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

• ClinicalTrials.gov Identifier: NCT02049138
• Recruitment Status: Completed
• First Posted: January 30, 2014
• Results First Posted: July 12, 2022
• Last Update Posted: July 12, 2022
• Sponsor: AbbVie
• Information provided by (Responsible Party): AbbVie

Study Description

Brief Summary:

The primary objective of the study is to evaluate the long-term safety, tolerability, and efficacy of upadacitinib in adults with rheumatoid arthritis (RA) who have completed a preceding randomized controlled trial with upadacitinib.

Condition or disease	Intervention/treatment	Phase
Rheumatoid Arthritis	Drug: Upadacitinib; Biological: Pneumococcal 13-valent conjugate vaccine (PCV-13)	Phase 2

Detailed Description:

This is an open-label extension study to assess the long-term safety, tolerability, and efficacy of upadacitinib in adults with RA who have completed Study M13-550 (NCT01960855) or Study M13-537 (NCT02066389) Phase 2 randomized controlled trial (RCT) with upadacitinib.

All participants received treatment with 6 mg upadacitinib twice a day at the start of the study. Participants may have been up-titrated to 12 mg BID based on protocol-specified criteria. In Protocol Amendment 2 (January 2016) the study treatment was changed to a once daily (QD) formulation. Participants receiving 6 mg BID were transitioned to 15 mg QD and participants receiving 12 mg BID were transitioned to 30 mg QD dosing.

An optional 12-week vaccine sub-study was added in Protocol Amendment 3 (November 2017) to assess the impact of upadacitinib treatment (15 mg QD and 30 mg QD) with background methotrexate on immunological responses to pneumococcal 13-valent conjugate vaccine (PCV-13; Prevnar 13®) in RA patients. The vaccine substudy included 111 participants who were enrolled in the main study, the first participant was enrolled on 13 February 2018 and the the last participant completed the sub-study on 9 April 2020.

In Protocol Amendment 5 (December 2019), the protocol was revised to allow a decrease in upadacitinib dosing from 30 mg QD to 15 mg QD, as appropriate, based on investigator's medical decision or for safety/tolerability concerns.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 493 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: January 24, 2014
• Actual Primary Completion Date: July 29, 2021
• Actual Study Completion Date: July 29, 2021

Arms and Interventions

Arm

Intervention/treatment

Experimental: Upadacitinib; Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg twice a day (BID). Participants who did not achieve a 20% improvement from RCT Baseline in both Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 6 or Week 12 were up-titrated to 12 mg BID. From January 2017 participants were transitioned to a once-daily (QD) regimen of upadacitinib, either 15 mg QD (participants who were taking 6 mg BID) or 30 mg QD (participants taking 12 mg BID). Starting with Protocol Amendment 5 participants receiving 30 mg QD upadacitinib had the option to decrease the dose to 15 mg QD at the investigator's discretion. A subset of participants who opted-in to the vaccine substudy received a single-dose of 0.5 mL intramuscular injection of pneumococcal 13-valent conjugate vaccine (PCV-13).

Drug: Upadacitinib; Tablet taken orally; Other Names: ABT-494; RINVOQ®; Biological: Pneumococcal 13-valent conjugate vaccine (PCV-13); Administered by intramuscular injection; Other Name: Prevnar 13®

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response Over Time [ Time Frame: Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312 ]

   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).
2. Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response Over Time [ Time Frame: Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312 ]

   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).
3. Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response Over Time [ Time Frame: Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312 ]

   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).
4. Percentage of Participants With Satisfactory Humoral Response to PCV-13 Four Weeks After Vaccination [ Time Frame: Vaccination Baseline (defined as the last non-missing observation on or before the date of receiving PCV-13 vaccination) and 4 weeks after vaccination ]
   Satisfactory humoral 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 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F).

Secondary Outcome Measures :

1. Percentage of Participants Achieving Low Disease Activity (LDA) Based on Disease Activity Score-28 (DAS28[CRP]) Over Time [ Time Frame: Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312 ]

   The DAS28(CRP) is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (measured on a VAS from 0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 (CRP) range from 0 to approximately 10, where higher scores indicate more disease activity.

   LDA is defined as a DAS28(CRP) score ≤ 3.2.

2. Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score-28 (DAS28[CRP]) Over Time [ Time Frame: Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312 ]

   The DAS28 (CRP) is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (measured on a VAS from 0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 (CRP) range from 0 to approximately 10, where higher scores indicate more disease activity.

   Clinical remission is defined as a DAS28(CRP) score < 2.6.

3. Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Over Time [ Time Frame: Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312 ]

   The clinical disease activity index (CDAI) is a composite index for assessing disease activity based on the summation of the counts of tender joint count (out of 28 evaluated joints) and swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm, and Physician's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity.

   LDA is defined as a CDAI score ≤ 10.

4. Percentage of Participants Achieving Clinical Remission (CR) Based on Clinical Disease Activity Index (CDAI) Over Time [ Time Frame: Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312 ]

   The clinical disease activity index (CDAI) is a composite index for assessing disease activity based on the summation of the counts of tender joint count (out of 28 evaluated joints) and swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm, and Physician's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity.

   Clinical remission is defined as a CDAI score ≤ 2.8.

5. Percentage of Participants Achieving Low Disease Activity (LDA) Based on Simplified Disease Activity Index (SDAI) Over Time [ Time Frame: Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312 ]

   The simplified disease activity index (SDAI) is a composite index for assessing disease activity based on the summation of the counts of tender joint count (out of 28 evaluated joints) and swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm, Physician's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm and hsCRP (mg/dL). The total SDAI score ranges from 0 to 86 with higher scores indicating higher disease activity.

   LDA is defined as a SDAI score ≤ 11.0.

6. Percentage of Participants Achieving Clinical Remission (CR) Based on Simplified Disease Activity Index (SDAI) Over Time [ Time Frame: Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312 ]

   The simplified disease activity index (SDAI) is a composite index for assessing disease activity based on the summation of the counts of tender joint count (out of 28 evaluated joints) and swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm, Physician's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm and hsCRP (mg/dL). The total SDAI score ranges from 0 to 86 with higher scores indicating higher disease activity.

   Clinical remission is defined as a SDAI score ≤ 3.3.

7. Change From Baseline in Disease Activity Score Based on CRP (DAS28 [CRP]) Over Time [ Time Frame: Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312 ]
   The disease activity score-28-CRP (DAS28 [CRP]) assesses RA disease activity based on a continuous scale of combined measures of 28 tender joint counts (TJC28), 28 swollen joint counts (SJC28), C-reactive protein (CRP), and the patient global assessment of disease activity (measured on a visual analog scale from 0 to 100 mm). DAS28(CRP) scores range from 0 to approximately 10 where higher scores indicate more disease activity. A negative change from Baseline in DAS28 (CRP) indicates improvement in disease activity.
8. Change From Baseline in Clinical Disease Activity Index (CDAI) Over Time [ Time Frame: Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312 ]
   The clinical disease activity index (CDAI) is a composite index for assessing disease activity based on the summation of the counts of tender joint count (out of 28 evaluated joints) and swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm, and Physician's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity. A negative change from Baseline indicates improvement in disease activity.
9. Change From Baseline in SimplifiedDisease Activity Index (SDAI) Over Time [ Time Frame: Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312 ]
   The simplified disease activity index (SDAI) is a composite index for assessing disease activity based on the summation of the counts of tender joint count (out of 28 evaluated joints) and swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm, Physician's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm and hsCRP (mg/dL). The total SDAI score ranges from 0 to 86 with higher scores indicating higher disease activity. A negative change from Baseline indicates improvement in disease activity.
10. Change From Baseline in Tender Joint Count (TJC68) Over Time [ Time Frame: Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312 ]
    Sixty-eight joints were assessed by an evaluator for tenderness or pain. The presence of tenderness was scored as a "1" and absence of tenderness as a "0". The total tender joint count is the sum of the scores, and ranges from 0 to 68 (worst).
11. Change From Baseline in Swollen Joint Count (SJC66) Over Time [ Time Frame: Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312 ]
    Sixty-six joints were assessed by an evaluator for swelling. The presence of swelling was scored as a "1" and absence of swelling as a "0". The total swollen joint count is the sum of the scores, and ranges from 0 to 66 (worst).
12. Change From Baseline in Physician's Global Assessment of Disease Activity Over Time [ Time Frame: Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312 ]
    The physician rated the participant's current global RA disease activity (independently from the participant's assessment) on a visual analog scale (VAS) from 0 to 100 mm, where 0 mm indicates no disease activity and 100 mm indicates severe disease activity
13. Change From Baseline in Patient's Global Assessment of Disease Activity Over Time [ Time Frame: Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312 ]
    The participant was asked to rate their current RA disease activity over the past 24 hours on a 100 mm VAS, where 0 mm indicates very low disease activity and 100 mm indicates very high disease activity.
14. Change From Baseline in Patient's Assessment of Pain Over Time [ Time Frame: Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312 ]
    Participants were asked to indicate the severity of their arthritis pain within the previous week on a visual analog scale from 0 to 100 mm. A score of 0 mm indicates "no pain" and a score of 100 mm indicates "worst possible pain."
15. Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Over Time [ Time Frame: Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312 ]
    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.
16. Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) Over Time [ Time Frame: Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312 ]
17. Change From Baseline in in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Scale Over Time [ Time Frame: Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 72, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312 ]
    The FACIT Fatigue scale is a 13-item tool that measures an individual's level of fatigue during their usual daily activities over the past 7 days. Each of the fatigue and impact of fatigue items are measured on a four point Likert scale (4 = not at all fatigued to 0 = very much fatigued). The FACIT Fatigue Scale is the sum of the individual 13 scores and ranges from 0 to 52 where higher scores indicate better quality of life. A positive change from Baseline indicates improvement.
18. Change From Baseline in Work Instability Scale for RA (RA-WIS) Over Time [ Time Frame: Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 72, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312 ]

    RA-WIS is a tool to evaluate work instability (the consequence of a mismatch between an individual's functional ability and their work tasks). RA-WIS consists of 23 questions relating to the participant's functioning in their work environment, each answered as Yes or No. The total score is the number of questions answered Yes, and ranges from 0 to 23.

    A score < 10 means low risk, scores between 10 and 17 indicate medium risk, and scores > 17 indicate high risk of work instability.

    A negative change from Baseline indicates improvement in work instability.

19. Change From Baseline in EuroQoL-5D (EQ-5D) Index Over Time [ Time Frame: Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 72, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312 ]

    The EQ-5D-5L is a generic measure of health status consisting of two parts. The first part (the descriptive system) assesses health in five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) each of which is rated on 5 levels of severity (1: no problem, 2: slight problems, 3: moderate problems, 4: severe problems, 5: extreme problems).

    A health state index score was calculated from individual health profiles using a UK scoring algorithm. Health state index scores generally range from less than 0 (where 0 is the value of a health state equivalent to dead; negative values representing values as worse than dead) to 1 (the value of full health), with higher scores indicating higher health utility. The higher the score the better the health status. A positive change from baseline indicates improvement in health status.

20. Change From Baseline in EuroQoL-5D VAS Score Over Time [ Time Frame: Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 72, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312 ]

    The EQ-5D-5L is a generic measure of health status consisting of two parts. The second part of the questionnaire consists of a visual analog scale (VAS) on which the participant rates his/her perceived health from 0 (the worst imaginable health) to 100 (the best imaginable health).

    A positive change from baseline indicates improvement.

21. Percentage of Participants With Satisfactory Humoral Response to PCV-13 12 Weeks After Vaccination [ Time Frame: Vaccination Baseline and 12 weeks after vaccination ]
    Satisfactory humoral 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 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F).
22. Geometric Mean Fold Rise (GMFR) of Anti-pneumococcal Antibody Levels to Each of the 12 Pneumococcal Antigens 4 and 12 Weeks After Vaccination [ Time Frame: Vaccination Baseline and 4 and 12 weeks after vaccination ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 100 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Subjects who have completed Study M13-550 (NCT01960855) or Study M13-537 (NCT02066389) with upadacitinib (ABT-494) and did not develop 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 be postmenopausal, OR permanently surgically sterile, OR for women of childbearing potential practicing at least one protocol-specified method of birth control, that is effective from Study Day 1 through at least 30 days after the last dose of study drug.
4. 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 < 40 mL/min/1.73m^2
   • 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 g/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 conventional synthetic disease modifying antirheumatic drugs (csDMARDs) other than methotrexate
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.

Contacts and Locations

Locations

United States, Alabama

Rheum Assoc of North Alabama /ID# 135926

Huntsville, Alabama, United States, 35801

United States, Arizona

AZ Arthritis and Rheumotology Research, PLLC /ID# 135902

Phoenix, Arizona, United States, 85032-9306

AZ Arthritis and Rheumotology Research, PLLC /ID# 135931

Phoenix, Arizona, United States, 85032-9306

United States, California

C.V. Mehta MD, Med Corporation /ID# 124092

Hemet, California, United States, 92543

Moores Cancer Center at UC San Diego /ID# 128747

La Jolla, California, United States, 92093

Desert Medical Advances - Palm Desert /ID# 135911

Palm Desert, California, United States, 92260

Orrin Troum, M.D. and Medical /ID# 135933

Santa Monica, California, United States, 90404

Duplicate_Robin K. Dore MD, Inc /ID# 135906

Tustin, California, United States, 92780

Inland Rheum Clin Trials Inc. /ID# 136716

Upland, California, United States, 91786

Duplicate_Desert Valley Medical Group /ID# 135932

Victorville, California, United States, 92395

United States, Colorado

Denver Arthritis Clinic /ID# 135901

Denver, Colorado, United States, 80230

United States, Connecticut

New England Research Associates, LLC /ID# 124085

Bridgeport, Connecticut, United States, 06606-1827

United States, Florida

Arthritis & Rheumatic Disease Specialties /ID# 135910

Aventura, Florida, United States, 33180

Rheumatology Associates of South Florida (RASF) - Clinical Research /ID# 124082

Boca Raton, Florida, United States, 33486

Omega Research Maitland, LLC /ID# 124094

DeBary, Florida, United States, 32713-2260

University of Florida /ID# 124087

Jacksonville, Florida, United States, 32209

Suncoast Research Group /ID# 137774

Miami, Florida, United States, 33135

Omega Research Maitland, LLC /ID# 137398

Orlando, Florida, United States, 32808

Millennium Research /ID# 135917

Ormond Beach, Florida, United States, 32174

Arthritis Center, Inc. /ID# 124090

Palm Harbor, Florida, United States, 34684

IRIS Research and Development, LLC /ID# 140362

Plantation, Florida, United States, 33324

Lovelace Scientific Resources /ID# 128745

Venice, Florida, United States, 34292

United States, Georgia

North Georgia Rheumatology Group /ID# 128746

Lawrenceville, Georgia, United States, 30045

United States, Kansas

Kansas City Internal Medicine /ID# 135916

Overland Park, Kansas, United States, 66209

PRN Professional Research Network of Kansas, LLC /ID# 124091

Wichita, Kansas, United States, 67205

United States, Maryland

Klein and Associates MD - Hagerstown /ID# 124086

Hagerstown, Maryland, United States, 21742

The Center for Rheumatology and Bone Research /ID# 124077

Wheaton, Maryland, United States, 20902

United States, Massachusetts

Clinical Pharmacology Study Group /ID# 124079

Worcester, Massachusetts, United States, 01605

United States, Michigan

June DO, PC /ID# 124081

Lansing, Michigan, United States, 48910

United States, New Jersey

Summit Medical Group /ID# 124076

Clifton, New Jersey, United States, 07012-1647

Arthritis and Osteoporosis Associates /ID# 135907

Freehold, New Jersey, United States, 07728-8307

Arthritis Rheumatic and Back Disease Associates. P.A. /ID# 135913

Voorhees, New Jersey, United States, 08043

United States, New Mexico

Arthritis and Osteo Assoc /ID# 132280

Las Cruces, New Mexico, United States, 88011

United States, North Carolina

DJL Clinical Research, PLLC /ID# 131936

Charlotte, North Carolina, United States, 28210-8508

United States, Ohio

Cincinnati Rheumatic Disease Study Group, Inc. /ID# 135921

Cincinnati, Ohio, United States, 45242-4468

STAT Research, Inc. /ID# 134906

Vandalia, Ohio, United States, 45377-9464

United States, Oklahoma

Health Research of Oklahoma /ID# 135904

Oklahoma City, Oklahoma, United States, 73103-2400

United States, Pennsylvania

Duplicate_East Penn Rheumatology Assoc /ID# 135920

Bethlehem, Pennsylvania, United States, 18015

Altoona Ctr Clinical Res /ID# 124089

Duncansville, Pennsylvania, United States, 16635

Emkey Arthritis and Osteoporosis Clinic /ID# 135908

Wyomissing, Pennsylvania, United States, 19610

United States, South Carolina

Articularis Healthcare Group, Inc d/b/a Low Country Rheumatology /ID# 124080

Summerville, South Carolina, United States, 29486-7887

United States, Tennessee

Dr. Ramesh Gupta /ID# 128744

Memphis, Tennessee, United States, 38119

United States, Texas

Austin Rheumatology Research /ID# 124083

Austin, Texas, United States, 78705

Accurate Clinical Management /ID# 128751

Baytown, Texas, United States, 77521

Accurate Clinical Management /ID# 128752

Houston, Texas, United States, 77004

Baylor College of Medicine - Baylor Medical Center /ID# 135905

Houston, Texas, United States, 77030-3411

Houston Institute for Clin Res /ID# 135912

Houston, Texas, United States, 77074

Accurate Clinical Research /ID# 128753

Houston, Texas, United States, 77089

Accurate Clinical Research /ID# 128754

Houston, Texas, United States, 77089

SW Rheumatology Res. LLC /ID# 135927

Mesquite, Texas, United States, 75150

United States, West Virginia

Mountain State Clinical Research /ID# 124088

Clarksburg, West Virginia, United States, 26301

United States, Wisconsin

Aurora Rheumatology and Immunotherapy Center /ID# 135922

Franklin, Wisconsin, United States, 53132

Belgium

UCL Saint-Luc /ID# 139348

Woluwe-Saint-Lambert, Bruxelles-Capitale, Belgium, 1200

ReumaClinic Genk-Hasselt /ID# 137775

Genk, Belgium, 3600

Bulgaria

MHAT Trimontsium /ID# 135328

Plovdiv, Bulgaria, 4000

Duplicate_MHAT Kaspela /ID# 136212

Plovdiv, Bulgaria, 4001

UHMAT Palmed Plovdiv /ID# 135355

Plovdiv, Bulgaria, 4002

UMHAT Sveti Ivan Rilski /ID# 135678

Sofia, Bulgaria, 1431

UMHAT Sveti Ivan Rilski /ID# 136210

Sofia, Bulgaria, 1431

Diagnostic Consultative Center /ID# 136736

Sofia, Bulgaria, 1612

Diagnostic consultative center Equita /ID# 136209

Varna, Bulgaria, 9000

Chile

Corporacion de Beneficiencia Osorno /ID# 136189

Osorno, Los Lagos, Chile, 1710216

Quantum Research /ID# 136188

Puerto Varas, Los Lagos, Chile, 5550170

Czechia

Duplicate_Artroscan s.r.o. /ID# 139347

Ostrava, Czechia, 722 00

L.K.N. Arthrocentrum, s.r.o /ID# 128782

Petrkovice, Czechia, 725 29

Revmatologicky ustav v Praze /ID# 137937

Praha, Czechia, 128 00

Revmatologicka ambulance - MUDr. Zuzana Urbanova /ID# 137776

Praha, Czechia, 140 00

Revmatologie Bruntal, s.r.o /ID# 137782

Prostejov, Czechia, 796 01

Hungary

Qualiclinic Kft. /ID# 134170

Budapest, Pest, Hungary, 1036

Orszagos Reumatologiai es Fizioterapias Intezet /ID# 128785

Budapest, Hungary, 1023

Szent Margit Szakrendelo /ID# 136676

Budapest, Hungary, 1032

MAV Korhaz ess Rendelointezet /ID# 139971

Szolnok, Hungary, 5000

Veszprem Megyei Csolnoky Ferenc Korhaz /ID# 128784

Veszprem, Hungary, 8200

Israel

The Chaim Sheba Medical Center /ID# 139295

Ramat Gan, Tel-Aviv, Israel, 5265601

Barzilai Medical Center /ID# 140199

Ashkelon, Israel, 7830604

Latvia

M & M Centrs LTD /ID# 132439

Adazi, Latvia, LV-2164

Arija's Ancane's Family Doctor Practice /ID# 132437

Baldone, Latvia, LV-2125

Clinic ORTO /ID# 132438

Riga, Latvia, LV-1005

Mexico

Clinstile, S.A. de C.V. /ID# 137075

Cuauhtemoc, Ciudad De Mexico, Mexico, 20313

Unidad de Investigacion de las Enfermedades Reumatologicas SA de CV /ID# 137307

Mexico City, Mexico, 06090

Cliditer SA de CV /ID# 136876

Mexico City, Mexico, 06700

New Zealand

Timaru Medical Specialists Ltd /ID# 131909

Timaru, Canterbury, New Zealand, 7910

Waikato Hospital /ID# 131908

Hamilton, Waikato, New Zealand, 3240

Porter Rheumatology Ltd /ID# 133983

Nelson, New Zealand, 7010

Poland

Reum-Medica S.C. /ID# 128841

Wroclaw, Dolnoslaskie, Poland, 50-244

Twoja Przychodnia Centrum Medyczne /ID# 128840

Nowa Sol, Lubuskie, Poland, 67-100

Pratia MCM Krakow /ID# 134749

Krakow, Malopolskie, Poland, 30-510

NZOZ Lecznica MAK-MED s.c. /ID# 128838

Nadarzyn, Mazowieckie, Poland, 05-830

Medicome sp. z o.o. /ID# 137397

Oswiecim, Mazowieckie, Poland, 32-600

Centrum Medyczne Amed Warszawa Zoliborz /ID# 128835

Warsaw, Mazowieckie, Poland, 01-518

Centrum Medyczne Pratia Warszawa /ID# 136650

Warsaw, Mazowieckie, Poland, 01-868

Centrum Medyczne Reuma Park w Warszawie /ID# 140198

Warsaw, Mazowieckie, Poland, 02-691

NBR Polska /ID# 136208

Warszawa, Mazowieckie, Poland, 00-465

Gabinet Internistyczno-Reumatologiczny /ID# 135876

Bialystok, Podlaskie, Poland, 15-077

Centrum Medyczne Pratia Gdynia /ID# 137362

Gdynia, Pomorskie, Poland, 81-338

Ambulatorium Sp. z o.o /ID# 138074

Elblag, Warminsko-mazurskie, Poland, 82-300

Prywatna Praktyka Lekarska /ID# 128837

Poznan, Wielkopolskie, Poland, 61-397

Duplicate_REUMED Filia nr 2 /ID# 128839

Lublin, Poland, 20-582

Puerto Rico

Dr. Ramon L. Ortega-Colon, MD /ID# 128760

Carolina, Puerto Rico, 00983

GCM Medical Group PSC - Hato Rey /ID# 128759

San Juan, Puerto Rico, 00917-3104

Mindful Medical Research /ID# 136211

San Juan, Puerto Rico, 00918-3756

Russian Federation

Kazan State Medical University /ID# 136734

Kazan, Tatarstan, Respublika, Russian Federation, 420012

Tver Regional Clinical Hospital /ID# 137576

Tver, Tverskaya Oblast, Russian Federation, 170036

St. Petersburg Research Institute of Emergency Medicine n.а. I. I. Dzhanelidze /ID# 136652

Sankt-Peterburg, Russian Federation, 192242

Slovakia

MEDMAN s.r.o. /ID# 136649

Martin, Slovakia, 036 01

Poliklinika Senica n.o. /ID# 134728

Senica, Slovakia, 905 01

South Africa

Dr MJ Prins /ID# 138540

Cape Town, Western Cape, South Africa, 7500

Winelands Medical Research Centre /ID# 134669

Stellenbosch, Western Cape, South Africa, 7600

Spain

Clinica Gaias /ID# 133868

Santiago de Compostela, A Coruna, Spain, 15702

Hospital General Universitario de Elche /ID# 128851

Elche, Alicante, Spain, 03203

Hospital Infanta Sofia /ID# 136653

San Sebastián de Los Reyes, Madrid, Spain, 28702

Hospital Regional de Malaga /ID# 128847

Málaga, Malaga, Spain, 29010

Hospital Universitario A Coruna - CHUAC /ID# 128846

A Coruna, Spain, 15006

Hospital CIMA Sanitas /ID# 128849

Barcelona, Spain, 08034

Hospital Clinico Universitario San Carlos /ID# 128852

Madrid, Spain, 28040

Hospital Universitario Virgen Macarena /ID# 128853

Sevilla, Spain, 41009

Hospital QuironSalud Infanta Luisa /ID# 135689

Sevilla, Spain, 41010

Hospital Universitario Virgen de Valme /ID# 134668

Sevilla, Spain, 41014

Ukraine

NSC Strazhesko Ist Cardiology /ID# 137330

Kiev, Ukraine, 03680

Municipal Non-profit Institution Kyiv City Clinical Hospital No. 3 of the Exec /ID# 137334

Kyiv, Ukraine, 02125

United Kingdom

Warrington and Halton Hospitals NHS Foundation Trust /ID# 137514

Warrington, Cheshire West And Chester, United Kingdom, WA5 1QG

Barts Health NHS Trust /ID# 135683

London, London, City Of, United Kingdom, E1 2ES

West Suffolk Hospital /ID# 128858

Bury St Edmunds, Suffolk, United Kingdom, IP33 2QZ

Duplicate_Leeds Teaching Hospitals NHS Trust /ID# 141308

Leeds, United Kingdom, LS9 7TF

Sponsors and Collaborators

AbbVie

Investigators

• Study Director: ABBVIE INC.; AbbVie

  Study Documents (Full-Text)

Documents provided by AbbVie:

Study Protocol  [PDF] December 1, 2020

Statistical Analysis Plan  [PDF] May 3, 2021

More Information

Additional Information:

Related Info. 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Winthrop K, Vargas JI, Drescher E, Garcia C, Friedman A, Hendrickson B, Li Y, Klaff J, Kivitz A. Evaluation of response to 13-valent conjugated pneumococcal vaccination in patients with rheumatoid arthritis receiving upadacitinib: results from a phase 2 open-label extension study. RMD Open. 2022 Mar;8(1):e002110. doi: 10.1136/rmdopen-2021-002110.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT02049138
• Other Study ID Numbers: M13-538; 2013-003530-33 ( EudraCT Number )
• First Posted: January 30, 2014
• Results First Posted: July 12, 2022
• Last Update Posted: July 12, 2022
• Last Verified: June 2022

Individual Participant Data (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; Statistical Analysis Plan (SAP); 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/

• 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

Keywords provided by AbbVie:

Musculoskeletal Disease; Arthritis; Joint Diseases; Anti-inflammatory Agents; Antirheumatic agents

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Upadacitinib; Janus Kinase Inhibitors; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents