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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02049138




Registration number
NCT02049138
Ethics application status
Date submitted
28/01/2014
Date registered
30/01/2014
Date last updated
13/01/2020

Titles & IDs
Public title
An Open-label Extension Study Evaluating the Safety and Efficacy of Upadacitinib (ABT-494) in Rheumatoid Arthritis Subjects
Scientific 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)
Secondary ID [1] 0 0
2013-003530-33
Secondary ID [2] 0 0
M13-538
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ABT-494

Experimental: Open-label extension - All subjects will start treatment with ABT-494.


Treatment: Drugs: ABT-494
Tablet; Oral

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in Work Instability Scale - Rheumatoid Arthritis (RA-WIS) - Using RA-WIS scale
Timepoint [1] 0 0
From Week 0 to Week 312
Primary outcome [2] 0 0
Change in EQ-5D - Using the EuroQol-5D scale
Timepoint [2] 0 0
From Week 0 to Week 312
Primary outcome [3] 0 0
ACR 70 Response Rate - ACR criteria measures improvement in tender or swollen joint counts.
Timepoint [3] 0 0
Up to Week 312
Primary outcome [4] 0 0
Change in Health Assessment Questionnaire Disability Index - Determined by the Health Assessment Questionnaire (HAQ-DI)
Timepoint [4] 0 0
From Week 0 to Week 312
Primary outcome [5] 0 0
Change in High-Sensitivity C-Reactive Protein (hsCRP) - Determined by hsCRP lab test
Timepoint [5] 0 0
From Week 0 to Week 312
Primary outcome [6] 0 0
Change in Patient's Global Assessment of Disease Activity - Determined by VAS
Timepoint [6] 0 0
From Week 0 to Week 312
Primary outcome [7] 0 0
Change in DAS28 [CRP] - DAS28 [CRP] calculation
Timepoint [7] 0 0
From Week 0 to Week 312
Primary outcome [8] 0 0
Change in Patient's Assessment of Pain - Determined by the Joint Evaluation, Visual Analog Scale (VAS), EuroQoL-5D (EQ-5D)
Timepoint [8] 0 0
From Week 0 to Week 312
Primary outcome [9] 0 0
Change in Swollen Joint Count - Swollen Joint Count will be assessed by a qualified Independent Joint Assessor or Principal Investigator using the Joint Evaluation Worksheet.
Timepoint [9] 0 0
From Week 0 to Week 312
Primary outcome [10] 0 0
Change in CDAI - The sum of tender and swollen joint counts [28 joints] and patient and physician global assessments
Timepoint [10] 0 0
From Week 0 to Week 312
Primary outcome [11] 0 0
ACR 50 Response Rate - ACR criteria measures improvement in tender or swollen joint counts.
Timepoint [11] 0 0
Up to Week 312
Primary outcome [12] 0 0
Proportion of subjects achieving Low Disease Activity - Determined by disease activity score using 28 joint counts (DAS28) [CRP] or clinical disease activity index (CDAI) criteria
Timepoint [12] 0 0
Up to Week 312
Primary outcome [13] 0 0
Change in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Scale - Using the FACIT Fatigue Scale
Timepoint [13] 0 0
From Week 0 to Week 312
Primary outcome [14] 0 0
American College Rheumatology (ACR) 20 Response Rate - ACR criteria measures improvement in tender or swollen joint counts.
Timepoint [14] 0 0
Up to Week 312
Primary outcome [15] 0 0
Proportion of subjects achieving Clinical Remission - Determined by DAS28 [CRP] and CDAI criteria
Timepoint [15] 0 0
Up to Week 312
Primary outcome [16] 0 0
Change in Tender Joint Count - Tender Joint Count will be assessed by a qualified Independent Joint Assessor or Principal Investigator using the Joint Evaluation Worksheet.
Timepoint [16] 0 0
From Week 0 to Week 312
Primary outcome [17] 0 0
Change in Clinical Laboratory Data - Clinical Laboratory Data include hematology, clinical chemistry and urinalysis
Timepoint [17] 0 0
From Week 0 through 30 day follow-up visit (30 days after last dose of study drug)
Primary outcome [18] 0 0
Proportion of subjects with satisfactory humoral response to Prevnar 13 - 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.
Timepoint [18] 0 0
Week 4 of the sub-study (approximately 136 weeks)
Secondary outcome [1] 0 0
Proportion of subjects with satisfactory humoral response to Prevnar 13 - 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
Timepoint [1] 0 0
Week 12 of the sub-study (approximately 252 weeks)
Secondary outcome [2] 0 0
Change in geometric mean fold rise of anti-pneumococcal antibody levels - Anti-pneumococcal antibody levels to each of the 12 pneumococcal antigens above vaccination baseline values.
Timepoint [2] 0 0
Up to Week 12 of the sub-study (approximately 252 weeks)

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
100 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
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Warrington

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AbbVie
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02049138
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
AbbVie Inc.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications