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

NCT ID: NCT02198651

Last Updated: 2019-06-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 149 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-05
• Study Completion Date: 2018-08-08

Brief Summary

The primary objective of the study was to investigate the association between residual disease activity at Baseline as detected by Magnetic Resonance Imaging (MRI) and the occurrence of flares in participants with rheumatoid arthritis (RA) randomized to an adalimumab dose tapering regimen controlled by adalimumab withdrawal.

Detailed Description

This was a Phase 4, multicenter, randomized, double-blind, parallel-group study. The study included a Screening period of up to 28 days (unless extended with justification approved by study-designated physician), a 4-week Lead-In Period with open label (OL) 40 mg adalimumab administered subcutaneously (sc) every other week (eow), and a randomized 36-week double-blind period with 40 mg adalimumab sc every 3 weeks (q3wks; tapering arm) or placebo sc q3wks (withdrawal arm). Participants were randomized in a 5:1 ratio (tapering arm: withdrawal arm) after confirmation of meeting the disease activity score (DAS) criteria. Participants who experienced a protocol-defined flare at any time were to enter a rescue arm with OL 40 mg adalimumab administered sc eow for 16 weeks.

Conditions

Rheumatoid Arthritis; Musculoskeletal and Connective Tissue Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Adalimumab 40 mg eow

40 mg adalimumab administered subcutaneously every other week (eow) from Week 0 to Week 4 (Lead-in Period)

Group Type: EXPERIMENTAL

Adalimumab

Intervention Type: BIOLOGICAL

Pre-filled syringe, administered by subcutaneous injection

Adalimumab Tapering

40 mg adalimumab administered subcutaneously every three weeks from Week 4 to Week 40 (Double-blind Period)

Group Type: ACTIVE_COMPARATOR

Adalimumab

Intervention Type: BIOLOGICAL

Pre-filled syringe, administered by subcutaneous injection

Adalimumab Withdrawal Arm

Placebo administered subcutaneously every three weeks from Week 4 to Week 40 (Double-blind Period)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Pre-filled syringe, administered by subcutaneous injection in the Double-blind period

Adalimumab 40 mg eow Rescue Arm

40 mg adalimumab administered subcutaneously every other week from Flare Week 0 to Flare Week 16 (Open-label Rescue Period)

Group Type: EXPERIMENTAL

Adalimumab

Intervention Type: BIOLOGICAL

Pre-filled syringe, administered by subcutaneous injection

Interventions

Adalimumab

Pre-filled syringe, administered by subcutaneous injection

Intervention Type: BIOLOGICAL

Placebo

Pre-filled syringe, administered by subcutaneous injection in the Double-blind period

Intervention Type: OTHER

Other Intervention Names

ABT-D2E7; Humira

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

AbbVie Inc.

Role: STUDY_DIRECTOR

AbbVie

Locations

J Michael Grelier Research /ID# 149772

Tuscaloosa, Alabama, United States

Westlake Medical Research (WMR) Clinical Trials /ID# 155386

Thousand Oaks, California, United States

University of Florida /ID# 144851

Jacksonville, Florida, United States

North Georgia Rheumatology Grp /ID# 155225

Lawrenceville, Georgia, United States

The Arthritis & Diabetes Clinic, Inc. /ID# 149017

Monroe, Louisiana, United States

Aa Mrc Llc /Id# 151933

Grand Blanc, Michigan, United States

North Mississippi Med Clinics /ID# 149443

Tupelo, Mississippi, United States

Montefiore Medical Center /ID# 155013

The Bronx, New York, United States

Shanahan Rheuma & Immuno /ID# 148689

Raleigh, North Carolina, United States

Altoona Ctr Clinical Res /ID# 148448

Duncansville, Pennsylvania, United States

Low Country Rheumatology, PA /ID# 154198

Summerville, South Carolina, United States

West Tennessee Research Inst /ID# 148391

Jackson, Tennessee, United States

Arthritis Centers of Texas /ID# 152843

Dallas, Texas, United States

Royal Prince Alfred Hospital /ID# 154649

Camperdown, New South Wales, Australia

Optimus Clinical Research Pty. /ID# 133881

Kogarah, New South Wales, Australia

John Hunter Hospital /ID# 133884

Newcastle, New South Wales, Australia

Rheumatology Research Unit /ID# 133883

Maroochydore, Queensland, Australia

AKH Wien /ID# 133885

Vienna, Vienna, Austria

St. Joseph's Healthcare /ID# 149233

Hamilton, Ontario, Canada

The Arthritis Program Res Grp /ID# 129056

Newmarket, Ontario, Canada

Institut de Rhum. de Montreal /ID# 129055

Montreal, Quebec, Canada

Groupe de Recherche en Maladies Osseuses /ID# 129057

Sainte-Foy, Quebec, Canada

CIUSSS de l'Estrie - CHUS /ID# 144839

Sherbrooke, Quebec, Canada

CHU de la miletrie /ID# 133928

Poitiers, Poitou-Charentes, France

CHU Amiens Picardie /ID# 144846

Amiens, Somme, France

Hospital Louis Pasteur /ID# 134708

Chartres, , France

CHU de Grenoble - Albet Michal /ID# 135953

Grenoble, , France

Asklepios Klinik /ID# 129146

Bad Abbach, , Germany

Charité Universitätsmedizin Campus Mitte /ID# 129142

Berlin, , Germany

Immanuel-Krankenhaus /ID# 129143

Buch, , Germany

Krankenhaus Porz am Rhein /ID# 129147

Cologne, , Germany

Rheumaforschungszentrum II /ID# 148554

Hamburg, , Germany

Klinikum der Univ Munich /ID# 129144

Munich, , Germany

Rheumazentrum Ratingen /ID# 129148

Ratingen, , Germany

Rheumatologische Praxis /ID# 151979

Rendsburg, , Germany

University General Hospital "Attikon" /ID# 134709

Athens, Attica, Greece

General Hospital of Athens /ID# 129202

Athens, , Greece

General UH of Heraklion /ID# 134712

Heraklion, , Greece

Budai Irgalmasrendi Korhaz /ID# 134714

Budapest, , Hungary

Orszagos Reumatologiai es Fizi /ID# 134710

Budapest, , Hungary

Debreceni Egyetem Klinikai Koz /ID# 134715

Debrecen, , Hungary

St Vincent's University Hosp /ID# 129210

Dublin, , Ireland

AP Romano Umberto I /ID# 132895

Rome, Lazio, Italy

A.O. Univ Consorziale Policlin /ID# 133932

Bari, , Italy

Azienda Istituto Gaetano Pini /ID# 132964

Milan, , Italy

Fondazione IRCCS Policlinico /ID# 133886

Pavia, , Italy

A.O.U.I. di Verona Policlinico /ID# 132973

Verona, , Italy

Jan van Breemen Instituut /ID# 133887

Amsterdam, , Netherlands

Rijnstate Hospital /ID# 129206

Arnhem, , Netherlands

Medisch Centrum Leeuwarden /ID# 133888

Leeuwarden, , Netherlands

UMC Utrecht /ID# 132896

Utrecht, , Netherlands

Hospital Parc de Salut del Mar /ID# 148670

Barcelona, , Spain

Hosp Sant J. Despi-Moises Brog /ID# 135368

Barcelona, , Spain

Hospital Universitario Basurto /ID# 135529

Bilbao, , Spain

Hosp Clinico Virgen Arrixaca /ID# 137020

El Palmar, , Spain

Hospital General Universitario Gregorio Maranon /ID# 133889

Madrid, , Spain

Hospital Universitario La Paz /ID# 135369

Madrid, , Spain

Hospital Univ De Mostoles /ID# 134489

Móstoles, , Spain

Complejo Hosp Santiago /ID# 133890

Santiago de Compostela, , Spain

Hosp General Univ de Valencia /ID# 134488

Valencia, , Spain

Akademiska Sjukhuset /ID# 148669

Uppsala, Uppsala County, Sweden

Uppsala University Hospital /ID# 133891

Uppsala, , Sweden

Vastmanlands Sjukhus /ID# 133892

Västerås, , Sweden

Whipps Cross Univ Hospital /ID# 133893

London, London, City of, United Kingdom

Guy's and St Thomas' NHS Found /ID# 132965

London, London, City of, United Kingdom

Mid Essex Hospitals NHS Trust /ID# 151636

Chelmsford, , United Kingdom

Western General Hospital /ID# 132966

Edinburgh, , United Kingdom

Chapel Allerton Hospital /ID# 129208

Leeds, , United Kingdom

University Hospital Aintree /ID# 132980

Liverpool, , United Kingdom

Queen Alexandra Hospital /ID# 132982

Portsmouth, , United Kingdom

Countries

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

References

Emery P, Burmester GR, Naredo E, Sinigaglia L, Lagunes I, Koenigsbauer F, Conaghan PG. Adalimumab dose tapering in patients with rheumatoid arthritis who are in long-standing clinical remission: results of the phase IV PREDICTRA study. Ann Rheum Dis. 2020 Aug;79(8):1023-1030. doi: 10.1136/annrheumdis-2020-217246. Epub 2020 May 13.

Reference Type: DERIVED

PMID: 32404343 (View on PubMed)

Emery P, Burmester GR, Naredo E, Zhou Y, Hojnik M, Conaghan PG. Design of a phase IV randomised, double-blind, placebo-controlled 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) patients (PREDICTRA). BMJ Open. 2018 Feb 28;8(2):e019007. doi: 10.1136/bmjopen-2017-019007.

Reference Type: DERIVED

PMID: 29490959 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.rxabbvie.com/

Related Info

Other Identifiers

2014-001114-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M14-500

Identifier Type: -

Identifier Source: org_study_id