An Extension Protocol for Virologically Suppressed Subjects Who Successfully Completed PRO140_CD03 Study

This study is a Phase 2b/3 multi-center extension study designed to evaluate the long term antiviral activity, safety, and tolerability of the strategy of continuing PRO 140 350mg, 525mg, or 700mg SC (subcutaneous) monotherapy to maintain viral suppression after initial 48 weeks in virologically suppressed subjects.

Consenting subjects will continue weekly PRO 140 350mg, 525mg, or 700mg monotherapy during the Treatment Extension Phase with the one-week overlap of existing retroviral regimen and PRO 140 350mg, 525mg, or 700 mg at the end of the treatment in subjects who do not experience virologic failure.

Study Overview

• Status: Terminated
• Conditions: HIV-1-infection
• Intervention / Treatment: Drug: PRO 140 350; Drug: PRO 140 525; Drug: PRO 140 700

Detailed Description

The objective is to assess the long-term safety of using PRO 140 350mg, 525mg, or 700mg SC as single-agent maintenance therapy for the chronic suppression of CCR5-tropic HIV-1 infection.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94115
      • Quest Clinical Research

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Subjects who have completed 48 weeks of treatment in PRO140_CD03 study.
2. Last known Plasma HIV-1 RNA < 50 copies/mL within PRO140_CD03 study.
3. 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.
4. 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. Not currently enrolled in PRO140_CD03 study.
2. Any active infection or malignancy requiring acute therapy (with the exception of local cutaneous Kaposi's sarcoma).
3. Females who are pregnant, lactating, or breastfeeding, or who plan to become pregnant during the study.
4. Subjects weighing < 35kg.
5. History of anaphylaxis to any oral or parenteral drugs.

6. History of Bleeding Disorder or patients on anti-coagulant therapy (except aspirin).

   Note: Subjects with well-controlled bleeding disorder while on stable anti-coagulant therapy dose with documented stable INRs can be enrolled as per discretion of the Investigator.

7. 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: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PRO 140 350 mg; PRO 140 350mg weekly SC injection.	Drug: PRO 140 350; Pro140 SC injection 350 mg; Other Names: leronlimab
Experimental: PRO 140 525 mg; PRO 140 525mg weekly SC injection.	Drug: PRO 140 525; 525 mg; Other Names: leronlimab
Experimental: PRO 140 700 mg; PRO 140 700mg weekly SC injection.	Drug: PRO 140 700; 700 mg; Other Names: leronlimab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long Term Clinical Safety of PRO 140 Monotherapy by Assessing the Number of Participants With Grade 2, 3 or 4 Adverse Events as Defined by the DAIDS Adverse Event Scale, and the Number of Participants With Treatment-emergent Serious Adverse Events.	The Division of AIDS (DAIDS) grading table provides an adverse event severity grading scale ranging from grades 1 to 5 with descriptions for each adverse event based on the following general guidelines: Grade 1 indicates a mild event; Grade 2 indicates a moderate event; Grade 3 indicates a severe event; Grade 4 indicates a potentially life-threatening event; Grade 5 indicates death (Note: This grade is not specifically listed on each page of the grading table). Treatment-Emergent Serious Adverse Events (TESAEs) are defined as serious adverse events with an onset on or after the first treatment.	From TE1 (first treatment administration) to last treatment visit, up to 197 weeks
Proportion of Participants Experiencing Virologic Failure for All Subjects Within Each Treatment Group.	Virological failure is defined as two consecutive HIV-1 RNA levels of ≥ 200 copies/mL for all subjects and within each treatment group.	From TE1 (first treatment administration) to last treatment visit, up to 197 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Virologic Failure After Initiating PRO 140 Monotherapy for All Subjects Within Each Treatment Group.	Virological failure (VF) is defined as two consecutive HIV-1 RNA levels of ≥ 200 copies/mL for all subjects and within each treatment group. The date of VF event is defined as the date of the second assessment of the two (2) consecutive HIV-1 RNA levels of >= 200 copies/mL when virological failure is confirmed. Subjects who did not have VF, the last visit date will be used as the date of the event.	From TE1 (first treatment administration) to last treatment visit, up to 197 weeks
Proportion of Participants Achieving Viral Re-suppression After Experiencing Virologic Failure Within Each Treatment Group.	Viral re-suppression is defined as having HIV-1 RNA levels of < 50 copies/mL after experiencing virologic failure within each treatment group.	From TE1 (first treatment administration) to last treatment visit, up to 197 weeks
Time to Achieving Viral Re-suppression After Experiencing Virologic Failure Within Each Treatment Group.	Viral re-suppression is defined as having HIV-1 RNA levels of < 50 copies/mL after experiencing virologic failure within each treatment group.	From TE1 (first treatment administration) to last treatment visit, up to 197 weeks
Proportion of Virologic Failure Subjects Achieving Viral Re-suppression With Re-initiation of Previous Baseline Antiretroviral Regimen Within Each Treatment Group.	Viral re-suppression is defined as having HIV-1 RNA levels of < 50 copies/mL after experiencing virologic failure within each treatment group. Subjects who experienced virologic failure during the treatment phase had an option to re-initiate their PRO 140 regimen to their previous baseline or dose escalate to the next dose level.	From TE1 (first treatment administration) to last treatment visit, up to 197 weeks
Mean Change in CD4 Cell Count, at Each Visit Within the Treatment Phase for All Subjects Within Each Treatment Group	The change from baseline in CD4 cell count was summarized for each visit during the treatment phase for each treatment group. The time-weighted mean of change of the post baseline (visit TE1) values was calculated. The time-weighted mean was adjusted AUC (area under the curve) by time.	From TE1 (first treatment administration) to last treatment visit, up to 197 weeks

Collaborators and Investigators

• Sponsor: CytoDyn, Inc.
• Investigators: Principal Investigator: Jacob Lalezari, MD, CytoDyn, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 29, 2017
• Primary Completion (Actual): June 20, 2022
• Study Completion (Actual): July 10, 2022

Study Registration Dates

• First Submitted: January 13, 2022
• First Submitted That Met QC Criteria: March 4, 2022
• First Posted (Actual): March 9, 2022

Study Record Updates

• Last Update Posted (Estimated): October 30, 2025
• Last Update Submitted That Met QC Criteria: October 2, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

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

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