A study with dose de-escalation of coventional or biologic treatments in early rheeumatoid arthritis in patients with low disease activity.

• Register: EUCTR
• Last refreshed on: 3 November 2021
• Main ID: EUCTR2014-002374-36-SE
• Date of registration: 27/08/2014
• Prospective Registration: Yes
• Primary sponsor: The Karolinska Institutet, ClinTRID
• Public title: A study with dose de-escalation of coventional or biologic treatments in early rheeumatoid arthritis in patients with low disease activity.
• Scientific 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 (active conventional therapy versus three biologic treatments) in the NORD-STAR study and have reached stable low disease activity - CO-STAR
• Date of first enrolment: 19/11/2014
• Target sample size: 500
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-002374-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Early and late dose-reduction Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Sweden

Contacts

• Name: Central Study Coordinating Team
• Affiliation: The Karolinska Institute

• Name: Central Study Coordinating Team
• Affiliation: The Karolinska Institute

Key inclusion & exclusion 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 joints 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 25

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:
a. Successfully treated cutaneous squamous cell or basal cell carcinoma
b. Localized carcinoma in situ of the cervix
c. 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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Rheumatoid arthritis (RA)
MedDRA version: 17.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Trade Name: Cimzia
Pharmaceutical Form: Injection

Trade Name: Orencia
Pharmaceutical Form: Solution for infusion in pre-filled syringe

Trade Name: RoActemra
Pharmaceutical Form: Infusion

Trade Name: Methotrexate
Pharmaceutical Form: Tablet

Trade Name: Metoject
Pharmaceutical Form:

Trade Name: Azathioprine
Pharmaceutical Form: Tablet

Trade Name: Leflunomide
Pharmaceutical Form: Tablet

Primary Outcome(s)

Main Objective: The aim of this study is to assess and compare de-escalation strategies in patients who respond to first-line therapy in the NORD-STAR study and have reached low disease activity (2.8 < CDAI = 10.0).

Secondary Objective: Safety.

Primary end point(s): The primary efficacy outcome is 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.

Timepoint(s) of evaluation of this end point: 24 weeks after the dose was first reduced.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. 24 weeks after randomization for all patients
2. a) 24 weeks after the dose was first reduced.
b) 24 weeks after randomization for all patients
3. Clinical outcomes are relevant at all time points throughout the study

Secondary end point(s): 1. The proportion of patients who maintain low disease activity (2.8 < CDAI = 10.0) 24 weeks after randomization, patients with early dose reduction vs patients where dose reduction has not been started.
2. The portion of patients in the 4 different treatment arms (active conventional- vs certolizumab-pegol- vs abatacept- vs tocilizumab -treatments) who maintain low disease activity at 24 weeks after a) dose reduction (compare primary outcome) and b) randomization (compare first secondary outcome). This to identify which treatment has the highest likelihood of inducing a sustained state of low disease activity according to CDAI:
3. Clinical (at all relevant time points) outcomes for patients in this study vs. patients who reached remission and were studied in treatment part 2 in the NORD-STAR study:
a. CDAI/SDAI/2010 ACR/EULAR low disease activity at all time points
b. ACR20/ACR50/ACR70/ACR-hybrid
c. DAS28-ESR
- values
- DAS28-ESR based disease categories
- EULAR responses
d. DAS28-CRP
- values
- DAS28-CRP based disease categories
- EULAR responses
e. SDAI, CDAI values
f. Core set variables (66/68 joint count)
g. FACIT fatigue score
h. WPAI
i. EQ5D
j. HAQ
k. SF36
l. Morning stiffness
m. Patient’s VAS for global health, pain and fatigue assessment
n. Physician’s VAS for global health

Secondary ID(s)

CO-STAR

Source(s) of Monetary Support

Reumatikerförbundet

SLL (Stockholms Läns Landsting)

Vetenskapsrådet

Ethics review

Status: Approved
Approval date: 19/11/2014
Contact: