A Clinical Trial of STP0404 in Treatment-Naïve Adults With HIV-1 Infection

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the antiviral effect, safety, tolerability, and pharmacokinetics of STP0404 in treatment naïve adult participants living with Human Immunodeficiency Virus Type 1 (HIV-1) infection.

Official Title
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A Phase 2a, Randomized, Double-Blinded, Placebo-Controlled, Multicenter Study to Investigate the Antiviral Effect, Safety, Tolerability, and Pharmacokinetics of STP0404 in Treatment-Naïve Adults With HIV-1 Infection

Conditions
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HIV-1-infection

Intervention / Treatment
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* Drug: Low-dose STP0404 (Pirmitegravir)
* Drug: Medium-dose STP0404 (Pirmitegravir)
* Drug: High-dose STP0404 (Pirmitegravir)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a confirmed HIV-1 infection in the documented medical record or at screening Have never received antiretroviral therapy (ART) after diagnosis of HIV-1 infection; Participants with a history of PrEP or PEP therapy are eligible for inclusion (except for monoclonal antibodies, maturation inhibitors, and INSTIs, such as cabotegravir) if they have discontinued therapy at least 8 weeks prior to screening Exclusion Criteria: Have a hepatitis B surface antigen or positive hepatitis C virus antibody at screening. An HCV confirmation (HCV RNA test) will be performed at a central laboratory if the HCV antibodies screening result is positive. If the HCV RNA test result is negative, the participant will be eligible. Have a positive drug screen for amphetamines, barbiturates, cocaine, opiates, benzodiazepines, heroin, or phencyclidine Have a history of regular alcohol consumption, defined as an average weekly intake of more than14 drinks (for males) or more than 7 drinks (for females), within 6 months of screening Have received the following antiretrovirals (ARVs): monoclonal antibodies, maturation inhibitors, and INSTIs (such as cabotegravir) used as PEP or PrEP Pregnant or lactating females Have a history of clinically relevant pancreatitis or hepatitis within the previous 6 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 STP0404<br> | Drug: Low-dose STP0404 (Pirmitegravir)<br>* Once daily, oral capsule taken after breakfast<br>|
| Placebo Comparator: Cohort 1<br> | Drug: Placebo<br>* Matching placebo capsule, taken orally once daily after breakfast<br>|
| Experimental: Cohort 2 STP0404<br> | Drug: Medium-dose STP0404 (Pirmitegravir)<br>* Once daily, oral capsule taken after breakfast<br>|
| Placebo Comparator: Cohort 2<br> | Drug: Placebo<br>* Matching placebo capsule, taken orally once daily after breakfast<br>|
| Experimental: Cohort 3 STP0404<br> | Drug: High-dose STP0404 (Pirmitegravir)<br>* Once daily, oral capsule taken after breakfast<br>|
| Placebo Comparator: Cohort 3<br> | Drug: Placebo<br>* Matching placebo capsule, taken orally once daily after breakfast<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HIV-1 RNA copies change in plasma | Ratio of change in plasma HIV-1 RNA from baseline to Day 11 following a 10-day treatment period at each dose level. | Day 1, Day 11 | 
| Total Number of Adverse Events (AEs) occurring through Day 11 | Cumulative number of AEs occurring from Day 1 through Day 11 at each dose level and placebo in treatment-naïve adults with HIV-1 infection, regardless of treatment discontinuation, and use of prohibited medications. The severity of the AE will be rated as per the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events Corrected Version 2.1, July 2017. These will be descriptively summarized. | Through day 11 | 
| Total Number of Serious Adverse Events (SAEs) occurring through Day 11 | Cumulative number of SAEs occurring from Day 1 through Day 11 at each dose level and placebo in treatment-naïve adults with HIV-1 infection, regardless of treatment discontinuation, use of prohibited medications, and death are included in the endpoint. These will be descriptively summarized. | Through day 11 | 
| Mean area under the concentration-time curve from zero to 24 hours (AUC0-24h) |  | Day 1, Day 10 | 
| Mean observed maximum concentration after administration (Cmax) |  | Day 1, Day 10 | 
| Mean time to reach Cmax (Tmax) |  | Day 1, Day 10 | 
| Mean observed concentration at 24 hours after administration (C24h) |  | Day 2, Day 4, Day 7, Day10, Day 11 | 
| Mean area under the concentration-time curve to infinite time (AUCinf) |  | Day 10 | 
| Mean area under the concentration-time curve to time t (AUCt) |  | Day 10 | 
| Mean terminal half-life (t1/2) |  | Day 10 | 
| Mean apparent oral clearance (CL/F) |  | Day 10 | 
| Mean apparent volume of distribution (Vd/F) |  | Day 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HIV-1 RNA copies change in plasma from baseline to post-dose timepoints |  | Day 1, Day 2, Day 4, Day 7, Day 10, Day 11 | 
| HIV-1 RNA change in plasma from baseline to nadir over 11 days. |  | Day 1 pre-dose, Day 11 | 
| Plasma HIV-1 RNA rate of decline over 11 days |  | Day 1, Day 2, Day 4, Day 7, Day 10, Day 11 | 
| Number of participants with HIV-1 RNA <400 copies/mL | descriptive statistics. | Day 1, Day 2, Day 4, Day 7, Day 10, Day 11 | 
| Number of participants with HIV-1 RNA <50 copies/mL |  | Day 1, Day 2, Day 4, Day 7, Day 10, Day 11 | 
| CD4+ cell count change |  | Day 1, Day 11 | 
| STP0404 exposure-efficacy relationship in plasma HIV-1 RNA copies / CD4+ cell count |  | Day 1, Day 11 | 
| Emergence of drug resistance mutations. |  | Screening, Day 1, Day 4, Day 7, Day 11 |