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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03435601
• Date of registration: 31/01/2018
• Prospective Registration: Yes
• Primary sponsor: Josef Smolen, Univ. Prof. Dr.
• Public title: A Study to Target the Type I IFN Receptor by Administrating Anifrolumab in RA Patients With a High IFN Signature (TarIFNiRA)
• Scientific title: A Randomised, Double-blind, Placebo-controlled Phase II Study to Target the Type I IFN Receptor by Administrating Anifrolumab in RA Patients With a High IFN Signature (TarIFNiRA)
• Date of first enrolment: April 18, 2018
• Target sample size: 24
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/show/NCT03435601
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Austria

Contacts

• Name: Josef Smolen, MD

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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 ß-human chorionic gonadotropin (ß-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.

- Meets all of the following tuberculosis (TB) criteria:

- No history of latent or active TB prior to screening, with the exception of
latent TB with documented completion of appropriate treatment

- No signs or symptoms suggestive of active TB from medical history or physical
examination

- No recent contact with a person with active TB OR if there has been such contact,
referral to a physician specialising in TB to undergo additional evaluation prior
to randomisation (documented appropriately in source), and, if warranted, receipt
of appropriate treatment for latent TB at or before the first administration of
investigational product

- 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 (eg, tuberculosis) or
old active TB, malignancy, or clinically significant abnormalities obtained during the
screening period or anytime within 12 weeks prior to signing of the informed consent

General Exclusion criteria:

- 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)

- 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 concomitant medications:

- 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

- A known history of allergy or reaction to any component of the investigational product
formulation or history of anaphylaxis to any human gamma globulin therapy

- Regul


Age minimum: 18 Years
Age maximum: 70 Years
Gender: All

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis

Intervention(s)

Drug: Anifrolumab

Drug: Placebos

Primary Outcome(s)

Achieving an ACR 20 response at week 24 [Time Frame: Week 24]

Secondary Outcome(s)

Change in Kessler Psychological Distress Scale (K10) [Time Frame: Week 24]

Absolute and relative change in Clinical Disease Activity Index (CDAI) at week 24 and at every visit before and after week 24 [Time Frame: Week 24]

Absolute and relative change in the Simplified Disease Activity Index (SDAI) after 24 weeks [Time Frame: Week 24]

Achieving a CDAI response (50%, 70%, 85%) [Time Frame: Week 24]

Achieving a EULAR response (good, moderate) [Time Frame: Week 24]

Achieving a SDAI response (50%, 70%, 85%) [Time Frame: Week 24]

Change in fatigue (visual analog scale, VAS) [Time Frame: Week 24]

Change in physical function (HAQ) [Time Frame: Week 24]

Change in quality of life (SF-36) [Time Frame: Week 24]

Proportion achieving DAS28=3.2 after 24 weeks [Time Frame: Week 24]

Achieving an ACR response (20%, 50%, 70%) [Time Frame: Week 24]

Change in sleep (visual analog scale, VAS) [Time Frame: Week 24]

Change in pain (visual analog scale, VAS) [Time Frame: Week 24]

Absolute and relative change in Disease Activity Score 28 (DAS28) after 24 weeks [Time Frame: Week 24]

Proportion achieving a low disease activity state (CDAI=10, SDAI=11) after 24 weeks [Time Frame: Week 24]

Proportion achieving a remission state (CDAI=2.8; SDAI=3.3; ACR/EULAR Boolean) after 24 weeks [Time Frame: Week 24]

Secondary ID(s)

2017-001717-92

TarIFNiRA

Source(s) of Monetary Support

Please refer to primary and secondary sponsors