Arthritis prevention with abatacept

• Register: EUCTR
• Last refreshed on: 8 November 2021
• Main ID: EUCTR2013-003413-18-NL
• Date of registration: 28/09/2015
• Prospective Registration: Yes
• Primary sponsor: Leiden University Medical Center
• Public title: Arthritis prevention with abatacept
• Scientific title: Arthritis Prevention In the Pre-clinical Phase of RA with Abatacept. - APIPPRA
• Date of first enrolment: 30/01/2017
• Target sample size: 206
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-003413-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Netherlands, United Kingdom

Contacts

• Name: M.E. Janson
• Affiliation: Leiden University Medical Center

• Name: M.E. Janson
• Affiliation: Leiden University Medical Center

Key inclusion & exclusion criteria

Inclusion criteria:
- Male or female subjects, aged = 18 years.
- Arthralgia that is considered to be inflammatory in nature.
- ACPA and RF positive, or high titre ACPA.
- Able and willing to give written informed consent and comply with the requirements of the 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 206
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 206

Exclusion criteria:
- Clinically apparent arthritis, as assessed by a rheumatologist.
- A history of inflammatory arthritis, as assessed by a rheumatologist.
- History or current use of DMARDs or biologics.
- History of oral or parenteral use of corticosteroids within the last 12 weeks.
- Co-morbidities requiring treatment with immunosuppressive or immune modulating therapy.
- Chronic illnesses that would, in the opinion of the investigator, put the subject at risk.
- Recipients of a live vaccine within 4 weeks of inclusion.
- Pregnant or breastfeeding
- Unable to give informed consent


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

Health Condition(s) or Problem(s) studied

The target population for therapeutic intervention will be subjects who carry serum autoantibodies (antibodies to citrullinated protein antigens – ACPA; rheumatoid factor – RF) and who have joint pains (arthralgia) but no joint swelling. These subjects are deemed to be at highest risk of developing rheumatoid arthritis.
MedDRA version: 20.0 Level: PT Classification code 10003239 Term: Arthralgia System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

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

Intervention(s)

Trade Name: ORENCIA 125 mg solution for injection
Pharmaceutical Form: Solution for infusion in pre-filled syringe
Pharmaceutical form of the placebo: Solution for infusion in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: To evaluate the feasibility, efficacy and acceptability of abatacept therapy in subjects at high risk of developing RA.

Primary end point(s): 1) The time to development of clinically apparent synovitis in = 3 joints, as determined by two independent assessors with experience in clinical assessment of RA
2) The time to development of RA according to the ACR/EULAR 2010 criteria, where joint involvement is defined as joint swelling.
In either case joint swelling will be confirmed by ultrasound.

Secondary Objective: To characterise immune and inflammatory responses associated with ACPA before, during and after therapy with abatacept.

Timepoint(s) of evaluation of this end point: Every 3 months for up to 24 months

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Secondary endpoints will be evaluated every 3 months for up to 24 months

The exploratory endpoints will be evaluated at the end of the study following analysis of the biological samples.

Secondary end point(s): 1) The development of RA according to the ACR/EULAR 2010 criteria where ultrasound
2) Assessments of disease activity and progression over time, using DAS28 (tender and swollen joint counts, patient global visual analogue score (VAS), ESR) and Extended Joint Count 68/66, Simple Disease Activity Score (SDAI) and Clinical Disease Activity Score (CDAI), Pain VAS, Lifestyle Factors Questionnaire, Health Assessment Questionnaire (HAQ), Modified Illness Perception Questionnaire (Modified IPQ-R), Euro-Quality of Life Questionnaire (EQ-5D), Hospital Anxiety and Depression Scale (HADS), Work Instability Scale (RA-WIS) and Functional Assessment Of Chronic Illness Therapy-Fatigue (FACIT-F).
3) The proportion of participants requiring DMARD therapy, and the time to commencing DMARD therapy, including oral or parenteral corticosteroids.
4) Progression of radiographic changes in X-rays of the hands and feet scored by van der Heijde Sharpe Modified Scores or using the Larsen score.
5) Changes in scores of synovitis and vascularity defined by high resolution ultrasonography and power Doppler over time.
6) Adverse events.

The exploratory endpoints of this study are:
1) Changes in serum ACPA levels over time.
2) ACPA isotype and antigenic fine specificity over time.
3) Signatures of immune and inflammatory responses as defined through analysis of serum, peripheral blood cell subsets, peripheral blood RNA expression profiling and urine.

Secondary ID(s)

2013-003413-18-GB

IM101

Source(s) of Monetary Support

King's College London

Ethics review

Status: Approved
Approval date: 30/01/2017
Contact: