A Randomized, Double-blind and Placebo-controlled Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of KN056 in Healthy Participants
Overview
- Phase
- Phase 1
- Intervention
- KN056 (0.3mg)
- Conditions
- Type 2 Diabetes
- Sponsor
- Suzhou Alphamab Co., Ltd.
- Enrollment
- 46
- Locations
- 1
- Primary Endpoint
- Number of treatment-emergent adverse events (TEAEs) and treatment related (TRAEs). TEAEs will be measured as per the Common Terminology Criteria for Adverse Events (CTCAE) v 5.0.
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a Phase 1, First-in-human, double-blinded, placebo-controlled study which aims to investigate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and the immunogenicity of KN056 in healthy participants.
Detailed Description
KN056 is a biological innovative drug developed as a treatment for type 2 diabetes. It is a recombinant human Fc-fused GLP-1 variant protein. GLP-1 can activate the intracellular pathway to cause the elevation of cAMP, thereby promoting insulin secretion and inhibiting glucagon secretion. The study will involve a single ascending (increasing) dose (SAD) study and will enroll up to 46 healthy participants across 7 dosing groups. Cohort 1 - 0.1mg (2 participants, both receiving KN056 separated by at least 1 day) Cohort 2 - 0.3mg (4 participants, dosed as 2 +2, separated by a safety observation of at least 3 days) Cohort 3 - 1.0mg (6 participants receiving KN056 + 2 receiving placebo) Cohort 4 - 3.0mg (6 participants receiving KN056 + 2 receiving placebo) Cohort 5 - 6.0mg (6 participants receiving KN056 + 2 receiving placebo) Cohort 6 - 12.0mg (6 participants receiving KN056 + 2 receiving placebo) Cohort 7 - 18.0mg (6 participants receiving KN056 + 2 receiving placebo) In Cohort 3 to 6; the first 2 subjects will be as sentries, and will be injected with KN056 or placebo randomly: at least 3 days after 2 sentries' administration, the remaining 6 participants will be randomized to receive KN056 or placebo in a 5:1 ratio. Additional dose group: the number and randomization of Cohort 7 participants are identical to those in Cohort 3 to Cohort 6. The dose will be given as a subcutaneous (SC) injection into the abdomen.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy male or female subjects (not be breastfeeding);
- •Aged between 18 and 55 (including thresholds) at the time of signing Informed Consent Form;
- •Body mass index (BMI) between 18.5 and 35.0 kg/m2 (excluding the threshold);
- •3.5mmol/L(63 mg/dL) less than or equal to Fasting blood glucose level less than 6.1mmol/L(110 mg/dL).
- •Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures and are willing to follow study restrictions;
- •Are able and willing to sign the ICF.
Exclusion Criteria
- •Those who have a history of chronic diseases or are currently suffering from obvious systemic diseases, such as diseases of cardiovascular system, respiratory system, endocrine and metabolic system, urinary system, digestive system, blood system, autoimmune system, neurological or psychiatric system, bacterial or viral infection;
- •History or presence of pancreatitis (history of chronic pancreatitis or idiopathic acute pancreatitis)
- •History of GI disorder (for example, relevant esophageal reflux or gall bladder disease) or any GI disease which impacts gastric emptying (for example, gastric bypass surgery, pyloric stenosis, with the exception of appendectomy) or could be aggravated by GLP-1 analogs or DPP-IV inhibitors;
- •Participants with dyslipidemia (Total Cholesterol more than 6mmol/L and/or Triglyceride more than or equal to 1.7 mmol/L);
- •Participants had cholecystolithiasis (removal of gallstones) and/or cholecystectomy (removal of gall bladder) in the past;
- •A personal or family history of medullary thyroid cancer or multiple endocrine adenoma syndrome type 2 (MEN2);
- •Allergies to GLP-1 analogues, or KN056 related compounds;
- •A history of medicine abuse/dependence or narcotics abuse within 1 year prior to the screening and/or show positive findings on urinary drug screening;
- •Previous alcoholism or have regular alcohol consumption (drinking more than 14 units of alcohol per week in the 3 months prior to the screening, are unwilling to stop alcohol consumption from at least 48 hours before landing in Phase I ward (D-2) to the end of discharge from the clinical research unit (CRU), or are unwilling to limit intake to a maximum of 2 units per day on all other days from screening through follow-up (1 unit =12oz or 360 mL of beer; 5oz or 150 mL of wine; 1.5oz or 45 mL of distilled spirits);
- •Smokers who have smoked more than 10 cigarettes or equivalent in nicotine (e-cigarettes/vaping) daily within 3 months prior to screening or are unwilling to refrain from smoking on the day of drug administration or are unable to abide by clinical research unit (CRU) restrictions;
Arms & Interventions
Cohort 2
Participant will receive 0.3mg of single dose by subcutaneous injection of KN056
Intervention: KN056 (0.3mg)
Cohort 1
Participant will receive 0.1mg of single dose by subcutaneous injection of KN056
Intervention: KN056 (0.1mg)
Cohort 3
Participant will receive 1.0mg of single dose by subcutaneous injection of KN056 or placebo
Intervention: KN056 (1.0mg)
Cohort 4
Participant will receive 3.0mg single subcutaneous dose of KN056 or placebo
Intervention: KN056 (3.0mg)
Cohort 5
Participant will receive 6.0mg of single dose by subcutaneous injection of KN056 or placebo
Intervention: KN056 (6.0mg)
Cohort 6
Participant will receive 12.0mg of single dose by subcutaneous injection of KN056 or placebo
Intervention: KN056 (12.0mg)
Cohort 7
Participant will receive 18.0mg of single dose by subcutaneous injection of KN056 or placebo
Intervention: KN056 (18.0mg)
Outcomes
Primary Outcomes
Number of treatment-emergent adverse events (TEAEs) and treatment related (TRAEs). TEAEs will be measured as per the Common Terminology Criteria for Adverse Events (CTCAE) v 5.0.
Time Frame: Up to 45 days
Severity of TEAEs and treatment related TEAEs. TEAEs will be measured as per the Common Terminology Criteria for (CTCAE) v5.0
Time Frame: Up to 45 days
Number of participants with abnormal clinically significant vital signs.
Time Frame: Up to 45 days
Vital signs include Includes blood pressure (systolic and diastolic), respiration, temperature and pulse.
Number of participants with abnormal clinically significant electrocardiogram (ECG)
Time Frame: Up to 45 days
12-lead ECG will be performed.
Number of participants with abnormal clinically significant laboratory results.
Time Frame: Up to 45 days
Clinical laboratory includes hematology, biochemistry, lipase, calcitonin, thyroid function, Abdominal and thyroid B-ultrasonography, and urinalysis.
Secondary Outcomes
- The efficacy of KN056 by analyzing fasting blood glucose(Up to 45 days)
- The efficacy of KN056 through Oral Glucose Tolerance test (OGTT)(Up to 45 days)
- The efficacy of KN056 by analyzing HbA1c (Glycosylated hemoglobin) changes(Up to 45 days)
- To evaluate the pharmacokinetic parameters of KN056. Pharmacokinetic parameters will be estimated using non-compartment model analysis with Phoenix WinNolin 8.0(Day 1, Day 7, Day 14, Day 21, Day 28, Day 42)
- Immunogenicity of KN056(Up to 45 days)