Clinical trial NCT02175680: Treatment Substitution With PRO 140 Monotherapy in Adult Subjects With HIV-1 Infection
Official title: A Phase 2b Study to Assess 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV
Human Immunodeficiency Virus
Keywords: HIV-1
HIV
Treatment Substitution
PRO 140
PRO140
CytoDyn
Amarex
Lead sponsor: CytoDyn, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Amarex Clinical Research
First posted: 2014-06-26
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is a Phase 2b study designed to evaluate the efficacy, safety, and tolerability of PRO 140 monotherapy for the maintenance of viral suppression in subjects who are stable on combination antiretroviral therapy.

Consenting subjects will be shifted from their combination antiretroviral regimen to PRO 140 monotherapy for 12 weeks. Total treatment duration with PRO 140 will be 14 weeks with the one week overlap of existing retroviral regimen and PRO 140 at the beginning of the study treatment, and one week overlap at the end of the treatment in subjects who do not experience virologic failure.

Detailed description: This study is a Phase 2b, multi-center study designed to evaluate the efficacy, safety, and tolerability of PRO 140 monotherapy for the maintenance of viral suppression in patients who are stable on combination antiretroviral therapy.

Patient enrollment will be staggered in this study to facilitate adequate safety monitoring. A lead cohort will include 12 subjects. Enrollment of additional 28 subjects will not be initiated until it is approved by the independent Data Monitoring Committee (DMC).

Consenting patients will be shifted from combination antiretroviral regimen to PRO 140 monotherapy for 12 weeks. Total treatment duration with PRO 140 will be up to 14 weeks 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.

PRO 140 will be administered as a 350 mg subcutaneous injection weekly for up to 14 weeks. 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.

The study will have three phases: Screening Phase, Treatment Phase and Follow-up Phase.

The primary objective is to assess efficacy of PRO 140 monotherapy for the maintenance of viral suppression following substitution of antiretroviral therapy in patients who are stable on combination antiretroviral therapy.

The secondary objective of the trial is to assess the clinical safety and tolerability parameters following substitution of antiretroviral therapy in patients who are stable on combination antiretroviral therapy.

Eligibility criteria: Inclusion Criteria:

1. Males and females, age ≥18 years
2. Exclusive CCR5-tropic virus at Screening Visit as determined by Trofile™ DNA Assay
3. On stable antiretroviral therapy for last 12 months
4. Subject has two or more potential alternative antiretroviral regimen options to consider.
5. No documented detectable viral loads (HIV-1 RNA \<50 copies/ml) within the last 12 months prior to Screening Visit
6. Nadir CD4 cell count of \>200 cells/mm3

Exclusion Criteria:

1. CXCR4-tropic virus or dual/mixed tropic (R5X4) virus determined by the Trofile™ DNA Assay at the Screening Visit
2. Hepatitis B infection as manifest by the presence of Hepatitis B surface antigen (HBsAg)
3. Any acquired immune deficiency syndrome (AIDS)-defining illness according to the 1993 Centers for Disease Control and Prevention (CDC) AIDS surveillance definition
4. Prior use of any entry, attachment, CCR5 co-receptor, or fusion inhibitor, including PRO 140.
5. Any other clinical condition that, in the Investigator's judgment, would potentially compromise study compliance or the ability to evaluate safety/efficacy

Primary outcomes:
measure: Time to Virologic Failure After Initiating PRO 140 Monotherapy.
timeFrame: From initiation of PRO 140 monotherapy through week 14 or virological failure
Secondary outcomes:
measure: Proportion of Subjects With Virologic Failure
timeFrame: From initiation of PRO 140 monotherapy through week 14
measure: Mean Change From Baseline in Viral Load
timeFrame: From initiation of PRO 140 monotherapy through week 14
measure: Change in Viral Load at the Last Virologic Failure Visit.
timeFrame: From baseline to virologic failure visit (VF). VF can occur at any time from Week 1 to Week 14.
measure: Mean Change in CD4 Cell Count by Visit
timeFrame: From baseline (week 2) through week 14
measure: Mean Change in CD4 Cell Count
timeFrame: From baseline (week 2) to last visit
measure: Q1 QOL Health Status
timeFrame: From baseline to virologic failure (VF occurring at any time from Week 1 to Week 12 or virologic failure which ever comes first)
measure: Q2 QOL Current State of Health
timeFrame: From week 1 through treatment weeks 4, 8, 12 or VF visit
Other outcomes:
measure: Injection Site Reaction - Pain (Site 1)
timeFrame: From initiation of PRO 140 monotherapy through week 14
measure: Injection Site Reaction - Pain (Site 2)
timeFrame: From initiation of PRO 140 monotherapy through week 14
measure: Injection Site Reaction - Injection Site Status (Site 1)
timeFrame: From initiation of PRO 140 monotherapy through week 14
measure: Injection SIte Reaction - Injection Site Status (Site 2)
timeFrame: From initiation of PRO 140 monotherapy through week 14
measure: Injection Site Reaction - Pruritus With Injection (Site 1)
timeFrame: From initiation of PRO 140 monotherapy through week 14
measure: Injection Site Reaction - Pruritus With Injection (Site 2)
timeFrame: From initiation of PRO 140 monotherapy through week14
measure: Injection Site Reaction - Bleeding Site 1
timeFrame: From initiation of PRO 140 monotherapy through week 14
measure: Injection Site Reaction - Bleeding - Site 2
timeFrame: From initiation of PRO 140 monotherapy through week14
measure: Injection Site Reaction - Drug Absorption - Site 1
timeFrame: From initiation of PRO 140 monotherapy through week14
measure: Injection Site Reaction - Drug Absorption - Site 2
timeFrame: From initiation of PRO 140 monotherapy through week 14
measure: Injection Site Reaction - Pain Post Injection - Site 1
timeFrame: From initiation of PRO 140 monotherapy through week 14
measure: Injection Site Reaction - Pain Post Injection - Site 2
timeFrame: From initiation of PRO 140 monotherapy through week 14
measure: Injection Site Reaction - Pain Pre Injection - Site 1
timeFrame: From week 2 through week 14
measure: Injection Site Reaction - Pain Pre Injection - Site 2
timeFrame: From week 2 through week 14
measure: Pro 140 Concentration
timeFrame: At week 4, week 8, week 12 and viral failure visits
Locations:
city: San Francisco
country: United States
facility: Quest Clinical Research
state: California
Study officials:
name: Jacob Lalezari, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.