Dose reduction and withdrawal of biological therapy in patients with rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis: Protocol for a 18 months multi-centre trial

• Register: EUCTR
• Last refreshed on: 10 December 2019
• Main ID: EUCTR2017-001970-41-DK
• Date of registration: 15/09/2017
• Prospective Registration: Yes
• Primary sponsor: MD, PhD Salome Kristensen
• Public title: Dose reduction and withdrawal of biological therapy in patients with rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis: Protocol for a 18 months multi-centre trial
• Scientific title: Dose reduction and discontinuation of biological therapy in patients with rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis: Protocol for a 18 months randomised, open label, parallel-group, multi-centre trial - The BIODOPT trial (BIOlogical Dose OPTimisation)
• Date of first enrolment: 21/12/2017
• Target sample size: 180
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-001970-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: usual care i.e. continuation of biological therapy unchanged or a small dosage 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

Denmark

Contacts

• Name: MD Line Uhrenholt
• Affiliation: The Department of Rheumatology Aalborg University Hospital

• Name: MD Line Uhrenholt
• Affiliation: The Department of Rheumatology Aalborg University Hospital

Key inclusion & exclusion criteria

Inclusion criteria:
A participant will be eligible for trial participation if he/she meets the following criteria:
- The participant is able and willing to provide written informed consent and comply with the requirements of this trial protocol.
- The participant is = 18 years of age
- Meets the diagnostic criteria for rheumatoid arthritis, psoriatic arthritis or axial spondyloarthritis as specified in the protocol.
- Participants must be treated with abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab or tocilizumab in stable dose (i.e. standard dose or reduced dose) during the last 12 months
- Participants must be in sustained clinical remission/LDA as defined in this protocol during the last 12 months measured by = 2 registrations in the Danish Rheumatology Database (DANBIO)
- Female participants with childbearing potential: negative pregnancy test at baseline and practicing safe birth control as described in the 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 120
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

Exclusion criteria:
A participant cannot be included in the trial if he/she meets any of the following criteria:
- Inability to provide informed consent or unwilling to comply with the trial protocol
- Current oral prednisolone treatment
- Intra-articular or parenteral administration of corticosteroids or a short course of oral prednisolone within the last year
- Dose reduction of the biological therapy is not suitable judged by medical expert assessment due to e.g. patients with previously severe arthritis with difficult to reach remission on biological therapy or patients who previously have tried dose reduction of the biological therapy resulting in flare
- Female participants who is pregnant or breast-feeding or considering becoming pregnant while on biological therapy, MTX and/or leflunomide or within 3-6 months after the last dose
- Participants who have a history of psychiatric or psychological conditions that, in the opinion of the investigator, will affect the ability to participate in the trial
- Addictive or previous addictive behaviour defined as abuse of alcohol, hash, opioids or other euphoric substances
- Participants who is considered an unsuitable candidate for the trial for any reason by the in-vestigator
Allergic reaction or significant sensitivity to constituents of the study drugs are not considered a relevant exclusion criterion in this trial as patients have been treated with the study drugs (biological therapy) > 1 year prior to inclusion.


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

Health Condition(s) or Problem(s) studied

Rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis
MedDRA version: 21.0 Level: LLT Classification code 10040107 Term: Seropositive rheumatoid arthritis System Organ Class: 100000004859
MedDRA version: 21.0 Level: LLT Classification code 10062719 Term: Seronegative rheumatoid arthritis System Organ Class: 100000004859
MedDRA version: 21.0 Level: LLT Classification code 10037160 Term: Psoriatic arthritis System Organ Class: 100000004859
MedDRA version: 20.0 Level: LLT Classification code 10076297 Term: Non-radiographic axial spondyloarthritis System Organ Class: 100000004859
MedDRA version: 21.1 Level: LLT Classification code 10041672 Term: Spondylitis ankylosing System Organ Class: 100000004859
MedDRA version: 20.0 Level: LLT Classification code 10002557 Term: Ankylosing spondylitis and other inflammatory spondylopathies System Organ Class: 100000004859
MedDRA version: 21.0 Level: LLT Classification code 10045966 Term: Unspecified inflammatory spondylopathy System Organ Class: 100000004859

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

Intervention(s)

Trade Name: Orencia
Product Name: Abatacept
Product Code: L04AA24
Pharmaceutical Form: Concentrate for solution for injection
INN or Proposed INN: ABATACEPT
CAS Number: 332348-12-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 125 -

Trade Name: Orencia
Product Name: Abatacept
Product Code: L04AA24
Pharmaceutical Form: Concentrate and solvent for solution for infusion
INN or Proposed INN: ABATACEPT
CAS Number: 332348-12-6
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: up to
Concentration number: 10 -

Trade Name: Humira
Product Name: Adalimumab
Product Code: L04AB04
Pharmaceutical Form: Concentrate and solvent for solution for injection
INN or Proposed INN: ADALIMUMAB
CAS Number: 331731-18-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40 -

Trade Name: Cimzia
Product Name: Certolizumab pegol
Product Code: L04AB05
Pharmaceutical Form: Concentrate and solvent for solution for injection
INN or Proposed INN: CERTOLIZUMAB PEGOL
CAS Number: 428863-50-7
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 200 -400

Trade Name: Enbrel
Product Name: Etanercept
Product Code: L04AB01
Pharmaceutical Form: Concentrate and solvent for solution for injection
INN or Proposed INN: ETANERCEPT
CAS

Primary Outcome(s)

Primary end point(s): The co-primary endpoint is:
- 1A Superiority: The proportion of patients who at 18 months is reduced to 50% or less of their inclusion dose of biological therapy.
- 1B Equivalence: Disease activity assessed 18 months from baseline.

Main Objective: To evaluate whether an interactive patient-involving dose optimisation tapering strategy for biological therapy will enable a significant dosereduction while being equivalent in maintaining disease activity assessed 18 months from baseline compared with “usual care”. The co-primary endpoints are thus:
- 1A Superiority: The proportion of patients who at 18 months is reduced to 50% or less of their inclusion dose of biological therapy.
- 1B Equivalence: Disease activity assessed 18 months from baseline
The aim of the BIODOPT trial is to assess whether disease activity can be sustained when doses of biological agents are reduced (= 50%) or completely withdrawn.

Timepoint(s) of evaluation of this end point: 18 months from baseline

Secondary Objective: Key secondary objectives at 18 months include the proportion of patients in remission/LDA and receiving reduced dose biological therapy and the proportion of patients in remission/LDA despite discontinuation of biological therapy. Exploratory objectives are to identify potential prognostic factors for flare after tapering of biological therapy and to explore potentially important factors associated with remission/LDA maintenance after the biological therapy is reduced or even discontinued

Secondary Outcome(s)

Secondary end point(s): - The proportion of patients in remission and receiving reduced dose biological therapy and the proportion of patients in remission/LDA despite discontinuation of biological therapy.
- Changes in the composite scores DAS28crp, CDAI and SDAI for rheumatoid arthritis, ASDAS and BASDAI for patients with axial spondyloarthritis and DAPSA, DAS28crp and MDA for patients with psoriatic arthritis.
- Changes in the following PROMs: Patient’s assessment of pain, fatigue and global assessment of disease activity, HAQ-DI, SF-36 and for patients with axial spondyloarthritis BASDAI and BASFI.
-Changes in the following clinical assessment by the physician: the physician’s global assessment of the patient’s disease activity, joint count and for patients with axial spondyloarthritis BASMI and for patients with axial spondyloarthritis or psoriatic arthritis PASI, mNAPSI, enthesitis score by SPARCC and dactylitis count by number of affected fingers/toes.

Timepoint(s) of evaluation of this end point: 4, 8, 12, 18, 24 and 60 months from baseline

Secondary ID(s)

20170508

Source(s) of Monetary Support

Health Science Research Fund of the Region of Northern Jutland

The Danish Regions (Regionernes Medicinpulje)

The Department of Rheumatology at Aalborg University Hospital

Ethics review

Status: Approved
Approval date:
Contact: