Study of an Anti-TLR4 mAb in Rheumatoid Arthritis
- Registration Number
- NCT03241108
- Lead Sponsor
- Light Chain Bioscience - Novimmune SA
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 90
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description NI-0101 NI-0101 A therapeutic humanized monoclonal antibody, administered by intravenous infusion every 2 weeks. Placebo Placebo The placebo matches NI-0101 without active ingredient, administered by intravenous infusion every 2 weeks.
- Primary Outcome Measures
Name Time Method Proportion of patient achieving remission From randomization to 24 weeks after first treatment administration Proportion of patient achieving remission (defined as DAS28 \< 2.6)
Incidence, severity, causality and outcomes of Adverse Events (AEs) From screening up to 24 weeks after first treatment administration Incidence, severity, causality and outcomes of Adverse Events (AEs) (serious and non-serious), with particular attention being paid to infusion-related reactions and infections
Withdrawal for safety reasons From randomization up to 24 weeks after first treatment administration Level of potential circulating antibodies against NI-0101 From screening up to 24 weeks after first treatment administration Level of potential circulating antibodies against NI-0101 to determine immunogenicity; i.e. the development of anti-drug antibodies (ADA).
Levels of CRP From screening up to 24 weeks after first treatment administration Levels of C-Reactive protein (CRP)
EULAR response From randomization to 24 weeks after first treatment administration Proportion of patients achieving European League Against Rheumatism (EULAR) response criteria - good, moderate and no response
Joint Count From screening to 24 weeks after first treatment administration Mean number of Tender Joint Count/Swollen Joint Count.
SDAI score From randomization to 24 weeks after first treatment administration Mean improvement from baseline in Simplified Disease Activity Index (SDAI) score
HAQ-DI score From randomization to 24 weeks after first treatment administration Mean improvement from baseline in the Health Assessment Questionnaire without Disability Index (HAQ-DI) score
SF-36 score from randomization to 24 weeks after first treatment administration Mean improvement from baseline in 36-Item Short-Form Health Survey (SF-36) score
DAS28-ESR From screening to 24 weeks after first treatment administration Measure of Disease Activity Scores (DAS) for Rheumatism in 28 tender or swollen joints and Erythrocyte Sedimentation Rate (ESR) levels - DAS28-ESR
CDAI score From randomization to 24 weeks after first treatment administration Mean improvement from baseline in Clinical Disease Activity Index (CDAI) score scores
Evolution of laboratory parameters From screening up to 24 weeks after first treatment administration ACR criteria From randomization to 24 weeks after first treatment administration Proportion of patients achieving American College of Rheumatology Criteria (ACR20, ACR50 and ACR70)
Levels of inflammatory cytokines/chemokines From screening up to 24 weeks after first treatment administration IL-6, TNFa, IP-10, MCP-1, sICAM, CXCL13
DAS28 CRP From screening to 24 weeks after first treatment administration Measure of Disease Activity Scores (DAS) for Rheumatism in 28 tender or swollen joints and C-Reactive protein (CRP) - DAS28-CRP
Exploratory PK analysis - Cmax From randomization to 24 weeks after first treatment administration Peak drug plasma concentration (Cmax)
Exploratory PK analysis - Tmax From screening up to 24 weeks after first treatment administration Time when plasma concentration is at peak (Tmax)
Exploratory PK analysis - Ctrough From randomization to 24 weeks after first treatment administration Plasma drug concentration immediately prior next dosing (Ctrough)
Exploratory PK analysis - AUC From randomization to 24 weeks after first treatment administration Area under the plasma concentration versus time curve (AUC)
Exploratory PK analysis - CL From randomization to 24 weeks after first treatment administration Systemic drug clearance (CL)
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (19)
University Multiprofile Hospital for Active TreatmenT "St. Ivan Rilski"
🇧🇬Sofia, Bulgaria
Special Hospital for Rheumatic Diseases "Novi Sad"
🇷🇸Novi Sad, Serbia
University Multiprofile Hospital for Active Treatment "Kaspela"
🇧🇬Plovdiv, Bulgaria
Clinic for internal medicine with centre for dialysis
🇧🇦Mostar, Bosnia and Herzegovina
Multi-profile Hospital for Active Treatment "Trimontsium"
🇧🇬Plovdiv, Bulgaria
ARENSIA Phase I Unit at the Research Institute of Clinical Medicine
🇬🇪Tbilisi, Georgia
Clinical Center Kragujevac
🇷🇸Kragujevac, Serbia
High Technology Medical Center; University clinic
🇬🇪Tbilisi, Georgia
CRU Hungary Ltd
🇭🇺Miskolc, Hungary
Republican Clinical Hospital, ARENSIA Phase I unit
🇲🇩Chisinau, Moldova, Republic of
Centrum Miriada
🇵🇱Bialystok, Poland
General Hospital "Djordje Joanovic"
🇷🇸Zrenjanin, Serbia
Multiprofile Hospital for Active Treatment - Shumen AD
🇧🇬Shumen, Bulgaria
Insitute of Clinical Cardiology
🇬🇪Tbilisi, Georgia
Emergency Cardiology Center by Acad. G.Chapidze
🇬🇪Tbilisi, Georgia
Tbilisi Central Hospital
🇬🇪Tbilisi, Georgia
Institute of Rheumatology
🇷🇸Belgrade, Serbia
Multiprofile Clinic Consilium Medulla
🇬🇪Tbilisi, Georgia
Zespól Poradni Specjalistycznych REUMED
🇵🇱Lublin, Poland