Clinical trial NCT03241108: Study of an Anti-TLR4 mAb in Rheumatoid Arthritis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Lead sponsor: Light Chain Bioscience - Novimmune SA
Sponsor class: INDUSTRY
First posted: 2017-08-07
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence, severity, causality and outcomes of Adverse Events (AEs)
timeFrame: From screening up to 24 weeks after first treatment administration
measure: Withdrawal for safety reasons
timeFrame: From randomization up to 24 weeks after first treatment administration
measure: Evolution of laboratory parameters
timeFrame: From screening up to 24 weeks after first treatment administration
measure: Level of potential circulating antibodies against NI-0101
timeFrame: From screening up to 24 weeks after first treatment administration
measure: Levels of CRP
timeFrame: From screening up to 24 weeks after first treatment administration
measure: Levels of inflammatory cytokines/chemokines
timeFrame: From screening up to 24 weeks after first treatment administration
measure: DAS28 CRP
timeFrame: From screening to 24 weeks after first treatment administration
measure: ACR criteria
timeFrame: From randomization to 24 weeks after first treatment administration
measure: Proportion of patient achieving remission
timeFrame: From randomization to 24 weeks after first treatment administration
measure: EULAR response
timeFrame: From randomization to 24 weeks after first treatment administration
measure: Joint Count
timeFrame: From screening to 24 weeks after first treatment administration
measure: SDAI score
timeFrame: From randomization to 24 weeks after first treatment administration
measure: HAQ-DI score
timeFrame: From randomization to 24 weeks after first treatment administration
measure: SF-36 score
timeFrame: from randomization to 24 weeks after first treatment administration
measure: DAS28-ESR
timeFrame: From screening to 24 weeks after first treatment administration
measure: CDAI score
timeFrame: From randomization to 24 weeks after first treatment administration
measure: Exploratory PK analysis - Cmax
timeFrame: From randomization to 24 weeks after first treatment administration
measure: Exploratory PK analysis - Tmax
timeFrame: From screening up to 24 weeks after first treatment administration
measure: Exploratory PK analysis - Ctrough
timeFrame: From randomization to 24 weeks after first treatment administration
measure: Exploratory PK analysis - AUC
timeFrame: From randomization to 24 weeks after first treatment administration
measure: Exploratory PK analysis - CL
timeFrame: From randomization to 24 weeks after first treatment administration
Secondary outcomes:
Other outcomes:
Locations:
city: Mostar
country: Bosnia and Herzegovina
facility: Clinic for internal medicine with centre for dialysis
city: Plovdiv
country: Bulgaria
facility: Multi-profile Hospital for Active Treatment "Trimontsium"
city: Plovdiv
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment "Kaspela"
city: Shumen
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment - Shumen AD
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active TreatmenT "St. Ivan Rilski"
city: Tbilisi
country: Georgia
facility: ARENSIA Phase I Unit at the Research Institute of Clinical Medicine
city: Tbilisi
country: Georgia
facility: High Technology Medical Center; University clinic
city: Tbilisi
country: Georgia
facility: Emergency Cardiology Center by Acad. G.Chapidze
city: Tbilisi
country: Georgia
facility: Insitute of Clinical Cardiology
city: Tbilisi
country: Georgia
facility: Tbilisi Central Hospital
city: Tbilisi
country: Georgia
facility: Multiprofile Clinic Consilium Medulla
city: Miskolc
country: Hungary
facility: CRU Hungary Ltd
city: Chisinau
country: Moldova, Republic of
facility: Republican Clinical Hospital, ARENSIA Phase I unit
city: Bialystok
country: Poland
facility: Centrum Miriada
city: Lublin
country: Poland
facility: Zespól Poradni Specjalistycznych REUMED
city: Belgrade
country: Serbia
facility: Institute of Rheumatology
city: Kragujevac
country: Serbia
facility: Clinical Center Kragujevac
city: Novi Sad
country: Serbia
facility: Special Hospital for Rheumatic Diseases "Novi Sad"
city: Zrenjanin
country: Serbia
facility: General Hospital "Djordje Joanovic"
Study officials:
affiliation: Institute of Infection and Immunity, Cardiff University School of Medicine
name: Ernest Choy, MD
role: PRINCIPAL_INVESTIGATOR
References: