High IFN siganture in patients with rheumatoid arthritis MedDRA version: 20.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Product Name: Anifrolumab (MEDI-546)
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ANIFROLUMAB
Other descriptive name: ANIFROLUMAB
Concentration unit: mg milligram(s
Sponsors
Medical University of Vienna
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •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
Exclusion criteria
Exclusion criteria: 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 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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Achieving an ACR response of =20% after 24 weeks of treatment is the primary endpoint in this study. The ACR 20% response will be summarized by treatment group and the difference between groups may be estimated. A non responder imputation method will be used for the handling of missing data, i.e., patients who discontinue from treatment and/or the study for any reason, as well as patients who require rescue medication beyond the protocol allowed threshold, will be imputed as non-responders.;Timepoint(s) of evaluation of this end point: Week 24;Main Objective: To evaluate the efficacy of Anifrolumab compared to placebo on RA disease activity in patients with an increased type I IFN gene signature. (Achieving an ACR 20 response at week 24) ;Secondary Objective: To evaluate the effect of Anifrolumab compared to placebo on: •Absolute and relative change in the Simplified Disease Activity Index (SDAI) after 24 weeks •Absolute and relative change in Clinical Disease Activity Index (CDAI) at week 24 and at every visit before and after week 24 •Absolute and relative change in Disease Activity Score 28 (DAS28) after 24 weeks •Achieving a EULAR response (good, moderate) •Achieving a SDAI response (50%, 70%, 85%) •Achieving a CDAI response (50%, 70%, 85%) •Achieving an ACR response (20%, 50%, 70%) •Change in quality of life (SF-36) and physical function (HAQ) •Change in pain, fatigue and sleep (visual analog scale, VAS) •Proportion achieving a low disease activity state (CDAI=10, SDAI=11) after 24 weeks •Proportion achieving a remission state (CDAI=2.8; SDAI=3.3; ACR/EULAR Boolean) after 24 weeks •Proportion achieving DAS28=3.2 after 24 weeks •Change in Kessler Psychological Distress Scale (K10) | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Screening to end of study;Secondary end point(s): To evaluate the effect of Anifrolumab compared to placebo on: •Absolute and relative change in the Simplified Disease Activity Index (SDAI) after 24 weeks •Absolute and relative change in Clinical Disease Activity Index (CDAI) at week 24 and at every visit before and after week 24 •Absolute and relative change in Disease Activity Score 28 (DAS28) after 24 weeks •Achieving a EULAR response (good, moderate) •Achieving a SDAI response (50%, 70%, 85%) •Achieving a CDAI response (50%, 70%, 85%) •Achieving an ACR response (20%, 50%, 70%) •Change in quality of life (SF-36) and physical function (HAQ) •Change in pain, fatigue and sleep (visual analog scale, VAS) •Proportion achieving a low disease activity state (CDAI=10, SDAI=11) after 24 weeks •Proportion achieving a remission state (CDAI=2.8; SDAI=3.3; ACR/EULAR Boolean) after 24 weeks •Proportion achieving DAS28=3.2 after 24 weeks Safety and tolerability endpoints: AEs (including adverse events of special interest [AESIs]), vital signs, physical examination, 12-lead electrocardiograms (ECG), and clinical laboratory tests (haematology, clinical chemistry, urinalysis) | — |
Countries
Austria, Italy, Switzerland
Contacts
Public ContactSponsor
Medical University of Vienna
Outcome results
None listed