HIV-1-infectionPhase 1NCT03705169
Pharmacokinetics and Safety of SAR441236
A Phase 1 study testing SAR441236 in people with HIV-1-infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 23 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- HIV-1-infection
- What is being tested?
- SAR441236
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 52 participants
- Where
- 23 sitesUnited States
- Study dates
- 20 May 2019to 4 Apr 2022
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- Breastfeeding or plans to become pregnant.
- Receipt of chimeric, humanized or human long-acting mAbs, whether licensed or investigational, within 12 months prior to entry, or receipt of chimeric, humanized or human regular mAbs, whether licensed or investigational, within 6 months prior to entry, unless reviewed and approved by the study's core team.
- Known allergy/sensitivity or any hypersensitivity to components of study treatment or its formulation (refer to the product's Investigator's Brochure).
- Vaccination within 30 days prior to entry or intent to receive an elective vaccination (e.g., hepatitis A vaccine, travel-related) during the course of the study except as noted in the study protocol.
- Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
- Acute or serious illness requiring systemic treatment and/or hospitalization within 45 days prior to entry.
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- Diagnosis of AIDS-defining illness using the current list on the US Centers for Disease Control and Prevention (CDC) website within 1 year prior to entry.
- Weight greater than 115 kg within 45 days prior to study entry.
- Use of maraviroc, ibalizumab, or enfuvirtide at any time.
- Additional Arms A- and C-specific Exclusion Criterion
- Within 6 months prior to study entry, any plasma HIV-1 RNA ≥50 copies/mL on any FDA-approved assay with a limit of quantification of <50 copies/mL performed by a US laboratory that has a CLIA certification or its equivalent.
- Additional Arm B-specific Exclusion Criterion
- Use of any anti-HIV ART, including FDA-approved pre-exposure prophylaxis (PrEP) within the preceding 3 months
- Additional Arm C-specific Exclusion Criterion
- Presence of abdominal scarring or tattooing that could interfere with assessment of injection-site reaction.
Trial locations and contacts
23 sites in 1 country.
23 sites in 1 country
United States23 sites
University of Colorado Hospital CRS
Aurora, Colorado, 80045
Alabama CRS
Birmingham, Alabama, 35294
Massachusetts General Hospital CRS (MGH CRS)
Boston, Massachusetts, 02114
Brigham and Women's Hospital Therapeutics Clinical Research Site (BWH TCRS) CRS
Boston, Massachusetts, 02115
Chapel Hill CRS
Chapel Hill, North Carolina, 27599
Northwestern University CRS
Chicago, Illinois, 60611
Rush University CRS
Chicago, Illinois, 60612
Cincinnati Clinical Research Site
Cincinnati, Ohio, 45219
Case Clinical Research Site
Cleveland, Ohio, 44106
Ohio State University CRS
Columbus, Ohio, 43210
UCLA CARE Center CRS
Los Angeles, California, 90035
Vanderbilt Therapeutics (VT) CRS
Nashville, Tennessee, 37204
Weill Cornell Chelsea CRS
New York, New York, 10010
Weill Cornell Uptown CRS
New York, New York, 10065
New Jersey Medical School Clinical Research Center CRS
Newark, New Jersey, 07103
Penn Therapeutics, CRS
Philadelphia, Pennsylvania, 19104
University of Pittsburgh CRS
Pittsburgh, Pennsylvania, 15213
The Miriam Hospital Clinical Research Site (TMH CRS) CRS
Providence, Rhode Island, 02906
University of Rochester Adult HIV Therapeutic Strategies Network CRS
Rochester, New York, 14642
UCSD Antiviral Research Center CRS
San Diego, California, 92103
Ucsf Hiv/Aids Crs
San Francisco, California, 94110
University of Washington Positive Research CRS
Seattle, Washington, 98104-9929
Washington University Therapeutics (WT) CRS
St Louis, Missouri, 63110-1010
About this study
Official title: A Phase I, First-in-Human Study of SAR441236, a Tri-specific Broadly Neutralizing Antibody, in Participants With HIV
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).
Read the 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.
- Conditions
- HIV-1-infection
- Being tested
- SAR441236, Placebo
- Keywords
- HIV, pharmacokinetics, pharmacodynamics, broadly neutralizing antibody, antiretroviral, Phase 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SAR441236Biological
Administered by intravenous (IV) infusion(s) or subcutaneous (SC) injection(s)
PlaceboBiological
Administered by intravenous (IV) infusion(s) or subcutaneous (SC) injection(s)
| Study group | Role | What they receive |
|---|---|---|
| Arm A: 1 mg/kg SAR441236 | Experimental | 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). Receives: Biological: SAR441236 |
| Arm A: 3 mg/kg for SAR441236 | Experimental | 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). Receives: Biological: SAR441236 |
| Arm A: 10 mg/kg SAR441236 | Experimental | Participants continued non-study-provided ART and received 10 mg/kg of SAR441236, administered as a single IV infusion on Day 0 (Cohort 3). Receives: Biological: SAR441236 |
| Arm A: 30 mg/kg SAR441236 | Experimental | 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). Receives: Biological: SAR441236 |
| Arm A: 0 mg/kg SAR441236 | Placebo comparator | 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. Receives: Biological: Placebo |
| Arm B: 1 mg/kg SAR441236 | Experimental | 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). Receives: Biological: SAR441236 |
| Arm B: 30 mg/kg SAR441236 | Experimental | 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). Receives: Biological: SAR441236 |
| Arm C: 0.3 mg/kg SAR441236 | Experimental | 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). Receives: Biological: SAR441236 |
| Arm C: 1 mg/kg SAR441236 | Experimental | Participants continued non-study-provided ART and received 1 mg/kg of SAR441236, administered as an SC injection(s) on Day 0 (Cohort 11). Receives: Biological: SAR441236 |
| Arm C: 0 mg/kg SAR441236 | Placebo comparator | 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. Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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).
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.
Measured: 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.
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.
Measured: Measured at Day 0 and Day 7
Secondary outcomes (18)
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.
Measured: Measured at Day 0 and at Day 1, 2, 3, and 4, and Week 1, 2, and 3
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.
Measured: Measured at Day 0 and Day 14
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).
Measured: Measured at Day 0 and at up to Day 28 (while on SAR441236 monotherapy)
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.
Measured: Measured at Day 0 and at Week 2, 4, 12, and 24
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.
Measured: 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
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.
Measured: Measured at Day 0 and Week 12
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.
Measured: Measured at Day 0 and at Week 12 after each infusion
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.
Measured: 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 (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.
Measured: 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).
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.
Measured: 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 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.
Measured: 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 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.
Measured: 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).
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.
Measured: 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.
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.
Measured: SAR441236 PK samples at Week 12, 24, 36, and 48.
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: SAR441236 PK samples taken at Week 12 (pre-dose #2) and at Week 48 (12 weeks after dose #4)
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.
Measured: Day 0 and at all study visits prior to ART initiation/re-initiation (up to Week 4)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2018
- Study start20 May 2019
- Primary completion4 Apr 2022
- Study completion4 Apr 2022
Why it stopped: The study closed to enrollment and follow-up in May 2023. There had been no enrollment since October 2021, and by 2023, the available study product had reached its expiration date. Enrollment targets in Arm B had not been met.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIV-1-infectionStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Sanofi, ModeX Therapeutics, An OPKO Health Company
- Responsible party
- Sponsor
- Investigators
- Athe Tsibris, MD, MS, Study chair, Brigham and Women's Hospital, Harvard Medical SchoolDaniel R. Kuritzkes, MD, Study chair, Brigham and Women's Hospital Therapeutics CRS, Harvard Medical SchoolPablo Tebas, MD, Study chair, Penn Therapeutics CRS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03705169
- Sponsor's protocol ID
- ACTG A5377
- Other IDs
- 38508, TDU15867
- Status last verified
- Jan 2024
- First submitted
- 10 Oct 2018
- Last updated
- 12 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie results in the publication, after deidentification.
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, First-in-Human Study of SAR441236, a Tri-specific Broadly Neutralizing Antibody, in Participants With HIV
- ClinicalTrials.gov ID
- NCT03705169
- Acronym / sponsor ID
- ACTG A5377
- Conditions
- HIV-1-infection
- Keywords
- HIV, pharmacokinetics, pharmacodynamics, broadly neutralizing antibody, antiretroviral, Phase 1
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study closed to enrollment and follow-up in May 2023. There had been no enrollment since October 2021, and by 2023, the available study product had reached its expiration date. Enrollment targets in Arm B had not been met.
- Enrolment
- 52 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Sanofi, ModeX Therapeutics, An OPKO Health Company
- Study start
- 20 May 2019 (actual)
- Primary completion
- 4 Apr 2022 (actual)
- Study completion
- 4 Apr 2022 (actual)
- First posted
- 15 Oct 2018 (actual)
- Results
- Posted 12 Jan 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 10
| Arm | Type | Receives |
|---|---|---|
| Arm A: 1 mg/kg SAR441236 | Experimental | Biological: SAR441236Participants 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). |
| Arm A: 3 mg/kg for SAR441236 | Experimental | Biological: SAR441236Experimental: 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). |
| Arm A: 10 mg/kg SAR441236 | Experimental | Biological: SAR441236Participants continued non-study-provided ART and received 10 mg/kg of SAR441236, administered as a single IV infusion on Day 0 (Cohort 3). |
| Arm A: 30 mg/kg SAR441236 | Experimental | Biological: SAR441236Participants 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). |
| Arm A: 0 mg/kg SAR441236 | Placebo comparator | Biological: PlaceboPlacebo 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. |
| Arm B: 1 mg/kg SAR441236 | Experimental | Biological: SAR441236Participants 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). |
| Arm B: 30 mg/kg SAR441236 | Experimental | Biological: SAR441236Participants 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). |
| Arm C: 0.3 mg/kg SAR441236 | Experimental | Biological: SAR441236Participants 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). |
| Arm C: 1 mg/kg SAR441236 | Experimental | Biological: SAR441236Participants continued non-study-provided ART and received 1 mg/kg of SAR441236, administered as an SC injection(s) on Day 0 (Cohort 11). |
| Arm C: 0 mg/kg SAR441236 | Placebo comparator | Biological: PlaceboPlacebo 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (47 listed)
- 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.
- 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.
- 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.
- 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.
Key exclusion criteria (15 listed)
- Breastfeeding or plans to become pregnant.
- Receipt of chimeric, humanized or human long-acting mAbs, whether licensed or investigational, within 12 months prior to entry, or receipt of chimeric, humanized or human regular mAbs, whether licensed or investigational, within 6 months prior to entry, unless reviewed and approved by the study's core team.
- Known allergy/sensitivity or any hypersensitivity to components of study treatment or its formulation (refer to the product's Investigator's Brochure).
- Vaccination within 30 days prior to entry or intent to receive an elective vaccination (e.g., hepatitis A vaccine, travel-related) during the course of the study except as noted in the study protocol.
- Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SAR441236Administered by intravenous (IV) infusion(s) or subcutaneous (SC) injection(s) | Biological | Arm A: 1 mg/kg SAR441236, Arm A: 10 mg/kg SAR441236, Arm A: 3 mg/kg for SAR441236, Arm A: 30 mg/kg SAR441236, Arm B: 1 mg/kg SAR441236, Arm B: 30 mg/kg SAR441236, Arm C: 0.3 mg/kg SAR441236, Arm C: 1 mg/kg SAR441236 |
| PlaceboAdministered by intravenous (IV) infusion(s) or subcutaneous (SC) injection(s) | Biological | Arm A: 0 mg/kg SAR441236, Arm C: 0 mg/kg SAR441236 |
Primary outcome
Proportion of Participants Experiencing a Grade 3 or Higher Adverse Event (AE) That is Related to Study Treatment.
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).
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
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.
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)
Time frame: 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.
18 secondary outcomes
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)
Time frame: Measured at Day 0 and at Day 1, 2, 3, and 4, and Week 1, 2, and 3
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)
Time frame: Measured at Day 0 and Day 14
Mean Maximum Reduction of Plasma HIV-1 RNA During up to 28 Days of SAR441236 Monotherapy for Viremic Participants With HIV (Arm B Cohorts)
Time frame: Measured at Day 0 and at up to Day 28 (while on SAR441236 monotherapy)
Attributions of Anti-SAR441236 Antibodies Among Participants in Single-dose Cohorts.
Time frame: Measured at Day 0 and at Week 2, 4, 12, and 24
Attributions of Anti-SAR441236 Antibodies Among Participants in Multi-dose Cohort.
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
Mean Change From Baseline in CD4+ T Cell Counts Following the First Treatment of SAR441236 or Placebo for All Cohorts
Time frame: Measured at Day 0 and Week 12
Mean Change From Baseline in CD4+ T Cell Counts Following Each Infusion for Cohort 4
Time frame: Measured at Day 0 and at Week 12 after each infusion
Mean Maximum Concentration (Cmax) of SAR441236 After a Single IV Infusion or SC Injection.
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).
Half-life (T1/2) of SAR441236 After a Single IV Infusion or SC Injection.
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).
Time to Maximum Concentration (Tmax) of SAR441236 After a Single IV Infusion of SC Injection.
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).
Clearance or Apparent Clearance of SAR441236 After a Single IV Infusion of SC Injection.
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).
Volume of Distribution of SAR441236 After a Single IV Infusion or SC Injection
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).
Mean Maximum Concentration (Cmax) of SAR441236 After the Fourth IV 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.
Mean SAR441236 Concentration 12 Weeks After Infusions 1, 2, 3, and 4
Time frame: SAR441236 PK samples at Week 12, 24, 36, and 48.
Mean AUC After Multiple Infusions of SAR441236
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.
Mean AUC Accumulation Index (AI) (12 Weeks Post-Dose 1 vs 12 Weeks Post-Dose 4).
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.
Mean Trough Accumulative Index (12 Weeks Post-Dose 1 vs 12 Weeks Post-Dose 4)
Time frame: SAR441236 PK samples taken at Week 12 (pre-dose #2) and at Week 48 (12 weeks after dose #4)
Dose-response Relationship Between SAR441236 Exposure and Changes in Plasma HIV-1 RNA
Time frame: Day 0 and at all study visits prior to ART initiation/re-initiation (up to Week 4)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017.Link provided by the sponsor.
- Manual for Expediated Reporting of Adverse Events to DAIDS, Version 2.0, January 2010Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie results in the publication, after deidentification.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Athe Tsibris, MD, MS study chair
Brigham and Women's Hospital, Harvard Medical School
Daniel R. Kuritzkes, MD study chair
Brigham and Women's Hospital Therapeutics CRS, Harvard Medical School
Pablo Tebas, MD study chair
Penn Therapeutics CRS
23 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SAR441236 in people with HIV-1-infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 23 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 47 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Participants Experiencing a Grade 3 or Higher Adverse Event (AE) That is Related to Study Treatment. (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).). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2024.