Pharmacokinetics and Pharmacodynamics of RPH-104 in Healthy Subjects

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

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Biological: RPH-104; Other: Sodium chloride Sterile Injection 0.9% w/v

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.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

• Turkey
  • Izmir, Turkey
    • ARGEFAR

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: R-Pharm
• Collaborators: MonitorCRO
• Investigators: Principal Investigator: Sibel Goksel, MD, PhD, ARGEFAR

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: January 20, 2016
• First Submitted That Met QC Criteria: January 26, 2016
• First Posted (Estimate): January 29, 2016

Study Record Updates

• Last Update Posted (Actual): December 28, 2021
• Last Update Submitted That Met QC Criteria: December 27, 2021
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: tolerability; safety; RPH-104; RPH104; Anti-IL1 beta; Anti-IL1
• Other Study ID Numbers: RPH104FIH01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No