Pharmacokinetics and Efficacy of Multiple Dosing of Lipovirtide for Injection in HIV-infected Patients

Study Overview
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Brief Summary
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Primary Objectives 1.Evaluation of safety and tolerability after repeated administration of injectable Lipivirtide in HIV-infected patients not receiving antiretroviral therapy Secondary Objectives Evaluation of the pharmacokinetic properties of injectable Lipovirtide after multiple administrations in HIV-infected patients not receiving antiretroviral therapy, to obtain pharmacokinetic parameters. Evaluation of the efficacy of injectable Lipovirtide for HIV in HIV-infected patients not receiving antiretroviral therapy. Evaluation of the immunogenicity of lipovirtide for injection.

Detailed Description
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PK parameters were calculated by Phoenix WinNonlin 8.2 (or higher) and other data were analyzed using SAS 9.4 (or higher) software. Full analysis set: will be used for efficacy analysis. Descriptive statistics of HIV viral load and CD4+ T-cell count at each time point, calculation of subject means, standard deviations, quartiles, minimum and maximum values, and comparison of changes from baseline at each time point. Safety analysis set: calculation of the incidence of adverse events and systematic categorization. Calculate the incidence of adverse events and systematically categorize them. Cross tabulation of clinical determination before and after drug administration for laboratory tests, ECG tests, and physical examination. Changes in measured values of vital signs over time. The actual measured values of the vital signs varied over time. Immunogenicity analysis: statistics of the results of each indicators (including the positive incidence and titer) over time, and a detailed list of the results of each visit. Pharmacokinetic analysis: individual and mean c-t curves were plotted; mean, standard deviation, interquartile, maximum, minimum and coefficient of variation of blood concentrations at each time point were listed. Pharmacokinetic parameters were calculated for each subject from the non-compartment model. and the arithmetic mean, standard deviation, quartiles, maximum value, minimum value and geometric mean and coefficient of variation were also calculated for each parameter.

Official Title
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A Clinical Study to Evaluate the Safety, Pharmacokinetics and Efficacy of Multiple Dosing of Lipovirtide for Injection in HIV-infected Patients Who Have Not Received Antiretroviral Therapy

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Lipovirtide for injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 60 years old (including the critical value), male and female are not limited. Body mass index BMI [weight (kg)/height2 (m2)] is 18.0 28.0 (including the critical value), male weight should be ≥50kg, female weight should be ≥45kg. Diagnosed with HIV-1 infection. Those who did not plan to have children within 2 weeks prior to screening and within 3 months after the end of the trial and who agreed to use effective non-pharmacological contraception during the trial. Subjects should fully understand the purpose, nature and methods of the test and the possible adverse effects and voluntarily participate in this test. Exclusion Criteria: Subjects meeting any of the following criteria will not be allowed to enter the trial The presence of any of the following 1）Unexplained persistent irregular fever of 38°C or more for >1 month. 2）Diarrhea (stools more than 3 times/day), >1 month. 3）Weight loss of 10% or more within 6 months. 4）Recurrent oral fungal infections. 5）Recurrent herpes simplex virus infection or herpes zoster virus infection. 6）Pneumocystis carinii pneumonia (PCP). 7）Recurrent bacterial pneumonia. 8）Active tuberculosis or non-tuberculous mycobacteriosis. 9）Deep fungal infection. 10）Occupational lesions of the central nervous system. 11）Dementia in young and middle-aged adults. 12）Active cytomegalovirus (CMV) infection. 13）Toxoplasma encephalopathy. 14）Malnefield basket disease. 15）Recurrent sepsis. 16）Kaposi's sarcoma, lymphoma. Patients who have received antiviral therapy and/or HIV vaccination; HBsAg of (+), and/or anti-HCV of (+); Abnormal liver function (ALT/AST>3XULN, or TBIL>2XULN); Creatinine clearance<70mL/min (Equation of calculation: Cockcroft-Gault) Existing severe chronic disease, metabolic disease (such as diabetes), neurological and psychiatric disease; History of pancreatitis; Regnant, lactating women and women of childbearing age who cannot use contraception as required; People with allergies or known allergies to the ingredients of this medicine; People with a history of smoking within 12 months before screening (the average number of cigarettes smoked per day is 35.); People with a history of alcoholism within 12 months before screening(Drink N14 units of alcohol per week on average: 1 unit = 285mL of beer, or 25mL of spirits, or 150mL of wine) or positive alcohol breath test before enrollment; People with have a history of drug abuse within 12 months before screening or those who tested positive for addictive substances before enrollment; Participated in other drug trials within 3 months before screening; The investigator believes that the subject has other conditions that are not suitable for participating in the trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose 5 mg<br>Injected subcutaneously at room temperature into the abdomen (moles, scar tissue, bruises or areas other than the navel) and administered once a week for 4 weeks, with no more than 2.0 mL volume administered to a single site. | Drug: Lipovirtide for injection<br>* Multiple dosing of Lipovirtide<br>* Other names: nothing;|
| Experimental: Dose 20 mg<br>Injected subcutaneously at room temperature into the abdomen (moles, scar tissue, bruises or areas other than the navel) and administered once a week for 4 weeks, with no more than 2.0 mL volume administered to a single site. | Drug: Lipovirtide for injection<br>* Multiple dosing of Lipovirtide<br>* Other names: nothing;|
| Experimental: Dose 40 mg<br>Injected subcutaneously at room temperature into the abdomen (moles, scar tissue, bruises or areas other than the navel) and administered once a week for 4 weeks, with no more than 2.0 mL volume administered to a single site. | Drug: Lipovirtide for injection<br>* Multiple dosing of Lipovirtide<br>* Other names: nothing;|

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 50 days after the first administration. | 
| Changes from baseline in Blood lactate of Laboratory Examination. | Changes of blood lactate will be recorded. | Within 50 days after the first administration. | 
| Changes from baseline in Pregnancy test of Laboratory Examination. | Pregnancy test will be tested in female subjects. | Within 50 days after the first administration. | 
| Changes from baseline in Drug resistance test of Laboratory Examination. | Changes of drug resistance test will be recorded.Evaluate the proportion of HIV resistance in subjects. | Within 50 days after the first administration. | 
| 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 50 days after the first administration. | 
| Changes from baseline in blood pressure of Vital Signs. | Blood pressure in mmHg | Within 50 days after the first administration. | 
| Changes from baseline in body temperature of Vital Signs. | Body temperature in Celsius degree | Within 50 days after the first 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 50 days after the first 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 50 days after the first administration. | 
| Changes from baseline in neutrophil count of Laboratory Examination. | Neutrophil count in whole blood is reported in the form of number. | Within 50 days after the first administration. | 
| Changes from baseline in lymphocyte count of Laboratory Examination. | Lymphocyte count in whole blood is reported in the form of number. | Within 50 days after the first administration. | 
| Changes from baseline in platelet count of Laboratory Examination. | Platelet count in whole blood is reported in the form of number. | Within 50 days after the first administration. | 
| Changes from baseline in hemoglobin of Laboratory Examination. | Changes of hemoglobin concentration（g/dL）in whole blood will be recorded. | Within 50 days after the first administration. | 
| Changes from baseline in PT of Laboratory Examination. | Prothrombin time (PT) is a screening test for exogenous coagulation factors. | Within 50 days after the first 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 50 days after the first administration. | 
| Changes from baseline in APTT of Laboratory Examination. | Activated partial thromboplastin time (APTT) is a screening test for endogenous coagulation factors. | Within 50 days after the first administration. | 
| Changes from baseline in total bilirubin of Laboratory Examination. | Changes of total bilirubin concentration (μmol/L) in serum will be recorded. | Within 50 days after the first administration. | 
| Changes from baseline in direct bilirubin of Laboratory Examination. | Changes of direct bilirubin concentration (μmol/L) in serum will be recorded. | Within 50 days after the first administration. | 
| Changes from baseline in ALT of Laboratory Examination. | Changes of ALT concentration (U/L) in serum will be recorded. | Within 50 days after the first administration. | 
| Changes from baseline in AST of Laboratory Examination. | Changes of AST concentration (U/L) in serum will be recorded. | Within 50 days after the first administration. | 
| Changes from baseline in total protein of Laboratory Examination. | Changes of total protein concentration (g/L) in serum will be recorded. | Within 50 days after the first administration. | 
| Changes from baseline in albumin of Laboratory Examination. | Changes of albumin concentration (g/L) in serum will be recorded. | Within 50 days after the first administration. | 
| Changes from baseline in total bile acid of Laboratory Examination | Changes of total bile acid concentration (μmol/L) in serum will be recorded. | Within 50 days after the first administration. | 
| Changes from baseline in urea of Laboratory Examination. | Changes of urea concentration (mmol/L) in serum will be recorded. | Within 50 days after the first administration. | 
| Changes from baseline in creatinine of Laboratory Examination. | Changes of creatinine concentration (μmol/L) in serum will be recorded. | Within 50 days after the first administration. | 
| Changes from baseline in uric acid of Laboratory Examination. | Changes of uric acid concentration (μmol/L) in serum will be recorded. | Within 50 days after the first administration. | 
| Changes from baseline in glucose of Laboratory Examination | Changes of glucose concentration (mmol/L) in serum will be recorded. | Within 50 days after the first administration. | 
| Changes from baseline in potassium of Laboratory Examination. | Changes of potassium concentration (mmol/L) in serum will be recorded. | Within 50 days after the first administration. | 
| Changes from baseline in sodium of Laboratory Examination. | Changes of sodium concentration (mmol/L) in serum will be recorded. | Within 50 days after the first administration. | 
| Changes from baseline in chlorine of Laboratory Examination. | Changes of chlorine concentration (mmol/L) in serum will be recorded. | Within 50 days after the first administration. | 
| Changes from baseline in urine specific gravity of Laboratory Examination. | Changes of urine specific gravity will be recorded. | Within 50 days after the first administration. | 
| Changes from baseline in urine pH of Laboratory Examination. | Changes of urine pH value will be recorded. | Within 50 days after the first administration. | 
| Changes from baseline in urine glucose of Laboratory Examination. | Changes of urine glucose will be examined by qualitative test (positive or negative). | Within 50 days after the first administration. | 
| Changes from baseline in urine protein of Laboratory Examination. | Changes of urine protein will be examined by qualitative test (positive or negative). | Within 50 days after the first 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 50 days after the first 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 50 days after the first administration. | 
| Changes from baseline in urine bilirubin of Laboratory Examination. | Changes of urine bilirubin will be examined by qualitative test (positive or negative). | Within 50 days after the first 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 50 days after the first administration. | 
| Changes from baseline in Electrocardiogram. | The cardiac rhythm is showed in electrocardiogram in the form of continuous curve. Changes of this continuous curve will be recorded，To evaluate the incidence of abnormal electrocardiogram. | Within 50 days after the first administration. | 
| Changes from baseline in CK of Laboratory Examination | Changes of CK concentration (U/L) in serum will be recorded. | Within 50 days after the first administration. | 
| Changes from baseline in CK-MB of Laboratory Examination | Changes of CK-MB concentration (ng/mL) in serum will be recorded. | Within 50 days after the first administration. | 
| Changes from baseline in LDH of Laboratory Examination | Changes of LDH concentration (U/L) in serum will be recorded. | Within 50 days after the first administration. | 
| Changes from baseline in ALP of Laboratory Examination | Changes of ALP concentration (U/L) in serum will be recorded. | Within 50 days after the first administration. | 
| Changes from baseline in Triglyceride of Laboratory Examination | Changes of Triglyceride concentration (mmol/L) in serum will be recorded. | Within 50 days after the first administration. | 
| Changes from baseline in CHOL of Laboratory Examination | Changes of CHOL concentration (mmol/L) in serum will be recorded. | Within 50 days after the first administration. | 
| Changes from baseline in TP of Laboratory Examination | Changes of TP concentration (g/L) in serum will be recorded. | Within 50 days after the first administration. | 
| Changes from baseline in ALB of Laboratory Examination | Changes of ALB concentration (g/L) in serum will be recorded. | Within 50 days after the first administration. | 
| Changes from baseline in UA of Laboratory Examination | Changes of UA concentration (μmol/L) in serum will be recorded. | Within 50 days after the first administration. | 
| Changes from baseline in GLU of Laboratory Examination | Changes of GLU concentration (mmol/L) in serum will be recorded. | Within 50 days after the first administration. | 
| Changes from baseline in AMY of Laboratory Examination | Changes of AMY concentration (U/L) in serum will be recorded. | Within 50 days after the first administration. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in HIV viral load detection of Laboratory Examination. | Changes of HIV viral load detection will be recorded. | Within 50 days after the first administration. | 
| Changes from baseline in CD4+T cell counts of Laboratory Examination. | Changes of CD4+T cell counts will be recorded. | Within 50 days after the first administration. | 
| Incidence of anti-Lipovetin antibody. | Incidence of anti-Lipovetin antibody. | Within 50 days after the first administration. |