Clinical Trials

MainTitle

A Randomized, Double-blind, Placebo-controlled Trial, Followed by Single-arm Treatment of PRO 140 in Combination w/ Optimized Background Therapy in Treatment-Experienced HIV Subjects (PRO 140)

This study has been completed
Sponsor
CytoDyn, Inc.

Collaborator
Amarex Clinical Research

Information provided by (Responsible Party)
CytoDyn, Inc.
ClinicalTrials.gov Identifier
NCT02483078

First received: June 24, 2015
Last updated: April 2, 2019
Last Verified: April 2019
History of Changes
Purpose

Purpose

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.

Condition Intervention Phase
HIV

Drug : PRO 140
Drug : Placebo
Drug : Optimized Background Regimen
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Further study details as provided by CytoDyn, Inc.:

Primary Outcome Measures

  • 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: 1 week ]
Secondary Outcome Measures:
  • 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: [ Time Frame: 1 week ]
    resistance to ART drugs within three drug classes resistance to ART drugs within two or more drug class with limited treatment option.
  • 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 [ Time Frame: 1 week ]
  • Percentage of participants achieving HIV-1 RNA < 400 copies/mL at week 25 for all patients and within each stratum [ Time Frame: 25 weeks ]
  • Percentage of participants achieving HIV-1 RNA < 50 copies/mL at week 25 for all patients and within each stratum [ Time Frame: 25 weeks ]
  • Mean change from Baseline in HIV-1 RNA levels (log10 copies/mL) at week 25 for all patients and within each stratum [ Time Frame: 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 [ Time Frame: 1 week ]
  • Mean change from Baseline in CD4 cell count at week 25 for all patients and within each stratum [ Time Frame: 25 weeks ]
  • 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 [ Time Frame: 1 weeks ]
Other Outcome Measures:
  • Tolerability of repeated subcutaneous administration of PRO 140 as assessed by study participants (using Visual Analogue Scale) and by investigator-evaluation of injection site reactions [ Time Frame: 25 weeks ]
  • Frequency of Grade 3 or 4 adverse events as defined by the DAIDS Adverse Event scale [ Time Frame: 25 weeks ]
  • Frequency of treatment-emergent serious adverse events [ Time Frame: 25 weeks ]
  • Emergence of Dual/Mixed (D/M)- and CXCR4-tropic virus in patients who had exclusive CCR5-tropic virus at study entry. [ Time Frame: 25 weeks ]

Enrollment: 52
Study Start Date: August 2015
Study Completion Date: July 2018
Primary Completion Date: February 2018 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Active Comparator: 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.
Drug: PRO 140

PRO 140 is a humanized IgG4,κ monoclonal antibody (mAb) to the chemokine receptor CCR5.

Other Name: PRO140, CCR5 antagonist, Humanized monoclonal antibody to CCR5
Drug: Optimized Background Regimen

Optimized background therapy (OBT) is chosen on the basis of a subject's resistance test results and treatment history.

Placebo Comparator: 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.
Drug: Placebo
Drug: Optimized Background Regimen

Optimized background therapy (OBT) is chosen on the basis of a subject's resistance test results and treatment history.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years and older  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

Inclusion Criteria:

  1. Males and females, age ≥ 18 years
  2. Exclusive CCR5-tropic virus at Screening Visit
  3. Have a history of at least 3 months on current antiretroviral regimen
  4. 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 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)
    • Platelets ≥ 75,000 /mm3
    • Serum alanine transaminase (SGPT/ALT) < 5 x upper limit of normal (ULN)
    • Serum aspartate transaminase (SGOT/AST) < 5 x ULN
    • Bilirubin (total) < 2.5 x ULN unless Gilbert's disease is present or subject is receiving atazanavir in the absence of other evidence of significant liver disease
    • Creatinine ≤ 1.5 x ULN
  • Clinically normal resting 12-lead ECG at Screening Visit or, if abnormal, considered not clinically significant by the Principal Investigator
  • Both male and female patients and their partners of childbearing potential must agree to use 2 medically accepted methods of contraception (e.g., barrier contraceptives [male condom, female condom, or diaphragm with a spermicidal gel], hormonal contraceptives [implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings], and intrauterine devices) during the course of the study (excluding women who are not of childbearing potential and men who have been sterilized). Females of childbearing potential must have a negative serum pregnancy test at Screening visit and negative urine pregnancy test prior to receiving the first dose of study drug.
  • Willing and able to participate in all aspects of the study, including use of SC medication, completion of subjective evaluations, attendance at scheduled clinic visits, and compliance with all protocol requirements as evidenced by providing written informed consent.

  • Note: Subjects diagnosed with either substance dependence or substance abuse or any history of a concomitant condition (e.g., medical, psychologic, or psychiatric) may be enrolled if in the opinion of site investigator these circumstances would not interfere with the subject's successful completion of the study requirements.
  • 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
  • Participation in an experimental drug trial(s) within 30 days of the Screening Visit or during the study
  • Any known allergy or antibodies to the study drug or excipients
  • Treatment with any of the following:
    • Radiation or cytotoxic chemotherapy with 30 days prior to the Screening Visit or during the study
    • Immunosuppressants within 60 days prior to the Screening Visit or during the study
    • Immunomodulating agents (e.g., interleukins, interferons), hydroxyurea, or foscarnet within 60 days prior to the Screening Visit or during the study
    • Oral or parenteral corticosteroids within 30 days prior to the Screening Visit or during the study. Subjects on chronic steroid therapy > 5 mg/day will be excluded with the following exception:
      • Subjects on inhaled, nasal, or topical steroids will not be excluded.
  • Any other clinical condition that, in the Investigator's judgment, would potentially compromise study compliance or the ability to evaluate safety/efficacy

    contacts and locations

    Contacts and Locations

    Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

    Please refer to this study by its ClinicalTrials.gov identifier: NCT02483078

    Locations

    United States, California
    CD02 Investigational site
    Fountain Valley, California, United States, 92708
    CD02 Investigational site
    Long Beach, California, United States, 90813
    CD02 Investigational site
    Los Angeles, California, United States, 90008
    CD02 Investigational Site
    Los Angeles, California, United States, 90036
    CD02 Investigational site
    Palm Springs, California, United States, 92262
    CD02 Investigational Site
    San Francisco, California, United States, 94115
    CD02 Investigational site
    San Francisco, California, United States, 94118
    United States, Connecticut
    CD02 Investigational Site
    New Haven, Connecticut, United States, 06510
    CD02 Investigational site
    Norwalk, Connecticut, United States, 06850
    United States, District of Columbia
    CD02 Investigational Site
    Washington, District of Columbia, United States, 20009
    CD02 Investigational site
    Washington, District of Columbia, United States, 20017
    United States, Florida
    CD02 Investigational Site
    Clearwater, Florida, United States, 33761
    CD02 Investigational site
    Fort Pierce, Florida, United States, 34982
    CD02 Investigational site
    Miami Beach, Florida, United States, 33139
    CD02 Investigational site
    Miami, Florida, United States, 20852
    CD02 Investigational site
    Miami, Florida, United States, 33136
    CD02 Investigational Site
    Miami, Florida, United States, 33169
    CD02 Investigational site
    Orlando, Florida, United States, 32803
    CD02 Investigational site
    Orlando, Florida, United States
    CD02 Investigational site
    West Palm Beach, Florida, United States, 33401
    United States, Illinois
    CD02 Investigational site
    Chicago, Illinois, United States, 60613
    United States, Kansas
    CD02 Investigational site
    Wichita, Kansas, United States, 67214
    United States, Nevada
    E Study Site
    Las Vegas, Nevada, United States, 89109
    United States, New York
    CD02 Investigational site
    New York, New York, United States, 10001
    CD02 Investigational site
    New York, New York, United States, 10011
    CD02 Investigational site
    Syracuse, New York, United States, 13210
    United States, North Carolina
    CD02 Investigational site
    Charlotte, North Carolina, United States, 28226
    United States, Ohio
    CD02 Investigational site
    Cincinnati, Ohio, United States, 45267
    United States, Texas
    CD02 Investigational Site
    Austin, Texas, United States, 78705
    CD02 Investigational Site
    Bellaire, Texas, United States, 77301
    CD02 Investigational site
    Dallas, Texas, United States, 75231
    CD02 Investigational Site
    Houston, Texas, United States, 77004
    CD02 Investigational site
    Houston, Texas, United States, 77098
    United States, Virginia
    CD02 Investigational Site
    Annandale, Virginia, United States, 22003
    United States, Washington
    CD02 Investigational Site
    Spokane, Washington, United States, 99202
    Puerto Rico
    CD02 Investigational site
    Ponce, Puerto Rico, 00716-2347
    CD02 Investigational site
    San Juan, Puerto Rico, 00909

    Sponsors and Collaborators

    CytoDyn, Inc.
    Amarex Clinical Research
    More Information

    More Information


    Responsible Party: CytoDyn, Inc.  
    ClinicalTrials.gov Identifier: NCT02483078   History of Changes  
    Other Study ID Numbers: PRO 140_CD 02  
    Study First Received: June 24, 2015  
    Last Updated: April 2, 2019  

    Additional relevant MeSH terms:
    PRO-140 monoclonal antibody
    HIV Antibodies

    ClinicalTrials.gov processed this data on November 22, 2019
    This information is provided by ClinicalTrials.gov.