A Study to Determine the Safety, Efficacy, and Pharmacokinetics of 80 mg, 160 mg, and 320 mg ALD518 versus Placebo Administered as Multiple Intravenous Infusions to Patients with Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Methotrexate.
- Conditions
- Active Rheumatoid ArthritisMedDRA version: 9.1Level: LLTClassification code 10039073Term: Rheumatoid arthritis
- Registration Number
- EUCTR2008-004931-39-PL
- Lead Sponsor
- Alder Biopharmaceuticals, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 120
Patients will be entered into this study only if they meet all of the following criteria:
1.Are able to provide written informed consent
2.Are aged between 18 and 80 years (inclusive)
3.Have a diagnosis of active RA (ACR criteria 1987) at least 16 weeks before the Screening visit. (See Appendix I)
4.Have an ACR global functional status class of 1 to 3. (See Appendix II)
5.Have a minimum of 6 swollen and 6 tender joints on a 66/68 joint analysis at screening and pre-dose
6.Have a CRP of = 10 mg/L
7.Have been on a stable dose of methotrexate (= 10 mg/week) for at least 3 months before study Day 1. (Patients must take their methotrexate during the study at a stable dose.)
8.Stable optional RA medication:
•Folic acid supplementation if already in use
•Non steroidal anti-inflammatory drugs (NSAIDs) including cyclooxengase 2 (Cox 2) inhibitors – doses must be stable for 4 weeks before Day 1 and consistent with labeling recommendations.
•Acetylsalicylic acid is allowed in low doses (e.g., = 100 mg/day) as cardiovascular prophylaxis.
•Oral glucocorticoids, daily doses of = 10 mg/day of prednisolone or equivalent for 4 weeks before Day 1
•Painkillers (acetaminophen, Tramadol and similar, alone or in combinations) usage as per routine instructions will be allowed, except for 24 hours before rheumatology evaluations
9.Are not pregnant and do not plan to become pregnant during the study. Females of childbearing potential must provide a negative pregnancy test within the Screening period and must be using adequate contraception (oral or injectable [depot] oestrogen, and/or progestogen, or selective estrogen receptor modulator contraceptive therapeutic, intrauterine contraceptive device, or double barrier method [e.g., condom and diaphragm or spermicidal gel]). Non childbearing potential is defined as post-menopausal for at least 1 year or surgical sterilization or hysterectomy at least 3 months before study start.
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
Patients will be entered into this study only if they meet none of the following criteria:
1.Arthritis onset prior to 16 years old
2.Ongoing systemic inflammatory condition which may interfere with the results of clinical or laboratory tests planned in the study (eg, systemic lupus erythematosus or any other systemic rheumatic disease other than RA)
3.Have been on any biological therapy in previous 12 months (before Day 1) or has had any evidence of immunogenicity during previous biological therapy
4.Have a previous history of tuberculosis
5.Have a positive tuberculin skin test at Screening (indicative of active tuberculosis infection)
6.Have a current or recent (last 3 months) serious infection (requiring treatment with parenteral antibiotics)
7.Have received treatment with any other investigational drug in the last 12 months (before Day 1)
8.Have participated in an investigational study within the last 30 days (before signing of the informed consent) or expect to be treated with an investigational product during this study period
9.Have severe disease likely to jeopardize the planned completion of the study (e.g., recent myocardial infarction, unstable angina pectoris, uncontrolled diabetes mellitus)
10.Have any clinically significant concurrent medical condition as shown by, but not limited to:
Hepatic
•ALT = 3 x ULN
•AST = 3 x ULN
Hematology
•Hemoglobin < 9 g/dL
•Absolute neutrophil count < 1.5 x 109/L
•Platelets < 100 x 109/L
11.Have present or previous malignancies, except history of cured squamous or basal skin cell carcinoma or cured breast or cervical cancer for = 10 years without evidence of recurrence
12.Require one or several of the following medications:
•Narcotics or any drug for treatment of RA other than:
•NSAIDs
•Cox-2 inhibitors
•Acetaminophen/paracetamol for pain and arthritis control
•Tramadol
•Low dose aspirin (except for cardiovascular prophylaxis)
•Use of disease modifying anti-rheumatic drugs (DMARDs) other than methotrexate, within 4 months before Day 1
•Intra-articular, intramuscular, or intravenous glucocorticoids within 4 weeks before Day 1.
13.Have any clinically significant abnormality on physical examination, laboratory testing, vital signs, or 12-lead ECG suggestive of a significant unstable medical condition
14.Are pregnant or a nursing mother
15.Have a history of (within 12 months of Screening), or known current problems with drug or alcohol abuse
16.Have a history or suspicion of unreliability, poor cooperation, or non compliance with medical treatment
17.Have any concurrent disease or condition that, in the opinion of the investigator, would make the patient unsuitable for participation in the study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine the safety of two IV infusions of ALD518 80, 160, and 320 mg compared to two IV infusions of placebo in patients with active RA with an inadequate response to methotrexate.;Secondary Objective: To determine the efficacy, PK, and immunogenicity of two IV infusions of ALD518 80, 160, and 320 mg compared to two IV infusions of placebo in patients with active RA with an inadequate response to methotrexate.;Primary end point(s): The primary endpoints are changes in safety as follows:<br>•Incidence and severity of AEs and SAEs during the study<br>•Changes in vital signs and 12 lead ECG during the study<br>•Changes in physical examination during the study<br>•Changes in anti nuclear antibody (ANA) and anti dsDNA during the study<br>•Changes in laboratory assessments (serum chemistry, hematology and urinalysis) during the study.<br>
- Secondary Outcome Measures
Name Time Method