A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of CCX168 in Healthy Participants

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

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.

Study Overview

• Status: Completed
• Conditions: Vasculitis; Systemic Lupus Erythematosus (SLE)
• Intervention / Treatment: Drug: Placebo; Drug: CCX168

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• Switzerland
  • Allschwil, Switzerland, CH-4123
    • Covance Clinical Research Unit (CRU) AG

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; During Period 1, participants will receive a single dose of CCX168 1 mg or placebo. During the second study period, participants will receive the same dose as during the first period but once daily (QD) for a period of 7 days continuously.	Drug: Placebo; Administered orally.; Drug: CCX168; Administered orally.
Experimental: Cohort 2; During Period 1, participants will receive a single dose of CCX168 3 mg or placebo. During the second study period, participants will receive the same dose as during the first period but QD for a period of 7 days continuously.	Drug: Placebo; Administered orally.; Drug: CCX168; Administered orally.
Experimental: Cohort 3; During Period 1, participants will receive a single dose of CCX168 10 mg or placebo. During the second study period, participants will receive the same dose as during the first period but QD for a period of 7 days continuously.	Drug: Placebo; Administered orally.; Drug: CCX168; Administered orally.
Experimental: Cohort 4; During Period 1, participants will receive a single dose of CCX168 30 mg or placebo. During the second study period, participants will receive the same dose as during the first period or placebo twice daily (BID) for a period of 7 days continuously.	Drug: Placebo; Administered orally.; Drug: CCX168; Administered orally.
Experimental: Cohort 5; During Period 1, participants will receive a single dose of CCX168 100 mg or placebo. During the second study period, participants will receive the same dose as during the first period or placebo BID for a period of 7 days continuously.	Drug: Placebo; Administered orally.; Drug: CCX168; Administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants Experiencing Adverse Events (AEs)	Up to 43 days
Number of Participants Experiencing Clinically Significant Changes in Laboratory Parameters	Up to 29 days
Number of Participants Experiencing Clinically Significant Changes in Electrocardiogram (ECG) Parameters	Up to 29 days
Number of Participants Experiencing Clinically Significant Changes in Vital Sign Parameters	Up to 29 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum Plasma Concentration (Cmax) of CCX168	Period 1: Up to Day 8; Period 2: Up to Day 15
Time of Cmax of CCX168	Period 1: Up to Day 8; Period 2: Up to Day 15
Terminal Phase Rate Constant of CCX168	Period 1: Up to Day 8; Period 2: Up to Day 15
Apparent Terminal Half-life of CCX168	Period 1: Up to Day 8; Period 2: Up to Day 15
Apparent Oral Clearance of CCX168	Period 1: Up to Day 8; Period 2: Up to Day 15
Apparent Volume of Distribution of CCX168	Period 1: Up to Day 8; Period 2: Up to Day 15
Area Under the Plasma Concentration-time Curve (AUC) of CCX168 From Time 0 to Time t	Period 1: Up to Day 8; Period 2: Up to Day 15
AUC of CCX168 From Time 0 to Infinity	Period 1: Up to Day 8; Period 2: Up to Day 15
AUC of CCX168 From Time 0 to 24 Hours	Periods 1 and 2: Up to Hour 24
AUC of CCX168 From Time 0 to 12 Hours	Periods 1 and 2: Up to Hour 12
AUC of CCX168 From Time 12 to 24 Hours	Periods 1 and 2: Hour 12 to Hour 24
Period 2: AUC of CCX168 From Time 0 to the end of the Dosing Interval	Cohorts 1-3: Up to Hour 24; Cohorts 4-5: Up to Hour 12
Period 2: Accumulation Ratio of CCX168	Up to Day 7
Percent Inhibition of complement 5a receptor (C5aR)-dependent Upregulation of CD11b in Peripheral Blood Neutrophils	Period 1: Up to Hour 24; Period 2: Up to 12 hours after the first dose on Day 7

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2009
• Primary Completion (Actual): September 19, 2010
• Study Completion (Actual): April 11, 2011

Study Registration Dates

• First Submitted: August 2, 2023
• First Submitted That Met QC Criteria: August 2, 2023
• First Posted (Actual): August 9, 2023

Study Record Updates

• Last Update Posted (Actual): August 9, 2023
• Last Update Submitted That Met QC Criteria: August 2, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Complement; Cardiovascular diseases; Vascular diseases; C5aR
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Vasculitis
• Other Study ID Numbers: CL001_168

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No