Dose Reduction for Early Rheumatoid Arthritis Patients With Low Disease Activity

NCT ID: NCT02466581

Last Updated: 2022-07-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-03
• Study Completion Date: 2023-12-31

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.

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.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Sulphasalazine + Hydroxychloroquine OR Prednisolone

Intervention Type: 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)

Cimzia

Intervention Type: BIOLOGICAL

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

Orencia

Intervention Type: BIOLOGICAL

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

RoActemra

Intervention Type: 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

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.

Group Type: ACTIVE_COMPARATOR

Sulphasalazine + Hydroxychloroquine OR Prednisolone

Intervention Type: 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)

Cimzia

Intervention Type: BIOLOGICAL

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

Orencia

Intervention Type: BIOLOGICAL

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

RoActemra

Intervention Type: 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

Interventions

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)

Intervention Type: DRUG

Cimzia

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

Intervention Type: BIOLOGICAL

Orencia

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

Intervention Type: 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

Intervention Type: BIOLOGICAL

Other Intervention Names

SSZ+HCQ or Prednisolone; Certolizumab-pegol; Abatacept; Tocilizumab

Eligibility Criteria

Inclusion Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Karolinska Institutet

OTHER

Sponsor Role: lead

Responsible Party

Ronald van Vollenhoven, prof.

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ronald van Vollenhoven, MD, Prof.

Role: PRINCIPAL_INVESTIGATOR

Karolinska Institutet

Locations

Sahlgrenska University Hospital

Gothenburg, , Sweden

The Karolinska University Hospital

Huddinge, , Sweden

Linköping University Hospital

Linköping, , Sweden

Skåne University Hospital

Lund, , Sweden

Skåne University Hospital

Malmo, , Sweden

The Karolinska University Hospital

Solna, , Sweden

Karolinska Institutet

Stockholm, , Sweden

Academic Specialist Center

Stockholm, , Sweden

Countries

Sweden

References

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.

Reference Type: DERIVED

PMID: 28376912 (View on PubMed)

Other Identifiers

2014-002374-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2014/1705-31/3

Identifier Type: OTHER

Identifier Source: secondary_id

CO-STAR

Identifier Type: -

Identifier Source: org_study_id