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Human Immunodeficiency VirusPhase 1NCT03554408

First-in-human Study of 10-1074-LS Alone and in Combination With 3BNC117-LS

A Phase 1 study testing 10-1074-LS and 3BNC117-LS in people with Human Immunodeficiency Virus, run by Rockefeller University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This first clinical study of 10-1074-LS will evaluate its safety, tolerability and pharmacokinetics profile when administered alone or in combination with 3BNC117-LS to HIV (human immunodeficiency virus) -infected and HIV-uninfected individuals. Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Human Immunodeficiency Virus
What is being tested?
10-1074-LS and 3BNC117-LS
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
77 participants
Where
1 siteUnited States
Study dates
20 Jun 2018to 4 Feb 2021
Phase
Phase 1
Are there results?
None posted in the registry

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 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Groups 1A-1B, 2A-2C, 4A-4B, 5, 7, 8, 9 (HIV-uninfected):
  • Males and females, age 18 to 65
  • Amenable to HIV risk reduction counseling and agrees to maintain behavior consistent with low risk of HIV exposure.
  • If sexually active male or female, and participating in sexual activity that could lead to pregnancy, agrees to use two effective methods of contraception (i.e.
  • condom with spermicide, diaphragm with spermicide, hormone-eluting IUD, hormone-based contraceptive with condom) from 10 days prior to and nine months after 10-1074-LS and/or 3BNC117-LS administration.
  • Female study participants of reproductive potential are defined as pre-menopausal women who have not had a sterilization procedure (e.g. hysterectomy, bilateral oophorectomy, tubal ligation or salpingectomy). Women are considered menopausal if they have not had a menses for at least 12 months and have a FSH of greater than 40 IU/L or if FSH testing is not available, they have had amenorrhea for 24 consecutive months.
Show all 12Show fewer
  • Groups 3B-3C, 6 (HIV-infected):
  • Males and females, age 18 to 65.
  • Confirmed HIV-1 infection.
  • HIV-infected individuals on ART with HIV-1 plasma RNA levels < 50 copies/mL.
  • Current CD4+ T cell count > 300 cells/μl.
  • If sexually active male or female, and participating in sexual activity that could lead to pregnancy or transmission of HIV, agrees to use two effective methods of contraception (i.e. condom with spermicide, diaphragm with spermicide, hormone-eluting IUD, hormone-based contraceptive with condom) from 10 days prior to and nine months after 10-1074-LS and/or 3BNC117-LS administration.

Who cannot join

  • Groups 1A-1B, 2A-2C, 4A-4B, 5, 7, 8, 9 (HIV-uninfected):
  • Confirmed HIV-1 or HIV-2 infection.
  • Weight > 110 kg (subcutaneous groups only: 1A-1B, 4A-4B).
  • History of immunodeficiency or autoimmune disease; use of systemic corticosteroids, immunosuppressive anti-cancer, or other medications considered significant
  • Any clinically significant acute or chronic medical condition (such as autoimmune diseases) that in the opinion of the investigator would preclude participation.
  • Within the 12 months prior to enrollment, the participant has a history of sexually transmitted infection.
Show all 40Show fewer
  • Hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood.
  • Laboratory abnormalities in the parameters listed:
  • Absolute neutrophil count ≤ 1,500 cells/μL;
  • Hemoglobin ≤ 11 gm/dL if female; ≤ 12.5 gm/dL if male;
  • Platelet count ≤ 125,000 cells/μL;
  • ALT ≥ 1.25 x ULN;
  • AST ≥ 1.25 x ULN;
  • Alkaline phosphatase ≥ 1.5 x ULN;by the trial physician within the last 6 months.
  • Pregnancy or lactation.
  • Any vaccination within 14 days prior to mAb infusions.
  • Receipt of any experimental HIV vaccine or monoclonal antibody therapy of any kind in the past.
  • History of severe reaction to a vaccine or drug infusion or history of severe allergic reactions.
  • Individuals with known hypersensitivity to any constituent of the investigational products.
  • Receipt of another investigational product currently or within the past 12 weeks, or expected concurrent participation in another study in which investigational products will be administered.
  • Groups 3B-3C, 6 (HIV-infected):
  • Have a history of AIDS-defining illness within 3 years prior to enrollment.
  • History of systemic corticosteroids, immunosuppressive anti-cancer, or other medications considered significant by the trial physician within the last 6 months.
  • Any clinically significant acute or chronic medical condition (such as autoimmune diseases), other than HIV infection, that in the opinion of the investigator would preclude participation.
  • Hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood.
  • Laboratory abnormalities in the parameters listed below:
  • Absolute neutrophil count ≤ 1,000 cells/μl;
  • Hemoglobin ≤ 10 gm/dL;
  • Platelet count ≤ 100,000 cells/μl;
  • ALT ≥ 1.5 x ULN;
  • AST ≥ 1.5 x ULN;
  • Alkaline phosphatase ≥ 1.5 x ULN;
  • Total bilirubin > 1 x ULN;
  • eGFR < 60 mL/min/1.73m2.
  • Pregnancy or lactation.
  • Any vaccination within 14 days prior to MAb infusions.
  • Receipt of any experimental HIV vaccine or monoclonal antibody therapy of any kind in the past.
  • History of severe reaction to a vaccine or drug infusion or history of severe allergic reactions.
  • Individuals with known hypersensitivity to any constituent of the investigational products.
  • Receipt of another investigational product currently or within the past 12 weeks, or expected concurrent participation in another study in which investigational products will be administered.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • The Rockefeller University

    New York, New York, 10065

Other trials in United States

About this study

Official title: A Phase 1, Dose Escalation, First-in-human Study of the Safety and Pharmacokinetics of the Subcutaneous and Intravenous Administration of 10-1074-LS Alone and in Combination With 3BNC117-LS in HIV-infected and HIV-uninfected Individuals

This first clinical study of 10-1074-LS will evaluate its safety, tolerability and pharmacokinetics profile when administered alone or in combination with 3BNC117-LS to HIV (human immunodeficiency virus) -infected and HIV-uninfected individuals.

Read the detailed description

The proposed study is a Phase 1, dose escalation cohort study of 10-1074-LS alone or in combination with 3BNC117-LS, administered intravenously and subcutaneously in HIV uninfected and HIV-1 infected individuals.

Study participants will be administered a single intravenous infusion of 10-1074-LS at 3, 10 or 30 mg/kg, single infusions of the combination of 10-1074-LS and 3BNC117-LS, each dosed at 30 mg/kg, or subcutaneous injections of 10-1074-LS alone or in combination with 3BNC117-LS, and three subcutaneous injections of 10-1074-LS in combination with 3BNC117-LS at three dose ratios. The first four groups administered subcutaneous injections of the product(s) will be randomized, double-blinded, and placebo-controlled to assess potential differences in safety and tolerability of the antibody formulation versus the formulation buffer alone. In the dose ratio portion of the study, participants will be randomized into one of three groups, but the products will be administered in an open-label manner. Groups administered intravenous infusions will be enrolled in an open-label manner.

PART A

Group 1A (n=8) - HIV-uninfected individuals will be administered one 1 mL (approximately 150 mg) subcutaneous injection of 10-1074-LS or placebo (formulation buffer), in a 3:1 ratio.

Group 1B (n=8) - HIV-uninfected individuals will be administered one 2 mL (approximately 300 mg) subcutaneous injection of 10-1074-LS or placebo (formulation buffer), in a 3:1 ratio.

Group 2A (n=3) - HIV-uninfected individuals will be administered one intravenous infusion of 10-1074-LS dosed at 3 mg/kg.

Group 2B (n=3) - HIV-uninfected individuals will be administered one intravenous infusion of 10-1074-LS dosed at 10 mg/kg.

Group 2C (n=3) - HIV-uninfected individuals will be administered one intravenous infusion of 10-1074-LS dosed at 30 mg/kg.

Group 3B (n=3) - HIV-infected individuals (on ART) will be administered one intravenous infusion of 10-1074-LS dosed at 10 mg/kg.

Group 3C (n=3) - HIV-infected individuals (on ART) will be administered one intravenous infusion of 10-1074-LS dosed at 30 mg/kg.

PART B

Part B will begin after the Safety Monitoring Committee (SMC) evaluates available safety data from Part A, as detailed below. The SMC will also review available safety data with 3BNC117-LS administered intravenously collected under protocol YCO-0946 prior to enrollment in Part B of this study. The SMC will also review subcutaneous dosing at approximately 150 mg (1 mL) and 300 mg (2 mL), collected under IND 131873 when available and prior to enrollment in Part B of this study.

Group 4A (n=8) - HIV-uninfected individuals will be administered one 2 mL (approximately 150 mg of each mAb) subcutaneous injection of 10-1074-LS admixed with 3BNC117-LS or placebo (formulation buffer), in a 3:1 ratio.

Group 4B (n=8) - HIV-uninfected individuals will be administered two 2 mL (approximately 300 mg of each mAb) subcutaneous injections of 10-1074-LS admixed with 3BNC117-LS or placebo (formulation buffer), in a 3:1 ratio.

Group 5 (n=5) - HIV-uninfected individuals will be administered one intravenous infusion of 10-1074-LS and one intravenous infusion of 3BNC117-LS, each dosed at 30 mg/kg.

Group 6 (n=5) - HIV-infected individuals (on ART) will be administered one intravenous infusion of 10-1074-LS and one intravenous infusion of 3BNC117-LS, each dosed at 30 mg/kg.

Group 7 (n=6) HIV-uninfected individuals will be administered three subcutaneous injections of 10-1074-LS (100 mg) admixed with 3BNC117-LS (200 mg) (2 mL).

Group 8 (n=6) HIV-uninfected individuals will be administered three subcutaneous injections of 10-1074-LS (75 mg) admixed with 3BNC117-LS (225 mg) (2 mL).

Group 9 (n=6) HIV-uninfected individuals will be administered three subcutaneous injections of 10-1074-LS (60 mg) admixed with 3BNC117-LS (240 mg) (2 mL).

Following mAb or placebo administration, study participants will return for safety assessments on days 1 and 3, and weeks 1, 2 and 4 following each dose, then bi-monthly or monthly until the end of study follow up.

All participants will be followed for 48 weeks after last mAb or placebo administration. Serum samples for PK measurements will be collected before and at the end each mAb or placebo administration and at multiple subsequent time points during study follow up.

Samples will also be collected for measurement of HIV-1 plasma RNA levels before 10-1074-LS and 3BNC117-LS infusions and at follow up visits according to protocol.

Being tested
10-1074-LS, 3BNC117-LS
Keywords
10-1074-LS, 3BNC117-LS, First in Human, Dose Escalation
Medical subject headings
Acquired Immunodeficiency Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 10-1074-LSDrug

    Also called Monoclonal antibody

    Subcutaneous injection of 10-1074-LS

  • 10-1074-LSDrug

    Also called Monoclonal antibody

    Intravenous infusion of 10-1074-LS

  • 3BNC117-LSDrug

    Also called Monoclonal antibody

    Subcutaneous injection of 3BNC117-LS

  • 3BNC117-LSDrug

    Also called Monoclonal antibody

    Intravenous infusion of 3BNC117-LS

Study groups in NCT03554408
Study groupRoleWhat they receive
Group 1AExperimentalHIV-uninfected individuals will be administered one 1 mL (approximately 150 mg) subcutaneous injection of 10-1074-LS or placebo (formulation buffer), in a 3:1 ratio.
Receives: Drug: 10-1074-LS
Group 1BExperimentalHIV-uninfected individuals will be administered one 2 mL (approximately 300 mg) subcutaneous injection of 10-1074-LS or placebo (formulation buffer), in a 3:1 ratio.
Receives: Drug: 10-1074-LS
Group 2AExperimentalHIV-uninfected individuals will be administered one intravenous infusion of 10-1074-LS dosed at 3 mg/kg.
Receives: Drug: 10-1074-LS
Group 2BExperimentalHIV-uninfected individuals will be administered one intravenous infusion of 10-1074-LS dosed at 10 mg/kg.
Receives: Drug: 10-1074-LS
Group 2CExperimentalHIV-uninfected individuals will be administered one intravenous infusion of 10-1074-LS dosed at 30 mg/kg.
Receives: Drug: 10-1074-LS
Group 3BExperimentalHIV-infected individuals (on ART) will be administered one intravenous infusion of 10-1074-LS dosed at 10 mg/kg
Receives: Drug: 10-1074-LS
Group 3CExperimentalHIV-infected individuals (on ART) will be administered one intravenous infusion of 10-1074-LS dosed at 30 mg/kg.
Receives: Drug: 10-1074-LS
Group 4AExperimentalHIV-uninfected individuals will be administered one 2 mL (approximately 150 mg of each mAb) subcutaneous injection of 10-1074-LS admixed with 3BNC117-LS or placebo (formulation buffer), in a 3:1 ratio.
Receives: Drug: 10-1074-LS; Drug: 3BNC117-LS
Group 4BExperimentalHIV-uninfected individuals will be administered two 2 mL (approximately 300 mg of each mAb) subcutaneous injections of 10-1074-LS admixed with 3BNC117-LS or placebo (formulation buffer), in a 3:1 ratio.
Receives: Drug: 10-1074-LS; Drug: 3BNC117-LS
Group 5ExperimentalHIV-uninfected individuals will be administered one intravenous infusion of 10-1074-LS and one intravenous infusion of 3BNC117-LS, each dosed at 30 mg/kg.
Receives: Drug: 10-1074-LS; Drug: 3BNC117-LS
Group 6ExperimentalHIV-infected individuals (on ART) will be administered one intravenous infusion of 10-1074-LS and one intravenous infusion of 3BNC117-LS, each dosed at 30 mg/kg.
Receives: Drug: 10-1074-LS; Drug: 3BNC117-LS
Group 7ExperimentalHIV-uninfected individuals will be administered three subcutaneous injections of 10-1074-LS (100 mg) admixed with 3BNC117-LS (200 mg) (2 mL) at weeks 0, 12, and 24.
Receives: Drug: 10-1074-LS; Drug: 3BNC117-LS
Group 8ExperimentalHIV-infected individuals (on ART) will be administered three subcutaneous injections of 10-1074-LS (75 mg) admixed with 3BNC117-LS (225 mg) (2 mL) at weeks 0, 12, and 24.
Receives: Drug: 10-1074-LS; Drug: 3BNC117-LS
Group 9ExperimentalHIV-infected individuals (on ART) will be administered three subcutaneous injections of 10-1074-LS (60 mg) admixed with 3BNC117-LS (250 mg) (2 mL) at weeks 0, 12, and 24.
Receives: Drug: 10-1074-LS; Drug: 3BNC117-LS

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The number of participants who experience adverse events within 2 weeks after 10-1074-LS intravenous infusions and subcutaneous injections.

    Adverse events include signs, symptoms and laboratory abnormalities, in addition to local and systemic reactogenicity adverse events.

    Measured: 2 weeks

  2. The number of participants who experience adverse events within 2 weeks after 10-1074-LS and 3BNC117-LS intravenous infusions and subcutaneous injections.

    Adverse events include signs, symptoms and laboratory abnormalities, in addition to local and systemic reactogenicity adverse events.

    Measured: 2 weeks

  3. Elimination half-life (t1/2) of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups.

    Elimination half-life (t1/2) of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups.

    Measured: 48-72 weeks

  4. The clearance (CL) of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups.

    The clearance (CL) of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups.

    Measured: 48-72 weeks

  5. The volume of distribution (Vz) of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups

    The volume of distribution (Vz) of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups

    Measured: 48-72 weeks

  6. Area under the curve of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups.

    Area under the curve of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups.

    Measured: 48-72 weeks

  7. Decay curve of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups.

    Decay curve of 10-1074-LS, when administered alone and in combination with 3BNC117-LS in all study groups.

    Measured: 48-72 weeks

Secondary outcomes (5)

  1. Frequency of induced anti-10-1074-LS antibodies

    Frequency of induced anti-10-1074-LS antibodies

    Measured: 48-72 weeks

  2. Level of induced anti-10-1074-LS antibodies

    Level of induced anti-10-1074-LS antibodies

    Measured: 48-72 weeks

  3. Frequency of induced anti-3BNC117-LS antibodies

    Frequency of induced anti-3BNC117-LS antibodies

    Measured: 48-72 weeks

  4. Level of induced anti-3BNC117-LS antibodies

    Level of induced anti-3BNC117-LS antibodies

    Measured: 48-72 weeks

  5. The number of participants that experience who experience adverse events during the study follow up period after 10-1074-LS and/or 3BNC117-LS administration in all study groups.

    Adverse events include signs, symptoms and laboratory abnormalities

    Measured: 48-72 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jun 2018
  2. Study start20 Jun 2018
  3. Primary completion4 Feb 2021
  4. Study completion4 Feb 2021

Resources

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
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
77 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03554408
Sponsor's protocol ID
YCO-0971
Status last verified
Aug 2021
First submitted
31 May 2018
Last updated
4 Aug 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Valente PK, Wu Y, Cohen YZ, Caskey M, Meyers K. Behavioral and social science research to support development of educational materials for clinical trials of broadly neutralizing antibodies for HIV treatment and prevention. Clin Trials. 2021 Feb;18(1):17-27. doi: 10.1177/1740774520948042. Epub 2020 Aug 24.

    PubMed 32838558

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 10-1074-LS and 3BNC117-LS in people with Human Immunodeficiency Virus, run by Rockefeller University at 1 site 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 12 inclusion and 40 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: finished, as of the sponsor's last update on 4 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

The number of participants who experience adverse events within 2 weeks after 10-1074-LS intravenous infusions and subcutaneous injections. (time frame: 2 weeks). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03554408, which also lists 1 linked publication.

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 4 Aug 2021; AzTrials last refreshed its copy on 6 Nov 2026.

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