First in Human Study of an Anti-Toll-like Receptor 4 (TLR4) Monoclonal Antibody (NI-0101) in Adult Healthy Volunteers

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety, tolerability and distribution and elimination of a novel therapeutic drug when administered to Healthy Volunteers. In addition its effects on some inflammatory parameters will be measured in presence or absence of lipopolysaccharide stimulation.

Official Title
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A Randomized, Double Blind, Placebo-controlled, Pharmacokinetics/Pharmacodynamics-guided, Phase I Study in Healthy Volunteers Given Escalating, Single Intravenous Doses of NI-0101 in the Absence and Then in the Presence of a Systemic Lipopolysaccharide Challenge.

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Biological: Monoclonal antibody


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults between 18 and 40 years old (inclusive) having a body mass index (BMI) between 18 and 30 kg/m2 (inclusive), able to adhere to study protocol requirements and having signed informed consent. Exclusion Criteria: Any abnormal past or present clinically relevant medical history or any relevant abnormal laboratory parameters at screening that will prevent to consider the volunteers as healthy for the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NI-0101<br>NI-0101 is an anti-Toll-like receptor monoclonal antibody. | Biological: Monoclonal antibody<br> <br> |
| Placebo Comparator: Placebo<br>The placebo to be used for the proposed clinical trial is a sterile solution for intravenous infusion. The placebo is identical to the NI-0101 drug product but does not include the active substance. | Biological: Monoclonal antibody<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of NI-0101 in healthy male/female subjects | 12 lead ECG Vital signs Physical examination Adverse events Routine laboratory assessments during 8 weeks post administration. | Up to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters of NI-0101 | Blood samples for plasma NI-0101 concentrations. The following pharmacokinetic parameters of NI-0101 will be measured: Area under the curve from the time of dosing extrapolated to infinity (AUCinf); Area under curve from the time of dosing to the last measurable concentration (AUClast); AUCinf - AUClast expressed in % of AUCinf (% AUCextr); Systemic drug clearance (CL); Mean residence time (MRT) extrapolated to infinity (MRTinf); Mean residence time (MRT) at last measurable concentration (MRTlast). | Up to 8 weeks | 
| Pharmacodynamic parameters of NI-0101 | Blood samples for inflammatory markers measured in blood with or without the presence of an exogenous stimulus (lipopolysaccharide). Cytokine levels induced by ex vivo lipopolysaccharide challenge and circulating cytokine levels induced by in vivo lipopolysaccharide challenge will be measured. | Up to 8 weeks |