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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02667639

Enrollment

Registered

2016-01-29

Start date

2016-01-31

Completion date

2017-06-30

Last updated

2021-12-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Keywords

safety, tolerability, RPH-104, RPH104, Anti-IL1 beta, Anti-IL1

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.

Interventions

BIOLOGICALRPH-104

Anti-IL-1 Mab

OTHERSodium chloride Sterile Injection 0.9% w/v

Sterile saline solution

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

OTHER

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 35 Years

Healthy volunteers

Yes

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.

Design outcomes

Primary

Measure	Time frame	Description
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.
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).
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

Secondary

Measure	Time frame	Description
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.
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)

Countries

Turkey (Türkiye)

Participant flow

Participants by arm

Arm	Count
Treatment A single dose of RPH-104 (4, 20, 40, 80 or 160 mg) is administered subcutaneously. RPH-104	25
Placebo A single 0.9% sodium chloride injection is administered subcutaneously. Sodium chloride Sterile Injection 0.9% w/v	10
Total	35

Baseline characteristics

Characteristic	Total	Treatment	Placebo
Age, Customized 18-35	10 participants	25 participants	10 participants
Race and Ethnicity Not Collected	0 Participants	—	—
Region of Enrollment Turkey	35 Participants	25 Participants	10 Participants
Sex: Female, Male Female	3 Participants	2 Participants	1 Participants
Sex: Female, Male Male	32 Participants	23 Participants	9 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 25	0 / 10
other Total, other adverse events	22 / 25	7 / 10
serious Total, serious adverse events	0 / 25	0 / 10

Outcome results

Primary

Adverse Events

Number of participants with study drug related adverse events

Time frame: Until 60 days after administration

Arm	Measure	Value (NUMBER)
Treatment	Adverse Events	0 participants
Placebo	Adverse Events	0 participants

Primary

Blood Pressure

Percentage of participants with abnormal blood pressure. An optimal blood pressure level is a reading under 120/80 mmHg