Randomized, Double-Blind, Placebo-Controlled Trial, Followed by Single-Arm Treatment of PRO 140

NCT02483078 | Completed Phase 2 Results DMC

• 1 other identifier: PRO 140_CD 02
• Study Type: interventional
• Target: 52
• Locations: 2 countries
• Sites: 36

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.

Conditions

HIV

Outcome Measures

Primary Outcomes (1)

• 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

  The primary efficacy endpoint will be proportion of participants with a 0.5 log10 or greater reduction in HIV-1 RNA viral load from baseline at the end of the one week double-blind treatment period (Part 1).

  From baseline visit to week 1 visit

Secondary Outcomes (9)

• 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: Resistance to ART Drugs Within Two Drug Class With Limited Treatment Option.

  From baseline visit to week 1 visit

• 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: Resistance to ART Drugs Within Three Drug Classes

  From baseline visit to week 1 visit

• 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

  From baseline visit to week 1 visit

• Percentage of Participants Achieving HIV-1 RNA < 400 Copies/mL at Week 25 for All Patients and Within Each Stratum

  25 weeks

• Percentage and Number of Participants Achieving HIV-1 RNA < 50 Copies/mL at Week 25 for All Patients and Within Each Stratum

  25 weeks

Other Outcomes (4)

• 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

  25 weeks

• Frequency of Grade 3 or 4 Adverse Events as Defined by the DAIDS Adverse Event Scale

  25 weeks

• Frequency of Treatment-Emergent Serious Adverse Events

  25 weeks

Study Arms (2)

PRO 140

ACTIVE COMPARATOR

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.

Drug: PRO 140; Drug: Optimized Background Regimen

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo; Drug: Optimized Background Regimen

Interventions

PRO 140 DRUG

PRO 140 is a humanized IgG4,κ monoclonal antibody (mAb) to the chemokine receptor CCR5.

Also known as: PRO140, CCR5 antagonist, Humanized monoclonal antibody to CCR5

PRO 140

Placebo DRUG

Placebo

Optimized Background Regimen DRUG

Optimized background therapy (OBT) is chosen on the basis of a subject's resistance test results and treatment history.

Also known as: Optimized background therapy (OBT) is chosen on the basis of a subject's resistance test results and treatment history.

PRO 140; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females, age ≥ 18 years
• Exclusive CCR5-tropic virus at Screening Visit
• Have a history of at least 3 months on current antiretroviral regimen
• Treatment-experienced HIV-infected patients with documented genotypic or phenotypic resistance to at least one ART drug within three drug classes
• 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.
• 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.
• 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.
• 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

You may not qualify if:

• Documented CXCR4-tropic virus or Dual/Mixed tropic (R5X4) virus
• Patients with no viable treatment options (≤ 1 fully active drug)
• 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.
• Laboratory test values of ≥ grade 3 DAIDS laboratory abnormality with the exception of the absolute CD4+ count criterion of \< 200/mm3
• Females who are pregnant, lactating, or breastfeeding, or who plan to become pregnant during the study
• Unexplained fever or clinically significant illness within 1 week prior to the first study dose
• Any vaccination within 2 weeks prior to the first study dose.
• Subjects weighing \< 35kg
• History of anaphylaxis
• History of Bleeding Disorder or patients on anti-coagulant therapy
• Participation in an experimental drug trial(s) within 30 days of the Screening Visit or during the study
• Any known allergy or antibodies to the study drug or excipients
• 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

Sponsors & Collaborators

• CytoDyn, Inc.: lead

Study Sites (36)

CD02 Investigational site

Fountain Valley, California, 92708, United States

Location

CD02 Investigational site

Long Beach, California, 90813, United States

Location

CD02 Investigational site

Los Angeles, California, 90008, United States

Location

CD02 Investigational Site

Los Angeles, California, 90036, United States

Location

CD02 Investigational site

Palm Springs, California, 92262, United States

Location

CD02 Investigational Site

San Francisco, California, 94115, United States

Location

CD02 Investigational site

San Francisco, California, 94118, United States

Location

CD02 Investigational Site

New Haven, Connecticut, 06510, United States

Location

CD02 Investigational site

Norwalk, Connecticut, 06850, United States

Location

CD02 Investigational Site

Washington D.C., District of Columbia, 20009, United States

Location

CD02 Investigational site

Washington D.C., District of Columbia, 20017, United States

Location

CD02 Investigational Site

Clearwater, Florida, 33761, United States

Location

CD02 Investigational site

Ft. Pierce, Florida, 34982, United States

Location

CD02 Investigational site

Miami, Florida, 20852, United States

Location

CD02 Investigational site

Miami, Florida, 33136, United States

Location

CD02 Investigational Site

Miami, Florida, 33169, United States

Location

CD02 Investigational site

Miami Beach, Florida, 33139, United States

Location

CD02 Investigational site

Orlando, Florida, 32803, United States

Location

CD02 Investigational site

West Palm Beach, Florida, 33401, United States

Location

CD02 Investigational site

Chicago, Illinois, 60613, United States

Location

CD02 Investigational site

Wichita, Kansas, 67214, United States

Location

E Study Site

Las Vegas, Nevada, 89109, United States

Location

CD02 Investigational site

New York, New York, 10001, United States

Location

CD02 Investigational site

New York, New York, 10011, United States

Location

CD02 Investigational site

Syracuse, New York, 13210, United States

Location

CD02 Investigational site

Charlotte, North Carolina, 28226, United States

Location

CD02 Investigational site

Cincinnati, Ohio, 45267, United States

Location

CD02 Investigational Site

Austin, Texas, 78705, United States

Location

CD02 Investigational Site

Bellaire, Texas, 77301, United States

Location

CD02 Investigational site

Dallas, Texas, 75231, United States

Location

CD02 Investigational Site

Houston, Texas, 77004, United States

Location

CD02 Investigational site

Houston, Texas, 77098, United States

Location

CD02 Investigational Site

Annandale, Virginia, 22003, United States

Location

CD02 Investigational Site

Spokane, Washington, 99202, United States

Location

CD02 Investigational site

Ponce, PR, 00716-2347, Puerto Rico

Location

CD02 Investigational site

San Juan, 00909, Puerto Rico

Location

Related Publications (1)

• Gathe JC, Dejesus E, Ramgopal MN, Rolle CP, Yang OO, Sanchez WE, Lalezari JP, Krishen A, Sacha JB, Hansen SG, Meidling J. Leronlimab Treatment for Multidrug-Resistant HIV-1 (OPTIMIZE): A Randomized, Double-Blind, Placebo-Controlled Trial. J Acquir Immune Defic Syndr. 2025 Jun 1;99(2):185-194. doi: 10.1097/QAI.0000000000003648.

  PMID: 39972543 DERIVED

MeSH Terms

Interventions

leronlimab

Results Point of Contact

• Title: Joseph Meidling Senior Director Clinical Operations
• Organization: CytoDyn

jmeidling@cytodyn.com

(360) 980-8524

Study Officials

• Edwin DeJesus, MD, FACP,

  Orlando Immunology Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2015
• First Posted: June 26, 2015
• Study Start: October 1, 2015
• Primary Completion: February 1, 2018
• Study Completion: July 1, 2018
• Last Updated: November 3, 2022
• Results First Posted: November 3, 2022

Record last verified: 2022-11

Locations

PR (2); US (34)