Dose Reduction for Early Rheumatoid Arthritis Patients With Low Disease Activity

NCT02466581 | Unknown Phase 4 DMC

• 3 other identifiers: CO-STAR2014-002374-362014/1705-31/3
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 8

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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Proportion of patients maintaining low disease activity 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

Study Arms (2)

Arm 1

ACTIVE COMPARATOR

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; Biological: Cimzia; Biological: Orencia; Biological: RoActemra

Arm 2

ACTIVE COMPARATOR

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; Biological: Cimzia; Biological: Orencia; Biological: RoActemra

Interventions

Sulphasalazine + Hydroxychloroquine OR Prednisolone DRUG

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)

Also known as: SSZ+HCQ or Prednisolone

Arm 1; Arm 2

Cimzia BIOLOGICAL

Certolizumab-pegol: 200 mg s.c. every other week. Methotrexate: 25mg/week

Also known as: Certolizumab-pegol

Arm 1; Arm 2

Orencia BIOLOGICAL

Abatacept: 125 mg s.c. every week. Methotrexate: 25mg/week

Also known as: Abatacept

Arm 1; Arm 2

RoActemra BIOLOGICAL

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

Also known as: Tocilizumab

Arm 1; Arm 2

Eligibility Criteria

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

You may not qualify if:

• 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.
• Subject has not more than 3 tender out of the 28 joints.
• According to the investigators opinion the remaining findings are not due to significant active disease (RA).
• 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
• Subject is judged to be in good general health as determined by the principal investigator.
• Subject must be able and willing to provide written informed consent and comply with the requirements of this study protocol.
• Subject has left the NORD-STAR study due to moderate or high disease activity (CDAI ≥ 10.0) or for other medically important event(s).
• Patient is eligible for treatment part 2 (A or B) in the NORD-STAR study.
• 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.
• 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.
• Subject has a history of clinically significant hematologic (e.g., severe anemia, leukopenia, thrombocytopenia), renal or liver disease (e.g., fibrosis, cirrhosis, hepatitis).
• Subject has history of neurologic symptoms suggestive of central nervous system (CNS) demyelinating disease and/or diagnosis of central demyelinating disease.

Sponsors & Collaborators

• Karolinska Institutet: lead

Study Sites (8)

Sahlgrenska University Hospital

Gothenburg, Sweden

Location

The Karolinska University Hospital

Huddinge, Sweden

Location

Linköping University Hospital

Linköping, Sweden

Location

Skåne University Hospital

Lund, Sweden

Location

Skåne University Hospital

Malmo, Sweden

Location

The Karolinska University Hospital

Solna, Sweden

Location

Karolinska Institutet

Stockholm, 171 76, Sweden

Location

Academic Specialist Center

Stockholm, Sweden

Location

Related Publications (1)

• Glinatsi D, Heiberg MS, Rudin A, Nordstrom D, Haavardsholm EA, Gudbjornsson B, Ostergaard M, Uhlig T, Grondal G, Horslev-Petersen K, van Vollenhoven R, Hetland ML. Head-to-head comparison of aggressive conventional therapy and three biological treatments and comparison of two de-escalation strategies in patients who respond to treatment: study protocol for a multicenter, randomized, open-label, blinded-assessor, phase 4 study. Trials. 2017 Apr 4;18(1):161. doi: 10.1186/s13063-017-1891-x.

  PMID: 28376912 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Sulfasalazine; Hydroxychloroquine; Prednisolone; Certolizumab Pegol; Abatacept; tocilizumab

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)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Polyethylene Glycols; Polymers; Macromolecular Substances; Immunoglobulin Fab Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Immunoconjugates

Study Officials

• Ronald van Vollenhoven, MD, Prof.

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 29, 2015
• First Posted: June 9, 2015
• Study Start: February 3, 2015
• Primary Completion: July 22, 2023
• Study Completion: December 1, 2023
• Last Updated: July 8, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

SE (8)