pain [ Time Frame: From Week 0 to Week 96 ]
  Determined by the Joint Evaluation, Visual Analog Scale (VAS), EuroQoL-5D (EQ-5D)
• Change in Patient's Global Assessment of Disease Activity [ Time Frame: From Week 0 to Week 96 ]
  Determined by VAS
• Change in High-Sensitivity C-Reactive Protein (hsCRP) [ Time Frame: From Week 0 to Week 96 ]
  Determined by hsCRP lab test
• Change in Health Assessment Questionnaire Disability Index [ Time Frame: From Week 0 to Week 96 ]
  Determined by the Health Assessment Questionnaire (HAQ-DI)
• Proportion of subjects achieving Low Disease Activity [ Time Frame: Up to Week 96 ]
  Determined by disease activity score using 28 joint counts (DAS28) [CRP] or clinical disease activity index (CDAI) criteria
• Proportion of subjects achieving Clinical Remission [ Time Frame: Up to Week 96 ]
  Determined by DAS28 [CRP] and CDAI criteria
• Change in DAS28 [CRP] [ Time Frame: From Week 0 to Week 96 ]
  DAS28 [CRP] calculation
• Change in CDAI [ Time Frame: From Week 0 to Week 96 ]
  The sum of tender and swollen joint counts [28 joints] and patient and physician global assessments
• Change in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Scale [ Time Frame: From Week 0 to Week 96 ]
  Using the FACIT Fatigue Scale
• Change in Work Instability Scale - Rheumatoid Arthritis (RA-WIS) [ Time Frame: From Week 0 to Week 96 ]
  Using RA-WIS scale
• Change in EQ-5D [ Time Frame: From Week 0 to Week 96 ]
  Using the EuroQol-5D scale
• Incidence of Adverse Events [ Time Frame: Up to 30 day follow-up visit (30 days after last dose of study drug) ]
• Change in Vital Signs [ Time Frame: From Week 0 to 30 day follow-up visit (30 days after the last dose of study drug) ]
  Vital Signs include blood pressure, pulse rate, respiratory rate and body temperature
• Change in Physical Examination [ Time Frame: From Week 0 through 30 day follow-up visit (30 days after last dose of study drug) ]
  A symptom-directed physical exam will be performed when necessary, as per Investigator's judgment.
• Change in Clinical Laboratory Data [ Time Frame: From Week 0 through 30 day follow-up visit (30 days after last dose of study drug) ]
  Clinical Laboratory Data include hematology, clinical chemistry and urinalysis

• Change History: Complete list of historical versions of study NCT02049138 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: March 12, 2018)

• Proportion of subjects with satisfactory humoral response to Prevnar 13 [ Time Frame: Week 12 of the sub-study (approximately 252 weeks) ]
  Satisfactory response is defined as greater than or equal to 2-fold increase in antibody concentration from the vaccination baseline in at least 6 out of the 12 pneumococcal antigens
• Change in geometric mean fold rise of anti-pneumococcal antibody levels [ Time Frame: Up to Week 12 of the sub-study (approximately 252 weeks) ]
  Anti-pneumococcal antibody levels to each of the 12 pneumococcal antigens above vaccination baseline values.

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

Descriptive Information

• Brief Title: An Open-label Extension Study Evaluating the Safety and Efficacy of Upadacitinib (ABT-494) in Rheumatoid Arthritis Subjects
• Official Title: A Phase 2 Study, Multicenter, Open-Label Extension (OLE) Study in Rheumatoid Arthritis Subjects Who Have Completed a Preceding Phase 2 Randomized Controlled Trial (RCT) With Upadacitinib (ABT-494)
• Brief Summary: This is a Phase 2, multicenter, open-label extension study in RA subjects. The sub-study is to assess the impact of upadacitinib treatment (15 mg QD and 30 mg QD) with background MTX on immunological responses to Prevnar 13® in RA patients.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Rheumatoid Arthritis

Intervention

Drug: ABT-494

Other Name: Upadacitinib

Study Arms

Experimental: Open-label extension

All subjects will start treatment with ABT-494.

Intervention: Drug: ABT-494

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 9, 2017): 494
• Original Estimated Enrollment (submitted: January 28, 2014): 470
• Estimated Study Completion Date: February 20, 2021
• Estimated Primary Completion Date: February 20, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Subjects who have completed Study M13-550 or Study M13-537 with Upadacitinib (ABT-494) and has not developed any discontinuation criteria.
2. If the subject has evidence of new latent Tuberculosis (TB) infection, the subject must initiate and complete a minimum of 2 weeks (or per local guidelines, whichever is longer) of an ongoing TB prophylaxis before continuing to receive study drug.

3. If female, subject must meet one of the following criteria:

   • Postmenopausal (defined as no menses for at least 1 year).
   • Surgically sterile (bilateral oophorectomy or hysterectomy).

   • Practicing from the time of screening until at least 30 days after the last dose of study drug at least TWO of the following methods of birth control:

     1. Tubal ligation
     2. Partner vasectomy (at least 6 months earlier) (the vasectomized male partner should be the sole partner for that female subject)
     3. Intrauterine device
     4. A male condom with spermicidal jelly or cream
     5. Diaphragm, contraceptive sponge or cervical cap with spermicidal jelly or cream
     6. Hormonal contraceptives (injected, oral, transdermal or implanted methods) must have been taking at least 2 months prior to dosing
4. Male subjects must agree to follow protocol-specified pregnancy avoidance measures, including refraining from donating sperm, for up to 30 days post last dose of study drug.
5. Subjects must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study specific procedures.

Substudy:

1. Must currently be enrolled in the main study.
2. Must have been receiving a stable dose of upadacitinib (either 15 mg QD or 30 mg QD) for a minimum of 4 weeks prior to the Vaccination visit.
3. Must have been on a stable dose of background methotrexate (no change in dose or frequency) for a minimum of 4 weeks prior to the Vaccination visit.
4. If subject is on corticosteroids, must remain on a stable dose of ≤ 10 mg/day of prednisone or equivalent corticosteroid therapy for at least 4 weeks after the vaccination visit.
5. Must meet the prescribing specifications as per local label requirements to receive Prevnar 13® vaccine.
6. Willing to receive Prevnar13® vaccine.

Exclusion Criteria:

1. Pregnant or breastfeeding female.
2. Ongoing infections at Week 0 that have NOT been successfully treated. Subjects with ongoing infections undergoing treatment may be enrolled BUT NOT dosed until the infection has been successfully treated.
3. Anticipated requirement or receipt of any live vaccine during study participation including up to 30 days after the last dose of study drug.

4. Laboratory values from the visit immediately prior to Baseline Visit (local requirements may apply) meeting the following criteria:

   • Serum aspartate transaminase (AST) or alanine transaminase (ALT) > 3.0 × Upper Limit of Normal (ULN)
   • Estimated glomerular filtration rate by simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula < 40mL/min/1.73m2
   • Total white blood cell count (WBC) < 2,000/μL
   • Absolute neutrophil count (ANC) < 1,000/μL
   • Platelet count < 50,000/μL
   • Absolute lymphocytes count < 500/μL
   • Hemoglobin < 8 gm/dL
5. Enrollment in another interventional clinical study while participating in this study.
6. Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive study drug.

Substudy:

1. Receiving any csDMARDs other than MTX
2. Receiving > 10 mg/day of prednisone or equivalent corticosteroid therapy.
3. Receipt of any steroid injection within 4 weeks prior to Vaccination visit.
4. History of severe allergic reaction (e.g., anaphylaxis) to any component of Prevnar 13®.
5. History of any documented pneumococcal infection within the last 6 months prior to the vaccination visit.
6. Receipt of any vaccine 4 weeks prior to the vaccination visit and/or anticipation of any vaccination for 4 weeks after the vaccination visit.
7. Receipt of any pneumococcal vaccine.
8. Subject is not suitable for the sub-study as per the Investigator's judgment.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 100 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Bulgaria, Chile, Czechia, Hungary, Israel, Latvia, Mexico, New Zealand, Poland, Puerto Rico, Russian Federation, Slovakia, South Africa, Spain, Ukraine, United Kingdom, United States
• Removed Location Countries: Australia, Czech Republic

Administrative Information

• NCT Number: NCT02049138
• Other Study ID Numbers: M13-538; 2013-003530-33 ( EudraCT Number )
• Has Data Monitoring Committee: No

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)
• Supporting Materials: Analytic Code
• Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• 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 Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
• URL: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html

• Responsible Party: AbbVie
• Study Sponsor: AbbVie
• Collaborators: Not Provided

Investigators

• Study Director: AbbVie Inc.; AbbVie

• PRS Account: AbbVie
• Verification Date: February 2019