Pharmacokinetics and Pharmacodynamics of RPH-104 in Healthy Subjects

Phase 1

Completed

Interventions: Other: Sodium chloride Sterile Injection 0.9% w/v
Biological: RPH-104

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

Detailed Description: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Placebo	Sodium chloride Sterile Injection 0.9% w/v	A single 0.9% sodium chloride injection will be administered subcutaneously.
Treatment	RPH-104	A single dose of RPH-104 (4, 20, 40, 80 or 160 mg) will be administered subcutaneously.

Primary Outcome Measures

Name	Time	Method
Adverse Events	Until 60 days after administration	Number of participants with study drug related adverse events
Serious Adverse Events	Until 60 days after administration	Number of Participants with Study Drug Related Serious Adverse Events
Respiratory Rate	Until 30 days after administration	Percentage of participants with abnormal respiratory rate. The normal respiration rate for an adult at rest is 12 to 20 breaths per minute.
Blood Pressure	Until 30 days after administration	Percentage of participants with abnormal blood pressure. An optimal blood pressure level is a reading under 120/80 mmHg
Oxygen Saturation	Until 30 days after administration	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.
Body Temperature	Until 30 days after administration	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).
Clinical Laboratory Tests	Until 30 days after administration	Percentage of participants with abnormal clinical laboratory tests. Normal laboratory ranges of the central laboratory were used.

Secondary Outcome Measures

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