Clincosm LogoSign in Get a demo

Active Conventional Therapy Compared to Three Different Biologic Treatments in Early Rheumatoid Arthritis With Subsequent Dose Reduction

Sponsor
Karolinska Institutet (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT01491815
Collaborator
(none)
812
Enrollment
30
Locations
4
Arms
131.5
Anticipated Duration (Months)
27.1
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is an international (Sweden, Finland, Norway, Denmark, Iceland and the Netherlands) trial designed to compare the safety and efficacy of active conventional therapy (ACT) and three biologic treatments in subjects with early rheumatoid arthritis (RA). The global aim of this study is to assess and compare

  1. the proportion of subjects who achieve remission with ACT versus three different biologic therapies (Certolizumab-pegol, Abatacept or Tocilizumab)

  2. two alternative de-escalation strategies in patients who respond to first-line therapy.

Condition or Disease Intervention/Treatment Phase
  • Drug: Non-biological DMARD's
  • Biological: Cimzia
  • Biological: Orencia
  • Biological: RoActemra
 Phase 4

Detailed Description

After completed enrollment a total of 812 patients were included in the study.

371 of the included patients have entered treatment part 2, 256 patients have exited the study after treatment part 1, 207 patients have had early termination and 322 patients have completed the full study.

Study Design

Study Type:
Interventional
Actual Enrollment :
812 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Randomized, Open-label, Blinded-assessor, Phase 4 Study in Patients With Early Rheumatoid Arthritis to Compare Active Conventional Therapy Versus Three Biologic Treatments, and Two De-escalation Strategies in Patients Who Respond to Treatment
Actual Study Start Date :
Dec 14, 2012
Anticipated Primary Completion Date :
Jul 1, 2023
Anticipated Study Completion Date :
Dec 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Active conventional therapy (ACT)

Non-biological DMARD's: Methotrexate plus steroids or Methotrexate plus Sulphasalazine and Hydroxychloroquine and steroids

Drug: Non-biological DMARD's
Methotrexate: 25mg/week. SSZ: 2 g/day. HCQ: 35 mg/kg/week (Finland and Denmark) Methotrexate: 25mg/week. Prednisolone 20 mg/day tapered in 9 weeks to 5 mg/day, discontinued after 9 months. (Sweden, Norway, Iceland, and the Netherlands)
Active Comparator: Biologic agent 1

Cimzia: Certolizumab-pegol plus Methotrexate and steroids

Biological: Cimzia
Certolizumab-pegol: 200 mg s.c. every other week. Methotrexate: 25mg/week
Active Comparator: Biologic agent 2

Orencia: Abatacept plus Methotrexate and steroids

Biological: Orencia
Abatacept: 125 mg s.c. every week. Methotrexate: 25mg/week
Active Comparator: Biologic agent 3

RoActemra: Tocilizumab plus Methotrexate and steroids

Biological: RoActemra
Tocilizumab is given as 4-weekly infusions at dosage 8 mg/kg or 162 mg in solution s.c. every week. Methotrexate: 25mg/week

Outcome Measures

Primary Outcome Measures

  1. The proportion of patients in remission at week 24 from baseline according to CDAI [24 weeks from BL]

    Treatment Part 1: The primary efficacy outcome is the proportion of patients in remission at week 24 from BL according to CDAI

  2. The proportion of patients in remission at week 24 after dose-reduction according to CDAI [24 weeks after dose-reduction]

    Treatment Part 2: The primary efficacy outcome is the proportion of patients in remission according to CDAI, at the time point 24 weeks after the dose was first reduced

  3. The radiographic progression of total Sharp van der Heijde score after 48 weeks from baseline [48 weeks from BL]

    The primary efficacy outcome is the progression of total Sharp van der Heijde score after 48 weeks from BL

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  1. Subject is ≥18 years of age.

  2. Subject has a diagnosis of RA as defined by the newly established ACR/EULAR criteria,

  3. (Patients should also be classified according to the 1987-revised ACR-classification criteria, without this being an inclusion criteria).

  4. <24 months from arthritis symptom debut (symptom duration will be registered).

  5. Subject must have DAS28 (CRP) > 3.2.

  6. ≥ 2 swollen joints AND ≥ 2 tender joints.

  7. Subject must fulfill one of the following three criteria: RF positive OR ACPA positive OR CRP >10 mg/L.

  8. Female subject is either not of childbearing potential (postmenopausal, surgically sterile etc.), or is of childbearing potential and practicing one of the following methods of birth control throughout the study and for 150 days after study completion:

  • Intrauterine device (IUD)

  • Contraceptives (oral, parenteral, patch) for three months prior to study drug administration)

  • A vasectomized partner

  1. Female subjects of childbearing potential must have a negative serum pregnancy test at the Screening visit.

  2. Subject is judged to be in good general health as determined by the principal investigator based upon the results of medical history, laboratory profile, physical examination, chest X-ray (CXR), and 12-lead electrocardiogram (ECG) performed at Screening.

  3. Subjects must be able and willing to provide written informed consent and comply with the requirements of this study protocol.

  4. Subjects must be able and willing to self-administer s.c. injections or have a qualified person available to administer s.c. injections.

Exclusion Criteria:

  1. Subject has been previously treated with disease modifying antirheumatic drugs (DMARDs) for rheumatic diseases.

  2. Current active inflammatory joint disease other than RA.

  3. Subjects has had a dose of prednisone (or equivalent) >7.5 mg/day or has had a dose change within the preceding 4 weeks.

  4. Subject has been treated with intra-articular or parenteral administration of corticosteroids in the preceding 4 weeks. Inhaled corticosteroids for stable medical conditions are allowed.

  5. Subject has undergone joint surgery within the preceding two months (at joints to be assessed within the study).

  6. Subject has chronic arthritis diagnosed before age 17 years.

  7. Subject has a history of an allergic reaction or significant sensitivity to constituents of study drugs.

  8. Subject has been treated with any investigational drug within one month prior to screening visit.

  9. Active infection of any kind (excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization within 4 weeks of screening.

  10. Subject has a poorly controlled medical condition, such as uncontrolled diabetes, unstable heart disease, congestive heart failure, recent cerebrovascular accidents and any other condition which, in the opinion of the investigator, would put the subject at risk by participation in the study.

  11. Subject has a history of clinically significant hematologic (e.g., severe anemia, leukopenia, thrombocytopenia), renal or liver disease (e.g., fibrosis, cirrhosis, hepatitis).

  12. Subject has history of neurologic symptoms suggestive of central nervous system (CNS) demyelinating disease and/or diagnosis of central demyelinating disease.

  13. Subject has history of cancer or lymphoproliferative disease. Allowable exceptions:

  14. Successfully treated cutaneous squamous cell or basal cell carcinoma

  15. Localized carcinoma in situ of the cervix

  16. Curatively treated malignancy (treatment terminated) > 5 years prior to screening

  17. Subject has a history of listeriosis, histoplasmosis, untreated TB, persistent chronic infections, or recent active infections requiring hospitalization or treatment with intravenous (iv) anti-infectives within 30 days or oral anti-infectives within 14 days prior to the BL visit.

  18. Subjects will be evaluated for latent TB infection with a PPD or QuantiFERON test and X-ray. Subjects with evidence for latent TB will not be enrolled but first assessed according to local guidelines.

  19. Subject is known to have immune deficiency, history of Human Immunodeficiency Virus (HIV) or is otherwise severely immunocompromised.

  20. Female subject who is pregnant or breast-feeding or considering becoming pregnant during the study or within 150 days after the last dose of study medication.

  21. Men who are planning to father a child during the time they are included in the study

  22. Subject has a history of clinically significant drug or alcohol usage in the last year.

  23. Subject has a chronic widespread pain syndrome.

  24. Subject is considered by the investigator, for any reason, to be an unsuitable candidate for the study.

  25. Subject is unwilling to comply with the study protocol.

  26. Screening clinical laboratory analyses show any of the following abnormal laboratory results:

  27. Aspartate transaminase (AST) or alanine transaminase (ALT) > 1.75 times upper limit of normal (ULN).

  28. Positive serum human chorionic gonadotropin (hCG).

  29. Positive tests for hepatitis B surface antigen (HBsAg) or hepatitis C serology indicative of current infection.

  30. Creatinine levels > 2x the ULN. If creatinine 1-2 times ULN, check GFR.

  31. Hemoglobin < 90 g/L.

  32. Absolute neutrophil count (ANC) < 1.5 x 10^3/microL.

  33. Serum total bilirubin > 1.5 mg/dL (>26 micromol/L).

Contacts and Locations

Locations

Site City State Country Postal Code
1 Aalborg University Hospital Aalborg Denmark
2 Aarhus University Hospital Aarhus Denmark
3 Rigshospitalet Copenhagen Denmark
4 Odense University Hospital Odense Denmark
5 Silkeborg University Clinic Silkeborg Denmark
6 Svendborg Hospital OUH Svendborg Denmark
7 University Hospital of Southern Denmark Sønderborg Denmark
8 Helsinki University Central Hospital Helsinki Finland
9 Central Finland Central Hospital Jyväskylä Finland
10 Kuopio University Hospital Kuopio Finland
11 Tampere University Hospital Tampere Finland
12 Landspitali University Hospital Reykjavík Iceland
13 Reade Amsterdam Netherlands
14 Haukeland University Hospital Bergen Norway
15 Diakonhjemmet Hospital Oslo Norway
16 University Hospital of North Norway Tromsø Norway
17 St. Olav's Hospital Trondheim Norway
18 Ålesund Hospital Ålesund Norway
19 Falu Hospital Falun Sweden
20 Sahlgrenska University Hospital Gothenburg Sweden
21 The Karolinska University Hospital Huddinge Sweden
22 Linköping University Hospital Linköping Sweden
23 Skåne University Hospital Lund Sweden
24 Skåne University Hospital Malmö Sweden
25 The Karolinska University Hospital Solna Sweden
26 Academic Specialist Center Stockholm Sweden
27 The Karolinska Institutet Stockholm Sweden
28 Uppsala University Hospital Uppsala Sweden
29 Västmanlands Hospital Västerås Sweden
30 Örebro University Hospital Örebro Sweden

Sponsors and Collaborators

  • Karolinska Institutet

Investigators

  • Principal Investigator: Ronald van Vollenhoven, MD, Prof., The Karolinska Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Ronald van Vollenhoven, prof., Principal Investigator, Karolinska Institutet
ClinicalTrials.gov Identifier:
NCT01491815
Other Study ID Numbers:
  • NORD-STAR
  • 2011-004720-35
  • 2011/2069-31/4
First Posted:
Dec 14, 2011
Last Update Posted:
Jul 8, 2022
Last Verified:
Jul 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Abatacept

Study Results

No Results Posted as of Jul 8, 2022