A study to explore the effect of a new antibody to treat patients with Rheumatoid Arthritis

• Register: EUCTR
• Last refreshed on: 20 August 2018
• Main ID: EUCTR2016-005017-45-PL
• Date of registration: 19/06/2017
• Prospective Registration: Yes
• Primary sponsor: NovImmune S.A.
• Public title: A study to explore the effect of a new antibody to treat patients with Rheumatoid Arthritis
• Scientific title: A 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: 27/09/2017
• Target sample size: 81
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-005017-45
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

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

Contacts

• Name: Emmanuel Monnet
• Affiliation: NovImmune S.A.

• Name: Emmanuel Monnet
• Affiliation: NovImmune S.A.

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 jointsout 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 if considered of child bearing potential must be using at least a highly effective contraception method for at least for 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), in addition to their partner(s) using another highly effective method
- Patients must give written informed consent for study participation
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 41
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

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
- Administration of anti-RANKL monoclonal antibody within 3 months
prior to screening.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis
MedDRA version: 20.0 Level: LLT Classification code 10040107 Term: Seropositive rheumatoid arthritis System Organ Class: 100000004859

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: NI-0101
Product Code: NI-0101
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: N/A
CAS Number: N/A
Current Sponsor code: NI-0101
Other descriptive name: Humanized immunoglobulin gamma 1 (IgG1) kappa monoclonal antibody
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: - To determine the preliminary tolerability and safety profile of multiple intravenous (i.v.) administrations of NI-0101
- To describe the Pharmacokinetic/Pharmacodynamic (PK/PD) profiles of NI-0101
- To determine NI-0101 preliminary efficacy
- To explore specific biomarkers as predictors of treatment response
- To explore the impact of the FcyRIIa genotype on the response to treatment
- To assess the immunogenicity of NI-0101

Timepoint(s) of evaluation of this end point: Safety:
1. See E.5.1
2. See E.5.1
3. Day 0, 7, 14, 28, 42, 56, 70, 84, 112, 140, 168
4. Day 0, 84, 168

PK:
5-7. See E.5.1

PD:
8-9. See E.5.1

Biomarker:
10. The biomarker score will be measured pre-dose, week 2 and week 12 samples, the analysis is optional and will be performed at the end of the study, if considered relevant. Other exploratory biomarkers are included as part of the optional analysis.

Efficacy:
11-19. See E.5.1

Primary end point(s): Safety:
1. Incidence, severity, causality and outcomes of AEs (serious and non-serious), with particular attention being paid to infusion-related
reactions and infections
2. Withdrawals for safety issues
3. Evolution of laboratory parameters
4. Level of potential circulating antibodies against NI-0101 to determine
immunogenicity; i.e. the development of anti-drug antibodies (ADA).

PK:
5. Descriptive non-compartmental PK analysis (NCA)
6. Exploratory compartmental PK analysis and population PK analysis
7. Detection of anti-drug antibodies (ADA) in human RA patient serum

PD:
8. Levels of CRP at all study visits prior to IMP infusion
9. Levels of inflammatory cytokines/chemokines at pre and post (week 2, 6 and 12) dose measured using ELISA and/or multiplex assays (e.g. MSD or equivalent).

Biomarker:
10. Multi Biomarker Disease Activity score (MBDA or Vectra DA®), calculated based on levels of 12 different biomarkers.

Efficacy:
11. DAS28-CRP/ESR score at Week 12
12. Proportion of patients achieving ACR20, ACR50 and ACR70 responses at Week 12
13. Proportion of patient achieving remission (defined as DAS28 < 2.6) at Week 12
14. Proportion of patients achieving EULAR good, moderate and no response at Week 12
15. Mean number of Tender Joint Count/Swollen Joint Count at week 12 and over time
16. Mean improvement from baseline to Week 12 in DAS28-CRP/ESR
17. Mean improvement from baseline to Week 12 in SDAI and CDAI scores
18. Mean improvement from baseline to Week 12 in HAQ-DI score
19. Mean improvement from baseline to Week 12 in SF-36 score

Secondary Objective: Not applicable

Secondary Outcome(s)

Secondary end point(s): Not applicable

Timepoint(s) of evaluation of this end point: Not applicable

Secondary ID(s)

2016-005017-45-HU

NI-0101-04

Source(s) of Monetary Support

NovImmune S.A.