Clinical trial NCT03366688: Single Ascending Dose Study of PCSK-9 Inhibitor (IBI306) in Healthy Subjects.
Official title: A Randomized, Double Blind, Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics/Pharmacodynamics of IBI306 in Healthy Subjects.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypercholesterolemia
Lead sponsor: Innovent Biologics (Suzhou) Co. Ltd.
Sponsor class: INDUSTRY
First posted: 2017-12-08
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: IBI306 is a fully human monoclonal antibody that binds proprotein convertase substilisin/kexin type 9 (PCSK9), preventing its interaction with the low-density lipoprotein cholesterol receptor (LDL-R) and thereby restoring LDL-R recycling and low-density lipoprotein cholesterol（LDL-C）uptake. This is a randomized, double-blind, placebo-controlled,single ascending dose study to evaluate the safety, tolerability, pharmacokinetics/pharmacodynamics and immunogenicity of IBI306 in healthy adults.

Detailed description: Ascending dose design includes 6 dose levels （25 mg, 75 mg, 150 mg, 300 mg, 450 mg and 600 mg). Tolerance and safety data up to 14 days after dosing from all subjects of the previous cohort will be reviewed before proceeding to the next dose. Total duration of the study per subject is 12 weeks.

Eligibility criteria: Inclusion Criteria:

* Chinese healthy men or women aged 18 to 55 years old at screening (inclusive）;
* Serum LDL-C concentration between 1.8 mmol/L and 4.9 mmol/L (inclusive）at screening;
* Body mass index between 19 and 28 kg/m2 (inclusive);
* Willing to maintain the current regular diet and physical activity;
* Female subjects and male subject's partner who could become pregnant should take effective contraceptions during the treatment period and 6 months after dosing;
* Without any medical history of serious diseases;
* Willing to comply with protocol required visit schedule and visit requirements and provide written informed consent.

Exclusion Criteria:

* Breast-feeding or pregnant women;
* History of allergic reaction;
* Previously received any anti-PCSK-9 treatment;
* Vital signs, physical examination, clinical laboratory test, 12-lead ECG, and chest X-ray are abnormal with clinical significance;
* Not willing to stop intense physical activities (such as weight lifting or long-distance running) before 72 hours of the scheduled visits;
* Any hospitalization within one month before screening, or major surgery within six months before screening, or any other unstable medical condition;
* Received an investigational chemical agent within 30 days before dosing；
* Received an investigational biological agent within 90 days before dosing；
* Use of medications including over-the-counter medication within 14 days or less than 5 half-lifes of the agent;
* Use of herb,vitamins or nutraceutical in order to alter serum lipids;
* Positive screen of hepatitis B surface antigen, hepatitis C virus, human immunodeficiency virus or syphilis infection at screening；
* History or clinical evidence of alcohol or drugs of abuse within 12 months before screening;
* With any consumption of alcohol and caffeinated beverages within 72 hours prior to and during the trial;
* Blood donations or blood loss 200 ml and more within 2 months before screening;
* History of organ transplantation or malignant tumor;
* Any conditions which, in the opinion of the Investigator, would make the subject unsuitable for enrollment.

Primary outcomes:
measure: Number of participants with adverse events（AEs) as assessed by the criteria of National Institute on Aging
timeFrame: up to 12 weeks
Secondary outcomes:
measure: The area under the curve (AUC) of serum concentration of the drug after the administration
timeFrame: up to 12 weeks
measure: Maximum concentration (Cmax) of the drug after the administration
timeFrame: up to 12 weeks
measure: Time at which maximum concentration (Tmax) occurs for the drug after the administration
timeFrame: up to 12 weeks
measure: The half-life (t1/2) of drug after the administration
timeFrame: up to 12 weeks
measure: Assessment of serum concentrations of PCSK-9
timeFrame: up to 12 weeks
measure: Change from baseline in lipid parameters
timeFrame: up to 12 weeks
measure: Number of participants with anti-drug antibodies or neutralizing antibodies
timeFrame: up to 12 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University First Hospital
Study officials:
References: