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

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ClinicalTrials.gov Identifier: NCT02859961
Recruitment Status : Recruiting
First Posted : August 9, 2016
Last Update Posted : February 11, 2019
Sponsor:
Information provided by (Responsible Party):
CytoDyn, Inc.

Tracking Information
First Submitted Date  ICMJE July 13, 2016
First Posted Date  ICMJE August 9, 2016
Last Update Posted Date February 11, 2019
Study Start Date  ICMJE October 2016
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 4, 2016)
Proportion of participants who remain on PRO 140 monotherapy regimen at the end of week 48 without experiencing virologic failure [ Time Frame: 48 weeks ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 4, 2016)
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: August 4, 2016)
  • 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 ]
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Study of PRO 140 SC as Single Agent Maintenance Therapy in Virally Suppressed Subjects With CCR5-tropic HIV-1 Infection
Official Title  ICMJE 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
Brief Summary

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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HIV
Intervention  ICMJE
  • Drug: PRO 140 (350 mg)
    PRO 140 350 mg (175 mg/mL) SC injection per week
    Other Name: Leronlimab
  • Drug: PRO 140 (525 mg)
    PRO 140 525 mg (175 mg/mL) SC injection per week
    Other Name: Leronlimab
  • Drug: PRO 140 (700 mg)
    PRO 140 700 mg (175 mg/mL) SC injection per week
    Other Name: Leronlimab
Study Arms  ICMJE
  • Experimental: PRO 140 SC 350 mg weekly injection (Group A)
    PRO 140 350 mg (175 mg/mL) SC injections per week
    Intervention: Drug: PRO 140 (350 mg)
  • Experimental: PRO 140 SC 525 mg weekly injections (Group B)
    PRO 140 525 mg (175 mg/mL) SC injections per week
    Intervention: Drug: PRO 140 (525 mg)
  • Experimental: PRO 140 SC 700 mg weekly injections (Group C)
    PRO 140 700 mg (175 mg/mL) SC injections per week
    Intervention: Drug: PRO 140 (700 mg)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 7, 2019)
500
Original Estimated Enrollment  ICMJE
 (submitted: August 4, 2016)
300
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Kush Dhody, MBBS,MS,CCRA 3019562536 kushd@amarexcro.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02859961
Other Study ID Numbers  ICMJE PRO 140_CD03
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party CytoDyn, Inc.
Study Sponsor  ICMJE CytoDyn, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account CytoDyn, Inc.
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP