Clinical trial NCT05349968: Pharmacokinetics and Efficacy of Multiple Dosing of Lipovirtide for Injection in HIV-infected Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Lead sponsor: Shanxi Kangbao Biological Product Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
First posted: 2022-04-27
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Primary Objectives

1.Evaluation of safety and tolerability after repeated administration of injectable Lipivirtide in HIV-infected patients not receiving antiretroviral therapy

Secondary Objectives

1. Evaluation of the pharmacokinetic properties of injectable Lipovirtide after multiple administrations in HIV-infected patients not receiving antiretroviral therapy, to obtain pharmacokinetic parameters.
2. Evaluation of the efficacy of injectable Lipovirtide for HIV in HIV-infected patients not receiving antiretroviral therapy.
3. Evaluation of the immunogenicity of lipovirtide for injection.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. 18\~60 years old (including the critical value), male and female are not limited.
2. 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.
3. Diagnosed with HIV-1 infection.
4. 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.
5. 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

1. 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.
2. Patients who have received antiviral therapy and/or HIV vaccination;
3. HBsAg of (+), and/or anti-HCV of (+);
4. Abnormal liver function (ALT/AST\>3XULN, or TBIL\>2XULN);
5. Creatinine clearance\<70mL/min (Equation of calculation: Cockcroft-Gault)
6. Existing severe chronic disease, metabolic disease (such as diabetes), neurological and psychiatric disease;
7. History of pancreatitis;
8. Regnant, lactating women and women of childbearing age who cannot use contraception as required;
9. People with allergies or known allergies to the ingredients of this medicine;
10. People with a history of smoking within 12 months before screening (the average number of cigarettes smoked per day is 35.);
11. 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;
12. People with have a history of drug abuse within 12 months before screening or those who tested positive for addictive substances before enrollment;
13. Participated in other drug trials within 3 months before screening;
14. The investigator believes that the subject has other conditions that are not suitable for participating in the trial.

Primary outcomes:
measure: Changes from baseline in respiration rate of Vital Signs.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in Blood lactate of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in Pregnancy test of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in Drug resistance test of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in Immunogenic blood collection of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in blood pressure of Vital Signs.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in body temperature of Vital Signs.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in red blood cell count of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in white blood cell count of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in neutrophil count of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in lymphocyte count of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in platelet count of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in hemoglobin of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in PT of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in INR of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in APTT of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in total bilirubin of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in direct bilirubin of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in ALT of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in AST of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in total protein of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in albumin of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in total bile acid of Laboratory Examination
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in urea of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in creatinine of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in uric acid of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in glucose of Laboratory Examination
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in potassium of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in sodium of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in chlorine of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in urine specific gravity of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in urine pH of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in urine glucose of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in urine protein of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in urine ketone body of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in urine white blood cell of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in urine bilirubin of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in urine occult blood of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in Electrocardiogram.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in CK of Laboratory Examination
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in CK-MB of Laboratory Examination
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in LDH of Laboratory Examination
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in ALP of Laboratory Examination
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in Triglyceride of Laboratory Examination
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in CHOL of Laboratory Examination
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in TP of Laboratory Examination
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in ALB of Laboratory Examination
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in UA of Laboratory Examination
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in GLU of Laboratory Examination
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in AMY of Laboratory Examination
timeFrame: Within 50 days after the first administration.
Secondary outcomes:
measure: Changes from baseline in HIV viral load detection of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Changes from baseline in CD4+T cell counts of Laboratory Examination.
timeFrame: Within 50 days after the first administration.
measure: Incidence of anti-Lipovetin antibody.
timeFrame: Within 50 days after the first administration.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing You'an Hospital, Beijing Medical University
Study officials:
affiliation: Beijing You'an Hospital, Beijing Medical University
name: Haibin Yu
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing You'an Hospital, Beijing Medical University
name: Hao Wu
role: PRINCIPAL_INVESTIGATOR
References: