A randomised, double-blind, placebo-controlled Phase II study to target the type I IFN receptor by administrating Anifrolumab in patients with rheumatoid arthritis who have a high interferon signature (TarIFNiRA)
- Conditions
- High IFN siganture in patients with rheumatoid arthritisMedDRA version: 20.0Level: PTClassification code 10039073Term: Rheumatoid arthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disordersTherapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2017-001717-92-AT
- Lead Sponsor
- Medical University of Vienna
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 24
•18 - 70 years at screening
•Written informed consent
•Weigh =50.0 kg and =100.0 kg at screening
•Diagnosis of RA according to the 2010 ACR/EULAR classification criteria for RA
•at least one conventional synthetic (cs)DMARD (methotrexate (MTX), leflunomide, sulfasalazine (SSZ)) regularly for at least 12 weeks, with stable doses for at least 8 weeks.
•moderately to severely active RA
•Received at least one TNF-inhibitor (TNFi) but not more than 3 biological (b)DMARDs and discontinued treatment because of an insufficient response after at least 3 months.
•Oral Glucocorticoids (OCS) are allowed at stable doses of =10 mg /day prednisone or equivalent, if already used before the screening visit, dose must be stable for at least 2 weeks
•High type I IFN gene signature test
•Seronegative for HIV, hep. B surface antigen and hep. C ¬antibodies
•Negative serum ß-hCG test at screening (females of childbearing potential only).
•Females of childbearing potential must use 2 effective methods of avoiding pregnancy
•All males (sterilised or non-sterilised) who are sexually active must use condom (with spermicide where commercially available)
•Male subjects must not donate sperm during the course of the study and for 12 weeks after the last dose of the investigational product.
•Females with an intact cervix must have documentation of a normal Pap smear with no documented malignancy
•Meets all of the following tuberculosis (TB) criteria:
-No history of latent or active TB, exception: latent TB with documented completion of appropriate treatment
-No signs or symptoms suggestive of active TB
-No recent contact with a person with active TB
-Negative QuantiFERON-tuberculosis Gold [QFT-G] test for tuberculosis within 3 months prior to randomisation
•A chest radiograph with no evidence of current active infection within 12 weeks prior to signing of the informed consent
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 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4
General exclusion criteria:
•Any condition that would interfere with evaluation of the investigational product or interpretation of patient safety or study results
•Participation in another clinical study with an investigational product
•Individuals involved with the conduct of the study, their employees, or immediate family members of such individuals
•Lactating or pregnant females or females who intend to become pregnant
•Current alcohol, drug or chemical abuse, or a history of such abuse
•Major surgery within 8 weeks before signing ICF or elective major surgery planned during the study period
•Low type I IFN transcript scores in peripheral whole blood (type I Interfern Gene signature test)
•At screening (within 4 weeks before Week 0 [Day 0]), any of the following:
-AST >2.0 × ULN
-ALT >2.0 × ULN
-Total bilirubin >ULN (unless due to Gilbert's syndrome)
-Serum creatinine >2.0 mg/dL (or >181 µmol/L)
-Urine protein/creatinine ratio >2.0 mg/mg (or >226.30 mg/mmol)
-Neutrophil count <1000/µL (or <1.0 × 109/L)
-Platelet count <150.000/µL (or <150 × 109/L)
-Haemoglobin <8 g/dL (or <80 g/L)
-Glycosylated haemoglobin (HbA1c) >8% (or >0.08) at screening (diabetic patients only)
Exclusion criteria related to con. Med.:
•Receipt of any investigational product (small molecule or biologic agent) within 4 weeks or 5 half lives prior to signing of the ICF.
•Prior receipt of Anifrolumab
•Prior receipt of a JAK-inhibitor
•known history of allergy or reaction to any component of the investigational product
•Regular use of >1 NSAID within 2 weeks prior to Day 0 OR receipt of fluctuating doses of a NSAID within 2 weeks prior to Day 0
•Receipt of any of the following:
-Intra-articular, intramuscular or intravenous glucocorticosteroids within 6 weeks prior to Day 0
-Any live or attenuated vaccine within 8 weeks prior to signing the ICF
-BCG vaccine within 1 year prior signing the ICF
-Blood transfusion within 4 weeks prior signing the ICF
Exclusion criteria related to other diseases:
•History of any non RA disease that required treatment with oral or parenteral corticosteroids for > 2 weeks within the last 24 weeks prior signing the ICF
Exclusion criteria related to infection and malignancy risk factors:
•Splenectomy
•Any severe herpes infection at any time prior to Day 0
•Any herpes zoster infection that has not completely resolved within 12 weeks prior signing the ICF
•Opportunistic infection requiring hospitalisation or parenteral antimicrobial treatment within 3 years of randomisation
•Any of the following:
-Clinically significant chronic infection within 8 weeks prior signing the ICF
-Any infection requiring hospitalisation or treatment with intravenous anti infectives not completed at least 4 weeks prior signing the ICF
•Any infection requiring oral anti-infectives (including antivirals) within 2 weeks prior to Day 0
•History of cancer, apart from:
-Squamous or basal cell carcinoma of the skin treated with documented success of curative therapy =3 months prior to Week 0 (Day 0)
-Cervical cancer in situ treated with apparent success with curative therapy =1 year prior to Week 0 (Day 0)
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