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Completed

NCT Number: NCT03241108

Study of an Anti-TLR4 mAb in Rheumatoid Arthritis

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

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Clinic for internal medicine with centre for dialysis, Mostar, Bosnia and Herzegovina

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

NI-0101

Drug

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

Placebo

Other

Placebo

Primary outcomes

  1. Incidence, severity, causality and outcomes of Adverse Events (AEs)

    Time frame: 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

  2. Withdrawal for safety reasons

    Time frame: From randomization up to 24 weeks after first treatment administration

  3. Evolution of laboratory parameters

    Time frame: From screening up to 24 weeks after first treatment administration

  4. Level of potential circulating antibodies against NI-0101

    Time frame: 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).

  5. Levels of CRP

    Time frame: From screening up to 24 weeks after first treatment administration

    Levels of C-Reactive protein (CRP)

  6. Levels of inflammatory cytokines/chemokines

    Time frame: From screening up to 24 weeks after first treatment administration

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

  7. DAS28 CRP

    Time frame: 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

  8. ACR criteria

    Time frame: From randomization to 24 weeks after first treatment administration

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

  9. Proportion of patient achieving remission

    Time frame: From randomization to 24 weeks after first treatment administration

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

  10. EULAR response

    Time frame: 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

  11. Joint Count

    Time frame: From screening to 24 weeks after first treatment administration

    Mean number of Tender Joint Count/Swollen Joint Count.

  12. SDAI score

    Time frame: From randomization to 24 weeks after first treatment administration

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

  13. HAQ-DI score

    Time frame: From randomization to 24 weeks after first treatment administration

    Mean improvement from baseline in the Health Assessment Questionnaire without Disability Index (HAQ-DI) score

  14. SF-36 score

    Time frame: from randomization to 24 weeks after first treatment administration

    Mean improvement from baseline in 36-Item Short-Form Health Survey (SF-36) score

  15. DAS28-ESR

    Time frame: 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

  16. CDAI score

    Time frame: From randomization to 24 weeks after first treatment administration

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

  17. Exploratory PK analysis - Cmax

    Time frame: From randomization to 24 weeks after first treatment administration

    Peak drug plasma concentration (Cmax)

  18. Exploratory PK analysis - Tmax

    Time frame: From screening up to 24 weeks after first treatment administration

    Time when plasma concentration is at peak (Tmax)

  19. Exploratory PK analysis - Ctrough

    Time frame: From randomization to 24 weeks after first treatment administration

    Plasma drug concentration immediately prior next dosing (Ctrough)

  20. Exploratory PK analysis - AUC

    Time frame: From randomization to 24 weeks after first treatment administration

    Area under the plasma concentration versus time curve (AUC)

  21. Exploratory PK analysis - CL

    Time frame: From randomization to 24 weeks after first treatment administration

    Systemic drug clearance (CL)

Sponsors and collaborators

Lead sponsor

Light Chain Bioscience - Novimmune SA

Industry

Registry information

Official study 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

Important dates

Study start
2017
Primary completion
2018
Study completion
2018
First posted
Aug 7, 2017
Registry last updated
Aug 14, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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