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

Phase 2

Completed

Conditions: Rheumatoid Arthritis

Interventions: Drug: Upadacitinib
Biological: Pneumococcal 13-valent conjugate vaccine (PCV-13)

Registration Number: NCT02049138

Lead Sponsor: AbbVie

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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 493

Inclusion Criteria

Subjects who have completed Study M13-550 (NCT01960855) or Study M13-537 (NCT02066389) with upadacitinib (ABT-494) and did not develop any discontinuation criteria.
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.
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.
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:

Must currently be enrolled in the main study.
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.
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.
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.
Must meet the prescribing specifications as per local label requirements to receive Prevnar 13® vaccine.
Willing to receive Prevnar13® vaccine.

Exclusion Criteria

Pregnant or breastfeeding female.
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.
Anticipated requirement or receipt of any live vaccine during study participation including up to 30 days after the last dose of study drug.
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
Enrollment in another interventional clinical study while participating in this study.
Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive study drug.

Substudy:

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Upadacitinib	Pneumococcal 13-valent conjugate vaccine (PCV-13)	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).
Upadacitinib	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).

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response Over Time	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).
Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response Over Time	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).
Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response Over Time	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).
Percentage of Participants With Satisfactory Humoral Response to PCV-13 Four Weeks After Vaccination	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

Name	Time	Method
Percentage of Participants Achieving Clinical Remission (CR) Based on Clinical Disease Activity Index (CDAI) Over Time	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.
Change From Baseline in Clinical Disease Activity Index (CDAI) Over Time	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.
Change From Baseline in SimplifiedDisease Activity Index (SDAI) Over Time	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.
Change From Baseline in Tender Joint Count (TJC68) Over Time	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).
Change From Baseline in Swollen Joint Count (SJC66) Over Time	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).
Percentage of Participants Achieving Low Disease Activity (LDA) Based on Simplified Disease Activity Index (SDAI) Over Time	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.
Change From Baseline in Physician's Global Assessment of Disease Activity Over Time	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
Percentage of Participants Achieving Clinical Remission (CR) Based on Simplified Disease Activity Index (SDAI) Over Time	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.
Change From Baseline in Patient's Global Assessment of Disease Activity Over Time	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.
Percentage of Participants Achieving Low Disease Activity (LDA) Based on Disease Activity Score-28 (DAS28[CRP]) Over Time	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.
Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score-28 (DAS28[CRP]) Over Time	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.
Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Over Time	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.
Change From Baseline in Disease Activity Score Based on CRP (DAS28 [CRP]) Over Time	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.
Change From Baseline in Patient's Assessment of Pain Over Time	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."
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Over Time	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.
Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) Over Time	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
Change From Baseline in in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Scale Over Time	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.
Change From Baseline in Work Instability Scale for RA (RA-WIS) Over Time	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.
Change From Baseline in EuroQoL-5D (EQ-5D) Index Over Time	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.
Change From Baseline in EuroQoL-5D VAS Score Over Time	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.
Percentage of Participants With Satisfactory Humoral Response to PCV-13 12 Weeks After Vaccination	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).
Geometric Mean Fold Rise (GMFR) of Anti-pneumococcal Antibody Levels to Each of the 12 Pneumococcal Antigens 4 and 12 Weeks After Vaccination	Vaccination Baseline and 4 and 12 weeks after vaccination

Trial Locations

Locations (124): IRIS Research and Development, LLC /ID# 140362
🇺🇸
Plantation, Florida, United States
Quantum Research /ID# 136188
🇨🇱
Puerto Varas, Los Lagos, Chile
The Center for Rheumatology and Bone Research /ID# 124077
🇺🇸
Wheaton, Maryland, United States
Omega Research Maitland, LLC /ID# 124094
🇺🇸
DeBary, Florida, United States
University of Florida /ID# 124087
🇺🇸
Jacksonville, Florida, United States
Clinical Pharmacology Study Group /ID# 124079
🇺🇸
Worcester, Massachusetts, United States
Articularis Healthcare Group, Inc d/b/a Low Country Rheumatology /ID# 124080
🇺🇸
Summerville, South Carolina, United States
Arthritis and Osteoporosis Associates /ID# 135907
🇺🇸
Freehold, New Jersey, United States
Summit Medical Group /ID# 124076
🇺🇸
Clifton, New Jersey, United States
MHAT Trimontsium /ID# 135328
🇧🇬
Plovdiv, Bulgaria
Diagnostic Consultative Center /ID# 136736
🇧🇬
Sofia, Bulgaria
Szent Margit Szakrendelo /ID# 136676
🇭🇺
Budapest, Hungary
Orszagos Reumatologiai es Fizioterapias Intezet /ID# 128785
🇭🇺
Budapest, Hungary
MAV Korhaz ess Rendelointezet /ID# 139971
🇭🇺
Szolnok, Hungary
The Chaim Sheba Medical Center /ID# 139295
🇮🇱
Ramat Gan, Tel-Aviv, Israel
M & M Centrs LTD /ID# 132439
🇱🇻
Adazi, Latvia
Unidad de Investigacion de las Enfermedades Reumatologicas SA de CV /ID# 137307
🇲🇽
Mexico City, Mexico
Twoja Przychodnia Centrum Medyczne /ID# 128840
🇵🇱
Nowa Sol, Lubuskie, Poland
NZOZ Lecznica MAK-MED s.c. /ID# 128838
🇵🇱
Nadarzyn, Mazowieckie, Poland
Medicome sp. z o.o. /ID# 137397
🇵🇱
Oswiecim, Mazowieckie, Poland
Centrum Medyczne Reuma Park w Warszawie /ID# 140198
🇵🇱
Warsaw, Mazowieckie, Poland
Tver Regional Clinical Hospital /ID# 137576
🇷🇺
Tver, Tverskaya Oblast, Russian Federation
Poliklinika Senica n.o. /ID# 134728
🇸🇰
Senica, Slovakia
Municipal Non-profit Institution Kyiv City Clinical Hospital No. 3 of the Exec /ID# 137334
🇺🇦
Kyiv, Ukraine
Gabinet Internistyczno-Reumatologiczny /ID# 135876
🇵🇱
Bialystok, Podlaskie, Poland
Kazan State Medical University /ID# 136734
🇷🇺
Kazan, Tatarstan, Respublika, Russian Federation
Orrin Troum, M.D. and Medical /ID# 135933
🇺🇸
Santa Monica, California, United States
Mountain State Clinical Research /ID# 124088
🇺🇸
Clarksburg, West Virginia, United States
Arthritis Rheumatic and Back Disease Associates. P.A. /ID# 135913
🇺🇸
Voorhees, New Jersey, United States
PRN Professional Research Network of Kansas, LLC /ID# 124091
🇺🇸
Wichita, Kansas, United States
Austin Rheumatology Research /ID# 124083
🇺🇸
Austin, Texas, United States
Denver Arthritis Clinic /ID# 135901
🇺🇸
Denver, Colorado, United States
Suncoast Research Group /ID# 137774
🇺🇸
Miami, Florida, United States
Rheum Assoc of North Alabama /ID# 135926
🇺🇸
Huntsville, Alabama, United States
Moores Cancer Center at UC San Diego /ID# 128747
🇺🇸
La Jolla, California, United States
Duplicate_Robin K. Dore MD, Inc /ID# 135906
🇺🇸
Tustin, California, United States
Arthritis & Rheumatic Disease Specialties /ID# 135910
🇺🇸
Aventura, Florida, United States
Duplicate_Desert Valley Medical Group /ID# 135932
🇺🇸
Victorville, California, United States
Klein and Associates MD - Hagerstown /ID# 124086
🇺🇸
Hagerstown, Maryland, United States
DJL Clinical Research, PLLC /ID# 131936
🇺🇸
Charlotte, North Carolina, United States
Millennium Research /ID# 135917
🇺🇸
Ormond Beach, Florida, United States
North Georgia Rheumatology Group /ID# 128746
🇺🇸
Lawrenceville, Georgia, United States
Lovelace Scientific Resources /ID# 128745
🇺🇸
Venice, Florida, United States
Accurate Clinical Management /ID# 128751
🇺🇸
Baytown, Texas, United States
New England Research Associates, LLC /ID# 124085
🇺🇸
Bridgeport, Connecticut, United States
Rheumatology Associates of South Florida (RASF) - Clinical Research /ID# 124082
🇺🇸
Boca Raton, Florida, United States
Arthritis Center, Inc. /ID# 124090
🇺🇸
Palm Harbor, Florida, United States
Kansas City Internal Medicine /ID# 135916
🇺🇸
Overland Park, Kansas, United States
UMHAT Sveti Ivan Rilski /ID# 136210
🇧🇬
Sofia, Bulgaria
Duplicate_East Penn Rheumatology Assoc /ID# 135920
🇺🇸
Bethlehem, Pennsylvania, United States
June DO, PC /ID# 124081
🇺🇸
Lansing, Michigan, United States
Dr. Ramesh Gupta /ID# 128744
🇺🇸
Memphis, Tennessee, United States
Altoona Ctr Clinical Res /ID# 124089
🇺🇸
Duncansville, Pennsylvania, United States
UCL Saint-Luc /ID# 139348
🇧🇪
Woluwe-Saint-Lambert, Bruxelles-Capitale, Belgium
Emkey Arthritis and Osteoporosis Clinic /ID# 135908
🇺🇸
Wyomissing, Pennsylvania, United States
ReumaClinic Genk-Hasselt /ID# 137775
🇧🇪
Genk, Belgium
Accurate Clinical Management /ID# 128752
🇺🇸
Houston, Texas, United States
Accurate Clinical Research /ID# 128753
🇺🇸
Houston, Texas, United States
UHMAT Palmed Plovdiv /ID# 135355
🇧🇬
Plovdiv, Bulgaria
UMHAT Sveti Ivan Rilski /ID# 135678
🇧🇬
Sofia, Bulgaria
Aurora Rheumatology and Immunotherapy Center /ID# 135922
🇺🇸
Franklin, Wisconsin, United States
Barzilai Medical Center /ID# 140199
🇮🇱
Ashkelon, Israel
Duplicate_Artroscan s.r.o. /ID# 139347
🇨🇿
Ostrava, Czechia
Diagnostic consultative center Equita /ID# 136209
🇧🇬
Varna, Bulgaria
Revmatologie Bruntal, s.r.o /ID# 137782
🇨🇿
Prostejov, Czechia
Corporacion de Beneficiencia Osorno /ID# 136189
🇨🇱
Osorno, Los Lagos, Chile
L.K.N. Arthrocentrum, s.r.o /ID# 128782
🇨🇿
Petrkovice, Czechia
Revmatologicky ustav v Praze /ID# 137937
🇨🇿
Praha, Czechia
Revmatologicka ambulance - MUDr. Zuzana Urbanova /ID# 137776
🇨🇿
Praha, Czechia
Qualiclinic Kft. /ID# 134170
🇭🇺
Budapest, Pest, Hungary
Arija's Ancane's Family Doctor Practice /ID# 132437
🇱🇻
Baldone, Latvia
Clinic ORTO /ID# 132438
🇱🇻
Riga, Latvia
Clinstile, S.A. de C.V. /ID# 137075
🇲🇽
Cuauhtemoc, Ciudad De Mexico, Mexico
Cliditer SA de CV /ID# 136876
🇲🇽
Mexico City, Mexico
Waikato Hospital /ID# 131908
🇳🇿
Hamilton, Waikato, New Zealand
Pratia MCM Krakow /ID# 134749
🇵🇱
Krakow, Malopolskie, Poland
Centrum Medyczne Pratia Warszawa /ID# 136650
🇵🇱
Warsaw, Mazowieckie, Poland
Timaru Medical Specialists Ltd /ID# 131909
🇳🇿
Timaru, Canterbury, New Zealand
Barts Health NHS Trust /ID# 135683
🇬🇧
London, London, City Of, United Kingdom
Centrum Medyczne Pratia Gdynia /ID# 137362
🇵🇱
Gdynia, Pomorskie, Poland
GCM Medical Group PSC - Hato Rey /ID# 128759
🇵🇷
San Juan, Puerto Rico
MEDMAN s.r.o. /ID# 136649
🇸🇰
Martin, Slovakia
Duplicate_REUMED Filia nr 2 /ID# 128839
🇵🇱
Lublin, Poland
Dr. Ramon L. Ortega-Colon, MD /ID# 128760
🇵🇷
Carolina, Puerto Rico
Mindful Medical Research /ID# 136211
🇵🇷
San Juan, Puerto Rico
Hospital Regional de Malaga /ID# 128847
🇪🇸
Málaga, Malaga, Spain
Hospital General Universitario de Elche /ID# 128851
🇪🇸
Elche, Alicante, Spain
Hospital Infanta Sofia /ID# 136653
🇪🇸
San Sebastián de Los Reyes, Madrid, Spain
Hospital Universitario A Coruna - CHUAC /ID# 128846
🇪🇸
A Coruna, Spain
Warrington and Halton Hospitals NHS Foundation Trust /ID# 137514
🇬🇧
Warrington, Cheshire West And Chester, United Kingdom
Duplicate_Leeds Teaching Hospitals NHS Trust /ID# 141308
🇬🇧
Leeds, United Kingdom
Hospital QuironSalud Infanta Luisa /ID# 135689
🇪🇸
Sevilla, Spain
NSC Strazhesko Ist Cardiology /ID# 137330
🇺🇦
Kiev, Ukraine
West Suffolk Hospital /ID# 128858
🇬🇧
Bury St Edmunds, Suffolk, United Kingdom
Hospital Clinico Universitario San Carlos /ID# 128852
🇪🇸
Madrid, Spain
Hospital Universitario Virgen Macarena /ID# 128853
🇪🇸
Sevilla, Spain
Hospital CIMA Sanitas /ID# 128849
🇪🇸
Barcelona, Spain
Hospital Universitario Virgen de Valme /ID# 134668
🇪🇸
Sevilla, Spain
Inland Rheum Clin Trials Inc. /ID# 136716
🇺🇸
Upland, California, United States
SW Rheumatology Res. LLC /ID# 135927
🇺🇸
Mesquite, Texas, United States
Arthritis and Osteo Assoc /ID# 132280
🇺🇸
Las Cruces, New Mexico, United States
Accurate Clinical Research /ID# 128754
🇺🇸
Houston, Texas, United States
Houston Institute for Clin Res /ID# 135912
🇺🇸
Houston, Texas, United States
C.V. Mehta MD, Med Corporation /ID# 124092
🇺🇸
Hemet, California, United States
STAT Research, Inc. /ID# 134906
🇺🇸
Vandalia, Ohio, United States
Baylor College of Medicine - Baylor Medical Center /ID# 135905
🇺🇸
Houston, Texas, United States
Duplicate_MHAT Kaspela /ID# 136212
🇧🇬
Plovdiv, Bulgaria
Veszprem Megyei Csolnoky Ferenc Korhaz /ID# 128784
🇭🇺
Veszprem, Hungary
St. Petersburg Research Institute of Emergency Medicine n.а. I. I. Dzhanelidze /ID# 136652
🇷🇺
Sankt-Peterburg, Russian Federation
Prywatna Praktyka Lekarska /ID# 128837
🇵🇱
Poznan, Wielkopolskie, Poland
Porter Rheumatology Ltd /ID# 133983
🇳🇿
Nelson, New Zealand
Reum-Medica S.C. /ID# 128841
🇵🇱
Wroclaw, Dolnoslaskie, Poland
Centrum Medyczne Amed Warszawa Zoliborz /ID# 128835
🇵🇱
Warsaw, Mazowieckie, Poland
NBR Polska /ID# 136208
🇵🇱
Warszawa, Mazowieckie, Poland
Clinica Gaias /ID# 133868
🇪🇸
Santiago de Compostela, A Coruna, Spain
Ambulatorium Sp. z o.o /ID# 138074
🇵🇱
Elblag, Warminsko-mazurskie, Poland
Winelands Medical Research Centre /ID# 134669
🇿🇦
Stellenbosch, Western Cape, South Africa
Dr MJ Prins /ID# 138540
🇿🇦
Cape Town, Western Cape, South Africa
AZ Arthritis and Rheumotology Research, PLLC /ID# 135902
🇺🇸
Phoenix, Arizona, United States
AZ Arthritis and Rheumotology Research, PLLC /ID# 135931
🇺🇸
Phoenix, Arizona, United States
Cincinnati Rheumatic Disease Study Group, Inc. /ID# 135921
🇺🇸
Cincinnati, Ohio, United States
Health Research of Oklahoma /ID# 135904
🇺🇸
Oklahoma City, Oklahoma, United States
Omega Research Maitland, LLC /ID# 137398
🇺🇸
Orlando, Florida, United States
Desert Medical Advances - Palm Desert /ID# 135911
🇺🇸
Palm Desert, California, United States