Human Immunodeficiency Virus (HIV)
Conditions
Keywords
HIV, Human Immunodeficiency Virus
Brief summary
PRO 140\_CD02 Extension study seeks to evaluate the long-term efficacy, safety and tolerability of PRO 140 weekly injection in combination with Optimized Background Therapy (OBT) in patients infected with Human Immunodeficiency virus (HIV-1).
Detailed description
This is an extension study, to provide continued access to PRO 140 to subjects who complete participation in PRO140\_CD02 and continue to receive clinical benefit and would require PRO 140 to form a viable regimen, in the opinion of the treating physician. The patient population for this trial are treatment-experienced HIV infected patients with C-C Chemokine Receptor Type 5 (CCR5)-tropic virus who demonstrate evidence of HIV-1 suppression after successfully completed 24 weeks of treatment in the PRO140\_CD02 or CD02\_OpenLabel study.
Interventions
DRUGPRO 140
PRO 140 is a humanized IgG4, monoclonal antibody (mAb) to the C-C chemokine receptor type 5 (CCR5). Participants received 350 or 700 mg weekly injections of PRO 140.
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
Potential subjects are required to meet all of the following criteria for enrollment into the study. 1. Subjects who have completed 24 weeks of treatment in PRO 140\_CD 02 or CD02\_OpenLabel study, and Investigator believes subject requires continued access to PRO 140 in order to continue deriving clinical benefit and maintain HIV-1 viral suppression. 2. HIV-1 RNA ≤ 50 copies/ml at T23 Visit in PRO140\_CD02 study 3. Both male and female patients and their partners of childbearing potential must agree to use 2 medically accepted methods of contraception (e.g., barrier contraceptives \[male condom, female condom, or diaphragm with a spermicidal gel\], hormonal contraceptives \[implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings\], and intrauterine devices) during the course of the study (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. 4. Willing and able to participate in all aspects of the study, including use of subcutaneous (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
Potential subjects meeting any of the following criteria will be excluded from enrollment. 1. Not currently enrolled in PRO 140\_CD 02 or CD02\_OpenLabel study 2. Any active infection or malignancy requiring acute therapy (with the exception of local cutaneous Kaposi's sarcoma) 3. Females who are pregnant, lactating, or breastfeeding, or who plan to become pregnant during the study 4. Any other clinical condition that, in the Investigator's judgment, would potentially compromise study compliance or the ability to evaluate safety measures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Viral Load (HIV-1 RNA Levels) at the Conclusion of Treatment Period | From TE1 (first treatment administration) to once every four weeks until last treatment visit (up to 56 months). | The change from baseline in HIV-1 RNA levels (log 10 copies/mL) was summarized at least once every four weeks during the treatment extension phase. The time-weighted mean of change of the post baseline values was calculated. The time-weighted mean was adjusted AUC (area under the curve) by time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Experiencing Emergence of Dual/Mixed (D/M)- and CXCR4-tropic Virus in Patients Who Had Exclusive CCR5-tropic Virus at Study Entry. | From TE1 (first treatment administration) to last treatment visit, up to 56 months. | All patients have exclusive C-C chemokine receptor type 5 (CCR5)-tropic virus at study entry. The proportion of patients with any tropism result of dual/mixed was summarized. |
| Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Investigator Evaluation of Injection Site Reactions (ISR) | From TE1 (first treatment administration) weekly until last treatment visit (up to 56 months). | At each visit during the treatment extension phase, an injection site reaction assessment was completed for the current and previous injection sites. To assess severity, subcutaneous (SC) injection related events were recorded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table). 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 Participants who had no symptoms of injection site reactions, 0 was assigned. |
| Mean Change in CD4 Cell Count at the Conclusion of Treatment Period | From first treatment administration to each weekly visit until the last treatment visit (up to 56 months) | The change from baseline in CD4 cell count was summarized for each visit during the treatment phase. The time-weighted mean of change of the post baseline values was calculated. The time-weighted mean was adjusted AUC (area under the curve) by time. |
| Number of Participants With Grade 3 or 4 Adverse Events as Defined by the DAIDS Adverse Event Scale | From TE1 (first treatment administration) to last treatment visit, up to 56 months. | 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). |
| Number of Participants With at Least One Treatment-related Serious Adverse Event. | From TE1 (first treatment administration) to last treatment visit, up to 56 months. | Treatment-related (as defined by the investigator) 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 Treatment-related Adverse Events Resulting in Study Drug Discontinuation | From TE1 (first treatment administration) to last treatment visit, up to 56 months. | Treatment-related adverse events are defined as events with an onset on or after the first treatment (TE1). |
Participant flow
Recruitment details
This trial was conducted in 43 participants in the United States.
Participants by arm
| Arm | Count |
|---|---|
| PRO 140 Eligible subjects received 350 mg or 700 mg PRO 140 (leronlimab) administered weekly as subcutaneous injections along with Optimized Background Therapy (OBT) until virologic failure or another reason for discontinuation. | 43 |
| Total | 43 |
Baseline characteristics
| Characteristic | PRO 140 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 43 Participants |
| Age, Continuous | 53.07 years STANDARD_DEVIATION 7.31 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 18 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 | 1 Participants |
| Race (NIH/OMB) White | 23 Participants |
| Region of Enrollment United States | 43 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 29 | 1 / 14 |
| other Total, other adverse events | 27 / 29 | 13 / 14 |
| serious Total, serious adverse events | 11 / 29 | 4 / 14 |
Outcome results
Primary
Mean Change in Viral Load (HIV-1 RNA Levels) at the Conclusion of Treatment Period
The change from baseline in HIV-1 RNA levels (log 10 copies/mL) was summarized at least once every four weeks during the treatment extension phase. The time-weighted mean of change of the post baseline values was calculated. The time-weighted mean was adjusted AUC (area under the curve) by time.
Time frame: From TE1 (first treatment administration) to once every four weeks until last treatment visit (up to 56 months).
Population: The analysis population is defined as all subjects who enrolled in the study and received at least one dose of PRO 140. Subjects who had undefined change from baseline due to missing data were excluded from the analysis population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRO 140 | Mean Change in Viral Load (HIV-1 RNA Levels) at the Conclusion of Treatment Period | 0.13 log10 copies/mL | Standard Deviation 1.11 |
Secondary
Mean Change in CD4 Cell Count at the Conclusion of Treatment Period
The change from baseline in CD4 cell count was summarized for each visit during the treatment phase. The time-weighted mean of change of the post baseline values was calculated. The time-weighted mean was adjusted AUC (area under the curve) by time.
Time frame: From first treatment administration to each weekly visit until the last treatment visit (up to 56 months)
Population: The analysis population is defined as all subjects who enrolled in the study and received at least one dose of PRO 140. Subjects who had undefined change from baseline due to missing data were excluded from the analysis population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRO 140 | Mean Change in CD4 Cell Count at the Conclusion of Treatment Period | 46 cells/uL | Standard Deviation 122 |
Secondary
Number of Participants With at Least One Treatment-related Serious Adverse Event.
Treatment-related (as defined by the investigator) 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 TE1 (first treatment administration) to last treatment visit, up to 56 months.
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. | 15 Participants |
Secondary
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 TE1 (first treatment administration) to last treatment visit, up to 56 months.
Population: All patients who received at least one dose of PRO 140 (leronlimab) were included in the baseline analysis population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PRO 140 | Number of Participants With Grade 3 or 4 Adverse Events as Defined by the DAIDS Adverse Event Scale | 12 participants |
Secondary
Number of Participants With Treatment-related Adverse Events Resulting in Study Drug Discontinuation
Treatment-related adverse events are defined as events with an onset on or after the first treatment (TE1).
Time frame: From TE1 (first treatment administration) to last treatment visit, up to 56 months.
Population: All patients who received at least one dose of PRO 140 (leronlimab) were included in the baseline analysis population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PRO 140 | Number of Participants With Treatment-related Adverse Events Resulting in Study Drug Discontinuation | 1 participants |
Secondary
Proportion of Participants Experiencing Emergence of Dual/Mixed (D/M)- and CXCR4-tropic Virus in Patients Who Had Exclusive CCR5-tropic Virus at Study Entry.
All patients have exclusive C-C chemokine receptor type 5 (CCR5)-tropic virus at study entry. The proportion of patients with any tropism result of dual/mixed was summarized.
Time frame: From TE1 (first treatment administration) to last treatment visit, up to 56 months.
Population: The analysis population is defined as all subjects who enrolled in the extension portion of the study and received at least one dose of PRO140. Participants who had no dual/mixed tropism data collected or had undefined change from baseline due to missing data were excluded from the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PRO 140 | Proportion of Participants Experiencing Emergence of Dual/Mixed (D/M)- and CXCR4-tropic Virus in Patients Who Had Exclusive CCR5-tropic Virus at Study Entry. | 0.093 proportion of participants |
Secondary
Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Investigator Evaluation of Injection Site Reactions (ISR)
At each visit during the treatment extension phase, an injection site reaction assessment was completed for the current and previous injection sites. To assess severity, subcutaneous (SC) injection related events were recorded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table). 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 Participants who had no symptoms of injection site reactions, 0 was assigned.
Time frame: From TE1 (first treatment administration) weekly until last treatment visit (up to 56 months).
Population: All patients who received at least one dose of PRO 140 (leronlimab) were included in the baseline analysis population. Subjects who had undefined value due to missing data were excluded from the analysis population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Investigator Evaluation of Injection Site Reactions (ISR) | Participants with no ISR symptoms | 20 participants |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Investigator Evaluation of Injection Site Reactions (ISR) | Participants with Grade 1 ISR | 19 participants |
| PRO 140 | Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Investigator Evaluation of Injection Site Reactions (ISR) | Participants with Grade 2 or higher ISR | 0 participants |