Study of an Anti-TLR4 mAb in Rheumatoid Arthritis

Rheumatoid Arthritis Clinical Trial

Official title:

Randomized, Placebo-Controlled, Double Blind, Multicenter Phase 2 Study to Explore Tolerability, Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of Intravenous Multiple Infusions of NI-0101, an Anti-Toll Like Receptor 4 Monoclonal Antibody in Patients With Rheumatoid Arthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03241108
• Other study ID #: NI-0101-04
• Secondary ID: 2016-005017-45
• Status: Completed
• Phase: Phase 2
• Start date: May 10, 2017
• Est. completion date: June 20, 2018

Study information

• Verified date: August 2017
• Source: NovImmune SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: June 20, 2018
• Est. primary completion date: June 20, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• NI-0101
Humanized immunoglobulin gamma 1 (IgG1) kappa monoclonal antibody targeting TLR4

Other:
• Placebo
Placebo

Locations

Country	Name	City	State
Bosnia and Herzegovina	Clinic for internal medicine with centre for dialysis	Mostar
Bulgaria	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
Georgia	ARENSIA Phase I Unit at the Research Institute of Clinical Medicine	Tbilisi
Georgia	Emergency Cardiology Center by Acad. G.Chapidze	Tbilisi
Georgia	High Technology Medical Center; University clinic	Tbilisi
Georgia	Insitute of Clinical Cardiology	Tbilisi
Georgia	Multiprofile Clinic Consilium Medulla	Tbilisi
Georgia	Tbilisi Central Hospital	Tbilisi
Hungary	CRU Hungary Ltd	Miskolc
Moldova, Republic of	Republican Clinical Hospital, ARENSIA Phase I unit	Chisinau
Poland	Centrum Miriada	Bialystok
Poland	Zespól Poradni Specjalistycznych REUMED	Lublin
Serbia	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

Sponsors (1)

Lead Sponsor	Collaborator
NovImmune SA

Countries where clinical trial is conducted

Bosnia and Herzegovina,  Bulgaria,  Georgia,  Hungary,  Moldova, Republic of,  Poland,  Serbia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence, severity, causality and outcomes of Adverse Events (AEs)	Incidence, severity, causality and outcomes of Adverse Events (AEs) (serious and non-serious), with particular attention being paid to infusion-related reactions and infections	From screening up to 24 weeks after first treatment administration
Primary	Withdrawal for safety reasons		From randomization up to 24 weeks after first treatment administration
Primary	Evolution of laboratory parameters		From screening up to 24 weeks after first treatment administration
Primary	Level of potential circulating antibodies against NI-0101	Level of potential circulating antibodies against NI-0101 to determine immunogenicity; i.e. the development of anti-drug antibodies (ADA).	From screening up to 24 weeks after first treatment administration
Primary	Levels of CRP	Levels of C-Reactive protein (CRP)	From screening up to 24 weeks after first treatment administration
Primary	Levels of inflammatory cytokines/chemokines	IL-6, TNFa, IP-10, MCP-1, sICAM, CXCL13	From screening up to 24 weeks after first treatment administration
Primary	DAS28 CRP	Measure of Disease Activity Scores (DAS) for Rheumatism in 28 tender or swollen joints and C-Reactive protein (CRP) - DAS28-CRP	From screening to 24 weeks after first treatment administration
Primary	ACR criteria	Proportion of patients achieving American College of Rheumatology Criteria (ACR20, ACR50 and ACR70)	From randomization to 24 weeks after first treatment administration
Primary	Proportion of patient achieving remission	Proportion of patient achieving remission (defined as DAS28 < 2.6)	From randomization to 24 weeks after first treatment administration
Primary	EULAR response	Proportion of patients achieving European League Against Rheumatism (EULAR) response criteria - good, moderate and no response	From randomization to 24 weeks after first treatment administration
Primary	Joint Count	Mean number of Tender Joint Count/Swollen Joint Count.	From screening to 24 weeks after first treatment administration
Primary	SDAI score	Mean improvement from baseline in Simplified Disease Activity Index (SDAI) score	From randomization to 24 weeks after first treatment administration
Primary	HAQ-DI score	Mean improvement from baseline in the Health Assessment Questionnaire without Disability Index (HAQ-DI) score	From randomization to 24 weeks after first treatment administration
Primary	SF-36 score	Mean improvement from baseline in 36-Item Short-Form Health Survey (SF-36) score	from randomization to 24 weeks after first treatment administration
Primary	DAS28-ESR	Measure of Disease Activity Scores (DAS) for Rheumatism in 28 tender or swollen joints and Erythrocyte Sedimentation Rate (ESR) levels - DAS28-ESR	From screening to 24 weeks after first treatment administration
Primary	CDAI score	Mean improvement from baseline in Clinical Disease Activity Index (CDAI) score scores	From randomization to 24 weeks after first treatment administration
Primary	Exploratory PK analysis - Cmax	Peak drug plasma concentration (Cmax)	From randomization to 24 weeks after first treatment administration
Primary	Exploratory PK analysis - Tmax	Time when plasma concentration is at peak (Tmax)	From screening up to 24 weeks after first treatment administration
Primary	Exploratory PK analysis - Ctrough	Plasma drug concentration immediately prior next dosing (Ctrough)	From randomization to 24 weeks after first treatment administration
Primary	Exploratory PK analysis - AUC	Area under the plasma concentration versus time curve (AUC)	From randomization to 24 weeks after first treatment administration
Primary	Exploratory PK analysis - CL	Systemic drug clearance (CL)	From randomization to 24 weeks after first treatment administration