Study of an Anti-TLR4 mAb in Rheumatoid Arthritis

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03241108
• Date of registration: 26/06/2017
• Prospective Registration: No
• Primary sponsor: NovImmune SA
• Public title: Study of an Anti-TLR4 mAb in Rheumatoid Arthritis
• Scientific 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
• Date of first enrolment: May 10, 2017
• Target sample size: 90
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03241108
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 2

Countries of recruitment

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

Contacts

• Name: Ernest Choy, MD
• Affiliation: Institute of Infection and Immunity, Cardiff University School of Medicine

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis

Intervention(s)

Other: Placebo

Drug: NI-0101

Primary Outcome(s)

Exploratory PK analysis - CL [Time Frame: From randomization to 24 weeks after first treatment administration]

Exploratory PK analysis - Cmax [Time Frame: From randomization to 24 weeks after first treatment administration]

Withdrawal for safety reasons [Time Frame: From randomization up to 24 weeks after first treatment administration]

Exploratory PK analysis - Ctrough [Time Frame: From randomization to 24 weeks after first treatment administration]

DAS28-ESR [Time Frame: From screening to 24 weeks after first treatment administration]

Evolution of laboratory parameters [Time Frame: From screening up to 24 weeks after first treatment administration]

Incidence, severity, causality and outcomes of Adverse Events (AEs) [Time Frame: From screening up to 24 weeks after first treatment administration]

Joint Count [Time Frame: From screening to 24 weeks after first treatment administration]

Proportion of patient achieving remission [Time Frame: From randomization to 24 weeks after first treatment administration]

SDAI score [Time Frame: From randomization to 24 weeks after first treatment administration]

EULAR response [Time Frame: From randomization to 24 weeks after first treatment administration]

Exploratory PK analysis - AUC [Time Frame: From randomization to 24 weeks after first treatment administration]

Levels of CRP [Time Frame: From screening up to 24 weeks after first treatment administration]

ACR criteria [Time Frame: From randomization to 24 weeks after first treatment administration]

CDAI score [Time Frame: 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]

HAQ-DI score [Time Frame: From randomization to 24 weeks after first treatment administration]

Levels of inflammatory cytokines/chemokines [Time Frame: 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]

SF-36 score [Time Frame: from randomization to 24 weeks after first treatment administration]

DAS28 CRP [Time Frame: From screening to 24 weeks after first treatment administration]

Secondary ID(s)

NI-0101-04

2016-005017-45

Source(s) of Monetary Support

Please refer to primary and secondary sponsors