Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of a Single Ascending Dose (SAD) of CAN106 Administered Intravenously (IV) in Healthy Subjects

This is a single site, single dose escalation study in healthy subject with CAN106. The study is to assess the safety and tolerability of single escalating doses of CAN106; to characterize the PK and PD profile of CAN106; and to evaluate the immunogenicity of CAN106 injection.

Study Overview

• Status: Completed
• Conditions: PNH
• Intervention / Treatment: Drug: Placebo; Drug: CAN106

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore
    • National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects must be able to understand and provide informed consent.
• Males or females, between 21 and 45 years of age, inclusive;
• Body mass index must be within the range of 18.5 to 32.0 kg/m2;
• 12-lead electrocardiogram (ECG) within normal limits with no clinically significant abnormalities in the opinion of the Investigator；
• Systolic blood pressure ≤140 mmHg and a diastolic blood pressure of ≤ 90 mmHg after 5 minutes with supine rest；
• non-pregnancy
• meningococcal vaccinations for at least 2 weeks before dosing

Exclusion Criteria:

• Disease or conditions interfere with participating the trial
• Active serious mental illness or psychiatric disorder
• clinically relevant abnormal test results in hepatic function
• unacceptable CBC lab test
• asymptomatic complement deficiency
• Any other clinical safety laboratory test
• HIV, HBV, HCV positive
• Alcohol and drug abuse
• etc.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Ascending Dose (SAD); In the SAD arm subjects will be sequentially included in one of up to six cohorts (dose levels). Additional subjects may be added in any cohort if necessary.	Drug: CAN106; CAN106 is a selective inhibitor of complement activation, which binds to the complement component C5.
Placebo Comparator: placebo; In the SAD arm subjects will be sequentially included in one of up to six cohorts (dose levels). In higher dose levels, subjects will be randomized to receive the treatment or placebo.	Drug: Placebo; placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of subjects with dose-limiting toxicity (DLTs)	TEAEs will be categorized as per the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria. a DLT is defined as one subject with a Grade 3 AE or higher, that are assessed as drug-related by the site investigator.	6-months after dosing
Incidence of adverse events (AEs)	An AE is defined as any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.	6-months after dosing
Incidence of severe adverse events (SAEs)	Any untoward medical occurrence that at any dose: Results in death,; Is life-threatening,; Requires inpatient hospitalization or prolongation of existing hospitalization,; Results in persistent or significant disability/incapacity, or; Is a congenital anomaly/birth defect. (ICH E6 (R2))	6-months after dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK parameters - tmax	time to reach maximum of concentration (days)	6-months after dosing
PK parameters-Cmax	peak plasma concentration	6-months after dosing
PK parameters - AUC0-t	Area under the plasma concentration versus time curve to the last visit (AUCt)	6-months after dosing
PK parameters - t1/2	terminal elimination half-life	6-months after dosing
PD endpoints-free C5	maximal change from baseline in free C5 concentrations at each of scheduled post baseline assessment time-points (µg/ml);	6-months after dosing
PD endpoints-CH50	maximal change from baseline total complement activity (CH50) at each of scheduled post baseline assessment time-points (%);	6-months after dosing
PD endpoints-total C5	meausure the absolute change from baseline in total C5 concentrations at each of scheduled post baseline assessment time-points (µg/ml);	6-months after dosing
Immunogenicity	Anti-drug Antibody (ADA) titers	6-months after dosing

Collaborators and Investigators

• Sponsor: CARE Pharma Shanghai Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2021
• Primary Completion (Actual): November 30, 2021
• Study Completion (Actual): November 30, 2021

Study Registration Dates

• First Submitted: September 22, 2021
• First Submitted That Met QC Criteria: October 14, 2021
• First Posted (Actual): October 27, 2021

Study Record Updates

• Last Update Posted (Actual): May 25, 2022
• Last Update Submitted That Met QC Criteria: May 19, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: CAN106-HV-101

Drug and device information, study documents

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