HIV-1-infection
Conditions
Keywords
HIV, pharmacokinetics, pharmacodynamics, broadly neutralizing antibody, antiretroviral, Phase 1
Brief summary
The purpose of this study was to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of SAR441236, a tri-specific broadly neutralizing antibody against the human immunodeficiency virus (HIV).
Detailed description
This study evaluated the safety, tolerability, pharmacokinetics, and antiviral activity of SAR441236, a tri-specific broadly neutralizing antibody against HIV. The study included three arms. In Arm A, three dose cohorts (1, 3, and 10 mg/kg) of antiretroviral-treated, virologically suppressed participants were randomized (2:1, active to placebo) to receive a single intravenous (IV) dose of SAR441236 or placebo on Day 0. After Cohort 1 (1 mg/kg, lowest Arm A dose), each subsequent, higher-dose, cohort opened for enrollment only after an evaluation of safety outcomes for all participants in the previous cohort indicated it was safe to increase the dose of SAR441236. All participants in Cohorts 1-3 were followed for up to 24 weeks. In Arm A, Cohort 4, participants were randomized (2:1, active to placebo) to receive an IV infusion of 30 mg/kg SAR441236 or placebo once every 12 weeks beginning at entry, for a total of 4 infusions. The first six Cohort 4 participants were enrolled after the safety evaluation of Cohort 3 participants and the rest of the Cohort 4 participants were accrued after a safety evaluation of the first 6 participants. The time between infusions was prolonged for some participants due to the COVID-19 pandemic, which occurred during the course of the study. Participants in this cohort were followed for up to 36 weeks after their final infusion. Participants in Arm A continued taking non-study-provided antiretroviral treatment throughout the study. In Arm B, two cohorts of viremic participants received a single IV dose of SAR441236 on Day 0. Cohort 5 (1 mg/kg, lowest planned Arm B dose) opened first. After reviewing the safety data from that cohort, as well as that from all Arm A cohorts (which had fully enrolled), and taking into consideration enrollment challenges, the study was redesigned to be a dose de-escalation study in Arm B only. With this redesign, the study began enrollment into the highest dose (Cohort 8, 30 mg/kg) after closing Cohort 5 enrollment. Each subsequent Arm B cohort (of lower doses) was planned to open for enrollment only after an evaluation of efficacy data from Day 14 for all participants in the previous cohort was completed. However, the highest dose cohort never fully enrolled, and no subsequent cohorts were opened. All Arm B participants were followed for up to 24 weeks. Participants in Arm B initiated or re-initiated non-study-provided combination antiretroviral therapy (ART) (selected by their primary HIV clinician) on or before Day 28. A later version of the protocol changed the duration of SAR441236 monotherapy to no more than 14 days, however, no participants enrolled under that version. In Arm C, two cohorts of ART-treated, virologically suppressed participants were randomized (2:1, active to placebo) to receive a single subcutaneous (SC) dose of SAR441236 or placebo on Day 0. Cohort 11 (1 mg/kg) opened for enrollment only after an evaluation of safety outcomes from Day 14 for all participants in Cohort 10 (0.3 mg/kg) and the cumulative data from that cohort indicated it was safe to dose escalate. All Arm C participants were followed for 24 weeks. Participants in Arm C continued taking non-study-provided ART throughout the study. The study closed to enrollment and follow-up in May 2023 due to the expiration of the available study product, despite failing to meet its enrollment targets in Arm B. There had been no enrollment to the study since October 2021, despite the team's revision of the protocol (Version 4.0) to adjust eligibility criteria to facilitate enrollment of participants with viremia. At the time of study closure, Arm A and C were fully enrolled. Two Arm B cohorts (1 mg/kg and 30 mg/kg) achieved partial enrollment. Although protocol version 4.0 was released in September 2022, the last participant was enrolled under protocol version 3.0 and completed study follow-up in April 2022.
Interventions
BIOLOGICALPlacebo
Administered by intravenous (IV) infusion(s) or subcutaneous (SC) injection(s)
BIOLOGICALSAR441236
Administered by intravenous (IV) infusion(s) or subcutaneous (SC) injection(s)
Sponsors
Sanofi
ModeX Therapeutics, An OPKO Health Company
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Note: The following inclusion and
Exclusion criteria
reflect those in protocol version 3.0, the last protocol version under which participants enrolled. Although a protocol version 4.0 was released, no participants enrolled under that version. Inclusion Criteria, Arms A, B, and C * HIV-1 infection, documented by any licensed rapid HIV-1 test or HIV-1 enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot, Geenius assay, or a second antibody test by a method other than the initial rapid HIV-1 and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load. * NOTE: The term licensed refers to a US Food and Drug Administration (FDA)-approved kit. * WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot, Geenius assay, or a plasma HIV-1 RNA viral load. * The following laboratory values obtained within 45 days prior to entry by any US laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent. * Absolute neutrophil count (ANC) greater than or equal to 1500 cells/mm\^3 * Hemoglobin greater than or equal to 12.0 g/dL for men and greater than or equal to 11.0 g/dL for women * Platelet count greater than or equal to 120,000/mm\^3 * Creatinine clearance (CrCl) greater than 60 mL/min * Refer to the calculator located on the FSTRF website (at https://www.frontierscience.org/): Calculated Creatinine Clearance - Cockcroft-Gault Equation (Adult). * Aspartate aminotransferase (AST) (SGOT) less than 1.25 x upper limit of normal (ULN) * Alanine aminotransferase (ALT) (SGPT) less than 1.25 x ULN * Alkaline phosphatase less than 2.0 x ULN * Total bilirubin less than 1.1 x ULN * Hepatitis C virus (HCV) antibody negative result within 45 days prior to study entry or, for study candidates who are HCV antibody positive (based on testing performed at any time prior to study entry), a negative HCV RNA result obtained within 45 days prior to study entry. * NOTE: A negative HCV RNA level may result from either spontaneous clearance or from HCV therapy. Participants must have completed any HCV therapy at least 6 months prior to enrollment. * Negative HBsAg result obtained within 45 days prior to study entry, or documented hepatitis B immunity, defined as positive hepatitis B surface antibody testing, at any time. * Female study candidates of reproductive potential must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL performed at screening and again within 24 hours before study entry by any US clinic or laboratory that has a CLIA certification or its equivalent, or is using a point of care (POC)/CLIA-waived test. * NOTE: Reproductive potential is defined as girls who have reached menarche, and women who have not been post-menopausal for at least 24 consecutive months, i.e., who have had menses within the preceding 24 months, and women who have not undergone surgical sterilization, specifically hysterectomy and/or bilateral oophorectomy. * All study candidates must agree not to participate in an assisted conception process (e.g., sperm donation, intrauterine insemination, in vitro fertilization) from screening until 12 weeks after the final study visit. * If participating in sexual activity that could lead to pregnancy, all study candidates must agree to use at least one reliable method of contraception from study entry until 12 weeks after the final study visit. At least one of the following methods must be used appropriately: * Condoms (male or female) with or without a spermicidal agent. Condoms are recommended because their appropriate use is the only contraception method effective for preventing HIV transmission. * Diaphragm or cervical cap with spermicide. * Intrauterine device. * Hormone-based contraceptive. * Study candidates who are not of reproductive potential are eligible without requiring the use of a contraceptive method. Acceptable documentation of sterilization, menopause, and reproductive potential is specified below. * Written documentation or oral communication from a clinician or clinician's staff documented in source documents of one of the following: * Physician report/letter * Operative report or other source documentation in the patient record * Discharge summary * Laboratory report of azoospermia (is required to document successful vasectomy) * Follicle-stimulating hormone (FSH) measurement elevated into the menopausal range as established by the reporting laboratory. * NOTE A: Female reproductive potential is defined in the criteria above. * NOTE B: Male candidates who are not of reproductive potential are defined as having documented azoospermia. * NOTE C: A female study candidate's oral report of her male partner's lack of reproductive potential should be recorded in the source documents if written proof is not available. * Ability and willingness of participant to provide informed consent. Additional Arms A- and C-specific Inclusion Criteria * Receiving combination ART for at least 12 months prior to study entry with no changes in ART regimen within the 12 weeks prior to entry. * NOTE A: Use of a two-drug ART regimen within the 12 months prior to entry is exclusionary. * NOTE B: Although ritonavir or cobicistat may be included in a combination ART regimen, neither of these counts in a tally of antiretroviral agents. * CD4+ cell count of greater than or equal to 200 cells/mm\^3 obtained within 45 days prior to study entry at any US laboratory that has a CLIA certification or its equivalent. * Within 45 days prior to study entry, plasma HIV-1 RNA \<50 copies/mL on any FDA-approved assay with a limit of quantification of \<50 copies/mL by a US laboratory that has a CLIA certification or its equivalent. * Within 12 months prior to study entry and before screening, at least one documented plasma HIV-1 RNA \<50 copies/mL on any FDA-approved assay with a limit of quantification of \<50 copies/mL by a US laboratory that has a CLIA certification or its equivalent. * NOTE: A single plasma HIV-1 RNA ≥50 but \<200 copies/mL at least 6 months prior to screening is permitted if followed within 2 months by an HIV-1 RNA \<50 copies/mL. Additional Arm B-specific Inclusion Criteria * Plasma HIV-1 RNA \>5000 and ≤200,000 copies/mL within 45 days prior to study entry. * CD4+ cell count of greater than or equal to 350 cells/mm\^3 obtained within 45 days prior to study entry at any US laboratory that has a CLIA certification or its equivalent. * Willingness and ability to start or re-start combination ART by or on Day 28 of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Experiencing a Grade 3 or Higher Adverse Event (AE) That is Related to Study Treatment. | Measured from Day 0 through entire study follow-up, up to 24 weeks post study treatment administration for single dose cohorts (all arms) and up to 36 weeks after the fourth study treatment administration for the multi-dose cohort (Arm A only). | The proportion of participants reporting a grade 3 (severe), grade 4 (potentially life-threatening), or grade 5 (death) adverse event, that was judged by the core safety team (blinded to active/placebo treatment in Arms A and C) to be at least possibly related to study treatment. Based on the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017 |
| Mean Dose-normalized AUC 0-12wk of SAR441236 | SAR441236 PK samples at pre-dose, Hours 0, 2 (Arm A, B only) , 4 (Arm A, B only), 6 (Arm A, B only), and 10, Days 1, 2, 3, 4 (Arm B only), 7, 10 (Arm B only), and Weeks 2, 4, 8 (single dose only), 10 (multi dose only), and 12. | Dose-normalized Area Under the Concentration time curve (AUC) for each participant was calculated from all available SAR441236 concentrations measured prior to and after first treatment and prior to any subsequent treatment instances (Arm A: 30 mg/kg only). Standard noncompartmental techniques, using Phoenix WinNonlin, were used to determine AUC 0-12WK. |
| Mean Change in Plasma HIV-1 RNA (log10 Copies/mL) From Baseline to Day 7 of SAR441236 Monotherapy for Viremic Participants With HIV (Arm B Cohorts) | Measured at Day 0 and Day 7 | Baseline was defined as the last measurement taken prior to treatment initiation. Change was calculated as the log10-transformed value on Day 7 minus the log10-transformed value at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | Measured at Day 0 and at Week 2, 4, 12, and 24 | Number of participants who were anti-drug antibody (ADA) negative, ADA positive (treatment induced), and missing were calculated at each sampled timepoint. |
| Attributions of Anti-SAR441236 Antibodies Among Participants in Multi-dose Cohort. | Measured at Day 0, at Weeks 2 and 4 after Infusion 1, at Infusion 2, at Infusion 3, at Infusion 4, and at Weeks 12 and 36 post-Infusion 4 | Number of participants who were anti-drug antibody (ADA) negative, ADA positive (treatment induced), and missing were calculated at each sampled timepoint. |
| Mean Change From Baseline in CD4+ T Cell Counts Following the First Treatment of SAR441236 or Placebo for All Cohorts | Measured at Day 0 and Week 12 | Baseline was defined as the last measurement obtained prior to treatment initiation. Change was calculated as the value of CD4+ T cell counts (cells/mm\^3) at Week 12 (prior to subsequent study treatment, if any) minus the value at baseline. |
| Mean Change From Baseline in CD4+ T Cell Counts Following Each Infusion for Cohort 4 | Measured at Day 0 and at Week 12 after each infusion | Baseline was defined as the last measurement obtained prior to treatment initiation. Change was calculated as the value of CD4 + T cell counts (cells/mm\^3) at Week 12 after each infusion minus the value at baseline. |
| Mean Maximum Concentration (Cmax) of SAR441236 After a Single IV Infusion or SC Injection. | SAR441236 PK samples at pre-dose, Hours 0, 2 (Arm A, B only) , 4 (Arm A, B only), 6 (Arm A, B only), and 10, Days 1, 2, 3, 4 (Arm B only), 7, 10 (Arm B only), and Weeks 2, 4, 8 (single dose only), 10 (multi dose only), 12, and 24 (single dose only). | Cmax for each participant was calculated as the maximum observed concentration from all available SAR441236 concentrations measured prior to and after first treatment and prior to any subsequent treatment instances (Arm A: 30 mg/kg only). Standard noncompartmental techniques, using Phoenix WinNonlin, were used to determine Cmax. |
| Half-life (T1/2) of SAR441236 After a Single IV Infusion or SC Injection. | SAR441236 PK samples at pre-dose, Hours 0, 2 (Arm A, B only) , 4 (Arm A, B only), 6 (Arm A, B only), and 10, Days 1, 2, 3, 4 (Arm B only), 7, 10 (Arm B only), and Weeks 2, 4, 8 (single dose only), 10 (multi dose only), 12, and 24 (single dose only). | Half-life for each participant was calculated using regression analysis on all available SAR441236 concentrations measured prior to and after first treatment and prior to any subsequent treatment instances (Arm A: 30 mg/kg only). Standard noncompartmental techniques, using Phoenix WinNonlin, were used to determine half-life. |
| Time to Maximum Concentration (Tmax) of SAR441236 After a Single IV Infusion of SC Injection. | SAR441236 PK samples at pre-dose, Hours 0, 2 (Arm A, B only) , 4 (Arm A, B only), 6 (Arm A, B only), and 10, Days 1, 2, 3, 4 (Arm B only), 7, 10 (Arm B only), and Weeks 2, 4, 8 (single dose only), 10 (multi dose only), 12, and 24 (single dose only). | Tmax for each participant was time to maximum observed SAR441236 measured from all available SAR441236 concentrations measured prior to and after first treatment and prior to any subsequent treatment instances (Arm A: 30 mg/kg only). Standard noncompartmental techniques, using Phoenix WinNonlin, were used to determine Tmax. |
| Mean Change in Plasma HIV-1 RNA (log10 Copies/mL) From Baseline to Post-infusion Time Points During SAR441236 Monotherapy for Viremic Participants With HIV (Arm B Cohorts) | Measured at Day 0 and at Day 1, 2, 3, and 4, and Week 1, 2, and 3 | Baseline was defined as the last measurement taken prior to treatment initiation. Change was calculated as the log10-transformed value of plasma HIV-1 RNA at the post-infusion time point minus the log10-transformed value at baseline. |
| Volume of Distribution of SAR441236 After a Single IV Infusion or SC Injection | SAR441236 PK samples at pre-dose, Hours 0, 2 (Arm A, B only) , 4 (Arm A, B only), 6 (Arm A, B only), and 10, Days 1, 2, 3, 4 (Arm B only), 7, 10 (Arm B only), and Weeks 2, 4, 8 (single dose only), 10 (multi dose only), 12, and 24 (single dose only). | Volume of distribution (Arms A and B) or apparent volume of distribution (Arm C) was calculated from all available SAR441236 concentrations measured prior to and after first treatment and prior to any subsequent treatment instances (Arm A: 30 mg/kg only). Standard noncompartmental techniques, using Phoenix WinNonlin, were used to determine volume of distribution and apparent volume of distribution. |
| Mean Maximum Concentration (Cmax) of SAR441236 After the Fourth IV Infusion | Intensive SAR441236 PK samples after Infusion 4 (Week 36) at Hours 0, 2, 4, 6, and 10, Days 1 and 2, and at non-intensive sampling at Weeks 37, 38, 40, 48, 60, and 72. | Cmax after the fourth infusion was calculated as the maximum observed SAR441236 concentration from SAR441236 PK samples obtained after the fourth infusion. Standard noncompartmental techniques, using Phoenix WinNonlin, were used to determine Cmax after the 4th infusion. |
| Mean SAR441236 Concentration 12 Weeks After Infusions 1, 2, 3, and 4 | SAR441236 PK samples at Week 12, 24, 36, and 48. | SAR441236 concentration for each participant was calculated as the observed SAR441236 concentration 12 weeks after each infusion. |
| Mean AUC After Multiple Infusions of SAR441236 | Intensive SAR441236 PK samples taken at Hours 0, 2, 4, 6, and 10 and Days 1 and 2 after infusions 1 and 4 and non-intensive sampling at pre-dose (Weeks 0, Week 12, 24, 36) and Weeks 2, 4 , 8, 10, 13, 14, 16, 22, 26, 28, 34, 37, 38, 40, and 48. | Area Under the Concentration time curve (AUC) for multiple infusions of SAR441236 was calculated using all available SAR441236 concentrations. Standard noncompartmental techniques, using Phoenix WinNonlin, were used to determine AUC. |
| Mean AUC Accumulation Index (AI) (12 Weeks Post-Dose 1 vs 12 Weeks Post-Dose 4). | Intensive SAR441236 PK samples taken at Hours 0, 2, 4, 6, and 10 and Days 1 and 2 after infusions 1 and 4 and non-intensive sampling at pre-dose (Weeks 0, Week 12, 24, 36) and Weeks 2, 4 , 8, 10, 13, 14, 16, 22, 26, 28, 34, 37, 38, 40, and 48. | The AUC AI (12 Weeks post-Dose 1 vs 12 Weeks post-Dose 4) was calculated as the ratio of AUC 36-48 Weeks and AUC 0-12 Weeks. Standard noncompartmental techniques, using Phoenix WinNonlin, were used to determine AUC AI. |
| Mean Trough Accumulative Index (12 Weeks Post-Dose 1 vs 12 Weeks Post-Dose 4) | SAR441236 PK samples taken at Week 12 (pre-dose #2) and at Week 48 (12 weeks after dose #4) | The Trough AI was calculated as the ratio of the SAR441236 concentration observed 12 weeks after the 4th dose and the SAR441236 concentration observed 12 weeks after the 1st dose. Standard noncompartmental techniques, using Phoenix WinNonlin, were used to determine trough AI. |
| Dose-response Relationship Between SAR441236 Exposure and Changes in Plasma HIV-1 RNA | Day 0 and at all study visits prior to ART initiation/re-initiation (up to Week 4) | This relationship is based on measured SAR441236 concentrations and HIV-1 RNA values prior to participants initiating ART. |
| Clearance or Apparent Clearance of SAR441236 After a Single IV Infusion of SC Injection. | SAR441236 PK samples at pre-dose, Hours 0, 2 (Arm A, B only) , 4 (Arm A, B only), 6 (Arm A, B only), and 10, Days 1, 2, 3, 4 (Arm B only), 7, 10 (Arm B only), and Weeks 2, 4, 8 (single dose only), 10 (multi dose only), 12, and 24 (single dose only). | Clearance (CL, in Arms A and B) or Apparent Clearance (CL/F, in Arm C) for each participant was calculated from all available SAR441236 concentrations measured prior to and after first treatment and prior to any subsequent treatment instances (Arm A: 30 mg/kg only). Standard noncompartmental techniques, using Phoenix WinNonlin, were used to determine CL and CL/F. |
| Mean Change in Plasma HIV-1 RNA (log10 Copies/mL) From Baseline to Day 14 of SAR441236 Monotherapy for Viremic Participants With HIV (Arm B Cohorts) | Measured at Day 0 and Day 14 | Baseline was defined as the last measurement taken prior to treatment initiation. Change was calculated as the value of plasma HIV-1 RNA on Day 14 minus the value at baseline. |
| Mean Maximum Reduction of Plasma HIV-1 RNA During up to 28 Days of SAR441236 Monotherapy for Viremic Participants With HIV (Arm B Cohorts) | Measured at Day 0 and at up to Day 28 (while on SAR441236 monotherapy) | The maximum reduction in plasma HIV-1 RNA was calculated as the largest decline from baseline, defined as the last measurement taken prior to treatment initiation, to any post-infusion timepoint while the participant was on SAR441236 monotherapy (i.e., prior to initiating or reinitiating ART). |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at 23 Clinical Research Sites (CRSs) in the United States between May 2019 and October 2021.
Pre-assignment details
Participants who enrolled in Arms A and C were randomized 2:1 SAR441236:placebo. Participants who enrolled in Arm B were not randomized and were assigned open-label SAR4412326. For analysis, participants receiving placebo (of any dose-volume equivalent) are pooled within arm per the pre-specified analysis plan.
Participants by arm
| Arm | Count |
|---|---|
| Arm A: 1 mg/kg SAR441236 Participants continued on non-study-provided ART and received 1 mg/kg of SAR441236, administered as a single intravenous (IV) infusion on Day 0 (Cohort 1).
SAR441236: Administered by intravenous (IV) infusion(s) or subcutaneous (SC) injection(s) | 4 |
| Arm A: 3 mg/kg for SAR441236 Experimental: Arm A: 3 mg/kg SAR441236 Participants continued on non-study-provided ART, and received 3 mg/kg of SAR441236, administered as a single IV infusion on Day 0 (Cohort 2).
SAR441236: Administered by intravenous (IV) infusion(s) or subcutaneous (SC) injection(s) | 4 |
| Arm A: 10 mg/kg SAR441236 Participants continued non-study-provided ART and received 10 mg/kg of SAR441236, administered as a single IV infusion on Day 0 (Cohort 3).
SAR441236: Administered by intravenous (IV) infusion(s) or subcutaneous (SC) injection(s) | 4 |
| Arm A: 30 mg/kg SAR441236 Participants continued non-study-provided ART and received 30 mg/kg of SAR441236, administered as an IV infusion on Day 0 and then every 12 weeks for a total of four doses (Cohort 4).
SAR441236: Administered by intravenous (IV) infusion(s) or subcutaneous (SC) injection(s) | 10 |
| Arm A: 0 mg/kg SAR441236 Placebo participants were pooled across those receiving:
* 1 mg/kg dose volume-equivalent administered as a single IV infusion (Cohort 1).
* 3 mg/kg dose volume-equivalent administered as a single IV infusion (Cohort 2).
* 10 mg/kg dose volume-equivalent administered as a single IV infusion (Cohort 3)
* 30 mg/kg dose volume-equivalent administered as an IV infusion on Day 0 and then every 12 weeks for a total of four doses (Cohort 4)
All continued on non-study provided ART.
Placebo: Administered by intravenous (IV) infusion(s) or subcutaneous (SC) injection(s) | 10 |
| Arm B: 1 mg/kg SAR441236 Participants received 1 mg/kg of SAR441236, administered as a single IV infusion on Day 0. Antiretroviral treatment was initiated or re-initiated by Day 28 (Cohort 5).
SAR441236: Administered by intravenous (IV) infusion(s) or subcutaneous (SC) injection(s) | 5 |
| Arm B: 30 mg/kg SAR441236 Participants received 30 mg/kg of SAR441236, administered as a single IV infusion on Day 0. Antiretroviral treatment was initiated or re-initiated by Day 28 (Cohort 8).
SAR441236: Administered by intravenous (IV) infusion(s) or subcutaneous (SC) injection(s) | 2 |
| Arm C: 0.3 mg/kg SAR441236 Participants continued non-study-provided ART and received 0.3 mg/kg of SAR441236, administered as a subcutaneous (SC) injection(s) on Day 0 (Cohort 10).
SAR441236: Administered by intravenous (IV) infusion(s) or subcutaneous (SC) injection(s) | 4 |
| Arm C: 1 mg/kg SAR441236 Participants continued non-study-provided ART and received 1 mg/kg of SAR441236, administered as an SC injection(s) on Day 0 (Cohort 11).
SAR441236: Administered by intravenous (IV) infusion(s) or subcutaneous (SC) injection(s) | 4 |
| Arm C: 0 mg/kg SAR441236 Placebo participants were pooled across those receiving:
* 0.3 mg/kg dose volume-equivalent administered as an SC injection(s) (Cohort 10).
* 1 mg/kg dose volume-equivalent administered as an SC injection(s) (Cohort 11).
All continued on non-study provided ART.
Placebo: Administered by intravenous (IV) infusion(s) or subcutaneous (SC) injection(s) | 4 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Concerns about study visit compliance | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Did not receive study treatment | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 2 | 0 | 2 | 1 | 0 | 0 | 1 |
| Overall Study | Site Closure | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Arm C: 0.3 mg/kg SAR441236 | Arm B: 30 mg/kg SAR441236 | Arm B: 1 mg/kg SAR441236 | Arm A: 0 mg/kg SAR441236 | Arm A: 30 mg/kg SAR441236 | Arm A: 10 mg/kg SAR441236 | Arm A: 3 mg/kg for SAR441236 | Total | Arm A: 1 mg/kg SAR441236 | Arm C: 0 mg/kg SAR441236 | Arm C: 1 mg/kg SAR441236 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 54 years | 25 years | 26 years | 57 years | 51 years | 51 years | 47 years | 53 years | 54 years | 53 years | 54 years |
| Baseline Weight | 86 kilograms | 83 kilograms | 67 kilograms | 88 kilograms | 83 kilograms | 96 kilograms | 83 kilograms | 87 kilograms | 91 kilograms | 82 kilograms | 97 kilograms |
| CD4 Cell Count 250-499 cells/mm^3 | 1 Participants | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 0 Participants | 2 Participants | 14 Participants | 0 Participants | 1 Participants | 0 Participants |
| CD4 Cell Count ≥500 cells/mm^3 | 3 Participants | 0 Participants | 3 Participants | 7 Participants | 7 Participants | 4 Participants | 2 Participants | 37 Participants | 4 Participants | 3 Participants | 4 Participants |
| HIV RNA 100,000-200,000 copies/mL | — | 1 Participants | 0 Participants | — | — | — | — | 1 Participants | — | — | — |
| HIV RNA 10,000-29,000 copies/mL | — | 0 Participants | 1 Participants | — | — | — | — | 1 Participants | — | — | — |
| HIV RNA ≥200,000 copies/mL | — | 0 Participants | 1 Participants | — | — | — | — | 1 Participants | — | — | — |
| HIV RNA 30,000-99,999 copies/mL | — | 1 Participants | 3 Participants | — | — | — | — | 4 Participants | — | — | — |
| HIV RNA <40 copies/mL | 4 Participants | — | — | 10 Participants | 8 Participants | 4 Participants | 4 Participants | 42 Participants | 4 Participants | 4 Participants | 4 Participants |
| HIV RNA ≥40 copies/mL | 0 Participants | — | — | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Black (Non-Hispanic) | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 6 Participants | 2 Participants | 2 Participants | 19 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Hispanic or Latino (regardless of race) | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 6 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Other (Non-Hispanic) | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race/Ethnicity White (Non-Hispanic) | 3 Participants | 0 Participants | 3 Participants | 6 Participants | 3 Participants | 2 Participants | 2 Participants | 24 Participants | 3 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 5 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 5 Participants | 10 Participants | 9 Participants | 3 Participants | 2 Participants | 46 Participants | 4 Participants | 4 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 11 | 0 / 10 | 0 / 5 | 0 / 2 | 0 / 4 | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 2 / 4 | 4 / 4 | 3 / 4 | 8 / 11 | 8 / 10 | 5 / 5 | 0 / 2 | 1 / 4 | 3 / 4 | 3 / 4 |
| serious Total, serious adverse events | 1 / 4 | 0 / 4 | 0 / 4 | 2 / 11 | 0 / 10 | 1 / 5 | 0 / 2 | 0 / 4 | 0 / 4 | 0 / 4 |
Outcome results
Primary
Mean Change in Plasma HIV-1 RNA (log10 Copies/mL) From Baseline to Day 7 of SAR441236 Monotherapy for Viremic Participants With HIV (Arm B Cohorts)
Baseline was defined as the last measurement taken prior to treatment initiation. Change was calculated as the log10-transformed value on Day 7 minus the log10-transformed value at baseline.
Time frame: Measured at Day 0 and Day 7
Population: Arm B participants who actually received ≥0.9 mg/kg SAR441236, had an entry plasma HIV-1 RNA ≥ 5000 copies/mL, and had Plasma HIV-1 RNA measured at the scheduled study visits were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: 1 mg/kg SAR441236 | Mean Change in Plasma HIV-1 RNA (log10 Copies/mL) From Baseline to Day 7 of SAR441236 Monotherapy for Viremic Participants With HIV (Arm B Cohorts) | -0.10 log10 copies/mL | Standard Deviation 0.42 |
| Arm A: 3 mg/kg for SAR441236 | Mean Change in Plasma HIV-1 RNA (log10 Copies/mL) From Baseline to Day 7 of SAR441236 Monotherapy for Viremic Participants With HIV (Arm B Cohorts) | -0.38 log10 copies/mL | Standard Deviation 0.24 |
Comparison: Arm B participants were pooled across doses for analysis.p-value: 0.2695% CI: [-0.53, 0.18]t-test, 2 sided
Primary
Mean Dose-normalized AUC 0-12wk of SAR441236
Dose-normalized Area Under the Concentration time curve (AUC) for each participant was calculated from all available SAR441236 concentrations measured prior to and after first treatment and prior to any subsequent treatment instances (Arm A: 30 mg/kg only). Standard noncompartmental techniques, using Phoenix WinNonlin, were used to determine AUC 0-12WK.
Time frame: SAR441236 PK samples at pre-dose, Hours 0, 2 (Arm A, B only) , 4 (Arm A, B only), 6 (Arm A, B only), and 10, Days 1, 2, 3, 4 (Arm B only), 7, 10 (Arm B only), and Weeks 2, 4, 8 (single dose only), 10 (multi dose only), and 12.
Population: All participants who have been exposed to SAR441236 and have evaluable levels of SAR441236 such that AUC 0-12WK can be calculated.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Arm A: 1 mg/kg SAR441236 | Mean Dose-normalized AUC 0-12wk of SAR441236 | 593 (ug*day/mL)/(mg/kg) | Standard Error 282 |
| Arm A: 3 mg/kg for SAR441236 | Mean Dose-normalized AUC 0-12wk of SAR441236 | 631 (ug*day/mL)/(mg/kg) | Standard Error 120 |
| Arm A: 10 mg/kg SAR441236 | Mean Dose-normalized AUC 0-12wk of SAR441236 | 610 (ug*day/mL)/(mg/kg) | Standard Error 54.5 |
| Arm A: 30 mg/kg SAR441236 | Mean Dose-normalized AUC 0-12wk of SAR441236 | 743 (ug*day/mL)/(mg/kg) | Standard Error 296 |
| Arm A: 0 mg/kg SAR441236 | Mean Dose-normalized AUC 0-12wk of SAR441236 | 552 (ug*day/mL)/(mg/kg) | — |
| Arm B: 1 mg/kg SAR441236 | Mean Dose-normalized AUC 0-12wk of SAR441236 | 159 (ug*day/mL)/(mg/kg) | — |
| Arm B: 30 mg/kg SAR441236 | Mean Dose-normalized AUC 0-12wk of SAR441236 | 254 (ug*day/mL)/(mg/kg) | Standard Error 145 |
| Arm C: 0.3 mg/kg SAR441236 | Mean Dose-normalized AUC 0-12wk of SAR441236 | 236 (ug*day/mL)/(mg/kg) | Standard Error 126 |
Comparison: As dose-normalized AUC 0-12WK values were considered, participants were pooled within Arm (i.e., Arm A participants receiving 1, 3, 10, or 30 mg/kg were pooled and Arm C participants 0.3 or 1.0 mg/kg were pooled).95% CI: [1.9, 5.3]
Primary
Proportion of Participants Experiencing a Grade 3 or Higher Adverse Event (AE) That is Related to Study Treatment.
The proportion of participants reporting a grade 3 (severe), grade 4 (potentially life-threatening), or grade 5 (death) adverse event, that was judged by the core safety team (blinded to active/placebo treatment in Arms A and C) to be at least possibly related to study treatment. Based on the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017
Time frame: Measured from Day 0 through entire study follow-up, up to 24 weeks post study treatment administration for single dose cohorts (all arms) and up to 36 weeks after the fourth study treatment administration for the multi-dose cohort (Arm A only).
Population: All participants exposed to SAR441236/placebo. Those receiving placebo of any dose-volume equivalent are pooled w/in arm per the analysis plan. The highest dose in ArmA (Cohort 4) was designed to with dual safety objectives: 1) evaluate the safety of a single dose for 12 weeks and 2) evaluate the safety of multiple doses if the initial dose proved safe.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: 1 mg/kg SAR441236 | Proportion of Participants Experiencing a Grade 3 or Higher Adverse Event (AE) That is Related to Study Treatment. | 0 Proportion of participants |
| Arm A: 3 mg/kg for SAR441236 | Proportion of Participants Experiencing a Grade 3 or Higher Adverse Event (AE) That is Related to Study Treatment. | 0 Proportion of participants |
| Arm A: 10 mg/kg SAR441236 | Proportion of Participants Experiencing a Grade 3 or Higher Adverse Event (AE) That is Related to Study Treatment. | 0 Proportion of participants |
| Arm A: 30 mg/kg SAR441236 | Proportion of Participants Experiencing a Grade 3 or Higher Adverse Event (AE) That is Related to Study Treatment. | 0 Proportion of participants |
| Arm A: 0 mg/kg SAR441236 | Proportion of Participants Experiencing a Grade 3 or Higher Adverse Event (AE) That is Related to Study Treatment. | 0 Proportion of participants |
| Arm B: 1 mg/kg SAR441236 | Proportion of Participants Experiencing a Grade 3 or Higher Adverse Event (AE) That is Related to Study Treatment. | 0 Proportion of participants |
| Arm B: 30 mg/kg SAR441236 | Proportion of Participants Experiencing a Grade 3 or Higher Adverse Event (AE) That is Related to Study Treatment. | 0 Proportion of participants |
| Arm C: 0.3 mg/kg SAR441236 | Proportion of Participants Experiencing a Grade 3 or Higher Adverse Event (AE) That is Related to Study Treatment. | 0 Proportion of participants |
| Arm C: 1 mg/kg SAR441236 | Proportion of Participants Experiencing a Grade 3 or Higher Adverse Event (AE) That is Related to Study Treatment. | 0 Proportion of participants |
| Arm C: 0 mg/kg SAR441236 | Proportion of Participants Experiencing a Grade 3 or Higher Adverse Event (AE) That is Related to Study Treatment. | 0 Proportion of participants |
Secondary
Attributions of Anti-SAR441236 Antibodies Among Participants in Multi-dose Cohort.
Number of participants who were anti-drug antibody (ADA) negative, ADA positive (treatment induced), and missing were calculated at each sampled timepoint.
Time frame: Measured at Day 0, at Weeks 2 and 4 after Infusion 1, at Infusion 2, at Infusion 3, at Infusion 4, and at Weeks 12 and 36 post-Infusion 4
Population: Participants who received SAR441236 (not placebo) were tested for the presence of anti-drug antibodies. Only participants enrolled in the multi-dose cohort were included. Samples for one 30 mg/kg SAR441236 were lost in a freezer malfunction and no results were able to be obtained.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Multi-dose Cohort. | ADA Status at Inf 1: Day 0 | Positive: Treatment-Induced | 0 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Multi-dose Cohort. | ADA Status at Inf 1: Day 0 | Negative | 9 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Multi-dose Cohort. | ADA Status at Inf 1: Day 0 | Missing | 0 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Multi-dose Cohort. | ADA Status at Inf 1: Week 2 | Positive: Treatment-Induced | 0 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Multi-dose Cohort. | ADA Status at Inf 1: Week 2 | Negative | 8 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Multi-dose Cohort. | ADA Status at Inf 1: Week 2 | Missing | 1 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Multi-dose Cohort. | ADA Status at Inf 1: Week 4 | Positive: Treatment-Induced | 0 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Multi-dose Cohort. | ADA Status at Inf 1: Week 4 | Negative | 7 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Multi-dose Cohort. | ADA Status at Inf 1: Week 4 | Missing | 2 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Multi-dose Cohort. | ADA Status at Inf 2: Day 0 | Positive: Treatment-Induced | 1 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Multi-dose Cohort. | ADA Status at Inf 2: Day 0 | Negative | 5 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Multi-dose Cohort. | ADA Status at Inf 2: Day 0 | Missing | 3 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Multi-dose Cohort. | ADA Status at Inf 3: Day 0 | Positive: Treatment-Induced | 0 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Multi-dose Cohort. | ADA Status at Inf 3: Day 0 | Negative | 6 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Multi-dose Cohort. | ADA Status at Inf 3: Day 0 | Missing | 3 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Multi-dose Cohort. | ADA Status at Inf 4: Day 0 | Positive: Treatment-Induced | 0 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Multi-dose Cohort. | ADA Status at Inf 4: Day 0 | Negative | 6 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Multi-dose Cohort. | ADA Status at Inf 4: Day 0 | Missing | 3 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Multi-dose Cohort. | ADA Status at Inf 4: Week 12 | Positive: Treatment-Induced | 0 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Multi-dose Cohort. | ADA Status at Inf 4: Week 12 | Negative | 6 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Multi-dose Cohort. | ADA Status at Inf 4: Week 12 | Missing | 3 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Multi-dose Cohort. | ADA Status at Inf 4: Week 36 | Positive: Treatment-Induced | 1 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Multi-dose Cohort. | ADA Status at Inf 4: Week 36 | Negative | 4 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Multi-dose Cohort. | ADA Status at Inf 4: Week 36 | Missing | 4 Participants |
Secondary
Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts.
Number of participants who were anti-drug antibody (ADA) negative, ADA positive (treatment induced), and missing were calculated at each sampled timepoint.
Time frame: Measured at Day 0 and at Week 2, 4, 12, and 24
Population: Participants who received SAR441236 (not placebo) were tested for the presence of anti-drug antibodies. Only participants enrolled in single-dose cohorts were included.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 4 | Negative | 3 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 12 | Positive: Treatment-Induced | 0 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 4 | Positive: Treatment-Induced | 0 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 12 | Negative | 4 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 4 | Missing | 1 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 24 | Positive: Treatment-Induced | 0 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 2 | Positive: Treatment-Induced | 0 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 2 | Missing | 0 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 12 | Missing | 0 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 24 | Negative | 4 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Day 0 | Negative | 4 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Day 0 | Positive: Treatment-Induced | 0 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 24 | Missing | 0 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 2 | Negative | 4 Participants |
| Arm A: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Day 0 | Missing | 0 Participants |
| Arm A: 3 mg/kg for SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 2 | Negative | 4 Participants |
| Arm A: 3 mg/kg for SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 4 | Negative | 4 Participants |
| Arm A: 3 mg/kg for SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 4 | Positive: Treatment-Induced | 0 Participants |
| Arm A: 3 mg/kg for SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 2 | Missing | 0 Participants |
| Arm A: 3 mg/kg for SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Day 0 | Positive: Treatment-Induced | 0 Participants |
| Arm A: 3 mg/kg for SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 24 | Positive: Treatment-Induced | 1 Participants |
| Arm A: 3 mg/kg for SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Day 0 | Missing | 0 Participants |
| Arm A: 3 mg/kg for SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 12 | Missing | 0 Participants |
| Arm A: 3 mg/kg for SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Day 0 | Negative | 4 Participants |
| Arm A: 3 mg/kg for SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 4 | Missing | 0 Participants |
| Arm A: 3 mg/kg for SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 12 | Negative | 3 Participants |
| Arm A: 3 mg/kg for SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 2 | Positive: Treatment-Induced | 0 Participants |
| Arm A: 3 mg/kg for SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 24 | Missing | 0 Participants |
| Arm A: 3 mg/kg for SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 24 | Negative | 3 Participants |
| Arm A: 3 mg/kg for SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 12 | Positive: Treatment-Induced | 1 Participants |
| Arm A: 10 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 12 | Positive: Treatment-Induced | 1 Participants |
| Arm A: 10 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 12 | Missing | 0 Participants |
| Arm A: 10 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 24 | Positive: Treatment-Induced | 0 Participants |
| Arm A: 10 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Day 0 | Positive: Treatment-Induced | 0 Participants |
| Arm A: 10 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Day 0 | Missing | 0 Participants |
| Arm A: 10 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 24 | Missing | 0 Participants |
| Arm A: 10 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 2 | Positive: Treatment-Induced | 1 Participants |
| Arm A: 10 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 2 | Negative | 3 Participants |
| Arm A: 10 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 2 | Missing | 0 Participants |
| Arm A: 10 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 4 | Positive: Treatment-Induced | 1 Participants |
| Arm A: 10 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 24 | Negative | 4 Participants |
| Arm A: 10 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 4 | Negative | 3 Participants |
| Arm A: 10 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 4 | Missing | 0 Participants |
| Arm A: 10 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Day 0 | Negative | 4 Participants |
| Arm A: 10 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 12 | Negative | 3 Participants |
| Arm A: 30 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 4 | Positive: Treatment-Induced | 4 Participants |
| Arm A: 30 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 2 | Negative | 3 Participants |
| Arm A: 30 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 24 | Positive: Treatment-Induced | 3 Participants |
| Arm A: 30 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 4 | Negative | 1 Participants |
| Arm A: 30 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 2 | Positive: Treatment-Induced | 1 Participants |
| Arm A: 30 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Day 0 | Positive: Treatment-Induced | 0 Participants |
| Arm A: 30 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Day 0 | Negative | 5 Participants |
| Arm A: 30 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 4 | Missing | 0 Participants |
| Arm A: 30 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Day 0 | Missing | 0 Participants |
| Arm A: 30 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 24 | Missing | 2 Participants |
| Arm A: 30 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 12 | Positive: Treatment-Induced | 2 Participants |
| Arm A: 30 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 12 | Missing | 3 Participants |
| Arm A: 30 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 2 | Missing | 1 Participants |
| Arm A: 30 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 24 | Negative | 0 Participants |
| Arm A: 30 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 12 | Negative | 0 Participants |
| Arm A: 0 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 4 | Missing | 0 Participants |
| Arm A: 0 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 4 | Positive: Treatment-Induced | 0 Participants |
| Arm A: 0 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 24 | Missing | 2 Participants |
| Arm A: 0 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 24 | Positive: Treatment-Induced | 0 Participants |
| Arm A: 0 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 2 | Negative | 1 Participants |
| Arm A: 0 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Day 0 | Positive: Treatment-Induced | 0 Participants |
| Arm A: 0 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 2 | Missing | 0 Participants |
| Arm A: 0 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Day 0 | Negative | 2 Participants |
| Arm A: 0 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 4 | Negative | 2 Participants |
| Arm A: 0 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 2 | Positive: Treatment-Induced | 1 Participants |
| Arm A: 0 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 12 | Missing | 1 Participants |
| Arm A: 0 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 12 | Negative | 1 Participants |
| Arm A: 0 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Day 0 | Missing | 0 Participants |
| Arm A: 0 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 24 | Negative | 0 Participants |
| Arm A: 0 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 12 | Positive: Treatment-Induced | 0 Participants |
| Arm B: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 2 | Positive: Treatment-Induced | 0 Participants |
| Arm B: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Day 0 | Positive: Treatment-Induced | 0 Participants |
| Arm B: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Day 0 | Negative | 4 Participants |
| Arm B: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Day 0 | Missing | 0 Participants |
| Arm B: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 2 | Negative | 4 Participants |
| Arm B: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 2 | Missing | 0 Participants |
| Arm B: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 4 | Positive: Treatment-Induced | 0 Participants |
| Arm B: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 4 | Negative | 4 Participants |
| Arm B: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 4 | Missing | 0 Participants |
| Arm B: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 12 | Positive: Treatment-Induced | 0 Participants |
| Arm B: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 12 | Negative | 4 Participants |
| Arm B: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 12 | Missing | 0 Participants |
| Arm B: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 24 | Positive: Treatment-Induced | 0 Participants |
| Arm B: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 24 | Negative | 4 Participants |
| Arm B: 1 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 24 | Missing | 0 Participants |
| Arm B: 30 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Day 0 | Positive: Treatment-Induced | 0 Participants |
| Arm B: 30 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 24 | Positive: Treatment-Induced | 2 Participants |
| Arm B: 30 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 4 | Missing | 0 Participants |
| Arm B: 30 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 4 | Negative | 4 Participants |
| Arm B: 30 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 4 | Positive: Treatment-Induced | 0 Participants |
| Arm B: 30 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 2 | Missing | 0 Participants |
| Arm B: 30 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 2 | Negative | 3 Participants |
| Arm B: 30 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 24 | Missing | 0 Participants |
| Arm B: 30 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 24 | Negative | 2 Participants |
| Arm B: 30 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 2 | Positive: Treatment-Induced | 1 Participants |
| Arm B: 30 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Day 0 | Missing | 0 Participants |
| Arm B: 30 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Day 0 | Negative | 4 Participants |
| Arm B: 30 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 12 | Missing | 0 Participants |
| Arm B: 30 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 12 | Negative | 3 Participants |
| Arm B: 30 mg/kg SAR441236 | Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts. | ADA Status at Week 12 | Positive: Treatment-Induced | 1 Participants |
Secondary
Clearance or Apparent Clearance of SAR441236 After a Single IV Infusion of SC Injection.
Clearance (CL, in Arms A and B) or Apparent Clearance (CL/F, in Arm C) for each participant was calculated from all available SAR441236 concentrations measured prior to and after first treatment and prior to any subsequent treatment instances (Arm A: 30 mg/kg only). Standard noncompartmental techniques, using Phoenix WinNonlin, were used to determine CL and CL/F.
Time frame: SAR441236 PK samples at pre-dose, Hours 0, 2 (Arm A, B only) , 4 (Arm A, B only), 6 (Arm A, B only), and 10, Days 1, 2, 3, 4 (Arm B only), 7, 10 (Arm B only), and Weeks 2, 4, 8 (single dose only), 10 (multi dose only), 12, and 24 (single dose only).
Population: All participants exposed to SAR441236 with evaluable levels of SAR441236 such that clearance (Arms A and B) or apparent clearance (Arm C) can be derived.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: 1 mg/kg SAR441236 | Clearance or Apparent Clearance of SAR441236 After a Single IV Infusion of SC Injection. | 181 (mL/day) | Standard Deviation 148 |
| Arm A: 3 mg/kg for SAR441236 | Clearance or Apparent Clearance of SAR441236 After a Single IV Infusion of SC Injection. | 116 (mL/day) | Standard Deviation 14.9 |
| Arm A: 10 mg/kg SAR441236 | Clearance or Apparent Clearance of SAR441236 After a Single IV Infusion of SC Injection. | 130 (mL/day) | Standard Deviation 43.5 |
| Arm A: 30 mg/kg SAR441236 | Clearance or Apparent Clearance of SAR441236 After a Single IV Infusion of SC Injection. | 122 (mL/day) | Standard Deviation 50.2 |
| Arm A: 0 mg/kg SAR441236 | Clearance or Apparent Clearance of SAR441236 After a Single IV Infusion of SC Injection. | 132 (mL/day) | Standard Deviation 28.1 |
| Arm B: 1 mg/kg SAR441236 | Clearance or Apparent Clearance of SAR441236 After a Single IV Infusion of SC Injection. | 348 (mL/day) | Standard Deviation 51.6 |
| Arm B: 30 mg/kg SAR441236 | Clearance or Apparent Clearance of SAR441236 After a Single IV Infusion of SC Injection. | 163 (mL/day) | Standard Deviation 36 |
| Arm C: 0.3 mg/kg SAR441236 | Clearance or Apparent Clearance of SAR441236 After a Single IV Infusion of SC Injection. | 399 (mL/day) | Standard Deviation 318 |
Secondary
Dose-response Relationship Between SAR441236 Exposure and Changes in Plasma HIV-1 RNA
This relationship is based on measured SAR441236 concentrations and HIV-1 RNA values prior to participants initiating ART.
Time frame: Day 0 and at all study visits prior to ART initiation/re-initiation (up to Week 4)
Population: Only Arm B participants (who were off ART and viremic at entry) were considered for this outcome. Summaries of viral response are provided in outcomes 3, 4, 5, and 6. However, the dose-response relationship cannot be modeled due to insufficient sample size.
Secondary
Half-life (T1/2) of SAR441236 After a Single IV Infusion or SC Injection.
Half-life for each participant was calculated using regression analysis on all available SAR441236 concentrations measured prior to and after first treatment and prior to any subsequent treatment instances (Arm A: 30 mg/kg only). Standard noncompartmental techniques, using Phoenix WinNonlin, were used to determine half-life.
Time frame: SAR441236 PK samples at pre-dose, Hours 0, 2 (Arm A, B only) , 4 (Arm A, B only), 6 (Arm A, B only), and 10, Days 1, 2, 3, 4 (Arm B only), 7, 10 (Arm B only), and Weeks 2, 4, 8 (single dose only), 10 (multi dose only), 12, and 24 (single dose only).
Population: All participants exposed to SAR441236 with evaluable levels of SAR441236 such that half-life can be derived.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: 1 mg/kg SAR441236 | Half-life (T1/2) of SAR441236 After a Single IV Infusion or SC Injection. | 34.8 (days) | Standard Deviation 4.73 |
| Arm A: 3 mg/kg for SAR441236 | Half-life (T1/2) of SAR441236 After a Single IV Infusion or SC Injection. | 38.1 (days) | Standard Deviation 4.94 |
| Arm A: 10 mg/kg SAR441236 | Half-life (T1/2) of SAR441236 After a Single IV Infusion or SC Injection. | 30.9 (days) | Standard Deviation 4.9 |
| Arm A: 30 mg/kg SAR441236 | Half-life (T1/2) of SAR441236 After a Single IV Infusion or SC Injection. | 37.0 (days) | Standard Deviation 6.46 |
| Arm A: 0 mg/kg SAR441236 | Half-life (T1/2) of SAR441236 After a Single IV Infusion or SC Injection. | 27.2 (days) | Standard Deviation 2.37 |
| Arm B: 1 mg/kg SAR441236 | Half-life (T1/2) of SAR441236 After a Single IV Infusion or SC Injection. | 23.2 (days) | Standard Deviation 3.97 |
| Arm B: 30 mg/kg SAR441236 | Half-life (T1/2) of SAR441236 After a Single IV Infusion or SC Injection. | 58.5 (days) | Standard Deviation 1.41 |
| Arm C: 0.3 mg/kg SAR441236 | Half-life (T1/2) of SAR441236 After a Single IV Infusion or SC Injection. | 47.7 (days) | Standard Deviation 6.13 |
Secondary
Mean AUC Accumulation Index (AI) (12 Weeks Post-Dose 1 vs 12 Weeks Post-Dose 4).
The AUC AI (12 Weeks post-Dose 1 vs 12 Weeks post-Dose 4) was calculated as the ratio of AUC 36-48 Weeks and AUC 0-12 Weeks. Standard noncompartmental techniques, using Phoenix WinNonlin, were used to determine AUC AI.
Time frame: Intensive SAR441236 PK samples taken at Hours 0, 2, 4, 6, and 10 and Days 1 and 2 after infusions 1 and 4 and non-intensive sampling at pre-dose (Weeks 0, Week 12, 24, 36) and Weeks 2, 4 , 8, 10, 13, 14, 16, 22, 26, 28, 34, 37, 38, 40, and 48.
Population: All participants exposed to 4 infusions of SAR441236 (30 mg/kg participants only) with evaluable levels of SAR441236. Only participants who maintained the every 12-week dosing schedule were considered for AUC AI.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: 1 mg/kg SAR441236 | Mean AUC Accumulation Index (AI) (12 Weeks Post-Dose 1 vs 12 Weeks Post-Dose 4). | 1.24 Ratio | Standard Deviation 0.18 |
Secondary
Mean AUC After Multiple Infusions of SAR441236
Area Under the Concentration time curve (AUC) for multiple infusions of SAR441236 was calculated using all available SAR441236 concentrations. Standard noncompartmental techniques, using Phoenix WinNonlin, were used to determine AUC.
Time frame: Intensive SAR441236 PK samples taken at Hours 0, 2, 4, 6, and 10 and Days 1 and 2 after infusions 1 and 4 and non-intensive sampling at pre-dose (Weeks 0, Week 12, 24, 36) and Weeks 2, 4 , 8, 10, 13, 14, 16, 22, 26, 28, 34, 37, 38, 40, and 48.
Population: All participants exposed to 4 infusions of SAR441236 (30 mg/kg participants only) with evaluable levels of SAR441236. Only participants who maintained the every 12-week dosing schedule were considered for AUC12-24WK, AUC 24-36 WK, AUC 36-48 WK, and AUC 0-48 WK.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A: 1 mg/kg SAR441236 | Mean AUC After Multiple Infusions of SAR441236 | AUC 12-24 Week | 26508.02 (ug*day)/mL | Standard Deviation 5914.53 |
| Arm A: 1 mg/kg SAR441236 | Mean AUC After Multiple Infusions of SAR441236 | AUC 24-36 Week | 21809.83 (ug*day)/mL | Standard Deviation 7210.58 |
| Arm A: 1 mg/kg SAR441236 | Mean AUC After Multiple Infusions of SAR441236 | AUC 36-48 Week | 26137.06 (ug*day)/mL | Standard Deviation 5336.72 |
| Arm A: 1 mg/kg SAR441236 | Mean AUC After Multiple Infusions of SAR441236 | AUC 0-48 Week | 96277.43 (ug*day)/mL | Standard Deviation 17105.7 |
Secondary
Mean Change From Baseline in CD4+ T Cell Counts Following Each Infusion for Cohort 4
Baseline was defined as the last measurement obtained prior to treatment initiation. Change was calculated as the value of CD4 + T cell counts (cells/mm\^3) at Week 12 after each infusion minus the value at baseline.
Time frame: Measured at Day 0 and at Week 12 after each infusion
Population: Arm A participants who received multiple infusions (SAR441236 or placebo) and had CD4 count measured at the scheduled study visits were included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A: 1 mg/kg SAR441236 | Mean Change From Baseline in CD4+ T Cell Counts Following Each Infusion for Cohort 4 | Change in from baseline to Week 12 after 2nd treatment | 73 cells/mm^3 | Standard Deviation 357 |
| Arm A: 1 mg/kg SAR441236 | Mean Change From Baseline in CD4+ T Cell Counts Following Each Infusion for Cohort 4 | Change in from baseline to Week 12 after 3rd treatment | 78 cells/mm^3 | Standard Deviation 232 |
| Arm A: 1 mg/kg SAR441236 | Mean Change From Baseline in CD4+ T Cell Counts Following Each Infusion for Cohort 4 | Change in from baseline to Week 12 after 4th treatment | -83 cells/mm^3 | Standard Deviation 253 |
| Arm A: 3 mg/kg for SAR441236 | Mean Change From Baseline in CD4+ T Cell Counts Following Each Infusion for Cohort 4 | Change in from baseline to Week 12 after 2nd treatment | 28 cells/mm^3 | Standard Deviation 190 |
| Arm A: 3 mg/kg for SAR441236 | Mean Change From Baseline in CD4+ T Cell Counts Following Each Infusion for Cohort 4 | Change in from baseline to Week 12 after 3rd treatment | 17 cells/mm^3 | Standard Deviation 252 |
| Arm A: 3 mg/kg for SAR441236 | Mean Change From Baseline in CD4+ T Cell Counts Following Each Infusion for Cohort 4 | Change in from baseline to Week 12 after 4th treatment | 77 cells/mm^3 | Standard Deviation 111 |
Secondary
Mean Change From Baseline in CD4+ T Cell Counts Following the First Treatment of SAR441236 or Placebo for All Cohorts
Baseline was defined as the last measurement obtained prior to treatment initiation. Change was calculated as the value of CD4+ T cell counts (cells/mm\^3) at Week 12 (prior to subsequent study treatment, if any) minus the value at baseline.
Time frame: Measured at Day 0 and Week 12
Population: All participants who received study treatment (SAR441236 or placebo) and had CD4 counts measured at the scheduled study visits were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: 1 mg/kg SAR441236 | Mean Change From Baseline in CD4+ T Cell Counts Following the First Treatment of SAR441236 or Placebo for All Cohorts | -6 cells/mm^3 | Standard Deviation 87 |
| Arm A: 3 mg/kg for SAR441236 | Mean Change From Baseline in CD4+ T Cell Counts Following the First Treatment of SAR441236 or Placebo for All Cohorts | -96 cells/mm^3 | Standard Deviation 222 |
| Arm A: 10 mg/kg SAR441236 | Mean Change From Baseline in CD4+ T Cell Counts Following the First Treatment of SAR441236 or Placebo for All Cohorts | 96 cells/mm^3 | Standard Deviation 249 |
| Arm A: 30 mg/kg SAR441236 | Mean Change From Baseline in CD4+ T Cell Counts Following the First Treatment of SAR441236 or Placebo for All Cohorts | -36 cells/mm^3 | Standard Deviation 246 |
| Arm A: 0 mg/kg SAR441236 | Mean Change From Baseline in CD4+ T Cell Counts Following the First Treatment of SAR441236 or Placebo for All Cohorts | -43 cells/mm^3 | Standard Deviation 117 |
| Arm B: 1 mg/kg SAR441236 | Mean Change From Baseline in CD4+ T Cell Counts Following the First Treatment of SAR441236 or Placebo for All Cohorts | 10 cells/mm^3 | Standard Deviation 273 |
| Arm B: 30 mg/kg SAR441236 | Mean Change From Baseline in CD4+ T Cell Counts Following the First Treatment of SAR441236 or Placebo for All Cohorts | 138 cells/mm^3 | — |
| Arm C: 0.3 mg/kg SAR441236 | Mean Change From Baseline in CD4+ T Cell Counts Following the First Treatment of SAR441236 or Placebo for All Cohorts | 61 cells/mm^3 | Standard Deviation 176 |
| Arm C: 1 mg/kg SAR441236 | Mean Change From Baseline in CD4+ T Cell Counts Following the First Treatment of SAR441236 or Placebo for All Cohorts | -136 cells/mm^3 | Standard Deviation 216 |
| Arm C: 0 mg/kg SAR441236 | Mean Change From Baseline in CD4+ T Cell Counts Following the First Treatment of SAR441236 or Placebo for All Cohorts | -53 cells/mm^3 | Standard Deviation 289 |
Secondary
Mean Change in Plasma HIV-1 RNA (log10 Copies/mL) From Baseline to Day 14 of SAR441236 Monotherapy for Viremic Participants With HIV (Arm B Cohorts)
Baseline was defined as the last measurement taken prior to treatment initiation. Change was calculated as the value of plasma HIV-1 RNA on Day 14 minus the value at baseline.
Time frame: Measured at Day 0 and Day 14
Population: Arm B participants who actually received ≥0.9 mg/kg SAR441236, had an entry plasma HIV-1 RNA ≥ 5000 copies/mL, and had Plasma HIV-1 RNA measured at the scheduled study visits were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: 1 mg/kg SAR441236 | Mean Change in Plasma HIV-1 RNA (log10 Copies/mL) From Baseline to Day 14 of SAR441236 Monotherapy for Viremic Participants With HIV (Arm B Cohorts) | -0.08 log10 copies/mL | Standard Deviation 0.08 |
| Arm A: 3 mg/kg for SAR441236 | Mean Change in Plasma HIV-1 RNA (log10 Copies/mL) From Baseline to Day 14 of SAR441236 Monotherapy for Viremic Participants With HIV (Arm B Cohorts) | 0.09 log10 copies/mL | Standard Deviation 0.38 |
Comparison: Arm B participants were pooled across doses for analysis.p-value: 0.7895% CI: [-0.24, 0.19]t-test, 2 sided
Secondary
Mean Change in Plasma HIV-1 RNA (log10 Copies/mL) From Baseline to Post-infusion Time Points During SAR441236 Monotherapy for Viremic Participants With HIV (Arm B Cohorts)
Baseline was defined as the last measurement taken prior to treatment initiation. Change was calculated as the log10-transformed value of plasma HIV-1 RNA at the post-infusion time point minus the log10-transformed value at baseline.
Time frame: Measured at Day 0 and at Day 1, 2, 3, and 4, and Week 1, 2, and 3
Population: Arm B participants who actually received ≥0.9 mg/kg SAR441236, had an entry plasma HIV-1 RNA ≥ 5000 copies/mL, and had Plasma HIV-1 RNA measured at the scheduled study visits were included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A: 1 mg/kg SAR441236 | Mean Change in Plasma HIV-1 RNA (log10 Copies/mL) From Baseline to Post-infusion Time Points During SAR441236 Monotherapy for Viremic Participants With HIV (Arm B Cohorts) | Change from baseline to Day 3 | -0.04 log10 copies/mL | Standard Deviation 0.2 |
| Arm A: 1 mg/kg SAR441236 | Mean Change in Plasma HIV-1 RNA (log10 Copies/mL) From Baseline to Post-infusion Time Points During SAR441236 Monotherapy for Viremic Participants With HIV (Arm B Cohorts) | Change from baseline to Week 1 | -0.10 log10 copies/mL | Standard Deviation 0.42 |
| Arm A: 1 mg/kg SAR441236 | Mean Change in Plasma HIV-1 RNA (log10 Copies/mL) From Baseline to Post-infusion Time Points During SAR441236 Monotherapy for Viremic Participants With HIV (Arm B Cohorts) | Change from baseline to Day 2 | 0.04 log10 copies/mL | Standard Deviation 0.14 |
| Arm A: 1 mg/kg SAR441236 | Mean Change in Plasma HIV-1 RNA (log10 Copies/mL) From Baseline to Post-infusion Time Points During SAR441236 Monotherapy for Viremic Participants With HIV (Arm B Cohorts) | Change from baseline to Week 2 | -0.08 log10 copies/mL | Standard Deviation 0.08 |
| Arm A: 1 mg/kg SAR441236 | Mean Change in Plasma HIV-1 RNA (log10 Copies/mL) From Baseline to Post-infusion Time Points During SAR441236 Monotherapy for Viremic Participants With HIV (Arm B Cohorts) | Change from baseline to Day 4 | 0.01 log10 copies/mL | Standard Deviation 0.4 |
| Arm A: 1 mg/kg SAR441236 | Mean Change in Plasma HIV-1 RNA (log10 Copies/mL) From Baseline to Post-infusion Time Points During SAR441236 Monotherapy for Viremic Participants With HIV (Arm B Cohorts) | Change from baseline to Week 3 | 0.03 log10 copies/mL | Standard Deviation 0.37 |
| Arm A: 1 mg/kg SAR441236 | Mean Change in Plasma HIV-1 RNA (log10 Copies/mL) From Baseline to Post-infusion Time Points During SAR441236 Monotherapy for Viremic Participants With HIV (Arm B Cohorts) | Change from baseline to Day 1 | 0.04 log10 copies/mL | Standard Deviation 0.07 |
| Arm A: 3 mg/kg for SAR441236 | Mean Change in Plasma HIV-1 RNA (log10 Copies/mL) From Baseline to Post-infusion Time Points During SAR441236 Monotherapy for Viremic Participants With HIV (Arm B Cohorts) | Change from baseline to Week 3 | 0.07 log10 copies/mL | Standard Deviation 0.48 |
| Arm A: 3 mg/kg for SAR441236 | Mean Change in Plasma HIV-1 RNA (log10 Copies/mL) From Baseline to Post-infusion Time Points During SAR441236 Monotherapy for Viremic Participants With HIV (Arm B Cohorts) | Change from baseline to Day 1 | 0.10 log10 copies/mL | Standard Deviation 0.12 |
| Arm A: 3 mg/kg for SAR441236 | Mean Change in Plasma HIV-1 RNA (log10 Copies/mL) From Baseline to Post-infusion Time Points During SAR441236 Monotherapy for Viremic Participants With HIV (Arm B Cohorts) | Change from baseline to Day 2 | -0.06 log10 copies/mL | Standard Deviation 0.07 |
| Arm A: 3 mg/kg for SAR441236 | Mean Change in Plasma HIV-1 RNA (log10 Copies/mL) From Baseline to Post-infusion Time Points During SAR441236 Monotherapy for Viremic Participants With HIV (Arm B Cohorts) | Change from baseline to Day 3 | -0.39 log10 copies/mL | Standard Deviation 0.04 |
| Arm A: 3 mg/kg for SAR441236 | Mean Change in Plasma HIV-1 RNA (log10 Copies/mL) From Baseline to Post-infusion Time Points During SAR441236 Monotherapy for Viremic Participants With HIV (Arm B Cohorts) | Change from baseline to Day 4 | -0.68 log10 copies/mL | Standard Deviation 0.03 |
| Arm A: 3 mg/kg for SAR441236 | Mean Change in Plasma HIV-1 RNA (log10 Copies/mL) From Baseline to Post-infusion Time Points During SAR441236 Monotherapy for Viremic Participants With HIV (Arm B Cohorts) | Change from baseline to Week 1 | -0.38 log10 copies/mL | Standard Deviation 0.24 |
| Arm A: 3 mg/kg for SAR441236 | Mean Change in Plasma HIV-1 RNA (log10 Copies/mL) From Baseline to Post-infusion Time Points During SAR441236 Monotherapy for Viremic Participants With HIV (Arm B Cohorts) | Change from baseline to Week 2 | 0.09 log10 copies/mL | Standard Deviation 0.38 |
Secondary
Mean Maximum Concentration (Cmax) of SAR441236 After a Single IV Infusion or SC Injection.
Cmax for each participant was calculated as the maximum observed concentration from all available SAR441236 concentrations measured prior to and after first treatment and prior to any subsequent treatment instances (Arm A: 30 mg/kg only). Standard noncompartmental techniques, using Phoenix WinNonlin, were used to determine Cmax.
Time frame: SAR441236 PK samples at pre-dose, Hours 0, 2 (Arm A, B only) , 4 (Arm A, B only), 6 (Arm A, B only), and 10, Days 1, 2, 3, 4 (Arm B only), 7, 10 (Arm B only), and Weeks 2, 4, 8 (single dose only), 10 (multi dose only), 12, and 24 (single dose only).
Population: All participants exposed to SAR441236 with evaluable levels of SAR441236 such that Cmax can be derived.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: 1 mg/kg SAR441236 | Mean Maximum Concentration (Cmax) of SAR441236 After a Single IV Infusion or SC Injection. | 25.2 (ug/mL) | Standard Error 11 |
| Arm A: 3 mg/kg for SAR441236 | Mean Maximum Concentration (Cmax) of SAR441236 After a Single IV Infusion or SC Injection. | 72.7 (ug/mL) | Standard Error 27.7 |
| Arm A: 10 mg/kg SAR441236 | Mean Maximum Concentration (Cmax) of SAR441236 After a Single IV Infusion or SC Injection. | 295 (ug/mL) | Standard Error 265 |
| Arm A: 30 mg/kg SAR441236 | Mean Maximum Concentration (Cmax) of SAR441236 After a Single IV Infusion or SC Injection. | 771 (ug/mL) | Standard Error 250 |
| Arm A: 0 mg/kg SAR441236 | Mean Maximum Concentration (Cmax) of SAR441236 After a Single IV Infusion or SC Injection. | 24.9 (ug/mL) | Standard Error 3.5 |
| Arm B: 1 mg/kg SAR441236 | Mean Maximum Concentration (Cmax) of SAR441236 After a Single IV Infusion or SC Injection. | 483 (ug/mL) | Standard Error 249 |
| Arm B: 30 mg/kg SAR441236 | Mean Maximum Concentration (Cmax) of SAR441236 After a Single IV Infusion or SC Injection. | 1.69 (ug/mL) | Standard Error 0.74 |
| Arm C: 0.3 mg/kg SAR441236 | Mean Maximum Concentration (Cmax) of SAR441236 After a Single IV Infusion or SC Injection. | 4.77 (ug/mL) | Standard Error 2.32 |
Secondary
Mean Maximum Concentration (Cmax) of SAR441236 After the Fourth IV Infusion
Cmax after the fourth infusion was calculated as the maximum observed SAR441236 concentration from SAR441236 PK samples obtained after the fourth infusion. Standard noncompartmental techniques, using Phoenix WinNonlin, were used to determine Cmax after the 4th infusion.
Time frame: Intensive SAR441236 PK samples after Infusion 4 (Week 36) at Hours 0, 2, 4, 6, and 10, Days 1 and 2, and at non-intensive sampling at Weeks 37, 38, 40, 48, 60, and 72.
Population: All participants exposed to 4 infusions of SASR441236 (30 mg/kg participants only) with evaluable levels of SAR441236 such that Cmax can be derived.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: 1 mg/kg SAR441236 | Mean Maximum Concentration (Cmax) of SAR441236 After the Fourth IV Infusion | 890.50 ug/mL | Standard Deviation 176.66 |
Secondary
Mean Maximum Reduction of Plasma HIV-1 RNA During up to 28 Days of SAR441236 Monotherapy for Viremic Participants With HIV (Arm B Cohorts)
The maximum reduction in plasma HIV-1 RNA was calculated as the largest decline from baseline, defined as the last measurement taken prior to treatment initiation, to any post-infusion timepoint while the participant was on SAR441236 monotherapy (i.e., prior to initiating or reinitiating ART).
Time frame: Measured at Day 0 and at up to Day 28 (while on SAR441236 monotherapy)
Population: Arm B participants who actually received ≥0.9 mg/kg SAR441236 and had an entry plasma HIV-1 RNA ≥ 5000 copies/mL.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: 1 mg/kg SAR441236 | Mean Maximum Reduction of Plasma HIV-1 RNA During up to 28 Days of SAR441236 Monotherapy for Viremic Participants With HIV (Arm B Cohorts) | -0.30 log10 copies/mL | Standard Deviation 0.23 |
| Arm A: 3 mg/kg for SAR441236 | Mean Maximum Reduction of Plasma HIV-1 RNA During up to 28 Days of SAR441236 Monotherapy for Viremic Participants With HIV (Arm B Cohorts) | -0.68 log10 copies/mL | Standard Deviation 0.03 |
Secondary
Mean SAR441236 Concentration 12 Weeks After Infusions 1, 2, 3, and 4
SAR441236 concentration for each participant was calculated as the observed SAR441236 concentration 12 weeks after each infusion.
Time frame: SAR441236 PK samples at Week 12, 24, 36, and 48.
Population: All participants exposed to 4 infusions of SAR441236 (30 mg/kg participants only) with evaluable levels of SAR441236. Only participants who maintained the every 12-week dosing schedule were considered for concentration levels 12 weeks after infusions 2-4.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A: 1 mg/kg SAR441236 | Mean SAR441236 Concentration 12 Weeks After Infusions 1, 2, 3, and 4 | SAR441236 Concentration at Infusion 1 + 12 Weeks | 88.28 ug/mL | Standard Deviation 46.73 |
| Arm A: 1 mg/kg SAR441236 | Mean SAR441236 Concentration 12 Weeks After Infusions 1, 2, 3, and 4 | SAR441236 Concentration at Infusion 2 + 12 Weeks | 136.87 ug/mL | Standard Deviation 48.78 |
| Arm A: 1 mg/kg SAR441236 | Mean SAR441236 Concentration 12 Weeks After Infusions 1, 2, 3, and 4 | SAR441236 Concentration at Infusion 3 + 12 Weeks | 120.00 ug/mL | Standard Deviation 40.84 |
| Arm A: 1 mg/kg SAR441236 | Mean SAR441236 Concentration 12 Weeks After Infusions 1, 2, 3, and 4 | SAR441236 Concentration at Infusion 4 + 12 Weeks | 122.40 ug/mL | Standard Deviation 45.43 |
Secondary
Mean Trough Accumulative Index (12 Weeks Post-Dose 1 vs 12 Weeks Post-Dose 4)
The Trough AI was calculated as the ratio of the SAR441236 concentration observed 12 weeks after the 4th dose and the SAR441236 concentration observed 12 weeks after the 1st dose. Standard noncompartmental techniques, using Phoenix WinNonlin, were used to determine trough AI.
Time frame: SAR441236 PK samples taken at Week 12 (pre-dose #2) and at Week 48 (12 weeks after dose #4)
Population: All participants exposed to 4 infusions of SAR441236 (30 mg/kg participants only) with evaluable levels of SAR441236. Only participants who maintained the every 12-week dosing schedule were considered for Trough AI (Dose 1 vs Dose 4)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: 1 mg/kg SAR441236 | Mean Trough Accumulative Index (12 Weeks Post-Dose 1 vs 12 Weeks Post-Dose 4) | 1.13 Ratio | Standard Deviation 0.04 |
Secondary
Time to Maximum Concentration (Tmax) of SAR441236 After a Single IV Infusion of SC Injection.
Tmax for each participant was time to maximum observed SAR441236 measured from all available SAR441236 concentrations measured prior to and after first treatment and prior to any subsequent treatment instances (Arm A: 30 mg/kg only). Standard noncompartmental techniques, using Phoenix WinNonlin, were used to determine Tmax.
Time frame: SAR441236 PK samples at pre-dose, Hours 0, 2 (Arm A, B only) , 4 (Arm A, B only), 6 (Arm A, B only), and 10, Days 1, 2, 3, 4 (Arm B only), 7, 10 (Arm B only), and Weeks 2, 4, 8 (single dose only), 10 (multi dose only), 12, and 24 (single dose only).
Population: All participants exposed to SAR441236 with evaluable levels of SAR441236 such that Cmax, and corresponding Tmax, can be derived.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: 1 mg/kg SAR441236 | Time to Maximum Concentration (Tmax) of SAR441236 After a Single IV Infusion of SC Injection. | 0.07 (days) | Standard Error 0.05 |
| Arm A: 3 mg/kg for SAR441236 | Time to Maximum Concentration (Tmax) of SAR441236 After a Single IV Infusion of SC Injection. | 2.11 (days) | Standard Error 4.06 |
| Arm A: 10 mg/kg SAR441236 | Time to Maximum Concentration (Tmax) of SAR441236 After a Single IV Infusion of SC Injection. | 0.12 (days) | Standard Error 0.08 |
| Arm A: 30 mg/kg SAR441236 | Time to Maximum Concentration (Tmax) of SAR441236 After a Single IV Infusion of SC Injection. | 0.16 (days) | Standard Error 0.15 |
| Arm A: 0 mg/kg SAR441236 | Time to Maximum Concentration (Tmax) of SAR441236 After a Single IV Infusion of SC Injection. | 0.09 (days) | Standard Error 0.12 |
| Arm B: 1 mg/kg SAR441236 | Time to Maximum Concentration (Tmax) of SAR441236 After a Single IV Infusion of SC Injection. | 0.09 (days) | Standard Error 0.06 |
| Arm B: 30 mg/kg SAR441236 | Time to Maximum Concentration (Tmax) of SAR441236 After a Single IV Infusion of SC Injection. | 6.71 (days) | Standard Error 5.19 |
| Arm C: 0.3 mg/kg SAR441236 | Time to Maximum Concentration (Tmax) of SAR441236 After a Single IV Infusion of SC Injection. | 5.07 (days) | Standard Error 2.49 |
Secondary
Volume of Distribution of SAR441236 After a Single IV Infusion or SC Injection
Volume of distribution (Arms A and B) or apparent volume of distribution (Arm C) was calculated from all available SAR441236 concentrations measured prior to and after first treatment and prior to any subsequent treatment instances (Arm A: 30 mg/kg only). Standard noncompartmental techniques, using Phoenix WinNonlin, were used to determine volume of distribution and apparent volume of distribution.
Time frame: SAR441236 PK samples at pre-dose, Hours 0, 2 (Arm A, B only) , 4 (Arm A, B only), 6 (Arm A, B only), and 10, Days 1, 2, 3, 4 (Arm B only), 7, 10 (Arm B only), and Weeks 2, 4, 8 (single dose only), 10 (multi dose only), 12, and 24 (single dose only).
Population: All participants exposed to SAR441236 with evaluable levels of SAR441236 such that volume of distribution (Arms A and B) or apparent volume of distribution (Arm C) can be derived.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A: 1 mg/kg SAR441236 | Volume of Distribution of SAR441236 After a Single IV Infusion or SC Injection | 8.02 (L) | Standard Deviation 3.13 |
| Arm A: 3 mg/kg for SAR441236 | Volume of Distribution of SAR441236 After a Single IV Infusion or SC Injection | 5.90 (L) | Standard Deviation 1.56 |
| Arm A: 10 mg/kg SAR441236 | Volume of Distribution of SAR441236 After a Single IV Infusion or SC Injection | 5.34 (L) | Standard Deviation 0.48 |
| Arm A: 30 mg/kg SAR441236 | Volume of Distribution of SAR441236 After a Single IV Infusion or SC Injection | 5.96 (L) | Standard Deviation 1.05 |
| Arm A: 0 mg/kg SAR441236 | Volume of Distribution of SAR441236 After a Single IV Infusion or SC Injection | 5.27 (L) | Standard Deviation 0.79 |
| Arm B: 1 mg/kg SAR441236 | Volume of Distribution of SAR441236 After a Single IV Infusion or SC Injection | 9.73 (L) | Standard Deviation 0.38 |
| Arm B: 30 mg/kg SAR441236 | Volume of Distribution of SAR441236 After a Single IV Infusion or SC Injection | 14.0 (L) | Standard Deviation 2.79 |
| Arm C: 0.3 mg/kg SAR441236 | Volume of Distribution of SAR441236 After a Single IV Infusion or SC Injection | 22.8 (L) | Standard Deviation 14.7 |