Rheumatoid Arthritis MedDRA version: 19.1 Level: LLT Classification code 10040107 Term: Seropositive rheumatoid arthritis System Organ Class: 100000004859
Conditions
Interventions
Product Name: NI-0101
Product Code: NI-0101
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: N/A
CAS Number: N/A
Current Sponsor code: NI-0101
Other descriptive name: Hu
Sponsors
NovImmune S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Male and female patients - Age >= 18 years old - BMI: 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 jointsout 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 41 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
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 |
|---|---|
| Main Objective: - To determine the preliminary tolerability and safety profile of multiple intravenous (i.v.) administrations of NI-0101 - To describe the Pharmacokinetic/Pharmacodynamic (PK/PD) profiles of NI-0101 - To determine NI-0101 preliminary efficacy - To explore specific biomarkers as predictors of treatment response - To explore the impact of the FcyRIIa genotype on the response to treatment - To assess the immunogenicity of NI-0101 ;Secondary Objective: Not applicable;Primary end point(s): Safety: 1. Incidence, severity, causality and outcomes of AEs (serious and non-serious), with particular attention being paid to infusion-related reactions and infections 2. Withdrawals for safety issues 3. Evolution of laboratory parameters 4. Level of potential circulating antibodies against NI-0101 to determine immunogenicity; i.e. the development of anti-drug antibodies (ADA). PK: 5. Descriptive non-compartmental PK analysis (NCA) 6. Exploratory compartmental PK analysis and population PK analysis 7. Detection of anti-drug antibodies (ADA) in human RA patient serum PD: 8. Levels of CRP at all study visits prior to IMP infusion 9. Levels of inflammatory cytokines/chemokines at pre and post (week 2, 6 and 12) dose measured using ELISA and/or multiplex assays (e.g. MSD or equivalent). Biomarker: 10. Multi Biomarker Disease Activity score (MBDA or Vectra DA®), calculated based on levels of 12 different biomarkers. Efficacy: 11. DAS28-CRP/ESR score at Week 12 12. Proportion of patients achieving ACR20, ACR50 and ACR70 responses at Week 12 13. Proportion of patient achieving remission (defined as DAS28 < 2.6) at Week 12 14. Proportion of patients achieving EULAR good, moderate and no response at Week 12 15. Mean number of Tender Joint Count/Swollen Joint Count at week 12 and over time 16. Mean improvement from baseline to Week 12 in DAS28-CRP/ESR 17. Mean improvement from baseline to Week 12 in SDAI and CDAI scores 18. Mean improvement from baseline to Week 12 in H | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Not applicable;Timepoint(s) of evaluation of this end point: Not applicable | — |
Countries
Bosnia and Herzegovina, Bulgaria, Georgia, Hungary, Moldova, Republic of, Poland, Serbia, United Kingdom
Contacts
Public ContactEmmanuel Monnet
NovImmune S.A.
Outcome results
None listed