An Extension of Protocol PRO 140_CD01 Study

Extension of Protocol PRO140_CD01 to Further Evaluate Long-term Suppression of HIV-1 Replication Following Substitution of Stable Combination ART With PRO 140 (Monoclonal CCR5 Antibody) Monotherapy in Adult Subjects With HIV-1 Infection

This is an extension of Protocol PRO 140_CD 01 to further evaluate the long-term suppression of HIV-1 replication following substitution of stable combination antiretroviral therapy with a PRO 140 (Monoclonal CCR5 antibody) monotherapy in adult subjects with HIV-1 infection

Study Overview

• Status: Terminated
• Conditions: HIV; Human Immunodeficiency Virus
• Intervention / Treatment: Drug: PRO 140 350mg weekly subcutaneous (SC) injection.

Detailed Description

This study is a Phase 2b, multi-center, extension study designed to evaluate the long-term efficacy, safety, and tolerability of PRO 140 monotherapy for the maintenance of viral suppression in patients who were stable on combination antiretroviral therapy and completed 12 weeks of treatment under PRO 140_CD 01 Treatment Substitution Study without experiencing virologic failure.

Consenting patients will continue to receive PRO 140 monotherapy until investigational product (IP) receives marketing approval or investigational new drug (IND) is withdrawn by Sponsor. There is one week overlap of existing retroviral regimen and PRO 140 at the end of the treatment extension phase in subjects who do not experience virologic failure.

PRO 140 will be administered as a 350 mg subcutaneous injection weekly during treatment extension phase. Study participants will be monitored for viral rebound on a weekly basis following initiation of PRO 140 monotherapy and will re-initiate their previous antiretroviral regimen if plasma HIV-1 RNA levels rise above 400 copies/ml on two consecutive blood draws at least 3 days apart.

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• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94115
      • CD01-Extension 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. Subjects who have completed 12 weeks of treatment in PRO 140_CD01 study without experiencing virologic failure.
2. Both male and female patients and their partners of childbearing potential must agree to use appropriate birth control methods (birth control pills, barriers, or abstinence) throughout the study duration (excluding women who are not of childbearing potential and men who have been sterilized). Females of childbearing potential must have a negative urine pregnancy test prior to receiving the first dose of study drug.
3. 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_CD01 Treatment Substitution Study
2. Any acquired immune deficiency syndrome (AIDS)-defining illness according to the 1993 Centers for Disease Control and Prevention (CDC) AIDS surveillance definition
3. Laboratory test values ≥ grade 4 DAIDS laboratory abnormality.
4. Females who are pregnant, lactating, or breastfeeding, or who plan to become pregnant during the study
5. Unexplained temperature >38.5C (101.3F) for seven consecutive days within 14 days prior to the first study dose
6. Diagnosed with either substance dependence or substance abuse or any history of a concomitant condition (e.g., medical, psychologic, or psychiatric) that in the opinion of the primary care provider and/or site investigator would interfere with the subject's successful completion of the study requirements
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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PRO 140; PRO 140 350mg weekly subcutaneous (SC) injection.	Drug: PRO 140 350mg weekly subcutaneous (SC) injection.; CCR5 Antagonist; Other Names: PRO 140

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Virologic Failure After Initiating PRO 140 Monotherapy	Virologic failure (VF) is defined as two consecutive HIV-1 RNA levels of ≥ 400 copies/ml separated by at least 3 days. The time to VF will be compared to a historical data (i.e., time to HIV-1 RNA viral load > 500 copies/mL of 29 days). The statistical comparison will be conducted using Wilcoxon rank sum test and the median time to Virologic Failure for this study will be compared to 30 days.	From treatment extension visit 1 (TE1) until virologic failure, assessed up to 125 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants With Virologic Failure After Initiating PRO 140 Monotherapy.	Virologic failure is defined as two consecutive HIV-1 RNA levels of ≥ 400 copies/ml separated by at least 3 days.	From treatment extension visit 1 (TE1) until virologic failure, assessed up to 125 weeks.
Mean Change in Viral Load (HIV-1 RNA Levels)	Mean change from baseline of HIV-1 RNA levels was assessed for each week during the treatment phase up until week 58. Weighted mean change in viral load (HIV-1 RNA levels) were calculated from baseline to week 58.	From treatment extension visit TE2 (defined as baseline), until week 58 of extension treatment.
Mean Change in CD4 Cell Count	Mean change in CD4 cell count from baseline (TE2 visit) was assessed for each week during the treatment phase up until week 58. The average mean change was calculated from baseline to week 58.	From treatment extension visit TE2 (defined as baseline), until week 58 of extension treatment.
Change in Quality of Life Metrics (up to TE107)	A Quality of Life (QoL) assessment using ACTG SF-21 was planned to be performed at screening visit (SV1), once every four weeks from treatment visit 4 (TE4) through treatment visit 107 (TE107), and at end of treatment (EOT). The ACTG SF-21 has 8 QoL domains with a standard score ranging from 0 (worst) to 100 (best).	From TE4 (baseline) through every fourth weekly visits to treatment visit 107 (TE107) or EOT, up to 125 weeks.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Tolerability of repeated subcutaneous administration of PRO 140 was planned to be assessed by the study participants using a Visual Analogue Scale, and by investigator-evaluation of injection site reactions. Injection site reaction assessment was not completed when subjects performed self-administration.	From TE1 (first treatment administration) weekly until last treatment visit (up to 125 weeks)
Number of Participants With Grade 3 or 4 Adverse Events as Defined by the DAIDS Adverse Event Scale	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).	From the first treatment visit (TE1) until final study visit, up to a 125 weeks.
Number of Participants With at Least One Treatment-related Serious Adverse Event.	Treatment-related serious adverse events are defined as serious events with an onset on or after the first treatment. A serious adverse event is defined as any adverse event that: Results in death; Is life threatening (the subject is at immediate risk of dying from the AE); Requires subject hospitalization or prolongs existing hospitalization; Results in persistent or significant disability/incapacity; Is a congenital anomaly/birth defect Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered a serious adverse event when, based upon appropriate medical judgment, they may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.	From the first treatment visit (TE1) until final study visit up to 125 weeks.

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Chang XL, Reed JS, Webb GM, Wu HL, Le J, Bateman KB, Greene JM, Pessoa C, Waytashek C, Weber WC, Hwang J, Fischer M, Moats C, Shiel O, Bochart RM, Crank H, Siess D, Giobbi T, Torgerson J, Agnor R, Gao L, Dhody K, Lalezari JP, Bandar IS, Carnate AM, Pang AS, Corley MJ, Kelly S, Pourhassan N, Smedley J, Bimber BN, Hansen SG, Ndhlovu LC, Sacha JB. Suppression of human and simian immunodeficiency virus replication with the CCR5-specific antibody Leronlimab in two species. PLoS Pathog. 2022 Mar 31;18(3):e1010396. doi: 10.1371/journal.ppat.1010396. eCollection 2022 Mar.

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2014
• Primary Completion (Actual): June 1, 2022
• Study Completion (Actual): July 15, 2022

Study Registration Dates

• First Submitted: January 30, 2015
• First Submitted That Met QC Criteria: January 30, 2015
• First Posted (Estimated): February 4, 2015

Study Record Updates

• Last Update Posted (Estimated): October 7, 2025
• Last Update Submitted That Met QC Criteria: September 18, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Therapeutics; Drug Administration Routes; Drug Therapy; Injections; leronlimab
• Other Study ID Numbers: PRO 140_CD 01-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