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Study of PRO 140 SC as Single Agent Maintenance Therapy in Virally Suppressed Subjects With CCR5-tropic HIV-1 Infection

This study is currently recruiting participants.
See Contacts and Locations
Verified February 2017 by CytoDyn, Inc.
Sponsor:
Information provided by (Responsible Party):
CytoDyn, Inc.
ClinicalTrials.gov Identifier:
NCT02859961
First received: July 13, 2016
Last updated: February 1, 2017
Last verified: February 2017
  Purpose

This study is a Phase 2b/3, multi-center study designed to evaluate the efficacy, safety, and tolerability of the strategy of shifting clinically stable patients receiving suppressive combination antiretroviral therapy to PRO 140 monotherapy and maintaining viral suppression for 48 weeks following study entry.

Consenting patients will be shifted from combination antiretroviral regimen to weekly PRO 140 monotherapy for 48 weeks during the Treatment Phase with the one week overlap of existing retroviral regimen and PRO 140 at the beginning of the study treatment and also one week overlap at the end of the treatment in subjects who do not experience virologic failure.


Condition Intervention Phase
HIV Drug: PRO 140 Phase 2 Phase 3

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2b/3, Multicenter Study to Assess the Treatment Strategy of Using PRO 140 SC as Long-Acting Single-Agent Maintenance Therapy for 48 Weeks in Virologically Suppressed Subjects With CCR5-tropic HIV-1 Infection

Resource links provided by NLM:


Further study details as provided by CytoDyn, Inc.:

Primary Outcome Measures:
  • Proportion of participants who remain on PRO 140 monotherapy regimen at the end of week 48 without experiencing virologic failure [ Time Frame: 48 weeks ]

Secondary Outcome Measures:
  • Proportion of participants experiencing virologic failure while on PRO 140 monotherapy regimen [ Time Frame: 48 weeks ]
  • Time to virologic failure after initiating PRO 140 monotherapy [ Time Frame: 48 weeks ]
  • Proportion of participants achieving viral suppression (HIV-1 RNA < 50 copies/mL) after experiencing virologic failure. [ Time Frame: 48 weeks ]
  • Time to achieving viral suppression (HIV-1 RNA < 50 copies/mL) after experiencing virologic failure [ Time Frame: 48 weeks ]
  • Proportion of participants with viral suppression (HIV-1 RNA < 50 copies/mL) at week 48 from the start of PRO 140 Treatment Phase. [ Time Frame: 48 weeks ]
  • Measurement of treatment adherence to the PRO 140 monotherapy regimen [ Time Frame: 48 weeks ]
  • Total time that participants remain off combination ART regimen, defined as the time between start of PRO 140 monotherapy and restart of combination ART Regimen [ Time Frame: 48 weeks ]
  • Mean change in CD4 cell count, at each visit within the Treatment Phase [ Time Frame: 48 weeks ]
  • Proportion of participants experiencing emerging resistance exhibited by fold increase in maraviroc and PRO 140 FC between baseline and the time of virologic failure, as a measure of post-baseline phenotypic resistance [ Time Frame: 48 weeks ]
  • Central Nervous System (CNS) sub-study: Level of HIV-1 RNA in CSF at T1 (prior to first dose of PRO 140), T4, T16 and VF visits [ Time Frame: 48 weeks ]
  • Central Nervous System (CNS) sub-study: PRO 140 concentration in CSF at T1 (prior to first dose of PRO 140), T4, T16 and VF visits [ Time Frame: 48 weeks ]
  • Central Nervous System (CNS) sub-study: Relationship between PRO 140 concentration in plasma and CSF [ Time Frame: 48 weeks ]
  • Central Nervous System (CNS) sub-study: Relationship between PRO 140 concentration in CSF and HIV-1 RNA in CSF [ Time Frame: 48 weeks ]
  • Genitourinary (GU) sub-study: Level of HIV-1 RNA in genital secretion at T1 (prior to first dose of PRO 140), T4, T16 and VF visits. [ Time Frame: 48 weeks ]
  • Genitourinary (GU) sub-study: PRO 140 concentration in genital secretion at T1 (prior to first dose of PRO 140), T4, T16 and VF visits. [ Time Frame: 48 weeks ]
  • Genitourinary (GU) sub-study: Relationship between PRO 140 concentration in plasma and genital secretion [ Time Frame: 48 weeks ]
  • Genitourinary (GU) sub-study: Relationship between PRO 140 concentration and HIV-1 RNA in genital secretion [ Time Frame: 48 weeks ]

Other Outcome Measures:
  • Tolerability of repeated subcutaneous administration of PRO 140 as assessed by study participants (using Visual Analogue Scale) [ Time Frame: 48 weeks ]
  • Tolerability of repeated subcutaneous administration of PRO 140 as assessed by investigator evaluation of injection site reactions. [ Time Frame: 48 weeks ]
  • Frequency of Grade 3 or 4 adverse events as defined by the DAIDS Adverse Event scale [ Time Frame: 48 weeks ]
  • Frequency of Treatment-emergent serious adverse events [ Time Frame: 48 weeks ]

Estimated Enrollment: 300
Study Start Date: October 2016
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PRO 140 SC injections
PRO 140 350 mg (175 mg/mL) SC injections per week
Drug: PRO 140
PRO 140 350 mg (175 mg/mL) SC injection per week
Other Name: PRO140

Detailed Description:

The primary objective is to assess the treatment strategy of using PRO 140 SC as long-acting, single-agent maintenance therapy for the chronic suppression of CCR5-tropic HIV-1 infection. In addition, the prognostic factors of therapeutic success of PRO 140 monotherapy will be evaluated.

The secondary objective of the trial is to assess the clinical efficacy, safety and tolerability parameters following substitution of combination antiretroviral therapy with weekly PRO 140 monotherapy.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males and females, age ≥18 years
  2. Receiving combination antiretroviral therapy for last 24 weeks
  3. No change in ART within last 4 weeks prior to Screening Visit
  4. Subject has two or more potential alternative approved ART drug options to consider.
  5. Exclusive CCR5-tropic virus at Screening Visit
  6. Plasma HIV-1 RNA < 50 copies/mL at Screening Visit
  7. CD4 cell count of > 200 cells/mm3 since initiation of anti-retroviral therapy
  8. CD4 cell count of > 350 cells/mm3 in preceding 24 weeks and at Screening Visit
  9. Laboratory values at Screening of:

    1. Absolute neutrophil count (ANC) ≥ 750/mm3
    2. Hemoglobin (Hb) ≥ 10.5 gm/dL (male) or ≥ 9.5 gm/dL (female)
    3. Platelets ≥ 75,000 /mm3
    4. Serum alanine transaminase (SGPT/ALT) < 5 x upper limit of normal (ULN)
    5. Serum aspartate transaminase (SGOT/AST) < 5 x ULN
    6. 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
    7. Creatinine ≤ 1.5 x ULN
  10. Clinically normal resting 12-lead ECG at Screening Visit or, if abnormal, considered not clinically significant by the Principal Investigator.
  11. Both male and female patients and their partners of childbearing potential must agree to use 2 medically accepted methods of contraception during the course of the study.
  12. 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.

Exclusion Criteria:

  1. CXCR4-tropic virus or dual/mixed tropic (R5X4) virus determined by the Trofile™ DNA Assay
  2. Hepatitis B infection as manifest by the presence of Hepatitis B surface antigen (HBsAg)
  3. Any active infection or malignancy requiring acute therapy (with the exception of local cutaneous Kaposi's sarcoma)
  4. Laboratory test values ≥ grade 4 DAIDS laboratory abnormality.
  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 or during the study.
  8. Subjects who have failed on a maraviroc containing regimen.
  9. Subjects weighing < 35kg
  10. History of anaphylaxis to any oral or parenteral drugs
  11. History of Bleeding Disorder or patients on anti-coagulant therapy
  12. Participation in an experimental drug trial(s) within 30 days of the Screening Visit
  13. Any known allergy or antibodies to the study drug or excipients
  14. Treatment with any of the following:

    1. Radiation or cytotoxic chemotherapy with 30 days prior to the screening visit
    2. Immunosuppressants within 60 days prior to the screening visit
    3. Immunomodulating agents (e.g., interleukins, interferons), hydroxyurea, or foscarnet within 60 days prior to the screening visit
    4. Oral or parenteral corticosteroids within 30 days prior to the Screening Visit. 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
  15. 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
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: NCT02859961

Contacts
Contact: Kush Dhody, MBBS,MS,CCRA 3019562536 kushd@amarexcro.com

Locations
United States, California
eStudySite Recruiting
La Mesa, California, United States, 91942
Contact: Thuy Pham    619-567-1550    tpham@estudysite.com   
Palmtree Clinical Research Recruiting
Palm Springs, California, United States, 92262
Contact: Erik Hernandez    760-778-7799    ehernandez@palmtreeclinical.com   
Quest Clinical Research/eStudy Recruiting
San Francisco, California, United States, 94115
Contact: Adrienne Moran    415-353-0800    adrienne@questclinical.com   
Contact: Steve Falbo    4153530800    sfalbo@estudysite.com   
United States, Connecticut
Yale University Not yet recruiting
New Haven, Connecticut, United States, 06510
Contact: Laurie Andrews    203-785-3557    laurie.andrews@yale.edu   
Circle CARE Center Recruiting
Norwalk, Connecticut, United States, 06850
Contact: Greg Ulrich    203-852-9525    gulrich@whcccc.org   
United States, Florida
Midway Immunology and Research Center Recruiting
Fort Pierce, Florida, United States, 34982
Contact: Brenda Jacobs    772-595-9830    bjacobs@midwayresearch.com   
Orlando Immunology Center Recruiting
Orlando, Florida, United States, 32803
Contact: Janiza Veloz    407-647-3960 ext 2136    jveloz@oicorlando.com   
Triple O Research Institute, P.A. Recruiting
West Palm Beach, Florida, United States, 33401
Contact: Whitney Schneider    561-855-7871    wrahfeldt@tripleoresearch.com   
United States, Kansas
Via Christi Research Recruiting
Wichita, Kansas, United States, 67214
Contact: Sheila Stauffer    316-268-6958    sheila.stauffer@viachristi.org   
United States, Nevada
eStudySite Recruiting
Las Vegas, Nevada, United States, 89109
Contact: Melissa McManus    702-410-2970    mmcmanus@estudysite.com   
United States, New York
Chelsea Village Medical Recruiting
New York, New York, United States, 10011
Contact: Lynne Bartell    212-929-2629    lynne@cvmnyc.com   
SUNY Upstate Medical University Recruiting
Syracuse, New York, United States, 13210
Contact: Kelly Bartlett    315-464-5729    bartletk@upstate.edu   
Sponsors and Collaborators
CytoDyn, Inc.
  More Information

Responsible Party: CytoDyn, Inc.
ClinicalTrials.gov Identifier: NCT02859961     History of Changes
Other Study ID Numbers: PRO 140_CD03
Study First Received: July 13, 2016
Last Updated: February 1, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: TBD

Additional relevant MeSH terms:
PRO-140 monoclonal antibody
HIV Antibodies
HIV Fusion Inhibitors
Viral Fusion Protein Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 21, 2017