Clinical trial NCT05984251: A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of CCX168 in Healthy Participants
Official title: A Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of CCX168 in Healthy Male and Female Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Vasculitis
Systemic Lupus Erythematosus (SLE)
Keywords: Complement
C5aR
Vascular diseases
Cardiovascular diseases
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2023-08-09
Enrollment: 48
Sex: ALL
Minimum age (years): 19
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

Brief summary: The primary objective of this study will be to evaluate the safety and tolerability of single and multiple oral doses of CCX168, over a range of dose levels, in healthy male and female participants.


Eligibility criteria: Inclusion Criteria:

* Male or female participants, aged 19-45 years inclusive, who are in generally good health, whose body mass index is 19 to 29 kg/m\^2;
* Willing and able to give written Informed Consent and to comply with the requirements of the study protocol;
* Negative result of the human immunodeficiency virus screen, the hepatitis B screen, and the hepatitis C screen;
* Judged to be healthy by the Investigator, based on medical history, physical examination (including ECG), and clinical laboratory assessments. Participants with clinical laboratory values that are outside of normal limits and/or with other abnormal clinical findings that are judged by the Investigator not to be of clinical significance may be entered into the study, and
* Female participants of childbearing potential, and male participants with partners of childbearing potential, may participate if adequate contraception is used during, and for at least the four weeks after, any administration of study medication.

Exclusion Criteria:

* Women who are pregnant, breastfeeding, or have a positive serum pregnancy test at Screening and/or on Study Day -1;
* Expected requirement for use of any medication (with the exception of continuing use by female participants of hormonal contraceptives in accordance with a regimen that has been stable for at least the three months prior to Screening) during the study period;
* History within the three months prior to study entry of use of tobacco and/or nicotine containing products;
* History within one year prior to study entry of illicit drug use;
* History of alcohol abuse at any time in the past;
* History of any form of cancer;
* Consumed alcoholic beverages, or any food or drink containing grapefruit or grapefruit juice within 24 hours of screening;
* History or presence of any medical condition or disease which, in the opinion of the Investigator, may place the participant at unacceptable risk for study participation;
* Donated or lost more than 350 mL of blood or blood products within 56 days prior to Screening, or donated plasma within 7 days of randomization;
* Participant's hemoglobin less than 12 g/dL (or less than 7.45 mmol/L);
* Participated in any clinical study of an investigational product within 30 days prior to randomization;
* Participant has any evidence of hepatic disease; aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, or bilirubin \> 1.5 x the upper limit of normal;
* Participant has any evidence of renal impairment; serum creatinine \> 1.5 x upper limit of normal, and
* Participant's urine tested positive at Screening and/or on Study Day -1 for any of the following: opioids, amphetamines, cannabinoids, benzodiazepines, barbiturates, cocaine, cotinine, or alcohol (Breathalyzer test allowed for alcohol).

Primary outcomes:
measure: Number of Participants Experiencing Adverse Events (AEs)
timeFrame: Up to 43 days
measure: Number of Participants Experiencing Clinically Significant Changes in Laboratory Parameters
timeFrame: Up to 29 days
measure: Number of Participants Experiencing Clinically Significant Changes in Electrocardiogram (ECG) Parameters
timeFrame: Up to 29 days
measure: Number of Participants Experiencing Clinically Significant Changes in Vital Sign Parameters
timeFrame: Up to 29 days
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax) of CCX168
timeFrame: Period 1: Up to Day 8; Period 2: Up to Day 15
measure: Time of Cmax of CCX168
timeFrame: Period 1: Up to Day 8; Period 2: Up to Day 15
measure: Terminal Phase Rate Constant of CCX168
timeFrame: Period 1: Up to Day 8; Period 2: Up to Day 15
measure: Apparent Terminal Half-life of CCX168
timeFrame: Period 1: Up to Day 8; Period 2: Up to Day 15
measure: Apparent Oral Clearance of CCX168
timeFrame: Period 1: Up to Day 8; Period 2: Up to Day 15
measure: Apparent Volume of Distribution of CCX168
timeFrame: Period 1: Up to Day 8; Period 2: Up to Day 15
measure: Area Under the Plasma Concentration-time Curve (AUC) of CCX168 From Time 0 to Time t
timeFrame: Period 1: Up to Day 8; Period 2: Up to Day 15
measure: AUC of CCX168 From Time 0 to Infinity
timeFrame: Period 1: Up to Day 8; Period 2: Up to Day 15
measure: AUC of CCX168 From Time 0 to 24 Hours
timeFrame: Periods 1 and 2: Up to Hour 24
measure: AUC of CCX168 From Time 0 to 12 Hours
timeFrame: Periods 1 and 2: Up to Hour 12
measure: AUC of CCX168 From Time 12 to 24 Hours
timeFrame: Periods 1 and 2: Hour 12 to Hour 24
measure: Period 2: AUC of CCX168 From Time 0 to the end of the Dosing Interval
timeFrame: Cohorts 1-3: Up to Hour 24; Cohorts 4-5: Up to Hour 12
measure: Period 2: Accumulation Ratio of CCX168
timeFrame: Up to Day 7
measure: Percent Inhibition of complement 5a receptor (C5aR)-dependent Upregulation of CD11b in Peripheral Blood Neutrophils
timeFrame: Period 1: Up to Hour 24; Period 2: Up to 12 hours after the first dose on Day 7
Other outcomes:
Locations:
city: Allschwil
country: Switzerland
facility: Covance Clinical Research Unit (CRU) AG
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: