pharmacokinetics and efficacy of multiple dosing of lp-98 for injection in hiv-infected patients

Conditions: Hiv

Summary: a randomized, double-blind, parallel-group, exploratory clinical study to evaluate the safety, pharmacodynamic effects, and pharmacokinetic characteristics of multiple subcutaneous injections of lp-98 in treatment-naive hiv-infected individuals

this is a randomized, double-blind, parallelize-designed, multicenter, exploratory clinical study to evaluate the safety, pd, and pk profile of multiple subcutaneous injections of lp-98 in hiv-infected individuals who have not received antiviral therapy. this study consisted of 4 cohorts with 10 subjects in each group, who were randomly assigned to receive lp-98 treatment of 1.25 mg, 2.5 mg, 5 mg, and 10 mg. the method of administration was subcutaneous injection, and the interval of administration was 14 days, a total of 4 doses. the study included screening period (d-28\~d-1), treatment period (d1-d57), and follow-up period (d58\~d71).

Eligibility criteria:
inclusion criteria: 1. voluntarily participate in the study and obtain informed consent prior to any study-related evaluation; 2. aged 18-65 years at the time of the screening visit (including the cut-off), male or female; 3. at the time of screening visit, the weight of male subjects is not less than 50 kg and that of female subjects is not less than 45 kg; 4. plasma hiv rna level ≥1000 copies /ml, cd4+t lymphocyte count ≥200 /μl; 5. for female subjects: only subjects with no reproductive potential were included, including surgical sterilization at least 6 weeks prior to the screening visit (documented hysterectomy or bilateral oopectomies), and menopause ≥12 months prior to the screening visit (menopause confirmed by follicle stimulating hormone (fsh) level ≥40iu/l); 6. for male subjects with fertile female partners, consent must be given to the use of non-drug contraception for 14 days prior to dosing, during the study period, and for 3 months after dosing. male subjects are not allowed to donate sperm during this period; 7. be willing to comply with visits, study treatments, laboratory tests, and other study-related procedures and requirements as specified in the study protocol. exclusion criteria: 1. is allergic to the investigational drug product or its excipients, or has a history of severe allergy (including any food allergy or drug allergy); 2. have received antiviral therapy (art), or been vaccinated against hiv; 3. have a history of serious illness or other serious chronic diseases; 4. have a history of mental illness, or have a family history of mental illness; 5. any of the following conditions exist: i. unexplained persistent irregular fever above 38 °c within 1 month before or during the screening period; ii. persistent diarrhea (more than 3 stools/day) within 1 month before or during the screening period; iii. severe infection, opportunistic infection, or sepsis in the 6 months prior to or during the screening period; 6. hepatitis b surface antigen (hbsag) positive, or hepatitis c antibody (hcv-ab) positive; 7. the 12-lead ecg was abnormal and clinically significant during screening, such as qtcf interval (fridericia correction) \> 450 ms in male and \> 470 ms in female; 8. alanine aminotransferase (alt), aspartate aminotransferase (ast) \> 1.5 times uln, or total bilirubin \> 1.5 times uln during screening; 9. serum creatinine clearance (ccr) at screening was \< 60 ml/min (calculated according to cockcroft-gault formula); 10. a known or suspected history of drug abuse (morphine, methamphetamine, ketamine, dimethylene dioxyamphetamine, thc, cocaine), or a positive baseline drug screening test; 11. heavy drinking in the year before screening (drinking more than 14 standard units per week, 1 standard unit containing 14 g of alcohol, such as 5% beer 360 ml, 40% spirits 45 ml, 12% wine 120 ml); or fail to comply with the no-alcohol policy for the duration of the study; 12. smoking more than 5 cigarettes per day in the 3 months prior to screening, or failing to comply with the no-smoking policy during the study period; 13. have received any vaccine in the three months prior to screening, or plan to receive any vaccine during the study period; 14. received any investigational drug therapy or participated in any drug/investigational device trial within 3 months prior to dosing; 15. had undergone a major surgical procedure within 30 days prior to dosing or planned to undergo a major surgical procedure during the study period; 16. those who have donated blood or lost blood ≥ 400 ml or received blood transfusion within 3 months before screening; 17. there are other circumstances that are not suitable for participation in this study.

Keywords: lp-98 double-blind treatment-naive hiv-infected individuals