Condition category
Musculoskeletal Diseases
Date applied
26/09/2014
Date assigned
26/09/2014
Last edited
17/10/2014
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Rheumatoid arthritis is a long-term condition causing pain, swelling and stiffness in the joints. The main aim of this study is to find out how much of the drug seliciclib can be given to patients with Rheumatoid Arthritis (RA) who have active RA despite treatment with anti-TNF monotherapy.

Who can participate?
Adult patients with rheumatoid arthritis can take part.

What does the study involve?
In stage 1, patients are grouped into seven groups of three patients each. They will receive 200mg, 400mg, 600mg, 800mg or 1000mg seliciclib once daily for 4 consecutive days every week for 4 cycles. This will find out the maximum dose of seliciclib for stage 2. In stage 2, 18 participants will receive seliciclib (at the dose found in stage 1) for twelve cycles.

What are the possible benefits and risks of participating?
Not provided at time of registration.

Where is the study run from?
The trial will run at Newcastle, Birmingham and Glasgow, UK

When is the study starting and how long is it expected to run for?
October 2014 to June 2017.

Who is funding the study?
Medical Research Council (MRC) (UK)

Who is the main contact?
Miss Amy Cranston
amy.cranston@ncl.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Miss Amy Cranston

ORCID ID

Contact details

Clinical Research Facility
4th Floor Leazes Wing
Royal Victoria Infirmary
Queen Victoria Road
Newcastle Upon Tyne
NE1 4LP
United Kingdom
amy.cranston@ncl.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

17409

Study information

Scientific title

Targeting the RA synovial fibroblast via cyclin dependent kinase inhibition – an early phase trial (TRAFIC): a non-randomised trial

Acronym

TRAFIC

Study hypothesis

Repurposing study, using an oncology drug, Seliciclib in rheumatoid arthritis in a 2 part trial to determine maximum tolerated dose and then assess clinical response at 12 weeks.

Ethics approval

NRES Committee North East – Tyne and Wear South; 15/09/2014; 14/NE/1075

Study design

Non-randomised; Interventional; Design type: Treatment

Primary study design

Interventional

Secondary study design

Non randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Topic: Musculoskeletal disorders; Subtopic: Musculoskeletal (all Subtopics); Disease: Musculoskeletal

Intervention

Seliciclib: Part 1: Participants will receive either 200mg, 400mg, 600mg, 800mg or 1000mg seliciclib once daily for 4 consecutive days every week for 4 weekly cycles*. Results from part 1 will determine the Maximum Tolerated Dose (MTD) of seliciclib for part 2.
Part 2: 18 participants will receive seliciclib (at the MTD determined in Part 1) for twelve cycles*
* one cycle equates to a week of treatment: a daily dose of seliciclib for four consecutive days followed by 3 days with no treatment.

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

Part 1:
1. Dose Limiting Toxicities (DLT) (at baseline (BL), week 2, 3, 4 and 5)
2. Adverse Events and Adverse Reactions (AE/AR) (at BL week 2, 3, 4 and 5).
Part 2:
1. EULAR and ACR20 response rates (at screening, BL, week 2, 3, 4, 7, 10 and within 5 days of final dose)
2. Macrophage number in the sub lining layer of synovium (at BL and week 12)
3. MRI (Rheumatoid Arthritis MRI Scoring System (RAMRIS)) (at pre BL and week 12)

Secondary outcome measures

Part 1:
1. Drug PK parameters and PD biomarkers in peripheral blood at BL and week 4.

Part 2:
1. Drug PK parameters and PD biomarkers in peripheral blood (at BL and week 12)
2. PD biomarkers in synovial tissue (at BL and week 12)
3. Fatigue questionnaire (at screening, BL, week 2, 3, 4, 7, 10 and within 5 days of final dose)
4. Urinary metabolomics (at screening, BL, week 2, 3, 4, 7, 10 and within 5 days of final dose)
5. Rheumatoid factor (RF) and anti-CP status (at screening and within 5 days of final dose)
6. Optional PET scan pre BL and within 10 days post week 12 visit.

Overall trial start date

01/10/2014

Overall trial end date

29/06/2017

Reason abandoned

Eligibility

Participant inclusion criteria

1. Rheumatoid arthritis fulfilling the 1987 ACR or 2010 ACR/EULAR criteria
2. Age 18 years or above
3. At least 6 months’ disease duration
4. ACR Functional Class IIII
5. DAS28 =4.0, with clinical synovitis in at least three joints, at least one of which is a joint amenable to ultrasound-guided synovial biopsy (knee, elbow, ankle, wrist, MCP or PIP joint). (For part 2 only).
6. Currently taking anti-TNF monotherapy as part of standard clinical care and have received anti-TNF therapy for at least 6 months upon entry to the study as per NICE guidelines.
7. Willing to undergo ultrasound guided synovial biopsy on two occasions (under local anaesthetic). (For part 2 only).
8. Stable dose of non-steroidal anti-inflammatory drug (NSAID) or corticosteroid (prednisolone=7.5mg) for =4 weeks.
9. No intramuscular glucocorticoid administration in the 6 week period prior to baseline visit.
10. Willing and able to undergo MRI scanning on two occasions (Part 2 only).

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 39; UK Sample Size: 39

Participant exclusion criteria

1. Patients currently taking, and planning to continue, methotrexate, other non-biologic DMARDs or biologic therapies other than anti-TNF
therapy. For patients recently receiving non-biologic DMARD therapy at least 8 weeks must have elapsed following discontinuation of treatment prior to enrolment into the current study. If patients were previously taking leflunomide this must have been washed out with cholestyramine or activated charcoal according to leflunomide’s Summary of Product Characteristics.
2. Patients receiving warfarin or other anticoagulation likely to interfere with biopsy procedures. (Part 2 only).
3. Previous participation in this trial (for Part 2 participants)
4. Use of other investigational medicinal products within 30 days prior to trial entry (defined as date of recruitment into trial)
5. Serious or unstable co-morbidity deemed unsuitable by PI e.g. COPD, cardiac failure, other significant auto-immune disease
6. Patient’s must not drink more than 2 units of alcohol per day and no more than 10 units of alcohol per week during the trial and for a 4 week period after completion of the trial.
7. Known active infection at screening visit or at baseline (except fungal nail infection)
8. Infection requiring hospitalization or IV antibiotics within 6 weeks prior to baseline
9. History of recurrent or chronic infection
10. Recent live vaccination (within 6 weeks of baseline)
11. Hb<10g/dL; neutrophils< 1.5 x109/L; platelets <100x109/L
12. Patients taking ketoconazole, voriconazole, erythromycin, clarithromycin.
13. ALT/AST/ALP>1.5x upper limit of normal
14. Glomerular filtration rate < 60ml/minute (Cockroft formula)
15. Major surgery within 8 weeks prior to baseline or planned within 3 months from baseline.
16. Pregnancy, or women planning to become pregnant within the trial period, or women who are breast feeding
17. Females or males of child bearing potential unwilling to use two forms of adequate contraception whilst taking the IMP and for one month afterwards.

Recruitment start date

01/10/2014

Recruitment end date

29/06/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Clinical Research Facility
Newcastle Upon Tyne
NE1 4LP
United Kingdom

Sponsor information

Organisation

Newcastle Hospitals Foundation NHS Trust (UK)

Sponsor details

Wolfson Unit of Clinical Pharmacology
Institute of Cellular Medicine
Framlington Place
Newcastle Upon Tyne
NE2 4HH
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Research council

Funder name

Medical Research Council (MRC) (UK); Grant Codes: MR/L005123/1

Alternative name(s)

MRC

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes