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
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PRO 140 monotherapy until investigational product (IP) receives marketing approval or investigational new drug (IND) is withdrawn by Sponsor.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. .
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
CCR5 Antagonist
CD01-Extension Investigational Site
San Francisco, California, United States
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.
Time frame: From treatment extension visit 1 (TE1) until virologic failure, assessed up to 125 weeks.
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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
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Time frame: From TE4 (baseline) through every fourth weekly visits to treatment visit 107 (TE107) or EOT, up to 125 weeks.