Study of an Anti-TLR4 mAb in Rheumatoid Arthritis

August 13, 2018 updated by: Light Chain Bioscience - Novimmune SA

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

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
90

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Bosnia and Herzegovina
      • Mostar, Bosnia and Herzegovina, 88000
        • Clinic for internal medicine with centre for dialysis
  • Bulgaria
      • Plovdiv, Bulgaria, 4000
        • Multi-profile Hospital for Active Treatment "Trimontsium"
      • Plovdiv, Bulgaria, 4001
        • University Multiprofile Hospital for Active Treatment "Kaspela"
      • Shumen, Bulgaria, 9705
        • Multiprofile Hospital for Active Treatment - Shumen AD
      • Sofia, Bulgaria, 1612
        • University Multiprofile Hospital for Active TreatmenT "St. Ivan Rilski"
  • Georgia
      • Tbilisi, Georgia, 0112
        • ARENSIA Phase I Unit at the Research Institute of Clinical Medicine
      • Tbilisi, Georgia, 0144
        • High Technology Medical Center; University clinic
      • Tbilisi, Georgia, 0159
        • Emergency Cardiology Center by Acad. G.Chapidze
      • Tbilisi, Georgia, 0159
        • Insitute of Clinical Cardiology
      • Tbilisi, Georgia, 0159
        • Tbilisi Central Hospital
      • Tbilisi, Georgia, 0186
        • Multiprofile Clinic Consilium Medulla
  • Hungary
      • Miskolc, Hungary, 3529
        • CRU Hungary Ltd
  • Moldova, Republic of
      • Chisinau, Moldova, Republic of, MD2025
        • Republican Clinical Hospital, ARENSIA Phase I unit
  • Poland
      • Bialystok, Poland, 15-297
        • Centrum Miriada
      • Lublin, Poland, 20-582
        • Zespol Poradni Specjalistycznych REUMED
  • Serbia
      • Belgrade, Serbia, 11000
        • Institute of Rheumatology
      • Kragujevac, Serbia, 34000
        • Clinical Center Kragujevac
      • Novi Sad, Serbia, 21112
        • Special Hospital for Rheumatic Diseases "Novi Sad"
      • Zrenjanin, Serbia, 23000
        • General Hospital "Djordje Joanovic"

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: NI-0101
A therapeutic humanized monoclonal antibody, administered by intravenous infusion every 2 weeks.
Drug: NI-0101
Humanized immunoglobulin gamma 1 (IgG1) kappa monoclonal antibody targeting TLR4
Placebo Comparator: Placebo
The placebo matches NI-0101 without active ingredient, administered by intravenous infusion every 2 weeks.
Other: Placebo
Placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
From screening up to 24 weeks after first treatment administration
Withdrawal for safety reasons
Time Frame: From randomization up to 24 weeks after first treatment administration
From randomization up to 24 weeks after first treatment administration
Evolution of laboratory parameters
Time Frame: From screening up to 24 weeks after first treatment administration
From screening up to 24 weeks after first treatment administration
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).
From screening up to 24 weeks after first treatment administration
Levels of CRP
Time Frame: From screening up to 24 weeks after first treatment administration
Levels of C-Reactive protein (CRP)
From screening up to 24 weeks after first treatment administration
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
From screening up to 24 weeks after first treatment administration
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
From screening to 24 weeks after first treatment administration
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)
From randomization to 24 weeks after first treatment administration
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)
From randomization to 24 weeks after first treatment administration
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
From randomization to 24 weeks after first treatment administration
Joint Count
Time Frame: From screening to 24 weeks after first treatment administration
Mean number of Tender Joint Count/Swollen Joint Count.
From screening to 24 weeks after first treatment administration
SDAI score
Time Frame: From randomization to 24 weeks after first treatment administration
Mean improvement from baseline in Simplified Disease Activity Index (SDAI) score
From randomization to 24 weeks after first treatment administration
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
From randomization to 24 weeks after first treatment administration
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
from randomization to 24 weeks after first treatment administration
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
From screening to 24 weeks after first treatment administration
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
From randomization to 24 weeks after first treatment administration
Exploratory PK analysis - Cmax
Time Frame: From randomization to 24 weeks after first treatment administration
Peak drug plasma concentration (Cmax)
From randomization to 24 weeks after first treatment administration
Exploratory PK analysis - Tmax
Time Frame: From screening up to 24 weeks after first treatment administration
Time when plasma concentration is at peak (Tmax)
From screening up to 24 weeks after first treatment administration
Exploratory PK analysis - Ctrough
Time Frame: From randomization to 24 weeks after first treatment administration
Plasma drug concentration immediately prior next dosing (Ctrough)
From randomization to 24 weeks after first treatment administration
Exploratory PK analysis - AUC
Time Frame: From randomization to 24 weeks after first treatment administration
Area under the plasma concentration versus time curve (AUC)
From randomization to 24 weeks after first treatment administration
Exploratory PK analysis - CL
Time Frame: From randomization to 24 weeks after first treatment administration
Systemic drug clearance (CL)
From randomization to 24 weeks after first treatment administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Light Chain Bioscience - Novimmune SA

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ernest Choy, MD, Institute of Infection and Immunity, Cardiff University School of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 10, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 20, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 20, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 26, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 4, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 7, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 14, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 13, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NI-0101-04
  • 2016-005017-45 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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