Condition category
Musculoskeletal Diseases
Date applied
23/08/2007
Date assigned
23/08/2007
Last edited
29/08/2007
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof P.P. Tak

ORCID ID

Contact details

Academic Medical Centre (AMC)
Department of Clinical Immunology and Rheumatology
P.O. Box 22660
Amsterdam
1100 DD
Netherlands
+31 (0)20 566 2171
p.p.tak@amc.nl

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

P03653

Study information

Scientific title

Acronym

Study hypothesis

SCH 351125 50 mg twice daily (BID) 2/days is an effective treatment for Rheumatoid Arthritis (RA).

Primary objectives of the study are to determine the effects of SCH 351125 on mononuclear cell migration into synovial tissue in subjects with rheumatoid arthritis, and to evaluate the safety and tolerability of multiple-dose administration of SCH 351125 50 mg BID in subjects with rheumatoid arthritis when administered for 28 days.

Ethics approval

Ethics approval received from the Medical Ethics Committee of the Academic Medical Centre (University of Amsterdam) on the 21st January 2004 (ref: 03/267).

Study design

Randomised, double-blind, placebo controlled, parallel group trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Condition

Rheumatoid arthritis

Intervention

Subjects with active Rheumatoid Arthritis (RA) were enrolled in a randomised double-blind, placebo-controlled, parallel-group study exposed to either SCH 351125 50 mg BID or matched placebo, in a 2:1 ratio, for 28 days.

Intervention type

Drug

Phase

Not Specified

Drug names

SCH 351125

Primary outcome measures

1. To determine the effects of SCH 351125, a CCR5 receptor antagonist, on mononuclear cell migration into synovial tissue in subjects with rheumatoid arthritis
2. To evaluate the safety and tolerability of multiple-dose administration of SCH 351125 50 mg twice-daily in subjects with rheumatoid arthritis when administered for 28 days

Secondary outcome measures

1. To explore the effects of SCH 351125 on:
1.1. Synovial inflammation via MRI
1.2. Chemokine expression and concentrations in the plasma, synovial tissue and synovial fluid (messenger Ribonucleic Acid [mRNA] expression only)
1.3. Mononuclear cell concentrations in the peripheral blood
1.4. Clinical signs and symptoms of rheumatoid arthritis
1.5. To determine the single-dose and multiple dose pharmacokinetic profile of SCH 351125 in subjects with rheumatoid arthritis

Overall trial start date

01/03/2004

Overall trial end date

01/05/2005

Reason abandoned

Eligibility

Participant inclusion criteria

1. Subjects 18 to 70 years of age, of either sex, and of any race
2. Diagnosis of RA according to the American College of Rheumatology (ACR) criteria, for at least six weeks prior to entry in the study
3. Active RA defined as:
3.1. Three or more tender joints
3.2. Three or more swollen joints, and
3.3. At least one of the following three:
3.3.1. Duration of morning stiffness equal to or greater than 45 minutes
3.3.2. Erythrocyte sedimentation rate equal to or greater than 28 mm/hour
3.3.3. C-reactive protein equal to or greater than 10 mg/L
4. Functional class I, II or III
5. Subjects must be free of any clinically significant disease (other than rheumatoid arthritis) that would interfere with the study evaluations and/or safety
6. Subjects must be willing to give written informed consent and able to adhere to dose and visit schedules
7. Females must not be breast-feeding, and either be of non-childbearing potential (i.e., sterilised via hysterectomy or bilateral tubal ligation or at least one year postmenopausal) or if of child bearing potential, must be practicing effective double barrier contraceptive methods from at least two weeks prior to day 1 and until 30 days following cessation of dosing
8. Female subjects of childbearing potential must have a negative serum pregnancy test (beta human Chorionic Gonadotropin [beta-hCG]) at screening
9. Males must practice an effective barrier method of contraception from day 1 until 30 days following cessation of dosing
10. A physical examination must be without clinically significant findings with exception of those finding related to rheumatoid arthritis
11. At screening, Electrocardiogram (ECG) conduction intervals must be within the gender specific normal range (i.e., QTc for males less than 430 msec and females less than 450 msec)

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

30

Participant exclusion criteria

1. Individuals with a history of any significant medical disorder which require a physician's care (excluding rheumatoid arthritis) and would interfere with the study evaluations or compromise subject safety
2. Individuals who have a history of any clinically significant local or systemic infectious disease within four weeks prior to drug administration
3. Any subject with an allergy to gadolinium
4. Any subject with a pacemaker, metal object implanted their body or any other device or condition which may interfere with a subject's safety during the Magnetic Resonance Imaging (MRI) procedure
5. Any subject who has received Disease Modifying Anti-Rheumatic Drug (DMARD) treatment within 30 days prior to enrolment (leflunomide requires a charcoal or cholestyramine washout)
6. Any subject who has received anti-Tumour Necrotising Factor (anti-TNF) therapy (except enteracept) or any biologic therapy within the previous 90 days
7. Any subject whose baseline Disease Activity Score (DAS-28) has significantly changed since screening to indicate unstable disease
8. Any individual who does not comply with the requirement that he should not have used:
8.1. Any drugs (including herbal and mineral supplements or vitamins), other than acetaminophen or an approved stable regimen of low dose prednisone (10 mg/day) and/or Non-Steroidal Anti-Inflammatory Drugs (NSAIDS), for at least two weeks prior to study drug administration
8.2. Alcohol in amounts of greater than 50 grams a day throughout the study
9. Subjects that have been diagnosed with Juvenile RA
10. A history of systemic lupus erythematosus, or signs and symptoms suggesting systemic lupus erythematosus
11. Subjects who are positive for hepatitis B surface antigen, hepatitis C Ribonucleic Acid (RNA) or for Human Immunodeficiency Virus (HIV) antibodies
12. Individuals who have participated in a clinical trial of an investigational drug within 90 days prior to the start of study drug administration, or have received prior treatment with a CCR5 receptor antagonist
13. Individuals with a positive screen for drugs of abuse
14. Individuals who have donated blood (greater than 300 mL) within the preceding 90 days
15. Males who are unwilling to use/practice an effective method of contraception (i.e., condom in conjunction with spermicide from study start until 30 days after the last study treatment
16. Females who are unwilling to use/practice an effective method of contraception (i.e., condom in conjunction with spermicide from two weeks prior to study start until 30 days after the last study treatment
17. Individuals who have received any vaccinations within 30 days prior to screening
18. Individuals with any clinically significant history of food or drug allergy or allergy to any component of SCH 351125
19. Subjects who are not willing to follow the study restrictions or procedures

Recruitment start date

01/03/2004

Recruitment end date

01/05/2005

Locations

Countries of recruitment

Netherlands

Trial participating centre

Academic Medical Centre (AMC)
Amsterdam
1100 DD
Netherlands

Sponsor information

Organisation

Schering Plough Research Institute (USA)

Sponsor details

Schering-Plough Corporation Headquarters
2000 Galloping Hill Road
Kenilworth
New Jersey
07033-0530
United States of America

Sponsor type

Industry

Website

http://www.schering-plough.com/schering_plough/research/research_institute.jsp

Funders

Funder type

Industry

Funder name

Schering Plough Research Institute (USA)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

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