Uno studio per indagare la sicurezza, la tollerabilità, l'immunogenicità e la farmacodinamica del VXX-401 rispetto al placebo nei partecipanti adulti
Uno studio di fase 1, primo sull'uomo, randomizzato, in doppio cieco, controllato con placebo, di aumento della dose per valutare la sicurezza, la tollerabilità, l'immunogenicità e la farmacodinamica del VXX-401 negli adulti sani
This first-in-human (FIH) study of VXX-401, an anti-PCSK9 peptide-based immunotherapeutic candidate, is designed to assess the safety, tolerability, immunogenicity, and pharmacodynamics (PD) of VXX-401 and to determine an optimal dose regimen for LDL-C lowering in subsequent clinical trials.
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
This is multisite, multidose regimen, phase 1, first-in-human study of VXX-401, a synthetic peptide-based active immunotherapy candidate for preventing and treating hypercholesterolemia. The study will include Screening, Treatment, and Follow-up Periods. This study will enroll participants who are naïve to statin use. Each cohort from A to D is planned to randomize approximately 12 participants to receive doses of VXX-401 or placebo in a 3:1 ratio. Cohorts E and F will dose approximately 8 participants in each cohort to receive doses of VXX-401. No participants will be administered placebo in Cohorts E and F. It is planned to test up to 6 dose regimens of VXX-401, administered by IM injection into the deltoid muscle (and additionally in the thigh for the first dose in Cohorts E-F.). All eligible participants will receive a priming regimen at Week 0 (Baseline, Day 1), Week 4, and Week 12, in Cohorts A, C, E and F, and additionally at Week 8 in Cohorts B and D. The last dose administration will be at Week 12.
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 1
Contatti e Sedi
Luoghi di studio
-
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New South Wales
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Brookvale, New South Wales, Australia
- Northern Beaches Clinical Research
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Miranda, New South Wales, Australia
- Sutherland Shire Clinical Research
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Sydney, New South Wales, Australia
- Emeritus Research
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Queensland
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Morayfield, Queensland, Australia
- University of the Sunshine Coast (USC)
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-
Victoria
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Melbourne, Victoria, Australia
- Emeritus Research
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-
Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Inclusion Criteria:
- Male or female participants aged 18 to 75 years old, inclusive, at time of informed consent.
- LDL-C level = 2.59 mmol/L - 4.89mmol/L
- Body mass index between 18 and 35 kg/m2, inclusive at Screening, and with a minimum weight of 50 kg.
- Male participants and their partners of childbearing potential must commit to the use of highly effective contraceptives for the study duration and for at least 12 weeks after the last dose. Men must refrain from donating sperm during this same period.
- Female participants must be of nonchildbearing potential, or, for women of childbearing potential, must be willing to practice at least one form of highly effective contraception throughout the duration of the study and for at least 24 weeks following the last dose. Female participants must refrain from donating reproductive tissue during this same period.
Exclusion Criteria:
- Subjects considered high risk or very high risk for ASCVD and requiring immediate treatment with LLT according to the clinical judgement of the investigator.
- History of confirmed anergy (i.e., not able to mount an immunological response) or history of immunization failure in the 5 years prior to the Screening Visit.
- Presence of fever >38°C or other signs or symptoms of acute disease within 1 week before the Screening and/or Visit 1; Screening and/or Visit 1 may be rescheduled at the discretion of the Investigator but must occur within the 4-week window.
- Known disturbance of coagulation or medication (see prohibited medications criterion below); bleeding disorder (e.g., factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venipuncture.
- Triglycerides > 5.65 mmol/L
- Has a history of clinically significant medical disorder or psychiatric conditions, which in the opinion of the investigator may compromise the participant's safety and ability to comply with study procedures or abide by study restrictions.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Quadruplicare
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
|
Sperimentale: VXX-401 Cohort A
VXX-401 100mcg administered by intramuscular (IM) injection at Week 0, Week 4, and Week 12 |
A synthetic PCSK9 peptide-based immunotherapy |
|
Sperimentale: VXX-401 Cohort B
VXX-401 100mcg administered by intramuscular (IM) injection at Week 0, Week 4, Week 8 and Week 12 |
A synthetic PCSK9 peptide-based immunotherapy |
|
Sperimentale: VXX-401 Cohort C
VXX-401 300mcg administered by intramuscular (IM) injection at Week 0, Week 4, and Week 12 |
A synthetic PCSK9 peptide-based immunotherapy |
|
Sperimentale: VXX-401 Cohort D
VXX-401 300mcg administered by intramuscular (IM) injection at Week 0, Week 4, Week 8 and Week 12 |
A synthetic PCSK9 peptide-based immunotherapy |
|
Comparatore placebo: Placebo Cohort A and C
Placebo administered by intramuscular (IM) injection at Week 0, Week 4, and Week 12 |
Normal saline |
|
Comparatore placebo: Placebo Cohort B and D
Placebo administered by intramuscular (IM) injection at Week 0, Week 4, Week 8 and Week 12 |
Normal saline |
|
Sperimentale: VXX-401 Cohort E
VXX-401 900mcg administered by intramuscular (IM) injection at Week 0. VXX-401 100 mcg administered by intramuscular (IM) injection at Week 4 and Week 12. |
A synthetic PCSK9 peptide-based immunotherapy |
|
Sperimentale: VXX-401 Cohort F
VXX-401 900mcg administered by intramuscular (IM) injection at Week 0. VXX-401 300 mcg administered by intramuscular (IM) injection at Week 4 and Week 12. |
A synthetic PCSK9 peptide-based immunotherapy |
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Frequency of adverse events
Lasso di tempo: 30 weeks
|
Safety and tolerability: rates of adverse events (AEs), medically attended adverse events (MAAEs), local (injection site) and systemic (generalized) reactions (i.e., reactogenicity), clinical laboratory assessments (e.g., chemistry, hematology, urinalysis, lipid profile), serum cytokine release, vital signs, physical examinations, and electrocardiograms (ECGs) through the end of the study. |
30 weeks
|
|
Immunogenicity
Lasso di tempo: Baseline to Week 16, 20, 24, and 30
|
Immunogenicity will be measured by serum anti-PCSK9 antibody titers |
Baseline to Week 16, 20, 24, and 30
|
|
Immunogenicity
Lasso di tempo: Baseline to Week 16, 20, 24, and 30
|
Seroconversion two-fold and four-fold from baseline |
Baseline to Week 16, 20, 24, and 30
|
|
Determine optimal VXX-401 dose regimen
Lasso di tempo: Baseline to Week 16, 20, 24, and 30
|
Measured by serum anti-PCSK9 antibody titers |
Baseline to Week 16, 20, 24, and 30
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Evaluation of low-density lipoprotein-cholesterol (LDL-C) reduction
Lasso di tempo: Baseline to Week 16, 20, 24, and 30
|
Percent change from baseline in serum LDL-C concentration |
Baseline to Week 16, 20, 24, and 30
|
Collaboratori e investigatori
Sponsor
Collaboratori
Investigatori
- Direttore dello studio: Sasha Rumyantsev, Vaxxinity, Inc.
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 (Effettivo)
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
Altri numeri di identificazione dello studio
- VXX-401-101
Piano per i dati dei singoli partecipanti (IPD)
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Informazioni su farmaci e dispositivi, documenti di studio
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