Clincosm LogoSign in Get a demo

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

Sponsor
CytoDyn, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02483078
Collaborator
Amarex Clinical Research (Other)
52
Enrollment
37
Locations
2
Arms
35
Actual Duration (Months)
1.4
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: PRO 140
  • Drug: Placebo
  • Drug: Optimized Background Regimen
 Phase 2/Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
52 participants
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
Actual Study Start Date :
Aug 1, 2015
Actual Primary Completion Date :
Feb 1, 2018
Actual Study Completion Date :
Jul 1, 2018

Arms and Interventions

Arm Intervention/Treatment
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 Names:
  • 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.

    Outcome Measures

    Primary Outcome Measures

    1. 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 [1 week]

    Secondary Outcome Measures

    1. 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: [1 week]

      resistance to ART drugs within three drug classes resistance to ART drugs within two or more drug class with limited treatment option.

    2. 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 [1 week]

    3. Percentage of participants achieving HIV-1 RNA < 400 copies/mL at week 25 for all patients and within each stratum [25 weeks]

    4. Percentage of participants achieving HIV-1 RNA < 50 copies/mL at week 25 for all patients and within each stratum [25 weeks]

    5. Mean change from Baseline in HIV-1 RNA levels (log10 copies/mL) at week 25 for all patients and within each stratum [25 weeks]

    6. 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 [1 week]

    7. Mean change from Baseline in CD4 cell count at week 25 for all patients and within each stratum [25 weeks]

    8. 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 [1 weeks]

    Other Outcome Measures

    1. 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 [25 weeks]

    2. Frequency of Grade 3 or 4 adverse events as defined by the DAIDS Adverse Event scale [25 weeks]

    3. Frequency of treatment-emergent serious adverse events [25 weeks]

    4. Emergence of Dual/Mixed (D/M)- and CXCR4-tropic virus in patients who had exclusive CCR5-tropic virus at study entry. [25 weeks]

    Eligibility Criteria

    Criteria

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

    1. 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.

    2. 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.

    3. 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

    1. Clinically normal resting 12-lead ECG at Screening Visit or, if abnormal, considered not clinically significant by the Principal Investigator

    2. 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.

    3. 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:

    1. Documented CXCR4-tropic virus or Dual/Mixed tropic (R5X4) virus

    2. Patients with no viable treatment options (≤ 1 fully active drug)

    3. 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.

    4. Laboratory test values of ≥ grade 3 DAIDS laboratory abnormality with the exception of the absolute CD4+ count criterion of < 200/mm3

    5. Females who are pregnant, lactating, or breastfeeding, or who plan to become pregnant during the study

    6. Unexplained fever or clinically significant illness within 1 week prior to the first study dose

    7. Any vaccination within 2 weeks prior to the first study dose.

    8. Subjects weighing < 35kg

    9. History of anaphylaxis

    10. History of Bleeding Disorder or patients on anti-coagulant therapy

    11. Participation in an experimental drug trial(s) within 30 days of the Screening Visit or during the study

    12. Any known allergy or antibodies to the study drug or excipients

    13. 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.

    1. 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

    Locations

    Site City State Country Postal Code
    1 CD02 Investigational site Fountain Valley California United States 92708
    2 CD02 Investigational site Long Beach California United States 90813
    3 CD02 Investigational site Los Angeles California United States 90008
    4 CD02 Investigational Site Los Angeles California United States 90036
    5 CD02 Investigational site Palm Springs California United States 92262
    6 CD02 Investigational Site San Francisco California United States 94115
    7 CD02 Investigational site San Francisco California United States 94118
    8 CD02 Investigational Site New Haven Connecticut United States 06510
    9 CD02 Investigational site Norwalk Connecticut United States 06850
    10 CD02 Investigational Site Washington District of Columbia United States 20009
    11 CD02 Investigational site Washington District of Columbia United States 20017
    12 CD02 Investigational Site Clearwater Florida United States 33761
    13 CD02 Investigational site Fort Pierce Florida United States 34982
    14 CD02 Investigational site Miami Beach Florida United States 33139
    15 CD02 Investigational site Miami Florida United States 20852
    16 CD02 Investigational site Miami Florida United States 33136
    17 CD02 Investigational Site Miami Florida United States 33169
    18 CD02 Investigational site Orlando Florida United States 32803
    19 CD02 Investigational site Orlando Florida United States
    20 CD02 Investigational site West Palm Beach Florida United States 33401
    21 CD02 Investigational site Chicago Illinois United States 60613
    22 CD02 Investigational site Wichita Kansas United States 67214
    23 E Study Site Las Vegas Nevada United States 89109
    24 CD02 Investigational site New York New York United States 10001
    25 CD02 Investigational site New York New York United States 10011
    26 CD02 Investigational site Syracuse New York United States 13210
    27 CD02 Investigational site Charlotte North Carolina United States 28226
    28 CD02 Investigational site Cincinnati Ohio United States 45267
    29 CD02 Investigational Site Austin Texas United States 78705
    30 CD02 Investigational Site Bellaire Texas United States 77301
    31 CD02 Investigational site Dallas Texas United States 75231
    32 CD02 Investigational Site Houston Texas United States 77004
    33 CD02 Investigational site Houston Texas United States 77098
    34 CD02 Investigational Site Annandale Virginia United States 22003
    35 CD02 Investigational Site Spokane Washington United States 99202
    36 CD02 Investigational site Ponce Puerto Rico 00716-2347
    37 CD02 Investigational site San Juan Puerto Rico 00909

    Sponsors and Collaborators

    • CytoDyn, Inc.
    • Amarex Clinical Research

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    CytoDyn, Inc.
    ClinicalTrials.gov Identifier:
    NCT02483078
    Other Study ID Numbers:
    • PRO 140_CD 02
    First Posted:
    Jun 26, 2015
    Last Update Posted:
    Sep 29, 2021
    Last Verified:
    Sep 1, 2021
    Additional relevant MeSH terms:
    Leronlimab

    Study Results

    No Results Posted as of Sep 29, 2021