- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT02824536
3BNC117 and 10-1074 in HIV Uninfected Adults
A Phase 1 Study of the Safety and Pharmacokinetics of the Combination of 3BNC117 and 10-1074 in HIV-uninfected Adults
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
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.
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 1
Contatti e Sedi
Luoghi di studio
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New York
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New York, New York, Stati Uniti, 10065
- The Rockefeller University
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Prevenzione
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Triplicare
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
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Sperimentale: 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.
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Infusione endovenosa di 3BNC117
Altri nomi:
Intravenous Infusion of 10-1074
Altri nomi:
Intravenous Infusion of Sterile Saline (NaCl 0.9%)
Altri nomi:
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Sperimentale: 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.
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Infusione endovenosa di 3BNC117
Altri nomi:
Intravenous Infusion of 10-1074
Altri nomi:
Intravenous Infusion of Sterile Saline (NaCl 0.9%)
Altri nomi:
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Sperimentale: 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.
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Infusione endovenosa di 3BNC117
Altri nomi:
Intravenous Infusion of 10-1074
Altri nomi:
Intravenous Infusion of Sterile Saline (NaCl 0.9%)
Altri nomi:
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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The number of participants who experience adverse events within 1 week after the combination of 3BNC117 and 10-1074 infusion in all study groups.
Lasso di tempo: 1 week following each combination of 3BNC117 and 10-1074 infusion
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Adverse events include signs, symptoms and laboratory abnormalities, in addition to local and systemic reactogenicity adverse events.
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1 week following each combination of 3BNC117 and 10-1074 infusion
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Number of participants with induced anti-3BNC117 and anti-10-1074 antibodies
Lasso di tempo: 8 weeks following each combination of 3BNC117 and 10-1074 infusion
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8 weeks following each combination of 3BNC117 and 10-1074 infusion
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Level of induced anti-3BNC117 and anti-10-1074 antibodies
Lasso di tempo: 8 weeks following each combination of 3BNC117 and 10-1074 infusion
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8 weeks following each combination of 3BNC117 and 10-1074 infusion
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The number of participants who experience adverse events that occur during study follow up after 3BNC117 and 10-1074 infusions in all study groups.
Lasso di tempo: 24-40 weeks
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Adverse events include signs, symptoms and laboratory abnormalities.
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24-40 weeks
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Altre misure di risultato
Misura del risultato |
Lasso di tempo |
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Neutralization activity of serum from study participants against a panel of viruses as measured by the TZM.bl neutralization assay.
Lasso di tempo: 24-40 weeks
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24-40 weeks
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Elimination half-life (t1/2) of 3BNC117 and 10-1074
Lasso di tempo: 24-40 weeks
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24-40 weeks
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Clearance (CL/F) of 3BNC117 and 10-1074
Lasso di tempo: 24-40 weeks
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24-40 weeks
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Volume of distribution (Vz/F) of 3BNC117 and 10-1074
Lasso di tempo: 24-40 weeks
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24-40 weeks
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Area under the plasma concentration versus time curve (AUC) of 3BNC117 and 10-1074
Lasso di tempo: 24-40 weeks
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24-40 weeks
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Decay Curve of of 3BNC117 and 10-1074
Lasso di tempo: 24-40 weeks
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24-40 weeks
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Collaboratori e investigatori
Sponsor
Investigatori
- Investigatore principale: Yehuda Cohen, MD, Rockefeller University
Pubblicazioni e link utili
Pubblicazioni generali
- 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.
- Cohen YZ, Butler AL, Millard K, Witmer-Pack M, Levin R, Unson-O'Brien C, Patel R, Shimeliovich I, Lorenzi JCC, Horowitz J, Walsh SR, Lin S, Weiner JA, Tse A, Sato A, Bennett C, Mayer B, Seaton KE, Yates NL, Baden LR, deCamp AC, Ackerman ME, Seaman MS, Tomaras GD, Nussenzweig MC, Caskey M. Safety, pharmacokinetics, and immunogenicity of the combination of the broadly neutralizing anti-HIV-1 antibodies 3BNC117 and 10-1074 in healthy adults: A randomized, phase 1 study. PLoS One. 2019 Aug 8;14(8):e0219142. doi: 10.1371/journal.pone.0219142. eCollection 2019.
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
- Infezioni da virus a RNA
- Malattie virali
- Infezioni
- Infezioni a trasmissione ematica
- Malattie trasmissibili
- Malattie sessualmente trasmissibili, virali
- Malattie trasmesse sessualmente
- Infezioni da lentivirus
- Infezioni da retroviridae
- Sindromi da deficit immunologico
- Malattie del sistema immunitario
- Malattie da virus lenti
- Infezioni da HIV
- Sindrome da immunodeficienza acquisita
- Effetti fisiologici delle droghe
- Agenti antineoplastici
- Fattori immunologici
- Anticorpi
- Immunoglobuline
- Anticorpi, monoclonali
- Agenti antineoplastici, immunologici
Altri numeri di identificazione dello studio
- YCO-0899
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .
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Rockefeller UniversityNational Institute of Allergy and Infectious Diseases (NIAID); Montefiore Medical... e altri collaboratoriCompletatoInfezione da HIV-1Stati Uniti
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AIDS Clinical Trials GroupNational Institute of Allergy and Infectious Diseases (NIAID)Non ancora reclutamentoInfezione da HIV-1Malawi, Sud Africa, Botswana
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AIDS Clinical Trials GroupNational Institute of Allergy and Infectious Diseases (NIAID)Non ancora reclutamento
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Rockefeller UniversityCompletato
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