Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Immunogenicity of LP-98 Injection in Healthy Subjects

Study Overview
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Brief Summary
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A randomized, placebo-controlled, single-administration, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics and immunogenicity of LP-98 injection in healthy subjects in a first-in-human clinical study

Detailed Description
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The study was divided into two parts, Part A and Part B. The Part A and Part B studies were carried out separately according to the protocol flow, with the Part A study carried out first. Part A is set up with 5 cohorts(5mg, 10mg, 20mg, 40mg, 80mg), administration is by subcutaneous, each subject entered only one cohort to receive the drug. 4 subjects were included in cohort 1, and 8 subjects were planned to be included in each cohort 2 to 5, to observe the safety, tolerability, PK and ADA of LP-98 injection by subcutaneous. Part B is set up with 6 cohorts (5mg,10mg,20mg,40mg,80mg, 160mg), administration is by intravenous drip, each subject entered only one cohort to receive the drug. 4 subjects were included in cohort 1, and 8 subjects were planned to be included in each cohort 2 to 6, to observe the safety, tolerability, PK and ADA of LP-98 injection by intravenous drip.

Official Title
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A Randomized, Placebo-controlled, Single-administration, Dose-escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Immunogenicity of LP-98 Injection in Healthy Subjects in a First-in-human Clinical Study

Conditions
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Hiv

Intervention / Treatment
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* Drug: LP-98 injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must meet all of the following inclusion criteria for study entry: Willing to participate in the study and sign ICF with clear date; Aged 18 to 55 years at the screening visit, male or female; Body weight ≥ 50 kg for males or body weight ≥ 45 kg for females, and body mass index (BMI) within the range of 19 to 28 kg/m2 (inclusive); Be in good health in the PI's judgment, with no clinical significance in previous medical history, laboratory tests, physical examinations, vital signs, and ECG findings; All subjects and his/her partners must agree to use effective non-drug contraception (except for subjects had permanent contraception, i.e., bilateral tubal ligation or vasectomy, etc.) from 2 weeks prior to screening to 3 months after finishing the study. Females must have a negative serum human chorionic gonadotropin (hCG) test for pregnancy confirmation at screening; Willing to comply with the visits, treatments, laboratory tests and other study process required by the protocol. Exclusion Criteria: Allergic to the IP or its excipients, or medicine of the same class , or having a history of severe allergies (including any food allergy or drug allergy); With history or family history of psychiatric, or history of chronic or serious disorders of the central nervous system, cardiovascular, hepatic, nephrological, pulmanory, digestive, metabolic, hematological or skeletal system etc., or definitive history of myelosuppression, orany other significant history of disease that may affect the safety or PK parameters in the PI's judgment; Having positive result for human immunodeficiency virus antibody (HIV-Ab), hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV-Ab), or Treponema pallidum antibody; Having clinically significant abnormal results of vital signs or laboratory tests required by the protocol; Having clinically significant abnormality of 12-lead ECG, or having a QTcF interval (using Fridericia's correction) > 450 ms for males or > 470 ms for females; With serum creatine clearance rate (Ccr) < 80 ml/min/1.73 m2 (based on Cockcroft-Gault formula); Known or suspected history of drug abuse (i.e., morphine, methamphetamine, ketamine, dimethylenedioxymethamphetamine, tetrahydrocannabinol acid, cocaine etc.), or having positive result for drug abuse; With history of heavy alcohol consumption within 1 year prior to screening (more than 21 units of alcohol per week, i.e., 360 ml of 5% beer, 45 ml of 40% hard liquor, 120 ml of 12% wine, or positive alcohol test; Smoking more than 5 cigarettes per day within 3 months prior to screening, or inability to comply with the prohibition of smoking during the study; Consuming amount > 6 servings of coffee, tea, cola, energy-drink, or other caffeine-containing product per day. One serving ≈ 120 mg of caffeine. Or consumed any caffeine-containing product within 24 hours prior to the dosing of the IP; Had received vaccination within 30 days prior to screening, or planning to receive vaccination during the study; Had received any prescription and non-prescription drugs, herbal remedies, or dietary supplements within 14 days prior to the dosing of the IP; Participated in any other clinical trial within 3 months prior to screening; Had received surgical operation within 3 months prior to screening, or planning to receive surgical operation during the study; Currently pregnant or lactating women； Had blood donation or blood loss over 200 mL within 3 months prior to screening, or planning to donate blood during the study； Cannot tolerate venipuncture blood collection and/or have a history of blood or needle sickness Other conditions considered to be ineligible for study entry in the PI's judgment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PartA:Dose level(5mg)<br>Part A is set up with 5 cohorts(5mg, 10mg, 20mg, 40mg, 80mg), administration is by subcutaneous, each subject entered only one cohort to receive the drug. 4 subjects were included in cohort 1, and 8 subjects were planned to be included in each cohort 2 to 5, to observe the safety, tolerability, PK and ADA of LP-98 injection by subcutaneous. | Drug: LP-98 injection<br>* Part A is administration is by subcutaneous LP98/placebo,Part B is administration is by intravenous drip LP98/placebo<br>* Other names: placebo-controlled;|
| Experimental: PartA:Dose level(10mg)<br>Part A is set up with 5 cohorts(5mg, 10mg, 20mg, 40mg, 80mg), administration is by subcutaneous, each subject entered only one cohort to receive the drug. 4 subjects were included in cohort 1, and 8 subjects were planned to be included in each cohort 2 to 5, to observe the safety, tolerability, PK and ADA of LP-98 injection by subcutaneous. | Drug: LP-98 injection<br>* Part A is administration is by subcutaneous LP98/placebo,Part B is administration is by intravenous drip LP98/placebo<br>* Other names: placebo-controlled;|
| Experimental: PartA:Dose level(20mg)<br>Part A is set up with 5 cohorts(5mg, 10mg, 20mg, 40mg, 80mg), administration is by subcutaneous, each subject entered only one cohort to receive the drug. 4 subjects were included in cohort 1, and 8 subjects were planned to be included in each cohort 2 to 5, to observe the safety, tolerability, PK and ADA of LP-98 injection by subcutaneous. | Drug: LP-98 injection<br>* Part A is administration is by subcutaneous LP98/placebo,Part B is administration is by intravenous drip LP98/placebo<br>* Other names: placebo-controlled;|
| Experimental: PartA:Dose level(40mg)<br>Part A is set up with 5 cohorts(5mg, 10mg, 20mg, 40mg, 80mg), administration is by subcutaneous, each subject entered only one cohort to receive the drug. 4 subjects were included in cohort 1, and 8 subjects were planned to be included in each cohort 2 to 5, to observe the safety, tolerability, PK and ADA of LP-98 injection by subcutaneous. | Drug: LP-98 injection<br>* Part A is administration is by subcutaneous LP98/placebo,Part B is administration is by intravenous drip LP98/placebo<br>* Other names: placebo-controlled;|
| Experimental: PartA:Dose level(80mg)<br>Part A is set up with 5 cohorts(5mg, 10mg, 20mg, 40mg, 80mg), administration is by subcutaneous, each subject entered only one cohort to receive the drug. 4 subjects were included in cohort 1, and 8 subjects were planned to be included in each cohort 2 to 5, to observe the safety, tolerability, PK and ADA of LP-98 injection by subcutaneous. | Drug: LP-98 injection<br>* Part A is administration is by subcutaneous LP98/placebo,Part B is administration is by intravenous drip LP98/placebo<br>* Other names: placebo-controlled;|
| Experimental: PartB:Dose level(5mg)<br>Part B is set up with 6 cohorts (5mg,10mg,20mg,40mg,80mg, 160mg), administration is by intravenous drip, each subject entered only one cohort to receive the drug. 4 subjects were included in cohort 1, and 8 subjects were planned to be included in each cohort 2 to 6, to observe the safety, tolerability, PK and ADA of LP-98 injection by intravenous drip. | Drug: LP-98 injection<br>* Part A is administration is by subcutaneous LP98/placebo,Part B is administration is by intravenous drip LP98/placebo<br>* Other names: placebo-controlled;|
| Experimental: PartB:Dose level(10mg)<br>Part B is set up with 6 cohorts (5mg,10mg,20mg,40mg,80mg, 160mg), administration is by intravenous drip, each subject entered only one cohort to receive the drug. 4 subjects were included in cohort 1, and 8 subjects were planned to be included in each cohort 2 to 6, to observe the safety, tolerability, PK and ADA of LP-98 injection by intravenous drip. | Drug: LP-98 injection<br>* Part A is administration is by subcutaneous LP98/placebo,Part B is administration is by intravenous drip LP98/placebo<br>* Other names: placebo-controlled;|
| Experimental: PartB:Dose level(20mg)<br>Part B is set up with 6 cohorts (5mg,10mg,20mg,40mg,80mg, 160mg), administration is by intravenous drip, each subject entered only one cohort to receive the drug. 4 subjects were included in cohort 1, and 8 subjects were planned to be included in each cohort 2 to 6, to observe the safety, tolerability, PK and ADA of LP-98 injection by intravenous drip. | Drug: LP-98 injection<br>* Part A is administration is by subcutaneous LP98/placebo,Part B is administration is by intravenous drip LP98/placebo<br>* Other names: placebo-controlled;|
| Experimental: PartB:Dose level(40mg)<br>Part B is set up with 6 cohorts (5mg,10mg,20mg,40mg,80mg, 160mg), administration is by intravenous drip, each subject entered only one cohort to receive the drug. 4 subjects were included in cohort 1, and 8 subjects were planned to be included in each cohort 2 to 6, to observe the safety, tolerability, PK and ADA of LP-98 injection by intravenous drip. | Drug: LP-98 injection<br>* Part A is administration is by subcutaneous LP98/placebo,Part B is administration is by intravenous drip LP98/placebo<br>* Other names: placebo-controlled;|
| Experimental: PartB:Dose level(80mg)<br>Part B is set up with 6 cohorts (5mg,10mg,20mg,40mg,80mg, 160mg), administration is by intravenous drip, each subject entered only one cohort to receive the drug. 4 subjects were included in cohort 1, and 8 subjects were planned to be included in each cohort 2 to 6, to observe the safety, tolerability, PK and ADA of LP-98 injection by intravenous drip. | Drug: LP-98 injection<br>* Part A is administration is by subcutaneous LP98/placebo,Part B is administration is by intravenous drip LP98/placebo<br>* Other names: placebo-controlled;|
| Experimental: PartB:Dose level(160mg)<br>Part B is set up with 6 cohorts (5mg,10mg,20mg,40mg,80mg, 160mg), administration is by intravenous drip, each subject entered only one cohort to receive the drug. 4 subjects were included in cohort 1, and 8 subjects were planned to be included in each cohort 2 to 6, to observe the safety, tolerability, PK and ADA of LP-98 injection by intravenous drip. | Drug: LP-98 injection<br>* Part A is administration is by subcutaneous LP98/placebo,Part B is administration is by intravenous drip LP98/placebo<br>* Other names: placebo-controlled;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in respiration rate of Vital Signs | Respiration rate in times / minute | Within 36 days after the first administration. | 
| Changes from baseline in blood pressure of Vital Signs. | Blood pressure in mmHg | Within 36 days after the first administration. | 
| Changes from baseline in body temperature of Vital Signs. | Body temperature in Celsius degree | Within 36 days after the first administration. | 
| Changes from baseline in ECG PR intervalThe cardiac rhythm is showed in 12 Leads | Ambulatory Electrocardiogram in the form of continuous curve. Changes of this continuous curve will be recorded. | within 36 days after administration | 
| Changes from baseline in ECG QRS intervalThe cardiac rhythm is showed in 12 Leads | Ambulatory Electrocardiogram in the form of continuous curve. Changes of this continuous curve will be recorded. | within 36 days after administration | 
| Changes from baseline in ECG QT intervalThe cardiac rhythm is showed in 12 Leads | Ambulatory Electrocardiogram in the form of continuous curve. Changes of this continuous curve will be recorded. | within 36 days after administration | 
| Changes from baseline in Blood lactate of Laboratory Examination. | Changes of blood lactate will be recorded. | within 36 days after administration | 
| Changes from baseline in Pregnancy test of Laboratory Examination. | Pregnancy test will be tested in female subjects. | within 36 days after administration | 
| Changes from baseline in red blood cell count of Laboratory Examination. | Red blood cell count in whole blood is reported in the form of number. | within 36 days after administration | 
| Changes from baseline in white blood cell count of Laboratory Examination. | White blood cell count in whole blood is reported in the form of number. | within 36 days after administration | 
| Changes from baseline in neutrophil count of Laboratory Examination. | Neutrophil count in whole blood is reported in the form of number. | within 36 days after administration | 
| Changes from baseline in lymphocyte count of Laboratory Examination. | Lymphocyte count in whole blood is reported in the form of number. | within 36 days after administration | 
| Changes from baseline in platelet count of Laboratory Examination. | Platelet count in whole blood is reported in the form of number. | within 36 days after administration | 
| Changes from baseline in hemoglobin of Laboratory Examination. | Changes of hemoglobin concentration（g/dL）in whole blood will be recorded. | within 36 days after administration | 
| Changes from baseline in PT of Laboratory Examination. | Prothrombin time (PT) is a screening test for exogenous coagulation factors. | within 36 days after administration | 
| Changes from baseline in INR of Laboratory Examination. | International standardized ratio (INR) is calculated from prothrombin time and international sensitivity index (ISI) of the reagent. | within 36 days after administration | 
| Changes from baseline in APTT of Laboratory Examination. | Changes of total bilirubin concentration (μmol/L) in serum will be recorded. | within 36 days after administration | 
| Changes from baseline in direct bilirubin of Laboratory Examination. | Changes of direct bilirubin concentration (μmol/L) in serum will be recorded. | within 36 days after administration | 
| Changes from baseline in ALT of Laboratory Examination. | Changes of ALT concentration (U/L) in serum will be recorded. | within 36 days after administration | 
| Changes from baseline in AST of Laboratory Examination. | Changes of AST concentration (U/L) in serum will be recorded. | within 36 days after administration | 
| Changes from baseline in total protein of Laboratory Examination. | Changes of total protein concentration (g/L) in serum will be recorded. | within 36 days after administration | 
| Changes from baseline in albumin of Laboratory Examination. | Changes of albumin concentration (g/L) in serum will be recorded. | within 36 days after administration | 
| Changes from baseline in creatinine of Laboratory Examination. | Changes of creatinine concentration (μmol/L) in serum will be recorded. | within 36 days after administration | 
| Changes from baseline in glucose of Laboratory Examination | Changes of glucose concentration (mmol/L) in serum will be recorded. | within 36 days after administration | 
| Changes from baseline in potassium of Laboratory Examination. | Changes of potassium concentration (mmol/L) in serum will be recorded. | within 36 days after administration | 
| Changes from baseline in sodium of Laboratory Examination. | Changes of sodium concentration (mmol/L) in serum will be recorded. | within 36 days after administration | 
| Changes from baseline in chlorine of Laboratory Examination. | Changes of chlorine concentration (mmol/L) in serum will be recorded. | within 36 days after administration | 
| Changes from baseline in urine specific gravity of Laboratory Examination. | Changes of urine specific gravity will be recorded. | within 36 days after administration | 
| Changes from baseline in urine pH of Laboratory Examination. | Changes of urine pH value will be recorded. | within 36 days after administration | 
| Changes from baseline in urine glucose of Laboratory Examination. | Changes of urine glucose will be examined by qualitative test (positive or negative). | within 36 days after administration | 
| Changes from baseline in urine protein of Laboratory Examination. | Changes of urine protein will be examined by qualitative test (positive or negative). | within 36 days after administration | 
| Changes from baseline in urine ketone body of Laboratory Examination. | Changes of urine ketone body will be examined by qualitative test (positive or negative). | within 36 days after administration | 
| Changes from baseline in urine white blood cell of Laboratory Examination. | Changes of white blood cell in urine will be examined by qualitative test (positive or negative). | within 36 days after administration | 
| Changes from baseline in urine occult blood of Laboratory Examination. | Changes of urine occult blood will be examined by qualitative test (positive or negative). | within 36 days after administration | 
| Changes from baseline in CK of Laboratory Examination | Changes of CK concentration (U/L) in serum will be recorded. | within 36 days after administration | 
| Changes from baseline in CK-MB of Laboratory Examination | Changes of CK-MB concentration (ng/mL) in serum will be recorded. | within 36 days after administration | 
| Changes from baseline in LDH of Laboratory Examination | Changes of LDH concentration (U/L) in serum will be recorded. | within 36 days after administration | 
| Changes from baseline in ALP of Laboratory Examination | Changes of ALP concentration (U/L) in serum will be recorded. | within 36 days after administration | 
| Changes from baseline in Triglyceride of Laboratory Examination | Changes of Triglyceride concentration (mmol/L) in serum will be recorded. | within 36 days after administration | 
| Changes from baseline in CHOL of Laboratory Examination | Changes of CHOL concentration (mmol/L) in serum will be recorded. | within 36 days after administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in Immunogenic blood collection of Laboratory Examination. | Changes of immunogenic blood collection will be recorded.The historical changes of test results (including positive rate and titer) of various indicators were counted. | within 36 days after administration | 
| Pharmacokinetics：Cmax | pharmacokinetic characteristics of Lipovirtide in infected patients：Cmax | within 36 days after administration | 
| Pharmacokinetics：AUC0-t | pharmacokinetic characteristics of Lipovirtide in infected patients：AUC0-t | within 36 days after administration | 
| Pharmacokinetics：AUC0-∞ | pharmacokinetic characteristics of Lipovirtide in infected patients：AUC0-∞ | within 36 days after administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy Subjects, safety and tolerability, pharmacokinetic (PK), immunogenicity