A Multi-center, Two-Part, Single-Arm, Open Label, 25-Week Trial With PRO 140 in Treatment-Experienced HIV-1 Subjects
Overview
- Phase
- Phase 2
- Intervention
- PRO 140
- Conditions
- HIV-1-infection
- Sponsor
- CytoDyn, Inc.
- Enrollment
- 6
- Locations
- 1
- Primary Endpoint
- Proportion of Participants With ≥ 0.5 log10 Reduction in HIV-1 RNA Viral Load From Baseline at the End of the Initial 1-week Treatment Period
- Status
- Completed
- Last Updated
- 7 months ago
Overview
Brief Summary
The primary objectives of the trial are to assess the efficacy, clinical safety and tolerability parameters of PRO 140 in combination with failing ART (antiretroviral therapy) during the initial one-week treatment period, and in combination with Optimized Background Therapy during the subsequent 24-week treatment period.
Detailed Description
PRO 140, in combination with other antiretroviral agents, is indicated for treatment experienced adult HIV-1 patients infected with CCR5-tropic virus (virus that uses the chemokine receptor type 5 to enter the cell). 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). The primary objectives of the trial are to assess the efficacy, clinical safety and tolerability parameters of PRO 140 in combination with failing ART during the initial one-week treatment period, and in combination with Optimized Background Therapy during the subsequent 24-week treatment period.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Males and females, age ≥18 years
- •Exclusive CCR5-tropic virus at Screening Visit as determined by Monogram Biosciences Trofile® Assay
- •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 OR 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 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.
- •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 as determined by Human Immunodeficiency Virus 1 (HIV-1) Quantitative, RNA (Roche Taqman® Real-Time PCR) 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)
- •Platelets ≥75,000 /mm3
Exclusion Criteria
- •Documented CXCR4-tropic virus or Dual/Mixed tropic (R5X4) virus as determined by HIV-1 tropism assay
- •Patients with no viable treatment options ( i.e., no fully active antiretroviral drug available which can be effectively combined to form a viable new OBT)
- •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 hepatitis C virus will be eligible for the study if they have no signs of hepatic decompensation and meet the liver function tests eligibility criteria
- •Laboratory test values of ≥ grade 3 DAIDS (Division of Acquired Immune Deficiency Syndrome) 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 to oral or parenteral drugs
- •History of Bleeding Disorder or patients on anti-coagulant therapy
Arms & Interventions
Leronlimab (PRO 140)
Subjects will be on existing ART for one week followed by PRO 140 700 mg weekly subcutaneous (SC) Inj. + existing ART for the next week. Subsequently, 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
Outcomes
Primary Outcomes
Proportion of Participants With ≥ 0.5 log10 Reduction in HIV-1 RNA Viral Load From Baseline at the End of the Initial 1-week Treatment Period
Time Frame: 1-week from baseline to the end of the initial PRO 140 and ART treatment period
The primary endpoint for this study is the proportion of participants with a ≥ 0.5 log10 reduction in HIV-1 RNA viral load from baseline to the end of the initial 1-week treatment period.
Secondary Outcomes
- Proportion of Participants With ≥ 1 log10 Reduction in HIV-1 RNA Viral Load From Baseline at the End of the Initial 1-week Treatment Period(1-week from baseline to the end of the initial PRO 140 and ART treatment period)
- Mean Change From Baseline in HIV-1 RNA Levels (log10 Copies/mL) at the End of the Initial 1-week Treatment Period(1-week from baseline to the end of the initial PRO 140 and ART treatment period)
- Percentage of Participants Achieving HIV-1 RNA < 400 Copies/mL at Week 25(25 weeks post-initiation of PRO 140 and existing ART treatment)
- Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Week 25(25 weeks post-initiation of PRO 140 and existing ART treatment)
- Mean Change From Baseline in HIV-1 RNA Levels (log10 Copies/mL)(25 weeks post-initiation of PRO 140 and existing ART treatment)
- Mean Change From Baseline in CD4 Cell Count at the End of the Initial 1-week Treatment Period(1-week post-initiation of PRO 140 and ART treatment.)
- Mean Change From Baseline in CD4 Cell Count at Week 23(23 weeks post-initiation of PRO 140 and existing ART treatment)