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)

• ClinicalTrials.gov Identifier: NCT02483078
• Recruitment Status: Completed
• First Posted: June 26, 2015
• Last Update Posted: April 4, 2019
• Sponsor: CytoDyn, Inc.
• Collaborator: Amarex Clinical Research
• Information provided by (Responsible Party): CytoDyn, Inc.

Tracking Information

• First Submitted Date: June 24, 2015
• First Posted Date: June 26, 2015
• Last Update Posted Date: April 4, 2019
• Actual Study Start Date: August 2015
• Actual Primary Completion Date: February 2018 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 5, 2016): 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 ]
• Original Primary Outcome Measures (submitted: June 25, 2015): Proportion of participants with ≥ 0.7 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 ]

Current Secondary Outcome Measures (submitted: October 5, 2016)

• 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 ]
  1. resistance to ART drugs within three drug classes
  2. 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 ]

Original Secondary Outcome Measures (submitted: June 25, 2015)

• 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 [ Time Frame: 1 weeks ]
• Mean change from Baseline in HIV-1 RNA levels (log10 copies/mL) at the end of the 1-week double-blind treatment period [ Time Frame: 1 week ]
• Percentage of participants achieving HIV-1 RNA < 400 copies/mL at week 25 [ Time Frame: 25 weeks ]
• Percentage of participants achieving HIV-1 RNA < 50 copies/mL at week 25 [ Time Frame: 25 weeks ]
• Mean change from Baseline in HIV-1 RNA levels (log10 copies/mL) at week 25 [ Time Frame: 25 weeks ]
• Mean change from Baseline in CD4 cell count at the end of the 1-week double-blind treatment period [ Time Frame: 1 week ]
• Mean change from Baseline in CD4 cell count at week 25 [ Time Frame: 25 weeks ]

Current Other Pre-specified Outcome Measures (submitted: October 5, 2016)

• 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 ]

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: HIV

Intervention

• 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: Placebo
• Drug: Optimized Background Regimen
  Optimized background therapy (OBT) is chosen on the basis of a subject's resistance test results and treatment history.

Study Arms

• 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.
  Interventions:

  • Drug: PRO 140
  • Drug: Optimized Background Regimen
• 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.
  Interventions:

  • Drug: Placebo
  • Drug: Optimized Background Regimen

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 2, 2019): 52
• Original Estimated Enrollment (submitted: June 25, 2015): 300
• Actual Study Completion Date: July 2018
• Actual Primary Completion Date: February 2018 (Final data collection date for primary outcome measure)

Eligibility 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.

5. 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.
6. 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.

7. 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
8. Clinically normal resting 12-lead ECG at Screening Visit or, if abnormal, considered not clinically significant by the Principal Investigator
9. 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.
10. 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.
14. Any other clinical condition that, in the Investigator's judgment, would potentially compromise study compliance or the ability to evaluate safety/efficacy

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Puerto Rico, United States

Administrative Information

• NCT Number: NCT02483078
• Other Study ID Numbers: PRO 140_CD 02
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: CytoDyn, Inc.
• Study Sponsor: CytoDyn, Inc.
• Collaborators: Amarex Clinical Research
• Investigators: Not Provided
• PRS Account: CytoDyn, Inc.
• Verification Date: April 2019