Rheumatoid Arthritis
Conditions
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.
Interventions
DRUGNI-0101
Humanized immunoglobulin gamma 1 (IgG1) kappa monoclonal antibody targeting TLR4
OTHERPlacebo
Placebo
Sponsors
Light Chain Bioscience - Novimmune SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Evolution of laboratory parameters | From screening 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) |
| 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 |
| ACR criteria | From randomization to 24 weeks after first treatment administration | Proportion of patients achieving American College of Rheumatology Criteria (ACR20, ACR50 and ACR70) |
| Proportion of patient achieving remission | From randomization to 24 weeks after first treatment administration | Proportion of patient achieving remission (defined as DAS28 \< 2.6) |
| 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 |
| 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) |
Countries
Bosnia and Herzegovina, Bulgaria, Georgia, Hungary, Moldova, Poland, Serbia
Outcome results
None listed