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Studio di fase 2a a dose crescente multipla in pazienti ospedalizzati con polmonite.

24 settembre 2026 aggiornato da: Vasomune Therapeutics, Inc.

Uno studio randomizzato, in doppio cieco, controllato con placebo, di fase 2a a dosi multiple ascendenti per esaminare la sicurezza, la tollerabilità e l'efficacia dell'iniezione di AV-001 in pazienti ricoverati con polmonite dovuta a COVID-19 o altre infezioni respiratorie.

A Phase 2a, randomized, double-blind, placebo-controlled, multiple ascending dose study in patients who are hospitalized with presumed pneumonia requiring supplemental oxygen therapy. The purpose of this study is to examine the safety, tolerability and efficacy of AV-001 Injection administration daily to the earlier of day 28 or EOT (day prior to hospital discharge). A total of 60 eligible patients (20 patients in each of cohort 1, 2 and 3) will be recruited from up to 25 participating institutions/hospitals. Patients will be randomized in a 1:1 ratio to receive either AV-001 Injection or AV-001 placebo Injection, together with standard of care (SOC).

Panoramica dello studio

Stato

Attivo, non reclutante

Condizioni

Intervento / Trattamento

Descrizione dettagliata

Pneumonia is a leading cause of hospitalization among adults and children in the United States and has ranked among the top 10 causes of death according to the CDC. A large variety of microorganisms can cause pneumonia including respiratory viruses, bacteria and fungi and there are great geographic variations in their prevalence. In the United States, common causes of viral pneumonia are SARS-CoV-2, influenza and respiratory syncytial virus (RSV) and bacterial pneumonia are Streptococcus pneumoniae (pneumococcus).

Emerging evidence indicates that the respiratory system mechanics of patients with typical ARDS, with or without COVID-19 are broadly similar in contrast to earlier reports that suggested COVID-19-associated ARDS has distinctive features. SOC for patients with ARDS remains limited with current interventions that focus primarily on supportive therapy, including fluid management strategies and further injury prevention via lung protective ventilation. Ventilation approaches remain the cornerstone in the treatment of ARDS and approaches to minimize ventilator-induced lung injury (VILI) resulting from the imposition of stretch-trauma to the lung, continue to be a major focus of clinical importance. Several techniques may be utilized to accomplish this objective. Clinical guidelines strongly recommend volume-limited or pressure-limited ventilator approaches for patients with severe ARDS and high positive-end expiratory pressure strategies for patients with moderate to severe ARDS. Despite decades of improving supportive care, mortality remains high, ranging from 34.9% of patients with mild ARDS to 46.1% of patients with severe ARDS.

Whatever the causative organism it is increasingly apparent that their impact on lung microvasculature is a major contributing factor to morbidity and mortality associated with those infections. Most deaths from influenza virus infections occur due to pulmonary complications, in particular the development of acute respiratory distress syndrome (ARDS), that is due to increased permeability of the lung microvasculature. Emerging evidence in COVID-19 infections suggest a similar pathophysiology where pulmonary endothelial cells and vascular dysfunction contribute to the initiation and propagation of ARDS by altering blood vessel integrity, promoting a pro-coagulative state, inducing endotheliitis and mediating inflammatory cell infiltration. Therefore, a therapeutic intervention that could modulate the course of pulmonary disease not by treating the causative organism but by reducing the deleterious inflammatory sequalae of those infections may have a significant positive impact

AV-001 is a synthetic Angiopoietin-1 (Angpt-1) mimetic that has been shown to activate the Tie2 receptor tyrosine kinase; a transmembrane protein target most highly expressed on the surface of endothelial cells in the vasculature. The Tie2/Angiopoietin signaling axis has been identified as a nonredundant gatekeeper of vascular homeostasis. In healthy individuals, Tie2 is highly activated and signals the endothelium to fortify intracellular junctions and reduce expression of adhesion molecules, which serve as leukocyte tethers upon inflammation. As such, homeostatic activation results in the promotion of barrier defense against vascular leakage.

A total of 60 eligible patients (20 patients each in cohorts 1, 2 and 3) will be recruited from participating institutions / hospitals. Patients will be randomized in a 1:1 ratio to receive either AV-001 Injection or AV-001 placebo Injection, together with SOC. All patients will receive supportive care according to the SOC for the trial site hospital likely to include remdesivir and or dexamethasone. Study drug will be administered by bolus IV injection (< 60 seconds). Doses of AV-001 Injection to be administered will start with the lowest proposed dose of 12.5 μg/kg/day in cohort 1 (DL1) and are anticipated to increase to 25μg/kg/day in cohort 2 (DL2), 56 μg/kg/day in cohort 3 (DL3).

The study population for this Phase 2a study will consist of male and non-pregnant female patients, ≥ 18 years of age, hospitalized with presumed pneumonia secondary to SARS-CoV-2 or other viral or bacterial infection with acute onset to a respiratory compromise requiring supplemental oxygen therapy.

Tipo di studio

Interventistico

Iscrizione (Effettivo)

60

Fase

  • Fase 2

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Stati Uniti
    • California
      • Newport Beach, California, Stati Uniti, 92658-6100
        • Hoag Memorial Hospital Presbyterian
    • Colorado
      • Denver, Colorado, Stati Uniti, 80203
        • Denver Health Medical Center
    • Illinois
      • Chicago, Illinois, Stati Uniti, 60611
        • Northwestern University Medical Center
    • Maryland
      • Hyattsville, Maryland, Stati Uniti, 20782
        • MedStar Health Research Institute, Inc.
    • Michigan
      • Detroit, Michigan, Stati Uniti, 48202
        • Henry Ford Health System
    • Ohio
      • Columbus, Ohio, Stati Uniti, 43210
        • The Ohio State University

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

Inclusion Criteria:

  • Able and willing to give signed informed consent
  • Patients hospitalized with a presumed diagnosis of pneumonia of < 48 hours duration requiring supplemental oxygen therapy. Eligible patients include those hospitalized for a separate non-infectious reason who subsequently develop a presumed pneumonia;
  • Radiologic imaging (chest x-ray, CT scan, etc.) evidence of pulmonary involvement with new and persistent or progressive and persistent infiltrate, consolidation or cavitation.

Signs and symptoms:

At least 1 of the following signs:

  • respiratory rate > 30 breaths/min;
  • fever (> 38.0ºC or > 100.4o F);
  • leukopenia (≤ 4,000 WBC/mm3 or leukocytosis (≥ 12,000 WBC/mm3);
  • adults ≥ 70 years of age; altered mental status with no other recognized cause;

AND at least 1 of the following symptoms:

  • New onset of purulent sputum or change in character of sputum or increased respiratory secretions;

  • New onset or worsening cough, or dyspnea, or tachypnea;

  • Rales or bronchial breath sounds;

    • Female patients of reproductive potential must be on an effective contraceptive method

Exclusion Criteria:

  • Pregnant and/or lactating women

  • Patients included in any other interventional trial

  • Use of endotracheal intubation and mechanical ventilation or extracorporeal membrane oxygenation (ECMO) at screening

  • Any concurrent serious medical condition or concomitant medication that would preclude participation in the study including but not limited to:

    • Septic shock as defined by systolic blood pressure (SBP) < 90 mmHg or diastolic blood pressure (DBP) of < 60 mmHg;
    • Multiple organ failure;
    • Are moribund irrespective of the provision of treatments;
    • Any significant bleeding disorder or vasculitis;
    • Any serious, nonhealing wound, peptic ulcer or bone fracture;
    • Liver cirrhosis;
    • History of a hypertensive crisis or hypertensive encephalopathy, or current, poorly controlled hypertension or hypotension;
    • Severe renal insufficiency or end stage renal disease as determined by estimated glomerular filtration rate <30mL/min/1.73m2;
    • ARDS risk factors of aspiration pneumonia, non-cardiac shock, trauma, blood transfusion or drug overdose.

  • Any thromboembolic event within the past 3 months;

  • Symptomatic congestive heart failure or symptomatic or poorly controlled cardiac arrhythmia > class II as per New York Heart Association (NYHA) classification;

  • History of autonomic disorders or uncontrolled hypotension

  • Hypersensitivity to drug products containing polyethylene glycol (PEG)

  • Any other condition which the Principal Investigator feels may jeopardize the safety of the patient or the objectives of the study

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione sequenziale
  • Mascheramento: Quadruplicare

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Comparatore attivo: AV-001 Injection with standard of care (SOC).

A total of 60 eligible patients (20 patients in each of cohort 1, 2 and 3) will be randomized in a 1:1 ratio to receive either AV-001 Injection or AV-001 placebo Injection, together with standard of care (SOC). Doses of AV-001 Injection will start with 12.5 μg/kg/day in cohort 1 and are anticipated to increase to 25 μg/kg/day in cohort 2, 56 μg/kg/day in cohort 3.
Droga: AV-001 Injection

AV-001 (mpaBr) Cl for Injection 2.5 mg/mL
Comparatore placebo: AV-001 Placebo Injection with standard of care (SOC).

A total of 60 eligible patients (20 patients in each of cohort 1, 2 and 3) will be randomized in a 1:1 ratio to receive either AV-001 Injection or AV-001 placebo Injection, together with standard of care (SOC).
Droga: AV-001 Placebo Injection

D-PBS

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Safety and tolerability of multiple doses of IV administrations of AV-001 Injection compared with AV-001 placebo Injection in hospitalized patients with pneumonia due to COVID-19 and/or other respiratory infections.
Lasso di tempo: Up to Day 60
  • Number of patients with any serious adverse event (SAE) (day 1 to 60/EOS)
  • Number of patients with any treatment emergent adverse event (TEAE) (day 1 to 60/EOS) AE assessments (day 1 to 60/EOS)
Up to Day 60

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Efficacy of multiple IV administrations of AV-001 Injection compared with AV-001 placebo Injection in patients hospitalized with pneumonia due to COVID-19 and/or other respiratory infections
Lasso di tempo: Up to Day 28

Measured as proportion of patients achieving a 2-point improvement in WHO COVID-19 CPS score from baseline and alive by day 28.
Up to Day 28
Efficacy of multiple IV administrations of AV-001 Injection compared with AV-001 placebo Injection in patients hospitalized with pneumonia due to COVID-19 and/or other respiratory infections
Lasso di tempo: Up to Day 28

Time to first 2-point WHO CPS improvement using a Kaplan-Meier lifetable
Up to Day 28
Efficacy of multiple IV administrations of AV-001 Injection compared with AV-001 placebo Injection in patients hospitalized with pneumonia due to COVID-19 and/or other respiratory infections
Lasso di tempo: Up to Day 28

Measured as survival at day 28, displayed with a Kaplan- Meier lifetable.
Up to Day 28
Efficacy of multiple IV administrations of AV-001 Injection compared with AV-001 placebo Injection in patients hospitalized with pneumonia due to COVID-19 and/or other respiratory infections
Lasso di tempo: Up to Day 28

Measured as proportion of patients that progress to respiratory failure by day 28.
Up to Day 28
Efficacy of multiple IV administrations of AV-001 Injection compared with AV-001 placebo Injection in patients hospitalized with pneumonia due to COVID-19 and/or other respiratory infections
Lasso di tempo: Up to Day 28

Measured as proportion of patients that progress to mechanical ventilation by day 28.
Up to Day 28
Efficacy of multiple IV administrations of AV-001 Injection compared with AV-001 placebo Injection in patients hospitalized with pneumonia due to COVID-19 and/or other respiratory infections
Lasso di tempo: Up to Day 28

Measured as proportion of patients with disease improvement of at least 1 point on the WHO COVID-19 CPS for 3 consecutive days and sustained the improvement through day 28.
Up to Day 28
Efficacy of multiple IV administrations of AV-001 Injection compared with AV-001 placebo Injection in patients hospitalized with pneumonia due to COVID-19 and/or other respiratory infections
Lasso di tempo: Up to Day 28

SpO2 saturation (up to day 28): measured as proportion of patients achieving normalization (last oxygen saturation of arterial blood [SaO2] value > 95%).
Up to Day 28
Efficacy of multiple IV administrations of AV-001 Injection compared with AV-001 placebo Injection in patients hospitalized with pneumonia due to COVID-19 and/or other respiratory infections.
Lasso di tempo: Up to Day 28

Oxygen delivery: measured as the product of flow rate and volume per day.
Up to Day 28
Efficacy of multiple IV administrations of AV-001 Injection compared with AV-001 placebo Injection in patients hospitalized with pneumonia due to COVID-19 and/or other respiratory infections.
Lasso di tempo: Up to Day 28

Measured as the acute kidney injury stage distribution over time using the Kidney Disease Improving Global Outcomes (KDIGO) definition of Acute Kidney Injury (AKI).
Up to Day 28
Efficacy of multiple IV administrations of AV-001 Injection compared with AV-001 placebo Injection in patients hospitalized with pneumonia due to COVID-19 and/or other respiratory infections
Lasso di tempo: Up to Day 28

Measured as proportion of patients alive and discharged from the intensive care unit (ICU) at day 28.
Up to Day 28
Efficacy of multiple IV administrations of AV-001 Injection compared with AV-001 placebo Injection in patients hospitalized with pneumonia due to COVID-19 and/or other respiratory infections
Lasso di tempo: Up to Day 28

Measured as proportion of patients alive and discharged from hospital at day 28.
Up to Day 28
Efficacy of multiple IV administrations of AV-001 Injection compared with AV-001 placebo Injection in patients hospitalized with pneumonia due to COVID-19 and/or other respiratory infections
Lasso di tempo: Up to Day 28

Measured as time to hospital discharge status (discharge or day 28, whichever is earlier).
Up to Day 28

Altre misure di risultato

Misura del risultato
Misura Descrizione
Lasso di tempo
Efficacy of multiple IV administrations of AV-001 Injection compared with AV-001 placebo Injection in patients hospitalized with pneumonia due to COVID-19 and/or other respiratory infections
Lasso di tempo: Up to Day 60

Measured as alive at day 60, displayed with a Kaplan- Meier lifetable.
Up to Day 60
Efficacy of multiple IV administrations of AV-001 Injection compared with AV-001 placebo Injection in patients hospitalized with pneumonia due to COVID-19 and/or other respiratory infections
Lasso di tempo: Up to Day 14

Measured as proportion of patients that progress to respiratory failure by day 14.
Up to Day 14
Efficacy of multiple IV administrations of AV-001 Injection compared with AV-001 placebo Injection in patients hospitalized with pneumonia due to COVID-19 and/or other respiratory infections
Lasso di tempo: Up to Day 14

Measured as proportion of patients that progress to mechanical ventilation by day 14.
Up to Day 14
Efficacy of multiple IV administrations of AV-001 Injection compared with AV-001 placebo Injection in patients hospitalized with pneumonia due to COVID-19 and/or other respiratory infections
Lasso di tempo: Up to Day 14

Proportion of patients achieving a 2-point improvement in WHO COVID-19 CPS score from baseline and alive by day 14.
Up to Day 14
Efficacy of multiple IV administrations of AV-001 Injection compared with AV-001 placebo Injection in patients hospitalized with pneumonia due to COVID-19 and/or other respiratory infections
Lasso di tempo: Up to Day 14

Measured as proportion of patients alive and discharged from the intensive care unit (ICU) at day 14.
Up to Day 14
Efficacy of multiple IV administrations of AV-001 Injection compared with AV-001 placebo Injection in patients hospitalized with pneumonia due to COVID-19 and/or other respiratory infections
Lasso di tempo: Up to Day 14

Measured as proportion of patients alive and discharged from hospital at day 14.
Up to Day 14
Efficacy of multiple IV administrations of AV-001 Injection compared with AV-001 placebo Injection in patients hospitalized with pneumonia due to COVID-19 and/or other respiratory infections
Lasso di tempo: Up to Day 60

Measured as durable loss of eGFR (by day 28 and day 60) from baseline (89-60 mL/min, 59-45 mL/min, 30-44 mL/min, <30 mL/min) or the development of severe AKI requiring continuous renal replacement therapy (CRRT), prolonged intermittent renal replacement therapy (PIRRT) or hemodialysis.
Up to Day 60
Effect of multiple IV administrations of AV-001 Injection compared with AV-001 placebo Injection on exploratory biomarkers of Tie2 target engagement
Lasso di tempo: Up to Day 28

Measured as ratio of phosphorylated Tie2/Total Tie2 using flow cytometry analysis.
Up to Day 28
Effect of multiple IV administrations of AV-001 Injection compared with AV-001 placebo Injection on exploratory biomarkers (Angpt-1, Angpt-2, and circulating Tie2).
Lasso di tempo: Up to Day 28

Measured using quantitative ELISA.
Up to Day 28
Effect of multiple IV administrations of AV-001 Injection compared with AV-001 placebo Injection on disease biomarkers IL-6 in patients with pneumonia due to COVID-19 and/or other respiratory infections.
Lasso di tempo: Up to Day 28

Measured at screening and at pre-dose on days 2, 4, 7, 10, 13, 16, 19, 22, 25 and the earlier of day 28 or EOT using quantitative reverse transcriptase polymerase chain reaction (RT-PCR) assay.
Up to Day 28
Effect of multiple IV administrations of AV-001 Injection compared with AV-001 placebo Injection on disease biomarker IL-8 in patients with pneumonia due to COVID-19 and/or other respiratory infections.
Lasso di tempo: Up to Day 28

Measured at screening and at pre-dose on days 2, 4, 7, 10, 13, 16, 19, 22, 25 and the earlier of day 28 or EOT using quantitative reverse transcriptase polymerase chain reaction (RT-PCR) assay.
Up to Day 28
Effect of multiple IV administrations of AV-001 Injection compared with AV-001 placebo Injection on disease biomarkers TNFr-1 in patients with pneumonia due to COVID-19 and/or other respiratory infections.
Lasso di tempo: Up to Day 28

Measured at screening and at pre-dose on days 2, 4, 7, 10, 13, 16, 19, 22, 25 and the earlier of day 28 or EOT using quantitative reverse transcriptase polymerase chain reaction (RT-PCR) assay.
Up to Day 28
Effect of multiple IV administrations of AV-001 Injection compared with AV-001 placebo Injection on disease biomarker MCP-1 in patients with pneumonia due to COVID-19 and/or other respiratory infections.
Lasso di tempo: Up to Day 28

Measured at screening and at pre-dose on days 2, 4, 7, 10, 13, 16, 19, 22, 25 and the earlier of day 28 or EOT using quantitative reverse transcriptase polymerase chain reaction (RT-PCR) assay.
Up to Day 28
Effect of multiple IV administrations of AV-001 Injection compared with AV-001 placebo Injection on disease biomarker IP-10 in patients with pneumonia due to COVID-19 and/or other respiratory infections.
Lasso di tempo: Up to Day 28

Measured at screening and at pre-dose on days 2, 4, 7, 10, 13, 16, 19, 22, 25 and the earlier of day 28 or EOT using quantitative reverse transcriptase polymerase chain reaction (RT-PCR) assay.
Up to Day 28
Effect of multiple IV administrations of AV-001 Injection compared with AV-001 placebo Injection on disease biomarker ICAM-1, in in patients with pneumonia due to COVID-19 and/or other respiratory infections.
Lasso di tempo: Up to Day 28

Measured at screening and at pre-dose on days 2, 4, 7, 10, 13, 16, 19, 22, 25 and the earlier of day 28 or EOT using quantitative reverse transcriptase polymerase chain reaction (RT-PCR) assay.
Up to Day 28
PK as measured by Cmax of AV-001 Injection in hospitalized patients with severe COVID-19 disease.
Lasso di tempo: Up to Day 28

Assessment of the PK of AV-001 Injection in hospitalized patients with severe COVID-19 disease using population PK for DL1, DL2 and DL3. PK measured as Cmax from sample timepoints Pre-dose, 5 min, 30 min, 1, 2, 4, and 24 hours post-dose on days 1, 7 and the earlier of day 28 or EOT.
Up to Day 28
PK as measured by Tmax of AV-001 Injection in hospitalized patients with pneumonia due to COVID-19 and/or other respiratory infections.
Lasso di tempo: Up to Day 28

Assessment of the PK of AV-001 Injection in hospitalized patients with pneumonia due to COVID-19 and/or other respiratory infections using population PK for DL1, DL2 and DL3. PK measured as Tmax, from sample timepoints Pre-dose, 5 min, 30 min, 1, 2, 4, and 24 hours post-dose on days 1, 7 and the earlier of day 28 or EOT.
Up to Day 28
PK as measured by AUC of AV-001 Injection in hospitalized patients with pneumonia due to COVID-19 and/or other respiratory infections.
Lasso di tempo: Up to Day 28

Assessment of the PK of AV-001 Injection in hospitalized patients with pneumonia due to COVID-19 and/or other respiratory infections using population PK for DL1, DL2 and DL3. PK measured as AUC from sample timepoints Pre-dose, 5 min, 30 min, 1, 2, 4, and 24 hours post-dose on days 1, 7 and the earlier of day 28 or EOT.
Up to Day 28

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Vasomune Therapeutics, Inc.

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

20 dicembre 2021

Completamento primario (Stimato)

1 settembre 2026

Completamento dello studio (Stimato)

1 settembre 2026

Date di iscrizione allo studio

Primo inviato

8 novembre 2021

Primo inviato che soddisfa i criteri di controllo qualità

15 novembre 2021

Primo Inserito (Effettivo)

17 novembre 2021

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

29 settembre 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

24 settembre 2026

Ultimo verificato

1 settembre 2026

Maggiori informazioni

Termini relativi a questo studio

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • AV001-004
  • CDMRP-PR203503 (Altro numero di sovvenzione/finanziamento: CDMRP)

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

NO

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

Sì

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

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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