Pharmacokinetics and Pharmacodynamics of RPH-104 in Healthy Subjects

Study Overview
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Brief Summary
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The purpose of this first in human study is to evaluate the safety and tolerability of RPH-104 in humans.

Detailed Description
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RPH-104 is a macromolecular compound with a molecular weight of 152.715 kilodalton (Data on file) and is capable of binding human interleukin-1 beta (IL-1β). It has also been shown in vitro to be a highly potent inhibitor of IL-1β signalling pathway, with low picomolar inhibitor activity. In this First in Human study, RPH-104 will be evaluated primarily for its safety and tolerability. In a phase I study conducted with health volunteers, a similar monoclonal antibody, canakinumab, was investigated in terms of pharmacokinetics and pharmacodynamics besides efficacy and safety. Similarly, this aimed to investigate effects of RPH-104 on selected pharmacodynamic parameters, including Anti-Drug Antibodies (ADA) along with obtaining first human data on pharmacokinetics of RPH-104 in humans will be investigated in the same study.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Single-center, Phase I, Single-dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RPH-104 in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Biological: RPH-104
* Other: Sodium chloride Sterile Injection 0.9% w/v


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects. Male or female subjects between 18 and 35 years old (inclusive). Subject who has normal body weight as determined by a body mass index (BMI) of between 18 kg/m² and 30 kg/m² (inclusive) and within a body weight of ≥50kg and ≤120kg. Exclusion Criteria: Subject who has a history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, dermatological, neurological, psychiatric, and hematological or immunological disorder(s), and/or any condition that could constitute a potential safety risk factor or could alter the absorption, distribution, metabolism or elimination of the study drugs. Subject who has positive immunoglobulin-M (IgM) antibodies against Epstein-Barr virus (EBV)-viral capsid antigen (VCA) (IgM-anti-EBV-VCA) and Cytomegalovirus (CMV). Subject who has a positive Quantiferon TB-Gold (TB) test Subject who is positive to Human Immunodeficiency Virus-1/2 antibody (HIV-1/2Ab). Subject who has serum hepatitis, or is a carrier of the Hepatitis B surface antigen (HBsAg), or is Hepatitis C virus antibody (HCV-Ab) positive.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment<br>A single dose of RPH-104 (4, 20, 40, 80 or 160 mg) will be administered subcutaneously. | Biological: RPH-104<br>* Anti-IL-1 Mab<br>|
| Placebo Comparator: Placebo<br>A single 0.9% sodium chloride injection will be administered subcutaneously. | Other: Sodium chloride Sterile Injection 0.9% w/v<br>* Sterile saline solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Number of participants with study drug related adverse events | Until 60 days after administration | 
| Serious Adverse Events | Number of Participants with Study Drug Related Serious Adverse Events | Until 60 days after administration | 
| Respiratory Rate | Percentage of participants with abnormal respiratory rate. The normal respiration rate for an adult at rest is 12 to 20 breaths per minute. | Until 30 days after administration | 
| Blood Pressure | Percentage of participants with abnormal blood pressure. An optimal blood pressure level is a reading under 120/80 mmHg | Until 30 days after administration | 
| Oxygen Saturation | Percentage of participants with abnormal oxygen saturation. Normal pulse oximeter readings usually range from 95 to 100 percent. Values under 90 percent are considered low. | Until 30 days after administration | 
| Body Temperature | Percentage of participants with abnormal body temperature. Among adults, the average body temperature ranges from 97°F (36.1°C) to 99°F (37.2°C). | Until 30 days after administration | 
| Clinical Laboratory Tests | Percentage of participants with abnormal clinical laboratory tests. Normal laboratory ranges of the central laboratory were used. | Until 30 days after administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RPH-104 - Area Under the Curve (AUC) | Mean AUC 0-t (area under the concentration- time curve from time zero to day 30) | Day 1, Day 2, Day3, Day 4, Day 5, Day 6, Day 9, Day 12, Day 15, Day 20, Day 25, Day 30 | 
| RPH-104 - Time to Maximum Concentration (Tmax) | Median Tmax. Definition of Tmax is time at which Cmax occurs. | Day 1, Day 2, Day3, Day 4, Day 5, Day 6, Day 9, Day 12, Day 15, Day 20, Day 25, Day 30 | 
| RPH-104 - Elimination Half-life (t1/2) | Mean t½. Definition of t½ is terminal elimination half-life. | Day 1, Day 2, Day3, Day 4, Day 5, Day 6, Day 9, Day 12, Day 15, Day 20, Day 25, Day 30 | 
| RPH-104 - Maximum Plasma Concentration (Cmax) | Mean Cmax. Highest concentration determined in the measuring interval. | Day 1, Day 2, Day3, Day 4, Day 5, Day 6, Day 9, Day 12, Day 15, Day 20, Day 25, Day 30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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safety, tolerability, RPH-104, RPH104, Anti-IL1 beta, Anti-IL1