A Multi-center, Randomized, Double-blind, Placebo-controlled Trial, Followed by Single-arm Treatment of PRO 140 in Combination With Optimized Background Therapy in Treatment-Experienced HIV-1 Subjects
Overview
- Phase
- Phase 2
- Intervention
- PRO 140
- Conditions
- HIV
- Sponsor
- CytoDyn, Inc.
- Enrollment
- 52
- Locations
- 3
- Primary Endpoint
- Proportion of Participants With ≥ 0.5 log10 Reduction in HIV-1 RNA Viral Load From Baseline at the End of the 1-week Double-blind Treatment Period
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a Phase 2b/3, multi-center, two part study, designed to evaluate the efficacy, safety, and tolerability of PRO 140 in conjunction with existing ART (failing regimen) for one week and Optimized Background Therapy (OBT) for 24 weeks respectively. Study population includes treatment-experienced HIV-infected patients with CCR5-tropic virus who demonstrates evidence of HIV-1 replication despite ongoing antiretroviral therapy with documented genotypic or phenotypic resistance to ART drugs within three drug classes (or within two or more drug classes with limited treatment options).The options may be limited as a result of drug antiviral class cross-resistance or documented treatment intolerance.
Detailed Description
PRO 140, in combination with other antiretroviral agents, is indicated for treatment experienced adult HIV-1 patients infected with CCR5-tropic virus. These patients must demonstrate evidence of HIV-1 replication despite ongoing antiretroviral therapy and have documented genotypic or phenotypic resistance to at least one ART drug within three drug classes (or within two or more drug classes with limited treatment option). The options may be limited as a result of drug antiviral class cross-resistance, documented treatment intolerance, documented objective assessments such as renal or hepatic insufficiency (e.g. high creatinine at baseline, limiting treatment options due to potential for toxicity), past adverse reactions such as hypersensitivity reactions or neuropsychiatric issues that could limit use of currently approved drugs. Study population includes treatment-experienced HIV-infected patients with CCR5-tropic virus who demonstrates evidence of HIV-1 replication despite ongoing antiretroviral therapy with documented genotypic or phenotypic resistance to ART drugs within three drug classes (or within two drug classes with limited treatment option). Enrollment will be stratified to have HIV-1 virus resistant to ART drugs within three drug classes or within two drug classes with limited treatment option. The primary objective is to assess the efficacy, clinical safety and tolerability parameters of PRO 140 compared to placebo in reducing HIV-1 viral load during the 1-week double-blind treatment period. The secondary objectives of the trial are to assess the efficacy, clinical safety and tolerability parameters of PRO 140 in combination with Optimized Background Therapy during the 24-week single-arm, open-label treatment period.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Males and females, age ≥ 18 years
- •Exclusive CCR5-tropic virus at Screening Visit
- •Have a history of at least 3 months on current antiretroviral regimen
- •Treatment-experienced HIV-infected patients with documented genotypic or phenotypic resistance to at least one ART drug within three drug classes
- •Treatment-experienced HIV-infected patients with documented genotypic or phenotypic resistance to at least one ART drug within two drug classes and have limited treatment options. The options may be limited as a result of drug antiretroviral class cross-resistance or documented treatment intolerance.
- •Be willing to remain on treatment without any changes or additions to the OBT regimen, except for toxicity management or upon meeting criteria for treatment failure.
- •Plasma HIV-1 RNA ≥ 400 copies/mL at Screening Visit and documented detectable viral load (HIV-1 RNA \>50 copies/ml) within the last 3 months prior to Screening Visit.
- •Laboratory values at Screening of:
- •Absolute neutrophil count (ANC) ≥ 750/mm3
- •Hemoglobin (Hb) ≥ 10.5 gm/dL (male) or ≥ 9.5 gm/dL (female)
Exclusion Criteria
- •Documented CXCR4-tropic virus or Dual/Mixed tropic (R5X4) virus
- •Patients with no viable treatment options (≤ 1 fully active drug)
- •Any active infection or malignancy requiring acute therapy (with the exception of local cutaneous Kaposi's sarcoma) Note: Subjects infected by the hepatitis B virus or early stage hepatitis C virus will be eligible for the study.
- •Laboratory test values of ≥ grade 3 DAIDS laboratory abnormality with the exception of the absolute CD4+ count criterion of \< 200/mm3
- •Females who are pregnant, lactating, or breastfeeding, or who plan to become pregnant during the study
- •Unexplained fever or clinically significant illness within 1 week prior to the first study dose
- •Any vaccination within 2 weeks prior to the first study dose.
- •Subjects weighing \< 35kg
- •History of anaphylaxis
- •History of Bleeding Disorder or patients on anti-coagulant therapy
Arms & Interventions
PRO 140
PRO140 350mg weekly SC Inj. + existing ART for one week. After one week, all subjects will enter the 24-week single-arm, open-label treatment period. During this period, all subjects will receive PRO 140 SC injection and Optimized Background Therapy.
Intervention: PRO 140
PRO 140
PRO140 350mg weekly SC Inj. + existing ART for one week. After one week, all subjects will enter the 24-week single-arm, open-label treatment period. During this period, all subjects will receive PRO 140 SC injection and Optimized Background Therapy.
Intervention: Optimized Background Regimen
Placebo
Placebo weekly SC Inj. + existing ART for one week. After one week, all subjects will enter the 24-week single-arm, open-label treatment period. During this period, all subjects will receive PRO 140 SC injection and Optimized Background Therapy.
Intervention: Placebo
Placebo
Placebo weekly SC Inj. + existing ART for one week. After one week, all subjects will enter the 24-week single-arm, open-label treatment period. During this period, all subjects will receive PRO 140 SC injection and Optimized Background Therapy.
Intervention: Optimized Background Regimen
Outcomes
Primary Outcomes
Proportion of Participants With ≥ 0.5 log10 Reduction in HIV-1 RNA Viral Load From Baseline at the End of the 1-week Double-blind Treatment Period
Time Frame: From baseline visit to week 1 visit
The primary efficacy endpoint will be proportion of participants with a 0.5 log10 or greater reduction in HIV-1 RNA viral load from baseline at the end of the one week double-blind treatment period (Part 1).
Secondary Outcomes
- Proportion of Participants With ≥ 0.5 log10 Reduction in HIV-1 RNA Viral Load From Baseline at the End of the 1-week Double-blind Treatment Period, Stratified to Each Group: Resistance to ART Drugs Within Two Drug Class With Limited Treatment Option.(From baseline visit to week 1 visit)
- Proportion of Participants With ≥ 0.5 log10 Reduction in HIV-1 RNA Viral Load From Baseline at the End of the 1-week Double-blind Treatment Period, Stratified to Each Group: Resistance to ART Drugs Within Three Drug Classes(From baseline visit to week 1 visit)
- Mean Change From Baseline in HIV-1 RNA Levels (log10 Copies/mL) at the End of the 1-week Double-blind Treatment Period for All Patients and Within Each Stratum(From baseline visit to week 1 visit)
- Proportion of Participants With ≥ 1 log10 Reduction in HIV-1 RNA Viral Load From Baseline at the End of the 1-week Double-blind Treatment Period for All Patients and Within Each Stratum(From baseline visit to week 1 visit)
- Percentage of Participants Achieving HIV-1 RNA < 400 Copies/mL at Week 25 for All Patients and Within Each Stratum(25 weeks)
- Mean Change From Baseline in CD4 Cell Count at the End of the 1-week Double-blind Treatment Period for All Patients and Within Each Stratum(From baseline visit to week 1 visit)
- Percentage and Number of Participants Achieving HIV-1 RNA < 50 Copies/mL at Week 25 for All Patients and Within Each Stratum(25 weeks)
- Mean Change From Baseline in CD4 Cell Count at Week 25 for All Patients and Within Each Stratum(25 weeks)
- Mean Change From Baseline in HIV-1 RNA Levels (log10 Copies/mL) at Week 25 for All Patients and Within Each Stratum(25 weeks)