A multi-centre, randomised, double-blind multiple dose study of increasing doses of XmAb5871 in patients with Rheumatoid Arthritis.
- Conditions
- XmAb5871 is a humanized Fc engineered monoclonal antibody that binds to the human B cell restricted cell surface antigen CD19. It has already entered Phase 1 clinical development. The available evidence suggests that XmAb5871 is a potentially useful immunomodulatory antibody for therapy of B cell mediated human disease states such as rheumatoid arthritis.MedDRA version: 16.1Level: HLTClassification code 10039075Term: Rheumatoid arthritis and associated conditionsSystem Organ Class: 100000004870Therapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2012-003057-29-CZ
- Lead Sponsor
- Xencor Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 58
1. Able to provide written informed consent.
2. Male or female between 18 to 65 years of age for part A or 18 to 70 years of age for Part B, inclusive at the time of screening.
3. Rheumatoid arthritis present for at least 6 months as defined by 1987 ACR RA classification criteria.
4. Global functional class I, II, or III according to the ACR 1991 revised criteria (Hochberg 1992).
5. For Part A: Active RA at screening defined as = 4 swollen joints (out of 28 joints examined) AND = 4 tender/painful joints (out of 28 joints examined) AND at least 1 of the following:
a) ESR = 28 mm/hr, OR
b) hsCRP = 10 mg/L, OR
c) Morning stiffness = 45 minutes.
6. For Part B: Active RA at screening defined as = 5 swollen joints (out of 28 joints examined) AND = 5 tender/painful joints (out of 28 joints examined), AND
a) positive RF OR ACPA, AND
b) hsCRP = 6 mg/L.
7. Part B only: Previous inadequate clinical response to at least 1, but not more than 5 oral DMARDs.
8. Currently taking methotrexate (MTX) consecutively for = 12 weeks and on a stable dose of oral or subcutaneous MTX at 7.5-25 mg weekly for = 4 weeks at Day -1. A lower MTX dose is acceptable if it is the highest tolerated dose; however, toxicity documentation by the Investigator is required. All patients will take folic acid to minimize toxicity, according to local guidelines. Patient may remain on a stable dose (= 8 weeks) of sulfasalazine (up to 3000 mg/day) and/or hydroxychloroquine (up to 400 mg/day) in combination with MTX. If previously experienced toxicity or lack of efficacy on MTX, patient may be on a stable dose (= 8 weeks) of sulfasalazine and/or leflunomide (up to 20 mg/day). Hydroxychloroquine (up to 400 mg/day) is allowed in combination with these DMARDs. Other oral DMARDs are not allowed within 4 weeks prior to screening.
9. Patients currently taking non steroidal anti-inflammatory drugs (NSAIDs) or oral corticosteroids (not to exceed the equivalent of 10 mg of prednisone per day), must be on a stable dose = 4 weeks prior to screening and remain on that stable dose during the treatment period of the study.
10. Normal or clinically acceptable electrocardiogram (ECG) values (12-lead reporting ventricular rate and PR, QRS, QT and QTc interval) at screening and baseline (Day -1) based on opinion of the Investigator.
11. Immunizations [tetanus, diphtheria, pertussis (Td/Tdap), seasonal influenza (during flu season), and pneumococcal (polysaccharide) vaccinations] up to date per local standards as determined by the Investigator.
12. Women can be of either childbearing or non-childbearing potential as per below:
a) Women of childbearing potential must have a negative pregnancy test during screening and at baseline (Day -1) and must agree to be sexually abstinent or use 2 highly effective methods of birth control during the study and for 3 months following last dose of XmAb5871, out of which one must be a physical barrier method. Highly effective methods of birth control include sexual abstinence, hormonal birth control, intrauterine devices (IUDs), or any barrier methods (sponges, female condoms) used by the woman in addition to contraception used by their male partner such as vasectomy or condom supplemented with spermicide.
b) Women of documented non-childbearing potential (i.e., postmenopausal by history with no menses for one year and confirmed by follicle stimulating hormone (FSH) level [using local reference ranges], OR history of hysterectomy, OR history of bilateral tubal ligati
1. History or evidence of a clinically unstable/uncontrolled disorder, condition or disease (including but not limited to cardiopulmonary, oncologic, renal, metabolic, hematologic or psychiatric) other than RA, that in the opinion of the Investigator or Xencor physician would pose a risk to patient safety or interfere with the study evaluation, procedures or completion.
2. Malignancy within 5 years (except successfully treated in situ cervical cancer or squamous or basal cell carcinoma of the skin)
3. Presence of recurrent or chronic infections, definedas = 3 infections requiring antibiotics over the past 12 months prior to screening
4. Evidence of any bacterial, viral, parasitic or systemic fungal infections within the 30 days prior to randomization.
5. Presence of a serious infection, defined as requiring hospitalization or iv antibiotics within 8 weeks before screening.
6. Prosthetic joint infection within 5 years of screening or native joint infection within 1 year of screening.
7. Prior or current history of untreated Mycobacterium tuberculosis infection.
8. Known residential exposure to an individual with tuberculosis (TB) prior to or during screening (if not treated with appropriate chemoprophylaxis) or positive Quantiferon test at screening.
9. Class IV RA according to the 1991 ACR revised response criteria (Hochberg 1992).
10. Diagnosed with Felty’s syndrome (RA, splenomegaly and granulocytopenia).
11. Positive test for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen, or hepatitis C antibodies.
12. White blood cell count < 3.0 x 103/L, or absolute neutrophil count (ANC) < 1.5 x 103/L.
13. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) at screening > 2.5 x upper limit of normal (ULN).
14. Elevated serum creatinine > 1.5 x ULN OR estimated creatinine clearance < 50 mL/min calculated by the Cockroft-Gault formula at screening.
15. Hemoglobin < 10 g/dL.
16. Platelet count < 75,000 x 109/L.
17. Received live vaccines within 3 months of first dose of investigational product.
18. Patient is pregnant or breast feeding, or planning to become pregnant while enrolled in the study, up to End of Study (EOS) visit.
19. Positive urine pregnancy test (i.e., urine human chorionic gonadotropin [hCG]) at screening or baseline (Day -1).
20. Male patient with a pregnant partner who is not willing to use a condom during the treatment and up to EOS visit.
21. Known or suspected sensitivity to mammalian cell-derived products or any components of the study drug.
22. History of alcohol and/or substance abuse within 12 months prior to screening.
23. Blood donation of > 500 mL within 60 days of study drug administration.
24. Positive alcohol breath test and/or positive urine screen for potential drugs of abuse at screening or baseline (Day-1).
25. Unable or unwilling to partake in follow-up assessments or required protocol procedures.
26. Leflunomide use in combination with methotrexate.
27. Use of cyclophosphamide or gold within the 3 months of randomization.
28. Use of cyclosporine or mycophenolic acid within 2 months of randomization.
29. Any prior use of rituximab (or other B cell depleting agents).
30. Use of anti-TNF monoclonal antibodies (mAbs; infliximab, adalimumab, golimumab, certolizumab), anti-IL-6R mAb (tocilizumab) or CTLA4-Ig (abatacept) within 2 months of randomization.
31. Use of etanercept, or anakinra within 28 days of randomization.
32. Patients who have received intra-articular or system
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method