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

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

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.

Study Overview

• Status: Completed
• Conditions: HIV
• Intervention / Treatment: Drug: PRO 140 (350 mg); Drug: PRO 140 (525 mg); Drug: PRO 140 (700 mg)

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: Interventional
• Enrollment (Actual): 562
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • La Mesa, California, United States, 91942
      • CD03 Investigational site
    • Palm Springs, California, United States, 92262
      • CD03 Investigational site
    • San Francisco, California, United States, 94115
      • CD03 Investigational site
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • CD03 Investigational site
    • Norwalk, Connecticut, United States, 06850
      • CD03 Investigational site
  • Florida
    • Ft. Pierce, Florida, United States, 34982
      • CD03 Investigational site
    • Orlando, Florida, United States, 32803
      • CD03 Investigational site
    • West Palm Beach, Florida, United States, 33401
      • CD03 Investigational site
  • Kansas
    • Wichita, Kansas, United States, 67214
      • CD03 Investigational site
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • CD03 Investigational site
  • New York
    • New York, New York, United States, 10011
      • CD03 Investigational site
    • Syracuse, New York, United States, 13210
      • CD03 Investigational site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 - 350 mg weekly injections of PRO 140, no VF (Group A); 350 mg SC injections of PRO 140 per week, patients who had no Virologic Failure (VF)	Drug: PRO 140 (350 mg); PRO 140 350 mg (175 mg/mL) SC injection per week; Other Names: Leronlimab
Experimental: Part 1 - 525 mg weekly injections of PRO 140, no VF (Group B); 525 mg SC injections of PRO 140 per week, patients who had no Virologic Failure (VF)	Drug: PRO 140 (525 mg); PRO 140 525 mg (175 mg/mL) SC injection per week; Other Names: Leronlimab
Experimental: Part 1 - 700 mg weekly injections of PRO 140 (Group C); 700 mg SC injections of PRO 140 per week	Drug: PRO 140 (700 mg); PRO 140 700 mg (175 mg/mL) SC injection per week; Other Names: Leronlimab
Experimental: Part 2 - Rescue Arm for Group A, 525 mg PRO 140; 525 mg SC injections of PRO 140 per week after experiencing virologic failure on 350 mg dose	Drug: PRO 140 (525 mg); PRO 140 525 mg (175 mg/mL) SC injection per week; Other Names: Leronlimab
Experimental: Part 2 - Rescue Arm for Group B, 700 mg PRO 140; 700 mg SC injections of PRO 140 per week after experiencing virologic failure on 525 mg dose	Drug: PRO 140 (700 mg); PRO 140 700 mg (175 mg/mL) SC injection per week; Other Names: Leronlimab
Experimental: Part 2 - Rescue Arm for Group A, 700 mg PRO 140; 700 mg SC injections of PRO 140 per week after experiencing virologic failure on 350 mg dose	Drug: PRO 140 (700 mg); PRO 140 700 mg (175 mg/mL) SC injection per week; Other Names: Leronlimab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants Who Remain on PRO 140 Monotherapy Regimen at the End of Week 48 Without Experiencing Virologic Failure	The proportion of participants experiencing virologic failure was analyzed and reported. Virological failure is defined as two consecutive plasma HIV-1 RNA levels of >= 200 copies/mL.	From T1 (first treatment administration) to week 48 (T48).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants Experiencing Virologic Failure While on PRO 140 Monotherapy Regimen	Proportion of participants experiencing virologic failure while on PRO 140 monotherapy arm of the study.	From T1 (first treatment administration) to week 48 (T48).
Time to Virologic Failure After Initiating PRO 140 Monotherapy	The average time to virologic failure after initiating PRO 140 monotherapy was measured in days for confirmed viral load. For the censored subjects (i.e. subjects who did not have an event) the date of event was the time of the last visit date. Virological failure is defined as two consecutive plasma HIV-1 RNA levels of >= 200 copies/mL.	From T1 (first treatment administration) to week 48 (T48).
Proportion of Participants Achieving Viral Suppression (HIV-1 RNA < 50 Copies/mL) After Experiencing Virologic Failure.	Virologic suppression was defined as plasma HIV-1 RNA levels < 50 copies/mL as quantified by Human Immunodeficiency Virus 1 (HIV-1) Quantitative, RNA (Taqman® Real-Time PCR) assay.	From T1 (first treatment administration) to subsequent visit when viral re-suppression achieved (up to 52 weeks).
Time to Achieving Viral Suppression (HIV-1 RNA < 50 Copies/mL) After Experiencing Virologic Failure	Virologic suppression was defined as plasma HIV-1 RNA levels < 50 copies/mL as quantified by Human Immunodeficiency Virus 1 (HIV-1) Quantitative, RNA (Taqman® Real-Time PCR) assay.	From T1 (first treatment administration) to subsequent visit when viral re-suppression achieved (up to 52 weeks).
Proportion of Participants With Viral Suppression (HIV-1 RNA < 50 Copies/mL) at Week 48 From the Start of PRO 140 Treatment Phase.	Virologic suppression was defined as plasma HIV-1 RNA levels < 50 copies/mL as quantified by Human Immunodeficiency Virus 1 (HIV-1) Quantitative, RNA (Taqman® Real-Time PCR) assay.	From T1 (first treatment administration) to week 48 (T48).
Measurement of Treatment Adherence to the PRO 140 Monotherapy Regimen	Treatment adherence in the Safety Population for all three treatment groups is provided. Measurement is proportion of subjects that reached treatment week 25 (T25)	From T1 (first treatment administration) to week 25 (T25).
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	Total time that participants remain off combination ART regimen will be calculated, defined as the time between start of PRO 140 monotherapy and restart of combination ART Regimen.	From T1 (first treatment administration) to last visit, up to 20 months.
Mean Change in CD4 Cell Count, at Each Visit Within the Treatment Phase	Mean change in CD4 cell count from baseline to final visit for each participant within the Treatment Phase was calculated and summarized. Visit 48 values were imputed using the last observation carried forward if missing.	From T1 (first treatment administration) to week 48 (T48).
Proportion of Participants Within Each Treatment Group Experiencing Emerging Resistance	Proportion of participants experiencing emerging resistance exhibited by fold increase (>= 3-fold increase) in maraviroc and PRO 140 FC (IC90 relative to wild-type virus) between baseline and the time of virologic failure, as a measure of post-baseline phenotypic resistance.	From T1 (first treatment administration) to VF visit (up to 7 months).
Mean HIV-1 RNA Concentrations in CSF in Central Nervous System (CNS) Sub-study	Central Nervous System (CNS) sub-study Data: mean level of HIV-1 RNA in CSF (cerebrospinal fluid) at T1 (prior to first dose of PRO 140), T4, and VF visits for each treatment group.	From T1 (first treatment administration), T4 (week 4), and VF visit (up to 7 months).
Mean PRO 140 Concentration in Plasma for Central Nervous System (CNS) Sub-study	PRO 140 concentrations were measured in plasma for a subset of participants at T1, T4, and VF timepoints. Participants contributed data only at timepoints where valid measurements were available. Timepoints with missing or invalid data were excluded.	From T1 (first treatment administration), T4 (week 4), and VF visit (up to 7 months).
Mean PRO 140 Concentrations in CSF for Central Nervous System (CNS) Sub-study	PRO 140 concentrations were measured in CSF (cerebrospinal fluid) in a subset of participants at visits T1, T4, and VF.	From T1 (first treatment administration), T4 (week 4), and VF visit (up to 7 months).
Mean HIV-1 RNA Concentrations in Genital Secretion in Genitourinary (GU) Sub-study	Level of HIV-1 RNA in genital secretion at T1 (prior to first dose of PRO 140), T4, and T16 visits.	From T1 (first treatment administration), T4 visit (week 4), and T16 visit (up to 16 weeks).

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerability of Repeated Subcutaneous Administration of PRO 140	Tolerability of repeated subcutaneous administration of PRO 140 as assessed by study participants (using Visual Analogue Scale). Subjects were asked to mark the point that best represents the average pain intensity at the injection site on a horizontal line (100 mm in length) anchored by the following word descriptors at each end, "no pain" on the left side and "pain as bad as it could possibly be" on the right side of the line. The VAS score is determined by measuring in millimeters from the left-hand end of the line to the point that the patient marks. Possible scores range from 0 to 100, with higher scores indicating greater pain.	From T1 (first treatment administration) to week 48 (T48)
Frequency of Grade 3 or 4 Adverse Events as Defined by the DAIDS Adverse Event Scale	Adverse Events (AEs) are presented based on severity, per Investigator discretion. Severity grades were based on the Division of Aids (DAIDS) grading guidelines. For safety analyses, Grade 3 and 4 AEs were summarized separately for treatment periods corresponding to Part 1 and Part 2 due to differences in dosing and treatment exposure. Participants who entered Part 2 (rescue treatment) received an increased dose of leronlimab and therefore constitute a distinct safety population. For this reason, AEs occurring during Part 2 are represented separately from Part 1, although Part 2 does not represent a separate study arm for efficacy analyses and participants remain attributed to their original Part 1 treatment arm in the overall study design.	From T1 (first treatment administration) to week 48 (T48).
Frequency of Treatment-Emergent Serious Adverse Events	Serious adverse events (SAEs) that occurred during the study include all adverse events that occurred from when the subject signed the informed consent form. For safety analyses, SAEs were summarized separately for treatment periods corresponding to Part 1 and Part 2 due to differences in dosing and treatment exposure. Participants who entered Part 2 (rescue treatment) received an increased dose of leronlimab and therefore constitute a distinct safety population. For this reason, SAEs occurring during Part 2 are represented separately from Part 1, although Part 2 does not represent a separate study arm for efficacy analyses and participants remain attributed to their original Part 1 treatment arm in the overall study design.	From T1 (first treatment administration) to week 48 (T48).

Collaborators and Investigators

• Sponsor: CytoDyn, Inc.
• Investigators: Study Director: Jacob Lalezari, MD, CytoDyn, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2016
• Primary Completion (Actual): September 16, 2020
• Study Completion (Actual): December 7, 2020

Study Registration Dates

• First Submitted: July 13, 2016
• First Submitted That Met QC Criteria: August 4, 2016
• First Posted (Estimated): August 9, 2016

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: February 12, 2026
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Anti-Infective Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; leronlimab
• Other Study ID Numbers: PRO 140_CD03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No