Study of an Anti-TLR4 mAb in Rheumatoid Arthritis

NCT ID: NCT03241108

Last Updated: 2018-08-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-10
• Study Completion Date: 2018-06-20

Brief Summary

This is a Phase 2, PoC, randomized, placebo-controlled, double blind, international multicentre study to explore the effect of a new antibody to treat patients with Rheumatoid Arthritis

Detailed Description

The study foresees the randomization of at least 81 moderate to severe, ACPA positive, RA patients who are inadequate responders to MTX, in two double blind arms (NI-0101:placebo, with a ratio of 2:1). Patients will receive NI-0101 or placebo infusions up to a maximum of 6 administrations (every two weeks for 12 weeks). All patients will continue receiving a stable dose of MTX. After 12 weeks, patients will enter the follow up period with monthly visits for a minimum of 12 weeks.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

NI-0101

A therapeutic humanized monoclonal antibody, administered by intravenous infusion every 2 weeks.

Group Type: EXPERIMENTAL

NI-0101

Intervention Type: DRUG

Humanized immunoglobulin gamma 1 (IgG1) kappa monoclonal antibody targeting TLR4

Placebo

The placebo matches NI-0101 without active ingredient, administered by intravenous infusion every 2 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo

Interventions

NI-0101

Humanized immunoglobulin gamma 1 (IgG1) kappa monoclonal antibody targeting TLR4

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Male and female patients
• Age >= 18 years old
• BMI: < 30 and > 18
• Diagnosis of RA according to 2010 ACR/EULAR criteria and with a disease duration of at least 6 months since diagnosis
• Patient must present with active RA, characterized by at least 6 swollen joints out of 66 assessed and 6 tender joints out of 68 assessed and by the presence of synovitis (measured by ultrasound) in at least one of the 6 swollen joints
• C-reactive protein (CRP) level > 0.7 mg/dL or if the CRP level is between 0.3 mg/dL and 0.7 mg/dL (included) then patient must also present an ESR > 30mm/hr
• Patients must have received MTX treatment for at least 3 months and have been on a stable dose of MTX for at least 6 weeks prior to start of screening
• ACPA-positive RA patients
• Women must be postmenopausal (> 12 months without menses) or surgically sterile or using two effective contraception methods for at least 4 weeks prior to the randomization date and agree to continue contraception for the duration of their participation in the study (until the end of follow up period)
• Sexually active male patients must use a barrier method of contraception during the course of the study (and until the end of the follow up period)
• Patients must give written informed consent for study participation

Exclusion Criteria

• A documented history of an autoimmune disease other than RA by ACR classification, or Sjögren syndrome
• Administration of cytotoxic drugs and immune suppressants (other than MTX) within 3 months prior to screening
• Previous multiple administrations of any biological DMARD or targeted synthetic DMARD
• Known primary immunodeficiency
• Pregnant or breastfeeding women
• Suspicion of active or latent tuberculosis
• HIV, HCV, HBV infection
• Infection reported during screening not recovered 72h prior to first dose
• History of anaphylactic reactions to any protein therapeutics or excipients
• Any history of malignancy, excluding cured basal or squamous cell carcinoma of the skin, or cervical in situ carcinoma
• Clinically significant cardiac disease requiring medication, such as congestive heart failure, unstable angina, myocardial infarction within 6 months prior to randomization
• Moderate to severe renal insufficiency, clinically relevant liver function test abnormalities or pancytopenia
• Major psychiatric or neurological disorder

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Light Chain Bioscience - Novimmune SA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ernest Choy, MD

Role: PRINCIPAL_INVESTIGATOR

Institute of Infection and Immunity, Cardiff University School of Medicine

Locations

Clinic for internal medicine with centre for dialysis

Mostar, , Bosnia and Herzegovina

Multi-profile Hospital for Active Treatment "Trimontsium"

Plovdiv, , Bulgaria

University Multiprofile Hospital for Active Treatment "Kaspela"

Plovdiv, , Bulgaria

Multiprofile Hospital for Active Treatment - Shumen AD

Shumen, , Bulgaria

University Multiprofile Hospital for Active TreatmenT "St. Ivan Rilski"

Sofia, , Bulgaria

ARENSIA Phase I Unit at the Research Institute of Clinical Medicine

Tbilisi, , Georgia

High Technology Medical Center; University clinic

Tbilisi, , Georgia

Emergency Cardiology Center by Acad. G.Chapidze

Tbilisi, , Georgia

Insitute of Clinical Cardiology

Tbilisi, , Georgia

Tbilisi Central Hospital

Tbilisi, , Georgia

Multiprofile Clinic Consilium Medulla

Tbilisi, , Georgia

CRU Hungary Ltd

Miskolc, , Hungary

Republican Clinical Hospital, ARENSIA Phase I unit

Chisinau, , Moldova

Centrum Miriada

Bialystok, , Poland

Zespól Poradni Specjalistycznych REUMED

Lublin, , Poland

Institute of Rheumatology

Belgrade, , Serbia

Clinical Center Kragujevac

Kragujevac, , Serbia

Special Hospital for Rheumatic Diseases "Novi Sad"

Novi Sad, , Serbia

General Hospital "Djordje Joanovic"

Zrenjanin, , Serbia

Countries

Bosnia and Herzegovina; Bulgaria; Georgia; Hungary; Moldova; Poland; Serbia

Other Identifiers

2016-005017-45

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NI-0101-04

Identifier Type: -

Identifier Source: org_study_id