HIV, Human Immunodeficiency Virus
Conditions
Brief summary
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
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PRO 140 monotherapy until investigational product (IP) receives marketing approval or investigational new drug (IND) is withdrawn by Sponsor.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. .
Interventions
DRUGPRO 140 350mg weekly subcutaneous (SC) injection.
CCR5 Antagonist
Sponsors
CytoDyn, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Virologic Failure After Initiating PRO 140 Monotherapy | From treatment extension visit 1 (TE1) until virologic failure, assessed up to 125 weeks. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Viral Load (HIV-1 RNA Levels) | From treatment extension visit TE2 (defined as baseline), until week 58 of extension treatment. | 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. |
| Proportion of Participants With Virologic Failure After Initiating PRO 140 Monotherapy. | From treatment extension visit 1 (TE1) until virologic failure, assessed up to 125 weeks. | Virologic failure is defined as two consecutive HIV-1 RNA levels of ≥ 400 copies/ml separated by at least 3 days. |
| Mean Change in CD4 Cell Count | From treatment extension visit TE2 (defined as baseline), until week 58 of extension treatment. | 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. |
| Change in Quality of Life Metrics (up to TE107) | From TE4 (baseline) through every fourth weekly visits to treatment visit 107 (TE107) or EOT, up to 125 weeks. | 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). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least One Treatment-related Serious Adverse Event. | From the first treatment visit (TE1) until final study visit up to 125 weeks. | 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. |
| Number of Participants With Grade 3 or 4 Adverse Events as Defined by the DAIDS Adverse Event Scale | From the first treatment visit (TE1) until final study visit, up to a 125 weeks. | 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). |
| 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. | From TE1 (first treatment administration) weekly until last treatment visit (up to 125 weeks) | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PRO 140 PRO 140 350mg weekly SQ (subcutaneous) injection.
PRO 140 350mg weekly SQ injection.: CCR5 Antagonist | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Study Terminated | 10 |
Baseline characteristics
| Characteristic | PRO 140 |
|---|---|
| Age, Continuous | 56.05 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 16 Participants |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 18 Participants |
| Time since HIV Diagnosis | 10 years |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 15 / 20 |
| serious Total, serious adverse events | 4 / 20 |
Outcome results
Primary
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.
Population: The efficacy population consists of all subjects who received at least one dose of leronlimab (PRO 140).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRO 140 | Time to Virologic Failure After Initiating PRO 140 Monotherapy | 228.8 days | Standard Deviation 225.6 |
Secondary
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).
Time frame: From TE4 (baseline) through every fourth weekly visits to treatment visit 107 (TE107) or EOT, up to 125 weeks.
Population: No QoL data was collected at screening visit (SV1) for any of the participants. For 5 participants Quality-of-life (QoL) results were either not collected or they had undefined change from baseline due to missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRO 140 | Change in Quality of Life Metrics (up to TE107) | 1.4 score | Standard Deviation 5.9 |
Secondary
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.
Population: The efficacy population consists of all subjects who received at least one dose of leronlimab (PRO 140). Baseline was defined as TE2. Any subjects with an undefined change from baseline due to missing data were excluded.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRO 140 | Mean Change in CD4 Cell Count | 22 cells/uL | Standard Deviation 111 |
Secondary
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.
Population: The efficacy population consists of all subjects who received at least one dose of leronlimab (PRO 140). Baseline was defined as TE2. Any subjects with an undefined change from baseline due to missing data were excluded. The following imputations were used in the statistical analysis: \<40 copies/mL as 40 Target not detected as 20.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRO 140 | Mean Change in Viral Load (HIV-1 RNA Levels) | 147.34 copies/mL | Standard Deviation 263.6 |
Secondary
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.
Population: The efficacy population consists of all subjects who received at least one dose of leronlimab (PRO 140).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PRO 140 | Proportion of Participants With Virologic Failure After Initiating PRO 140 Monotherapy. | 0.3 proportion of participants |
Other Pre-specified
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.
Time frame: From the first treatment visit (TE1) until final study visit up to 125 weeks.
Population: All patients who received at least one dose of PRO 140 (leronlimab) were included in the baseline analysis population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PRO 140 | Number of Participants With at Least One Treatment-related Serious Adverse Event. | 0 Participants |
Other Pre-specified
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).
Time frame: From the first treatment visit (TE1) until final study visit, up to a 125 weeks.
Population: All patients who received at least one dose of PRO 140 (leronlimab) were included in the baseline analysis population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PRO 140 | Number of Participants With Grade 3 or 4 Adverse Events as Defined by the DAIDS Adverse Event Scale | 7 Participants |
Other Pre-specified
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.
Time frame: From TE1 (first treatment administration) weekly until last treatment visit (up to 125 weeks)
Population: Data on tolerability of repeated subcutaneous (SC) administration of PRO 140 was not collected.