A Phase 4 Trial Assessing the ImPact of Residual Inflammation Detected Via Imaging TEchniques, Drug Levels and Patient Characteristics on the Outcome of Dose TaperIng of Adalimumab in Clinical Remission Rheumatoid ArThritis (RA) Subjects

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02198651
• Date of registration: 22/07/2014
• Prospective Registration: Yes
• Primary sponsor: AbbVie
• Public title: A Phase 4 Trial Assessing the ImPact of Residual Inflammation Detected Via Imaging TEchniques, Drug Levels and Patient Characteristics on the Outcome of Dose TaperIng of Adalimumab in Clinical Remission Rheumatoid ArThritis (RA) Subjects PREDICTRA
• Scientific title: A Phase 4 Trial Assessing the ImPact of Residual Inflammation Detected Via Imaging TEchniques, Drug Levels and Patient Characteristics on the Outcome of Dose TaperIng of Adalimumab in Clinical Remission Rheumatoid ArThritis (RA) Subjects (PREDICTRA)
• Date of first enrolment: January 5, 2015
• Target sample size: 149
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02198651
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 4

Countries of recruitment

Australia, Austria, Canada, France, Germany, Greece, Hungary, Ireland, Italy, Netherlands, Spain, Sweden, United Kingdom, United States

Contacts

• Name: AbbVie Inc.
• Affiliation: AbbVie

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Participant had a diagnosis of rheumatoid arthritis (RA) as defined by the 1987
revised American College of Rheumatology (ACR) classification criteria and/or the ACR
/European League Against Rheumatism (EULAR) 2010 classification criteria (any duration
since diagnosis).

2. Participant must have met the following criteria:

- Must have been treated with adalimumab 40 mg subcutaneously every other week (sc
eow) for at least 12 months prior to Week 0 Visit

- Must have been treated with concomitant methotrexate (MTX) at a stable dose
(oral, sc or intramuscular (im) at any dose) for at least 12 weeks prior to Week
0 Visit or if not on MTX, must have been treated with other allowed conventional
synthetic disease-modifying anti-rheumatic drugs (csDMARDs) at a stable dose for
at least 12 weeks prior to Week 0 Visit or if not treated with csDMARDs must
maintain this regimen for at least 12 weeks prior to Week 0 Visit.

3. Participant must be in sustained clinical remission based on the following:

- At least one documented 4 or 3 (if Patient's Global Assessment ; PGA is not
available) variables Disease Activity Score 28 Erythrocyte sedimentation rate
(DAS28 ESR) or DAS28 C-reactive protein (CRP) < 2.6 (or calculated based on
documented components of the DAS28) in the participant's chart 6 months or longer
prior to the Screening Visit;

- 4 variables DAS28 (ESR) assessed at Screening < 2.6, with all components
including ESR assessed at Screening.

4. If participant was receiving concomitant allowed csDMARDs (in addition or not to MTX)
the dose must have been stable for at least 12 weeks prior to the Week 0 Visit (e.g.,
chloroquine, hydroxychloroquine, sulfasalazine, gold formulations [including
auranofin, gold sodium thiomalate, and aurothioglucose] and/or leflunomide).

5. If participant was receiving concomitant oral corticosteroids, prednisone or
equivalent must have been < 10 mg/day and the dose must have been stable for at least
4 weeks prior to the Week 0 Visit.

6. If participant was receiving concomitant non-steroidal anti-inflammatory drugs
(NSAIDs), tramadol or other equivalent opioids and/or non-opioid analgesics, the dose
and/or therapeutic scheme must have been stable for at least 4 weeks prior to the Week
0 Visit.

7. Participant must have been able and willing to provide written informed consent and
comply with the requirements of this study protocol.

Exclusion Criteria:

1. Any 4 or 3 (if PGA is not available) variables DAS28 (ESR) or DAS28 (CRP) (or
calculated based on documented components of the DAS28) assessed within 6 months prior
to the Screening Visit = 2.6.

2. Participant was on an additional concomitant biological disease-modifying
anti-rheumatic drug (bDMARD) (including but not limited to abatacept, anakinra,
certolizumab, etanercept, golimumab, infliximab, rituximab or tocilizumab).

3. Participant had been treated with intra-articular or parenteral corticosteroids within
the last four weeks before Screening.

4. Participant had undergone joint surgery within 12 weeks of Screening (at joints to be
assessed by magnetic resonance imaging (MRI) and/or ultrasound).

5. Participant had a medical condition precluding an MRI (e.g. magnetic activated
implanted devices - cardiac pace-maker, insulin pump, neuro stimulators, etc. and
metallic devices or fragments or clips in the eye, brain or spinal canal and in the
hand/wrist undergoing MRI)

6. Participant had a medical condition precluding a contrast MRI with gadolinium [e.g.
nephrogenic systemic fibrosis, previous anaphylactic/anaphylactoid reaction to
gadolinium containing contrast agent, pregnancy or breast feeding, severe renal
insufficiency with an estimated Glomerular Filtration Rate (eGFR) below 30
mL/min/1.73m^2 at Screening, hepato-renal syndrome, severe chronic liver function
impairment]

7. Participant had been treated with any investigational drug of chemical or biologic
nature within a minimum of 30 days or five half-lives (whichever is longer) of the
drug prior to the Screening Visit.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Musculoskeletal and Connective Tissue Diseases

Rheumatoid Arthritis

Intervention(s)

Biological: Adalimumab

Other: Placebo

Primary Outcome(s)

Association Between Baseline Hand and Wrist Synovitis Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) Score and Flare up to Week 40 in the Tapering Arm [Time Frame: From Week 4 to Week 40]

Association Between Baseline Bone Marrow Edema RAMRIS Score and Flare up to Week 40 in the Tapering Arm [Time Frame: From Week 4 to Week 40]

Association Between a Composite of Baseline Hand and Wrist Synovitis and Bone Marrow Edema RAMRIS Scores and Flare up to Week 40 in the Tapering Arm [Time Frame: From Week 4 to Week 40]

Secondary Outcome(s)

Mean Change From Double-blind Baseline in Physician's Global Assessment of Disease Activity [Time Frame: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

Mean Change From Double-blind Baseline in Short-Form 36 Version 2 Health Survey (SF-36v2) Mental Component Summary (MCS) Score [Time Frame: At Weeks 4, 28, and 40 and from Flare Week 0 to Flare Week 16]

Mean Change From Double-blind Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale [Time Frame: At Weeks 4, 16, 28, and 40 and from Flare Week 0 to Flare Week 16]

Mean Change From Double-blind Baseline in Tender Joint Count 28 [Time Frame: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

Mean Change From Double-blind Baseline in Morning Stiffness Duration [Time Frame: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

Mean Change From Double-blind Baseline in Work Productivity and Activity Impairment (WPAI) Overall Work Impairment and Activity Impairment Scores [Time Frame: At Weeks 4, 28, and 40 and Flare Weeks 0, 10, and 16]

Mean Change From Double-blind Baseline in Participant's Global Assessment of Rheumatoid Arthritis Pain [Time Frame: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

Mean Change From Flare Week 0 in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed at Home [Time Frame: Flare Week 0 and Flare Weeks 1, 2, 3, 5, 6, 7, 8, 9, 11, 12, 13, 14, 15]

Mean Change From Double-blind Baseline in Serum Levels of C-reactive Protein (CRP) [Time Frame: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

Mean Change From Double-blind Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) Score Over Time [Time Frame: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

Mean Change From Double-blind Baseline in Clinical Disease Activity Index (CDAI) Score [Time Frame: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

Mean Change From Double-blind Baseline in Serum Levels of Erythrocyte Sedimentation Rate (ESR) [Time Frame: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

Mean Change From Double-blind Baseline in Swollen Joint Count 28 [Time Frame: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Side Effects Score [Time Frame: At Weeks 4, 16, 28, and 40 and from Flare Week 0 to Flare Week 16]

Median Time to Flare [Time Frame: From Week 4 to Week 40]

Mean Change From Double-blind Baseline in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed During In-office Visits [Time Frame: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

Mean Change From Double-blind Baseline in Simplified Disease Activity Index (SDAI) Score [Time Frame: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

Mean Change From Double-blind Baseline in Swollen Joint Count 66 [Time Frame: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

Mean Change From Double-blind Baseline in Participant's Assessment of Sleep Disturbance [Time Frame: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

Mean Change From Double-blind Baseline to Week 40 or Final Visit in Bone Marrow Edema (BME) Score [Time Frame: From Week 4 to Week 40 or Final visit]

Number of Participants Who Regained Clinical Remission in the Open-Label Rescue Arm Over Time [Time Frame: From Flare Week 0 to Flare Week 16]

Median Time to Clinical Remission From the Occurrence of Flare [Time Frame: From Flare Week 0 to Flare Week 16]

Number of Participants With Health Assessment Questionnaire- Disability Index (HAQ-DI) Score = 0.5 at Double-blind Baseline and at Week 40 [Time Frame: Week 4 and Week 40]

Physicians' Assessment of Flare Severity [Time Frame: At the Flare Week 0 Visit]

Mean Change From Double-blind Baseline in Participant's Global Assessment of Disease Activity [Time Frame: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Global Satisfaction Score [Time Frame: At Weeks 4, 16, 28, and 40 and from Flare Week 0 to Flare Week 16]

Mean Change From Double-blind Baseline in Short-Form 36 Version 2 Health Survey (SF-36v2) Physical Component Summary (PCS) Score [Time Frame: At Weeks 4, 28, and 40 and from Flare Week 0 to Flare Week 16]

Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Convenience Score [Time Frame: At Weeks 4, 16, 28, and 40 and from Flare Week 0 to Flare Week 16]

Mean Change From Double-blind Baseline to Week 40 or Final Visit in Bone Erosions Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) Score [Time Frame: From Week 4 to Week 40 or Final Visit]

Mean Change From Double-blind Baseline in Tender Joint Count 68 [Time Frame: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

Number of Participants Maintaining Clinical Remission Defined By DAS28 (ESR) < 2.6, SDAI = 3.3, and CDAI = 2.8 at Each Visit By Treatment Arm [Time Frame: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

Participants' Assessment of Flare Severity [Time Frame: At the Flare Week 0 Visit]

Percentage of Participants With a Flare [Time Frame: From Week 4 to Week 40]

Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Effectiveness Score [Time Frame: At Weeks 4, 16, 28, and 40 and from Flare Week 0 to Flare Week 16]

Mean Change From Double-blind Baseline to Week 40 or Final Visit in Magnetic Resonance Imaging (MRI) Synovitis Score [Time Frame: From Week 4 to Week 40 or Final visit]

Mean Change From Double-blind Baseline in Disease Activity Score 28 (DAS28) [Time Frame: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

Mean Change From Double-blind Baseline in Morning Stiffness Severity [Time Frame: From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

Secondary ID(s)

M14-500

2014-001114-26

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 25/06/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02198651