Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Dose Reduction for Early Rheumatoid Arthritis Patients With Low Disease Activity

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02466581
Recruitment Status : Recruiting
First Posted : June 9, 2015
Last Update Posted : December 4, 2018
Sponsor:
Information provided by (Responsible Party):
Ronald van Vollenhoven, prof., Karolinska Institutet

Brief Summary:
This is an international (Nordic) trial designed to compare the safety and efficacy of active conventional therapy (ACT) and three biologic treatments (Certolizumab-pegol, Abatacept or Tocilizumab) in subjects with early rheumatoid arthritis (RA). The global aim of this study is to assess and compare two alternative de-escalation strategies in patients who achieved low disease activity during first-line therapy in the NORD-STAR study.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: Sulphasalazine + Hydroxychloroquine OR Prednisolone Biological: Cimzia Biological: Orencia Biological: RoActemra Phase 4

Detailed Description:
There are currently 23 patients included in the study of which 1 has had an early termination an 17 have terminated the full study.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Open-label, Blinded-assessor, Follow-up, Phase 4 Study in Patients With Rheumatoid Arthritis Who Have Completed the Initial Treatment Part in the NORD-STAR Study and Have Reached Stable Low Disease Activity
Study Start Date : February 2015
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Arm 1

Patients keep the intervention they had in the NORD-STAR-study (NCT01491815), i.e. one of the four below:

  1. Sulphasalazine + Hydroxychloroquine OR Prednisolone plus Methotrexate and steroids
  2. Cimzia plus Methotrexate and steroids
  3. Orencia plus Methotrexate and steroids
  4. RoActemra plus Methotrexate and steroids

This intervention is de-escalated starting at randomization.

Drug: Sulphasalazine + Hydroxychloroquine OR Prednisolone
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, and Iceland)
Other Name: SSZ+HCQ or Prednisolone

Biological: Cimzia
Certolizumab-pegol: 200 mg s.c. every other week. Methotrexate: 25mg/week
Other Name: Certolizumab-pegol

Biological: Orencia
Abatacept: 125 mg s.c. every week. Methotrexate: 25mg/week
Other Name: Abatacept

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
Other Name: Tocilizumab

Active Comparator: Arm 2

Patients keep the intervention they had in the NORD-STAR-study (NCT01491815), i.e. one of the four below:

  1. Sulphasalazine + Hydroxychloroquine OR Prednisolone plus Methotrexate and steroids
  2. Cimzia plus Methotrexate and steroids
  3. Orencia plus Methotrexate and steroids
  4. RoActemra plus Methotrexate and steroids

This intervention is de-escalated starting 24 weeks after randomization.

Drug: Sulphasalazine + Hydroxychloroquine OR Prednisolone
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, and Iceland)
Other Name: SSZ+HCQ or Prednisolone

Biological: Cimzia
Certolizumab-pegol: 200 mg s.c. every other week. Methotrexate: 25mg/week
Other Name: Certolizumab-pegol

Biological: Orencia
Abatacept: 125 mg s.c. every week. Methotrexate: 25mg/week
Other Name: Abatacept

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
Other Name: Tocilizumab




Primary Outcome Measures :
  1. Proportion of patients maintaining low disease activity after dose reduction [ Time Frame: 24 weeks after dose reduction ]
    The proportion of patients, with early dose reduction vs late dose reduction, who maintain low disease activity (2.8 < CDAI ≤ 10.0) at the time point 24 weeks after the dose was first reduced.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject has been enrolled in the NORD-STAR study according to that study inclusion criteria (and did not meet any of the exclusion criteria in that study).
  2. Subject has low-disease-activity according to: 2.8 < CDAI ≤ 10.0, from week 56 in the NORD-STAR study, i.e. during 24 weeks before randomization.
  3. Subject has not more than 3 tender out of the 28 joints.
  4. According to the investigators opinion the remaining findings are not due to significant active disease (RA).
  5. 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
  6. Subject is judged to be in good general health as determined by the principal investigator.
  7. Subject must be able and willing to provide written informed consent and comply with the requirements of this study protocol.

Exclusion Criteria:

  1. Subject has left the NORD-STAR study due to moderate or high disease activity (CDAI ≥ 10.0) or for other medically important event(s).
  2. Patient is eligible for treatment part 2 (A or B) in the NORD-STAR study.
  3. Active infection of any kind (excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization within 4 weeks prior to randomization.
  4. 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.
  5. Subject has a history of clinically significant hematologic (e.g., severe anemia, leukopenia, thrombocytopenia), renal or liver disease (e.g., fibrosis, cirrhosis, hepatitis).
  6. Subject has history of neurologic symptoms suggestive of central nervous system (CNS) demyelinating disease and/or diagnosis of central demyelinating disease.
  7. Subject has history of cancer or lymphoproliferative disease. Allowable exceptions:

    1. Successfully treated cutaneous squamous cell or basal cell carcinoma
    2. Localized carcinoma in situ of the cervix
    3. Curatively treated malignancy (treatment terminated) > 5 years prior to randomization.
  8. Subject has a history of listeriosis, histoplasmosis, untreated TB, persistent chronic infections, or recent active infections requiring hospitalization or treatment with intravenous (i.v.) anti-infectives within 30 days or oral anti-infectives within 14 days prior to randomization.
  9. 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.
  10. Men who are planning to father a child during the time they are included in the study.
  11. Subject has a history of clinically significant drug or alcohol usage in the last year.
  12. Subject has a chronic widespread pain syndrome.
  13. Subject is considered by the investigator, for any reason, to be an unsuitable candidate for the study.
  14. Subject is unwilling to comply with the study protocol.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02466581


Contacts
Layout table for location contacts
Contact: Ronald van Vollenhoven, MD, Prof. +46(0)851776077 ronald.van.vollenhoven@ki.se
Contact: Johanna Estelius, PhD +46(0)851771110 johanna.estelius@ki.se

Locations
Layout table for location information
Sweden
Karolinska Institutet Recruiting
Stockholm, Sweden, 171 76
Contact: Ronald van Vollenhoven, MD, prof    +46(8)51776077    ronald.van.vollenhoven@ki.se   
Contact: Monica Ryden Aulin, PhD    +46(8)51771110    monica.ryden.aulin@ki.se   
Sponsors and Collaborators
Karolinska Institutet

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Ronald van Vollenhoven, prof., Professor, Karolinska Institutet
ClinicalTrials.gov Identifier: NCT02466581     History of Changes
Other Study ID Numbers: CO-STAR
2014-002374-36 ( EudraCT Number )
2014/1705-31/3 ( Other Identifier: Regional Ethical Review Board )
First Posted: June 9, 2015    Key Record Dates
Last Update Posted: December 4, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Hydroxychloroquine
Sulfasalazine
Prednisolone
Methylprednisolone Acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone acetate
Methotrexate
Abatacept
Certolizumab Pegol
Prednisolone hemisuccinate
Prednisolone phosphate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors