Repeat Dose Subcutaneous Rhumatoid Arthritis Efficacy Study
A Randomised, Single-blind, Placebo-controlled, Study Toevaluate the Safety, Tolerability, Pharmacodynamics Andpharmacokinetics of Repeat Subcutaneous Administration Ofotelixizumab in Subjects With Rheumatoid Arthritis
1 other identifier
interventional
28
1 country
1
Brief Summary
This study is a randomised, single-blind, placebo-controlled, repeat dose study of otelixizumab administered subcutaneously in rheumatoid arthritis patients. One cohort will receive a single dose of adalimumab (HUMIRA, Abbott) as rescue medication to assess additional concomitant safety and tolerability issues.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started May 2010
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 8, 2010
CompletedFirst Posted
Study publicly available on registry
April 12, 2010
CompletedStudy Start
First participant enrolled
May 12, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 16, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
November 29, 2012
CompletedNovember 16, 2022
November 1, 2022
1.3 years
April 8, 2010
November 15, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (6)
Adverse Events (AEs)
1 month
Change from baseline and number of subjects outside the normal range for blood pressure, heart rate, temperature, electrocardiography parameters (12-lead)
1 month
Change from baseline in clinical chemistry and haematology parameters
1 month
Epstein-Barr Virus viral load
1 month
Individual absolute and percentage circulating peripheral T lymphocytes and CD4+ and CD8+ subset counts
1 month
Saturation of CD3 antigen on peripheral blood T cells
1 month
Secondary Outcomes (2)
Individual serum concentrations of otelixizumab and data permitting summary PK parameters
1 month
Serum levels of anti-otelixizumab binding antibodies. Where binding antibodies are detected, proportion which are anti-otelixizumab neutralising antibodies.
1 month
Study Arms (7)
COHORT 1: CUMULATIVE DOSE 1.5MG, ADMINISTERED SUBCUTANEOUSLY
EXPERIMENTALDuration of treatment 3 days, dose 0.3, 0.5, 0.7, four patients in cohort, one of which is on placebo, escalation increment N/A
COHORT 2: CUMULATIVE DOSE 3.5MG, ADMINISTERED SUBCUTANEOUSLY
EXPERIMENTALDuration of treatment 5 days, dose 0.3, 0.5, 0.7, 1.0, 1.0 four patients in cohort, one of which is on placebo, escalation increment 2.3 fold.
COHORT 3: CUMULATIVE DOSE 6.0MG, ADMINISTERED SUBCUTANEOUSLY
EXPERIMENTALDuration of treatment 7 days, dose 0.3, 0.7, 5 x 1.0 four patients in cohort, one of which is on placebo, escalation increment 1.7 fold.
COHORT 4: CUMULATIVE DOSE 8.0MG, ADMINISTERED SUBCUTANEOUSLY
EXPERIMENTALDuration of treatment 5 days, dose 0.3, 0.7, 1.0, 2 x 3.0 four patients in cohort, one of which is on placebo, escalation increment 1.33 fold.
COHORT 5: CUMULATIVE DOSE 10MG, ADMINISTERED SUBCUTANEOUSLY
EXPERIMENTALDuration of treatment 10 days, dose 10 x 1.0 four patients in cohort, one of which is on placebo, escalation increment 1.25 fold.
COHORT 6: CUMULATIVE DOSE 15MG, ADMINISTERED SUBCUTANEOUSLY
EXPERIMENTALDuration of treatment 15 days, dose 15 x 1.0 six patients in cohort, one of which is on placebo, escalation increment 1.5 fold.
COHORT 7: CUMULATIVE DOSE 15MG, ADMINISTERED SUBCUTANEOUSLY
EXPERIMENTALDuration of treatment 5 days, dose 5 x 3.0 six patients in cohort, one of which is on placebo, escalation increment N/A
Interventions
drug will be administered subcutaneously in varying amounts over a verying time period according to details stated in the 'arms' section
Placebo will be given to one member of each cohort.
Eligibility Criteria
You may qualify if:
- Male or female subjects between 18 and 75 years of age inclusive.
- A female subject is eligible to participate if she is of:
- Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 mIU/ml and estradiol \<40 pg/ml (\<140 pmol/L) is confirmatory\]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in Section 8.1.1 if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
- Child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1.1 for an appropriate period of time to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception for at least two weeks prior to dosing and for at least 60 days after the last dose.
- Male subjects must agree to use one of the contraception methods listed in Section 8.1.2. This criterion must be followed from the time of the first dose of study medication until at least 60 days after the last dose of otelixizumab or two months after adalimumab (Cohort 6 only).
- Body mass index within the range 18.5 - 35 kg/m\^2 inclusive
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form and willing and able to follow the procedures outlined in the protocol.
- A 12-lead ECG at pre-study screening measured in triplicate, which in the opinion of the Principal Investigator or physician designee has no abnormalities that will compromise safety in this study. QTcB \< 450 msec; or QTc \< 480 msec in subjects with Bundle Branch Block.
- No significant and/or active disease in any body system. Examples of significant diseases include but are not limited to: coronary artery disease, congestive heart failure, uncontrolled hypertension, emphysema, seizure disorder, chronic infectious disease ( e.g., chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis (TB) or latent tuberculosis, hepatitis B and C).
- The subject has a diagnosis of RA according to the revised 1987 criteria of the American College of Rheumatology
- The subject tests positive for Rheumatoid factor
- The subject has not previously received otelixizumab or any other anti-CD3 monoclonal antibody, e.g., OKT3 (muromonab or Orthoclone), ChAglyCD3, or hOKT3γ1 (ala ala), and is willing to refrain from using any such antibody for 2 years after the last dose of study drug unless invited to participate in possible future studies with otelixizumab.
- If taking methotrexate, the patient must have been taking methotrexate for at least 12 weeks and to be on a stable dose of methotrexate (7.5-25 mg/week) for at least four weeks prior to dosing and be willing to remain on this dose until day 28 of the study unless change required for clinical management of disease activity or safety.
- If sulfasalazine is being taken, the patient must have been taking sulfasalazine for at least 12 weeks and to be on a stable dose within local treatment guidelines for at least four weeks prior to dosing and be willing to remain on this dose until day 28 of the study unless change required for clinical management of disease activity or safety.
- If leflunomide is being taken, the patient must have been receiving this DMARD for at least six months prior to dosing with otelixizumab and the DMARD dose has been stable dose within local treatment guidelines for four weeks prior to dosing with study drug and be willing to remain on this dose until day 28 of the study unless change required for clinical management of disease activity or safety.
- +4 more criteria
You may not qualify if:
- Subjects with a history of significant systemic involvement secondary to RA (e.g., vasculitis, pulmonary fibrosis, or Felty's syndrome)
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening; current or chronic history of liver disease.
- The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
- A positive test for HIV antibody or risk factors which predispose subject to HIV infection.
- A positive test for syphilis according to local guidelines.
- History of regular alcohol consumption within 6 months of the study defined as:
- an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males), or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). One unit is equivalent to a half-pint (220mL) of beer or 1 (25ml) measure of spirits or 1 glass (125ml) of wine.
- The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, five half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) or planning to take any investigational drug within six months of the last dose of study drug
- The subject is currently receiving or has received an anti-rheumatic biological therapy within the following specified periods prior to dosing:
- Within four weeks:
- Glucocorticoid unless given in doses equivalent to \<=10 mg of prednisolone/day
- Intramuscular. or i.v. corticosteroids
- Live/attenuated vaccinations
- Cyclosporine
- Etanercept
- +34 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- GlaxoSmithKlinelead
Study Sites (1)
GSK Investigational Site
Moscow, 117292, Russia
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
GSK Clinical Trials
GlaxoSmithKline
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- PARTICIPANT
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 8, 2010
First Posted
April 12, 2010
Study Start
May 12, 2010
Primary Completion
September 16, 2011
Study Completion
November 29, 2012
Last Updated
November 16, 2022
Record last verified: 2022-11
Data Sharing
- IPD Sharing
- Will not share