A study of subjects with rheumatoid arthritis who are in clinical remission to investigate patient and disease characteristics that could help identify which subjects may lose disease control upon reducing their adalimumab dose

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2014-001114-26-GB
• Date of registration: 14/08/2014
• Prospective Registration: Yes
• Primary sponsor: AbbVie Deutschland GmbH & Co. KG
• Public title: A study of subjects with rheumatoid arthritis who are in clinical remission to investigate patient and disease characteristics that could help identify which subjects may lose disease control upon reducing their adalimumab dose
• 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: 25/11/2014
• Target sample size: 150
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001114-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

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

Contacts

• Name: EU Clinical Trials Helpdesk
• Affiliation: AbbVie Ltd

• Name: EU Clinical Trials Helpdesk
• Affiliation: AbbVie Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female subjects = 18 years of age.
2. Subject has a diagnosis of RA as defined by the 1987 revised ACR classification criteria and/or the ACR /EULAR 2010 classification criteria (any duration since diagnosis).
3. Subject must meet the following criteria:
• Must be treated with adalimumab 40 mg sc eow for at least 12 months prior to Week 0 Visit
• Must be treated with concomitant MTX at a stable dose (oral, sc or im at any dose) for at least 12 weeks prior to Week 0 Visit or if not on MTX, must be treated with other allowed csDMARDs at 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.
4. Subject must be in sustained clinical remission based on the following:
• At least one documented 4 or 3 (if PGA is not available) variables DAS28 (ESR) or DAS28 (CRP) < 2.6 (or calculated based on documented components of the DAS28) in the patient 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.
5. If subjects are receiving concomitant allowed csDMARDs (in addition or not to MTX) the dose must be 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).
6. If subjects are receiving concomitant oral corticosteroids, prednisone or equivalent must be < 10 mg/day and the dose must be stable for at least 4 weeks prior to the Week 0 Visit.
7. If subjects are 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 be stable for at least 4 weeks prior to the Week 0 Visit.
8. Subject must be able and willing to provide written informed consent and comply with the requirements of this study protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 91
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 59

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. Subject is 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. Subject has been treated with intra-articular or parenteral corticosteroids within the last four weeks before Screening.
4. Subject has undergone joint surgery within 12 weeks of Screening (at joints to be assessed by MRI and/or ultrasound).
5. Subject has a medical condition precluding an MRI (e.g. magnetic activated implanted devices - cardiac pace-maker, insulin pump, neurostimulators, etc. and metallic devices or fragments or clips in the eye, brain or spinal canal and in the hand/wrist undergoing MRI)
6. Subject has 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 30mL/min/1.73m2 at Screening, hepato-renal syndrome, severe chronic liver function
impairment]
7. Subject has 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:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Rheumatoid arthritis
MedDRA version: 20.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Trade Name: Humira 40 mg/0.8 ml solution for injection
Product Name: ADALIMUMAB
Product Code: 331731-18-1
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ADALIMUMAB
CAS Number: 331731-18-1
Current Sponsor code: Humira
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: The primary objective is to investigate the association between residual disease activity at Baseline as detected by magnetic resonance imaging (MRI) and the occurrence of flares in RA subjects randomized to an adalimumab dose tapering regimen controlled by adalimumab withdrawal

Primary end point(s): The primary explanatory variables are the Baseline hand and wrist synovitis and bone marrow edema (BME) RAMRIS scores as well as a composite of both and the dependent variable is the occurrence of flare up to Week 40 in the tapering arm.

Secondary Objective: • To assess the occurrence and severity of flares and the time to flare in both taper and withdrawal arms.
• To investigate the association between Double-Blind Baseline (dbBaseline) subject demographic and disease characteristics and the occurrence of flares.
• To investigate the association between dbBaseline adalimumab trough concentrations and the occurrence of flares.
• To evaluate the effectiveness of rescue therapy with open-label adalimumab 40 mg every other week (eow) over 16 weeks in subjects experiencing a flare.

Timepoint(s) of evaluation of this end point: Up to Week 40

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: From dbBaseline up to Week 40 in the Double-Blind period and up to Week 16 in the Open-Label Rescue Arm

Secondary end point(s): • Time to flare
• Flare severity (Lickert scale)
• Proportion of subjects experiencing a flare
• Subject demographics and clinical disease characteristics at dbBaseline
• Proportion of subjects who regain clinical remission [defined as DAS28 (ESR) < 2.6 and defined as DAS28 (ESR) decrease >1.2 if DAS28 (ESR) was less than 2.6 at flare] in the Open-Label Rescue Arm over time
• Time to regain clinical remission in the Open-Label Rescue Arm
• Proportion of subjects who achieve low disease activity [defined as DAS28 (ESR) < 3.2] in the Open-Label Rescue Arm over time
• Change from dbBaseline in DAS28 (ESR), Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI)
• Proportion of subjects maintaining clinical remission [defined by DAS, SDAI and CDAI: DAS28(ESR) < 2.6; SDAI = 3.3; CDAI = 2.8)] throughout the study
• Change from dbBaseline to Week 40 or final Visit in MRI synovitis, BME and erosions RAMRIS scores
• Change from dbBaseline in Health Assessment Questionnaire – Disability Index (HAQ-DI) over time
• Proportion of subjects with HAQ-DI normal (HAQ-DI = 0.5) at dbBaseline and at Week 40
• Change from dbBaseline in RAPID 3 scores assessed during Visits
• Change from Flare Week 0 visit week 0 in RAPID 3 at home assessments
• Change from dbBaseline in Treatment Satisfaction Questionnaire for Medication (TSQM)
• Change from dbBaseline in Work Productivity and Activity Impairment (WPAI)
• Change from dbBaseline in Short Form-36 (SF-36)
• Change from dbBaseline in Functional Assessment of Chronic Illness Therapy - fatigue (FACIT-fatigue)

Secondary ID(s)

2014-001114-26-DE

M14-500

Source(s) of Monetary Support

AbbVie Inc.

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 11/08/2019
• Date Completed: 08/08/2018
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-001114-26/results