A Study to Target the Type I IFN Receptor by Administrating Anifrolumab in RA Patients With a High IFN Signature (TarIFNiRA)

NCT03435601 | Unknown Phase 2

• 2 other identifiers: TarIFNiRA2017-001717-92
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 3

Brief Summary

A multicenter, randomised, double-blind, placebo-controlled Phase 2A/ proof-of-concept study to evaluate the efficacy and safety of an intravenous treatment regimen of 300 mg Anifrolumab versus placebo in patients with moderately to severely active RA who did not respond to biological disease-modifying anti-rheumatic drugs (bDMARDs) and who have a high type I IFN gene signature.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis; RA; IFN-Signature; Anifrolumab

Outcome Measures

Primary Outcomes (1)

• Achieving an ACR 20 response at week 24

  To evaluate the efficacy of Anifrolumab compared to placebo on RA disease activity in patients with an increased type I IFN gene signature

  Week 24

Secondary Outcomes (16)

• Absolute and relative change in the Simplified Disease Activity Index (SDAI) after 24 weeks

  Week 24

• Absolute and relative change in Clinical Disease Activity Index (CDAI) at week 24 and at every visit before and after week 24

  Week 24

• Absolute and relative change in Disease Activity Score 28 (DAS28) after 24 weeks

  Week 24

• Achieving a EULAR response (good, moderate)

  Week 24

• Achieving a SDAI response (50%, 70%, 85%)

  Week 24

Other Outcomes (7)

• To evaluate the safety and tolerability of Anifrolumab, relative to placebo

  Week 24

• To evaluate the safety and tolerability of Anifrolumab, relative to placebo

  Week 24

• To evaluate the safety and tolerability of Anifrolumab, relative to placebo

  Week 24

Study Arms (2)

Anifrolumab

EXPERIMENTAL

Anifrolumab 300 mg IV administration Q4W, a total of 6 doses

Drug: Anifrolumab

Placebo

PLACEBO COMPARATOR

Placebo IV administration Q4W, a total of 6 doses

Drug: Placebos

Interventions

Anifrolumab DRUG

IV Administration of Anifrolumab 300 mg every 4 weeks from week 0 to week 20 for a total of 6 doses. At week 24 patients will continue the current study for another 8 weeks to complete a 12-week safety follow-up after the last dose of investigational products (last dose of investigational product will be given at week 20). The total study duration could be up to approximately 36 weeks (including the screening period).

Anifrolumab

Placebos DRUG

Placebo IV administration Q4W, a total of 6 doses At week 24 patients will continue the current study for another 8 weeks to complete a 12-week safety follow-up after the last dose of investigational products (last dose of investigational product will be given at week 20). The total study duration could be up to approximately 36 weeks (including the screening period).

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 through 70 years at the time of 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 study entry, patients must take at least one conventional synthetic (cs)DMARD (methotrexate (MTX), leflunomide, sulfasalazine (SSZ)) regularly for at least the preceding 12 weeks, with stable doses for at least the preceding 8 weeks.
• moderately to severely active RA: ≥4 tender joints of 28 joints examined, ≥4 swollen joints of 28 joints examined and an elevated serum C-reactive protein level (CRP).
• 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, and will be kept stable throughout the course of the study
• High type I IFN gene signature test
• Seronegative for human immunodeficiency virus (HIV) and negative test for hepatitis B surface antigen and hepatitis C - antibodies
• Negative serum β-human chorionic gonadotropin (β-hCG) test at screening (females of childbearing potential only).
• Females of childbearing potential must use 2 effective methods of avoiding pregnancy, only one of which is a barrier method, from screening until 12 weeks after the final dose of the investigational product unless the subject is surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy), has a sterile male partner, is 1 year post-menopausal, or practices sustained abstinence.Cessation of birth control after the specified period for investigational product should be discussed with a responsible physician. Post-menopausal is defined as at least 1 year since last menses and the subject having an elevated follicle- stimulating hormone (FSH) level greater than the central laboratory value of post-menopausal at screening
• All males (sterilised or non-sterilised) who are sexually active must use condom (with spermicide where commercially available for contraception if sexually active with a woman of child bearing potential) from Day 0 until at least 12 weeks after receipt of the final dose of the investigational product. It is strongly recommended that female partners of child bearing potential of male subjects also use a highly effective method of contraception (other than a barrier method) throughout this period.
• 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 (e.g., cervical intraepithelial neoplasia grade III \[CIN III\], carcinoma in situ \[CIS\], or adenocarcinoma in situ \[AIS\]) within 2 years prior to randomization. Any abnormal Pap smear result documented within 2 years prior to randomization must be repeated to confirm patient eligibility.

You may not qualify if:

• Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of patient safety or study results
• Concurrent enrolment 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 anytime from initiation of screening until the 12-week safety follow-up period following last dose of investigational product
• Current alcohol, drug or chemical abuse, or a history of such abuse within 1 year before Week 0 (Day 0)
• Major surgery within 8 weeks before signing informed consent form (ICF) or elective major surgery planned during the study period
• Spontaneous or induced abortion, still or live birth, or pregnancy ≤4 weeks prior to signing the ICF
• Low type I IFN transcript scores in peripheral whole blood (type I Interferon Gene signature test)
• At screening (within 4 weeks before Week 0 \[Day 0\]), any of the following:
• Aspartate aminotransferase (AST) \>2.0 × upper limit of normal (ULN)
• Alanine aminotransferase (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)

Sponsors & Collaborators

• Josef Smolen, Univ. Prof. Dr.: lead

Study Sites (3)

Medizinische Universität Graz, Klinische Abteilung für Rheumatologie und Immunologie

Graz, 8036, Austria

RECRUITING

Medizinische Universität Wien, Innere Medizin III, Abteilung für Rheumatologie

Vienna, 1090, Austria

RECRUITING

Krankenhaus Hietzing, 2. Medizinische Abteilung

Vienna, 1130, Austria

RECRUITING

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

anifrolumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Central Study Contacts

Josef Smolen, MD

CONTACT

+ 43 1 40400; josef.smolen@meduniwien.ac.at

Thomas Karonitsch, MD

CONTACT

+ 43 1 40400; thomas.karonitsch@meduniwien.ac.at

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: January 31, 2018
• First Posted: February 19, 2018
• Study Start: April 18, 2018
• Primary Completion: March 1, 2021
• Study Completion: March 1, 2021
• Last Updated: March 2, 2020

Record last verified: 2020-02

Locations

AU (3)