Study of an Anti-TLR4 mAb in Rheumatoid Arthritis

NCT03241108 | Completed Phase 2

• 2 other identifiers: NI-0101-042016-005017-45
• Study Type: interventional
• Target: 90
• Locations: 7 countries
• Sites: 19

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

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (21)

• 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

• 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

  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

• Levels of CRP

  Levels of C-Reactive protein (CRP)

  From screening up to 24 weeks after first treatment administration

• Levels of inflammatory cytokines/chemokines

  IL-6, TNFa, IP-10, MCP-1, sICAM, CXCL13

  From screening up to 24 weeks after first treatment administration

• 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

• ACR criteria

  Proportion of patients achieving American College of Rheumatology Criteria (ACR20, ACR50 and ACR70)

  From randomization to 24 weeks after first treatment administration

• Proportion of patient achieving remission

  Proportion of patient achieving remission (defined as DAS28 \< 2.6)

  From randomization to 24 weeks after first treatment administration

• 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

• Joint Count

  Mean number of Tender Joint Count/Swollen Joint Count.

  From screening to 24 weeks after first treatment administration

• SDAI score

  Mean improvement from baseline in Simplified Disease Activity Index (SDAI) score

  From randomization to 24 weeks after first treatment administration

• 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

• 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

• 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

• CDAI score

  Mean improvement from baseline in Clinical Disease Activity Index (CDAI) score scores

  From randomization to 24 weeks after first treatment administration

• Exploratory PK analysis - Cmax

  Peak drug plasma concentration (Cmax)

  From randomization to 24 weeks after first treatment administration

• Exploratory PK analysis - Tmax

  Time when plasma concentration is at peak (Tmax)

  From screening up to 24 weeks after first treatment administration

• Exploratory PK analysis - Ctrough

  Plasma drug concentration immediately prior next dosing (Ctrough)

  From randomization to 24 weeks after first treatment administration

• Exploratory PK analysis - AUC

  Area under the plasma concentration versus time curve (AUC)

  From randomization to 24 weeks after first treatment administration

• Exploratory PK analysis - CL

  Systemic drug clearance (CL)

  From randomization to 24 weeks after first treatment administration

Study Arms (2)

NI-0101

EXPERIMENTAL

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

Drug: NI-0101

Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

NI-0101 DRUG

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

NI-0101

Placebo OTHER

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Light Chain Bioscience - Novimmune SA: lead

Study Sites (19)

Clinic for internal medicine with centre for dialysis

Mostar, 88000, Bosnia and Herzegovina

Location

Multi-profile Hospital for Active Treatment "Trimontsium"

Plovdiv, 4000, Bulgaria

Location

University Multiprofile Hospital for Active Treatment "Kaspela"

Plovdiv, 4001, Bulgaria

Location

Multiprofile Hospital for Active Treatment - Shumen AD

Shumen, 9705, Bulgaria

Location

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

Sofia, 1612, Bulgaria

Location

ARENSIA Phase I Unit at the Research Institute of Clinical Medicine

Tbilisi, 0112, Georgia

Location

High Technology Medical Center; University clinic

Tbilisi, 0144, Georgia

Location

Emergency Cardiology Center by Acad. G.Chapidze

Tbilisi, 0159, Georgia

Location

Insitute of Clinical Cardiology

Tbilisi, 0159, Georgia

Location

Tbilisi Central Hospital

Tbilisi, 0159, Georgia

Location

Multiprofile Clinic Consilium Medulla

Tbilisi, 0186, Georgia

Location

CRU Hungary Ltd

Miskolc, 3529, Hungary

Location

Republican Clinical Hospital, ARENSIA Phase I unit

Chisinau, MD2025, Moldova

Location

Centrum Miriada

Bialystok, 15-297, Poland

Location

Zespól Poradni Specjalistycznych REUMED

Lublin, 20-582, Poland

Location

Institute of Rheumatology

Belgrade, 11000, Serbia

Location

Clinical Center Kragujevac

Kragujevac, 34000, Serbia

Location

Special Hospital for Rheumatic Diseases "Novi Sad"

Novi Sad, 21112, Serbia

Location

General Hospital "Djordje Joanovic"

Zrenjanin, 23000, Serbia

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

NI-0101

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Ernest Choy, MD

  Institute of Infection and Immunity, Cardiff University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2017
• First Posted: August 7, 2017
• Study Start: May 10, 2017
• Primary Completion: June 20, 2018
• Study Completion: June 20, 2018
• Last Updated: August 14, 2018

Record last verified: 2017-08

Locations

BO (1); SE (4); HU (1); PL (2); GE (6); BU (4); MO (1)