Dose Reduction for Early Rheumatoid Arthritis Patients With Low Disease Activity

July 7, 2022 updated by: Ronald van Vollenhoven, prof., Karolinska Institutet

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

25 patients have been included in the study of which 1 has had an early termination an 22 have completed the full study.

Study Type

Interventional

Enrollment (Actual)

25

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Sweden
      • Gothenburg, Sweden
        • Sahlgrenska University Hospital
      • Huddinge, Sweden
        • The Karolinska University Hospital
      • Linköping, Sweden
        • Linköping University Hospital
      • Lund, Sweden
        • Skåne University Hospital
      • Malmö, Sweden
        • Skåne University Hospital
      • Solna, Sweden
        • The Karolinska University Hospital
      • Stockholm, Sweden, 171 76
        • Karolinska Institutet
      • Stockholm, Sweden
        • Academic Specialist Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / 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 Names:
  • SSZ+HCQ or Prednisolone
Biological: Cimzia
Certolizumab-pegol: 200 mg s.c. every other week. Methotrexate: 25mg/week
Other Names:
  • Certolizumab-pegol
Biological: Orencia
Abatacept: 125 mg s.c. every week. Methotrexate: 25mg/week
Other Names:
  • 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 Names:
  • 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 Names:
  • SSZ+HCQ or Prednisolone
Biological: Cimzia
Certolizumab-pegol: 200 mg s.c. every other week. Methotrexate: 25mg/week
Other Names:
  • Certolizumab-pegol
Biological: Orencia
Abatacept: 125 mg s.c. every week. Methotrexate: 25mg/week
Other Names:
  • 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 Names:
  • Tocilizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
24 weeks after dose reduction

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Karolinska Institutet

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 3, 2015

Primary Completion (Anticipated)

July 22, 2023

Study Completion (Anticipated)

December 1, 2023

Study Registration Dates

First Submitted

May 29, 2015

First Submitted That Met QC Criteria

June 8, 2015

First Posted (Estimate)

June 9, 2015

Study Record Updates

Last Update Posted (Actual)

July 8, 2022

Last Update Submitted That Met QC Criteria

July 7, 2022

Last Verified

July 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Co-STAR
  • 2014-002374-36 (EudraCT Number)
  • 2014/1705-31/3 (Other Identifier: Regional Ethical Review Board)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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