Optimized Treatment Algorithm for Patients With Early Rheumatoid Arthritis (RA)

NCT00660647 | Completed Phase 3 DMC

• 1 other identifier: VEK-20070008
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

Optimized treatment algorithm in early rheumatoid arthritis: Methotrexate and intra-articular glucocorticosteroid plus adalimumab or placebo in the treatment of early rheumatoid arthritis. A Randomised, double-blind and placebo-controlled, two arms, parallel group study of the additive effect of adalimumab concerning inflammatory control and inhibition of erosive development. Optimized Treatment Algorithms for Patients with Early RA

Conditions

Arthritis, Rheumatoid

Keywords

Rheumatoid arthritis, adalimumab, efficacy, adverse events

Outcome Measures

Primary Outcomes (1)

• Number of patients who achieve a DAS28 < 3.2

  0, 1, 3, 6, 9, 12 and 24 months (DAS28)

Secondary Outcomes (1)

• Changes in DAS28 from start of treatment

  1, 3, 6, 9, 12 and 24 months

Study Arms (2)

methotrexate + adalimumab

EXPERIMENTAL

Methotrexate and intraarticular triamcinolone hexacetonide plus adalimumab.

Drug: Adalimumab

methotrexate + placebo

PLACEBO COMPARATOR

Methotrexate and intraarticular triamcinolone hexacetonide and placebo

Drug: Placebo

Interventions

Adalimumab DRUG

Adalimumab injection 0.8 ml (40 mg) s.c. every second week in up to 2 years

Also known as: Humira

methotrexate + adalimumab

Placebo DRUG

Saline injection 0.9%, 0.8 ml s.c. every second week up to 2 years

Also known as: Saline

methotrexate + placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Patients (more than 18 years) with rheumatoid arthritis according to the ACR classification criteria (1) who have had the diagnose \< 6 months.
• \. Moderate to severe rheumatoid arthritis defined as DAS28 (CRP-based) \> 3.2.
• \. Negative pregnancy test (serum HCG) for women of childbearing potential prior to trial start. (Non-fertile women are defined as postmenopausal for at least 1 year or surgical sterilisation (bilateral tubal ligation, bilateral oophorectomy or hysterectomy)). Fertile women included in the trial should use contraception during the entire trial period (i.e. one of the following methods: Oral contraception, intrauterine device (IUD), depot injection of progesterone, subdermal implantation, contraceptive vaginal ring, transdermal depot plaster). In addition, contraception should be used for a period of 150 days after any discontinuation of trial medicine.
• \. Ability and willingness to inject the sc. injections him/herself or to have an assistant give the injections.
• \. Ability and willingness to give written informed consent and to meet the requirements of the trial protocol.

You may not qualify if:

• \. Persons with latent TB defined with a positive Mantoux test (\>12 mm for vaccinated and 6 mm for non-vaccinated), positive cultivation of mycobacteria in tissue samples, chest X-ray indicating TB,or other risk factors for activation of untreated latent TB, and persons not been given adequate TB prophylaxis according to the instructions of the department.
• \. Positive serology for Hepatitis B or C indicating active infection.
• \. Medical history with a positive HIV status (Check of HIV test upon suspicion).
• \. Medical history with histoplasmosis or listeriosis.
• \. Previous cancer or lymph proliferative disease except cases teated radically and have been without relapse for a minimum of 5 years.
• Patients with previous squamous cell carcinoma, basal cell skin carcinoma or cervical dysplasia, who have been treated successfully and radically can be included.
• \. Previous diagnosis or signs of demyelinized disease in the CNS system (e.g. optic neuritis, visual disorder, disturbed gait, facial paralysis, apraxia).
• \. Severe renal insufficiency (creatinine clearance \< 35 ml/min - nomogram).
• \. Affected liver function: Liver enzymes \> 2 x above normal limit value.
• \. Clinical significant drug or alcohol abuse during the past year and/or current daily alcohol consumption.
• \. Unstable diabetes, unstable ischemic heart disease, heart insufficiency (NYHA III-IV), active chronic inflammatory intestinal disease, recent cerebral apoplexia (within 3 months), chronic leg ulcer or any other condition (e.g. kateter a demeure)which according to the investigator imposes an increased risk to the subject, if he/she participates in the protocol.
• \. Anticoagulant therapy.
• \. Pregnancy or breast-feeding.
• \. Other inflammatory rheumatic diseases.
• \. Aggressive parvovirus B19 infection.

Sponsors & Collaborators

• University of Aarhus: lead
• Abbott: collaborator
• Meda Pharmaceuticals: collaborator
• Aarhus University Hospital: collaborator

Study Sites (1)

Aarhus University Hospital

Aarhus, DK-8000, Denmark

Location

Related Publications (9)

• Skejoe C, Hansen AS, Stengaard-Pedersen K, Junker P, Hoerslev-Pedersen K, Hetland ML, Oestergaard M, Greisen S, Hvid M, Deleuran M, Deleuran B. T-cell immunoglobulin and mucin domain 3 is upregulated in rheumatoid arthritis, but insufficient in controlling inflammation. Am J Clin Exp Immunol. 2022 Jun 15;11(3):34-44. eCollection 2022.

  PMID: 35874466 DERIVED

• Masic D, Stengaard-Pedersen K, Logstrup BB, Horslev-Petersen K, Hetland ML, Junker P, Ostergaard M, Ammitzboll C, Moller S, Christensen R, Ellingsen T. Similar lipid level changes in early rheumatoid arthritis patients following 1-year treat-to-target strategy with adalimumab plus methotrexate versus placebo plus methotrexate: secondary analyses from the randomised controlled OPERA trial. Rheumatol Int. 2021 Mar;41(3):543-549. doi: 10.1007/s00296-020-04756-5. Epub 2021 Jan 2.

  PMID: 33386898 DERIVED

• Sode J, Krintel SB, Carlsen AL, Hetland ML, Johansen JS, Horslev-Petersen K, Stengaard-Pedersen K, Ellingsen T, Burton M, Junker P, Ostergaard M, Heegaard NHH. Plasma MicroRNA Profiles in Patients with Early Rheumatoid Arthritis Responding to Adalimumab plus Methotrexate vs Methotrexate Alone: A Placebo-controlled Clinical Trial. J Rheumatol. 2018 Jan;45(1):53-61. doi: 10.3899/jrheum.170266. Epub 2017 Nov 15.

  PMID: 29142030 DERIVED

• Glinatsi D, Baker JF, Hetland ML, Horslev-Petersen K, Ejbjerg BJ, Stengaard-Pedersen K, Junker P, Ellingsen T, Lindegaard HM, Hansen I, Lottenburger T, Moller JM, Ornbjerg L, Vestergaard A, Jurik AG, Thomsen HS, Torfing T, Moller-Bisgaard S, Axelsen MB, Ostergaard M. Magnetic resonance imaging assessed inflammation in the wrist is associated with patient-reported physical impairment, global assessment of disease activity and pain in early rheumatoid arthritis: longitudinal results from two randomised controlled trials. Ann Rheum Dis. 2017 Oct;76(10):1707-1715. doi: 10.1136/annrheumdis-2017-211315. Epub 2017 Jun 13.

  PMID: 28611080 DERIVED

• Horslev-Petersen K, Hetland ML, Ornbjerg LM, Junker P, Podenphant J, Ellingsen T, Ahlquist P, Lindegaard H, Linauskas A, Schlemmer A, Dam MY, Hansen I, Lottenburger T, Ammitzboll CG, Jorgensen A, Krintel SB, Raun J, Johansen JS, Ostergaard M, Stengaard-Pedersen K; OPERA Study-Group. Clinical and radiographic outcome of a treat-to-target strategy using methotrexate and intra-articular glucocorticoids with or without adalimumab induction: a 2-year investigator-initiated, double-blinded, randomised, controlled trial (OPERA). Ann Rheum Dis. 2016 Sep;75(9):1645-53. doi: 10.1136/annrheumdis-2015-208166. Epub 2015 Oct 21.

  PMID: 26489704 DERIVED

• Ammitzboll CG, Steffensen R, Bogsted M, Horslev-Petersen K, Hetland ML, Junker P, Johansen JS, Podenphant J, Ostergaard M, Ellingsen T, Stengaard-Pedersen K. CRP genotype and haplotype associations with serum C-reactive protein level and DAS28 in untreated early rheumatoid arthritis patients. Arthritis Res Ther. 2014 Oct 31;16(5):475. doi: 10.1186/s13075-014-0475-3.

  PMID: 25359432 DERIVED

• Laustsen JK, Rasmussen TK, Stengaard-Pedersen K, Horslev-Petersen K, Hetland ML, Ostergaard M, Junker P, Hvid M, Deleuran B. Soluble OX40L is associated with presence of autoantibodies in early rheumatoid arthritis. Arthritis Res Ther. 2014 Oct 30;16(5):474. doi: 10.1186/s13075-014-0474-4.

  PMID: 25359291 DERIVED

• Greisen SR, Schelde KK, Rasmussen TK, Kragstrup TW, Stengaard-Pedersen K, Hetland ML, Horslev-Petersen K, Junker P, Ostergaard M, Deleuran B, Hvid M. CXCL13 predicts disease activity in early rheumatoid arthritis and could be an indicator of the therapeutic 'window of opportunity'. Arthritis Res Ther. 2014 Sep 24;16(5):434. doi: 10.1186/s13075-014-0434-z.

  PMID: 25249397 DERIVED

• Ammitzboll CG, Thiel S, Jensenius JC, Ellingsen T, Horslev-Petersen K, Hetland ML, Junker P, Krogh NS, Ostergaard M, Stengaard-Pedersen K. M-ficolin levels reflect disease activity and predict remission in early rheumatoid arthritis. Arthritis Rheum. 2013 Dec;65(12):3045-50. doi: 10.1002/art.38179.

  PMID: 24022747 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Adalimumab; Sodium Chloride

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Kristian Stengaard-Pedersen, Professor

  Aarhus University/Aarhus University Hospital

  PRINCIPAL INVESTIGATOR

• Kim Hørslev-Petersen, Professor

  King Christian X's Rheumatism Hospital, Graasten, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2008
• First Posted: April 17, 2008
• Study Start: September 1, 2007
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: November 24, 2015

Record last verified: 2015-11

Locations

DK (1)