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3BNC117 and 10-1074 in HIV Uninfected Adults

13. april 2018 oppdatert av: Rockefeller University

A Phase 1 Study of the Safety and Pharmacokinetics of the Combination of 3BNC117 and 10-1074 in HIV-uninfected Adults

This is a phase 1 clinical trial to evaluate the safety and pharmacokinetics of the highly neutralizing anti-human immunodeficiency virus-1 monoclonal antibodies 3BNC117 and 10-1074, when given in combination, in human immunodeficiency virus (HIV)-uninfected individuals. This study is intended to support the development of the combination of 3BNC117 and 10-1074 mAbs for use as prophylaxis against HIV infection in healthy HIV-uninfected individuals at risk for HIV infection.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

The study will be conducted under a placebo-controlled, double blind, randomized allocation of the study products. Study participants in each study group will be randomized to receive intravenous infusions of 3BNC117 and 10-1074 or placebo. 3BNC117 and 10-1074 will be administered at 2 dose levels (3 mg/kg and 10 mg/kg). These doses were selected based on the planned development of subcutaneous formulations for the prophylactic use of these products. The study will consist of 3 groups. Enrollment in Group 1 will begin first and participants will be enrolled at least one day apart. Eight participants will be enrolled in each group; 6 will be randomized receive the study drugs and 2 will be randomized to receive placebo. Participants in Group 1 will receive a single infusion of each antibody at 10mg/kg at Week 0. Enrollment in Group 2 will begin only after Day 28 safety data from all participants in Group 1, including ophthalmologic exams, are available. Enrollment in Group 3 will begin only after the Day 28 safety data from all participants in Group 2 is available. If > 1 grade 3 or higher adverse events deemed probably or definitely related to the study drugs occurs in a single group, the next group will not be enrolled pending safety monitoring committee (SMC) review. Participants in Groups 2 and 3 will receive 3 infusions of each antibody at Weeks 0, 8, and 16, at a dose of either 3mg/kg or 10mg/kg. The antibodies will be administered sequentially via intravenous infusion. Each antibody will be administered over 60 minutes.

Following product infusions, study participants will return for safety assessments at multiple time points. Blood samples will be collected for safety testing at weeks 1, 2, and 4 following each infusion, then at multiple time points until the end of study follow up.

Baseline pharmacokinetic (PK) assessments will be performed before the start of the first infusion. Peak PK sampling for 3BNC117 will occur following the completion of the 3BNC117 infusion prior to the start of the 10-1074 infusion. Peak PK sampling for 10-1074 will occur following the completion of the 10-1074 infusion. Additional PK assessments will occur at multiple time points during study follow up. Study participants will be followed for a total of 24 weeks following the final antibody infusion.

Studietype

Intervensjonell

Registrering (Faktiske)

24

Fase

  • Fase 1

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Forente stater
    • New York
      • New York, New York, Forente stater, 10065
        • The Rockefeller University

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år til 65 år (Voksen, Eldre voksen)

Tar imot friske frivillige

Ja

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion Criteria:

  • 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) for the duration of the study.

Exclusion Criteria:

  • Confirmed HIV-1 or HIV-2 infection.
  • History of immunodeficiency or autoimmune disease; use 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) 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.
  • Chronic Hepatitis B or Hepatitis C infection.
  • Laboratory abnormalities in the parameters listed:
  • Absolute neutrophil count ≤ 2,000;
  • Hemoglobin ≤ 12 gm/dL if female; ≤ 13.5 gm/dL if male;
  • Platelet count ≤ 125,000;
  • Alanine Aminotransferase (ALT) ≥ 1.25 x ULN; Aspartate Aminotransferase (AST) ≥ 1.25 x ULN;
  • Alkaline phosphatase ≥ 1.5 x ULN
  • Total bilirubin > 1.0 x ULN;
  • Creatinine ≥1.1 x ULN;
  • Pregnancy or lactation.
  • Any vaccination within 14 days prior to infusion
  • Receipt of any experimental HIV vaccine in the past.
  • History of severe reaction to a vaccine or drug infusion or history of severe allergic reactions.
  • Participation in another clinical study of an investigational product currently or within past 12 weeks, or expected participation during this study.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Forebygging
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Trippel

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Group 1
Participants will be randomized in a 3:1 ratio to receive one intravenous infusion of 3BNC117 and one intravenous infusion of 10-1074, each dosed at 10 mg/kg OR placebo (sterile saline), on day 0.
Legemiddel: 3BNC117
Intravenøs infusjon av 3BNC117
Andre navn:
  • Monoklonalt antistoff 3BNC117
Legemiddel: 10-1074
Intravenous Infusion of 10-1074
Andre navn:
  • Monoclonal Antibody 10-1074
Legemiddel: Placebo
Intravenous Infusion of Sterile Saline (NaCl 0.9%)
Andre navn:
  • Sterile Saline (NaCl 0.9%)
Eksperimentell: Group 2
Participants will be randomized in a 3:1 ratio to receive three intravenous infusions of 3BNC117 and three intravenous infusions of 10-1074, each dosed at 3 mg/kg OR placebo (sterile saline), on day 0, week 8, and week 16.
Legemiddel: 3BNC117
Intravenøs infusjon av 3BNC117
Andre navn:
  • Monoklonalt antistoff 3BNC117
Legemiddel: 10-1074
Intravenous Infusion of 10-1074
Andre navn:
  • Monoclonal Antibody 10-1074
Legemiddel: Placebo
Intravenous Infusion of Sterile Saline (NaCl 0.9%)
Andre navn:
  • Sterile Saline (NaCl 0.9%)
Eksperimentell: Group 3
Participants will be randomized in a 3:1 ratio to receive three intravenous infusions of 3BNC117 and three intravenous infusions of 10-1074, each dosed at 10 mg/kg OR placebo (sterile saline), on day 0, week 8, and week 16.
Legemiddel: 3BNC117
Intravenøs infusjon av 3BNC117
Andre navn:
  • Monoklonalt antistoff 3BNC117
Legemiddel: 10-1074
Intravenous Infusion of 10-1074
Andre navn:
  • Monoclonal Antibody 10-1074
Legemiddel: Placebo
Intravenous Infusion of Sterile Saline (NaCl 0.9%)
Andre navn:
  • Sterile Saline (NaCl 0.9%)

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
The number of participants who experience adverse events within 1 week after the combination of 3BNC117 and 10-1074 infusion in all study groups.
Tidsramme: 1 week following each combination of 3BNC117 and 10-1074 infusion
Adverse events include signs, symptoms and laboratory abnormalities, in addition to local and systemic reactogenicity adverse events.
1 week following each combination of 3BNC117 and 10-1074 infusion

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Number of participants with induced anti-3BNC117 and anti-10-1074 antibodies
Tidsramme: 8 weeks following each combination of 3BNC117 and 10-1074 infusion
8 weeks following each combination of 3BNC117 and 10-1074 infusion
Level of induced anti-3BNC117 and anti-10-1074 antibodies
Tidsramme: 8 weeks following each combination of 3BNC117 and 10-1074 infusion
8 weeks following each combination of 3BNC117 and 10-1074 infusion
The number of participants who experience adverse events that occur during study follow up after 3BNC117 and 10-1074 infusions in all study groups.
Tidsramme: 24-40 weeks
Adverse events include signs, symptoms and laboratory abnormalities.
24-40 weeks

Andre resultatmål

Resultatmål
Tidsramme
Neutralization activity of serum from study participants against a panel of viruses as measured by the TZM.bl neutralization assay.
Tidsramme: 24-40 weeks
24-40 weeks
Elimination half-life (t1/2) of 3BNC117 and 10-1074
Tidsramme: 24-40 weeks
24-40 weeks
Clearance (CL/F) of 3BNC117 and 10-1074
Tidsramme: 24-40 weeks
24-40 weeks
Volume of distribution (Vz/F) of 3BNC117 and 10-1074
Tidsramme: 24-40 weeks
24-40 weeks
Area under the plasma concentration versus time curve (AUC) of 3BNC117 and 10-1074
Tidsramme: 24-40 weeks
24-40 weeks
Decay Curve of of 3BNC117 and 10-1074
Tidsramme: 24-40 weeks
24-40 weeks

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Rockefeller University

Etterforskere

  • Hovedetterforsker: Yehuda Cohen, MD, Rockefeller University

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

23. juni 2016

Primær fullføring (Faktiske)

9. januar 2018

Studiet fullført (Faktiske)

9. januar 2018

Datoer for studieregistrering

Først innsendt

28. juni 2016

Først innsendt som oppfylte QC-kriteriene

1. juli 2016

Først lagt ut (Anslag)

6. juli 2016

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

17. april 2018

Siste oppdatering sendt inn som oppfylte QC-kriteriene

13. april 2018

Sist bekreftet

1. april 2018

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • YCO-0899

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

NEI

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