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Safety and Effectiveness of an Immunobiological Drug in CoViD-19 (INPB001)

11. september 2021 oppdatert av: Guillermo Alberto Keller, Administracion Nacional de Laboratorios e Institutos de Salud Dr. Carlos G. Malbran

Study to Evaluate the Safety and Effectiveness of an Immunobiological Drug (Anti SARS-CoV-2) in the Treatment of Coronavirus Disease 2019 (CoViD-19)

The aims of this study is to analyze the efficacy and safety of a passive immunotherapy strategy using hyperimmune equine serum known as Anti-SARS-CoV-2 elaborated by the National Institute for the Production of Biologicals (ANLIS-Malbrán) as an addition to the standard therapeutic approach for hospitalized patients with COVID-19, in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection aged 18 to 80 years.

Studieoversikt

Status

Rekruttering

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

This is an adaptive phase II/III study that aims to analyze the efficacy and safety of a immunobiological drug (Anti SARS-CoV-2) in the treatment of CoViD-19. This treatment is a passive immunotherapy strategy developed as a purified F(ab')2 fraction of equine hyperimmune serum (Anti-SARS-CoV-2). The equine serum was generated from antigenic stimulation with the SARS-CoV-2 receptor binding domain (RBD) purified protein.

This type of product (equine hyperimmune serum F(ab')2) has been widely used in our country in the last 100 years with satisfactory results and an acceptable safety profile in the treatment of accidents with poisonous animals such as anti-loxosceles, anti -latrodectus, anti-scorpionic, and anti-phoneutria, anti-bothropic, anti-micrurus, and anti-crotalic sera, all developed by the National Institute of Biological Production (ANLIS-Malbrán) and distributed free of charge in public hospitals in the country .

In the present study, evaluates the effect and safety of this immunobiological treatment in patients with COVID-19 that require hospitalization.

Studietype

Intervensjonell

Registrering (Forventet)

200

Fase

  • Fase 2
  • Fase 3

Kontakter og plasseringer

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

Studiekontakt

Studer Kontakt Backup

Studiesteder

  • Argentina
      • Ciudad Autónoma De Buenos Aires, Argentina, 1408
        • Rekruttering
        • Hospital General de Agudos Donación Francisco J. Santojanni
        • Ta kontakt med:
        • Ta kontakt med:
        • Hovedetterforsker:
          • Guillermo A Keller, MD PhD
        • Underetterforsker:
          • Guillermo Di Girolamo, MD PhD

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 80 år (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion Criteria:

  1. Subjects over 18 years old and under 80 years old.
  2. Positive results by RT-PCR for SARS CoV-2
  3. Clinical picture compatible with respiratory compromise in the form of pneumonia attributed to COVID-19 (Stage 3, 4 or 5 according to the WHO scale), lasting up to 72 hours from the onset of symptoms to their evaluation to be incorporated into the study.
  4. Patient with good disposition towards the study and that signs the informed consent.

Exclusion Criteria:

  1. Patients with clinical disease corresponding to mild / asymptomatic forms (Absence of radiological infiltrate and risk factors, with normal auscultation and arterial saturation of oxygen (SatO2) greater than 95%)
  2. Patients with clinical disease corresponding to severe forms (Severe pneumonia: presence of severity criteria (ATS / IDSA), one of two major or three minor criteria.)
  3. Patients who have received other therapeutic strategies in the framework of an experimental study that make it difficult to evaluate the results obtained, including (but not limited to): convalescent plasma, lopinavir / ritonavir, hydroxychloroquine, and azithromycin.
  4. Pregnant or lactating women.
  5. Women of childbearing potential not using an effective contraceptive method (withdrawal, intrauterine device, or oral contraceptives).
  6. History of severe anaphylactic reaction with the administration of equine plasma.
  7. Patients with comorbidities that justify a risk of high mortality from causes independent of SARS-CoV-2 infection (eg, stage IV cancer)
  8. Patient who does not consent to participate.

Studieplan

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

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Firemannsrom

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Aktiv komparator: Anti-SARS-CoV-2
Administration of 10 ml of a concentrated equine hyperimmune serum solution with neutralizing activity of SARS-CoV-2 not less than1/5120, administered in slow intravenous infusion (10 ml diluted in100 ml of physiological solution, administered over 50 to 60 minutes in slow drip), produced by ANLIS-Malbrán, administered twice (time 0 when incorporated into the study -initial dose- and at 48 hours -second dose-).
Legemiddel: Anti-SARS-CoV-2
Purified F(ab')2 Fragments of Equine hyperimmune Serum with anti-SARS-CoV-2 neutralizing activity (titer 1/5120 or higher)
Andre navn:
  • Behandlingsgruppe
  • Purified F(ab')2 Fragments of Equine hyperimmune Serum
  • F(ab')2 Fragments
  • Passive Immunotherapy
  • Equine F(ab')2 Fragments
  • Hyperimmune Equine Serum
Placebo komparator: Placebo
Administration of 10 ml of a control-solution with no-neutralizing activity of SARS-CoV-2, administered in slow intravenous infusion (10ml diluted in 100 ml of physiological solution, administered over 50 to60 minutes in slow drip), produced by ANLIS-Malbrán, administered twice (time 0when incorporated into the study -initial dose- and at 48 hours -second dose-).
Legemiddel: Placebo
Administration of 10 ml of a control-solution without neutralizing activity against SARS-CoV-2, administered in slow intravenous infusion (10 ml diluted in 100 ml of saline solution, administered over 50 to 60 minutes in slow drip), produced by ANLIS-Malbrán, administered twice (time 0 when incorporated into the study -initial dose- and at 48 hours -second dose-).
Andre navn:
  • Kontrollgruppe

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Change in time needed to clinical improvement
Tidsramme: Reached each day between day 1 and 28 post-inclusion in the study
In subjects admitted to the general ward for active infection by SARS-CoV-2 and a clinical picture of pneumonia who receive supportive treatment recommended by the guidelines of the Ministry of Health of the Argentine Nation (Population), if slow intravenous administration of Anti SARS-CoV-2 in two doses 48 hours apart (Intervention) added to supportive treatment, compared to supportive treatment alone (patients will receive slow intravenous administration of a placebo solution in two doses 48 hours apart to maintain the "blind" as Comparator), changes the time needed to clinical improvement (Outcome), during 28 days after the assignment (Time).
Reached each day between day 1 and 28 post-inclusion in the study

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Change in the number of patients in each World Health Organization (WHO) Ordinal Scale Category (0 to 8 being 0 better and 8 worse)
Tidsramme: days 7, 14 and 21 post-inclusion
(a) Change in the number of patients in each World Health Organization Ordinal Scale Category (0 to 8 being 0 better and 8 worse), expecting a lower proportion of patients in categories 4, 5, 6, and 7 (OUTCOME - Efficacy);
days 7, 14 and 21 post-inclusion
Change in Mortality rate
Tidsramme: 28 days post-inclusion
(b) Change of all-cause mortality at day 28 (OUTCOME - Efficacy);
28 days post-inclusion
Change in Mechanical Ventilation Requirement rate
Tidsramme: 28 days post-inclusion
(c) Determination of the frequency of invasive mechanical ventilation in the total analysis period (OUTCOME - Efficacy);
28 days post-inclusion
Change in duration of oxygen treatment requirement
Tidsramme: 28 days post-inclusion
(d) Change of the duration of oxygen therapy quantified in days of oxygen therapy (OUTCOME - Efficacy);
28 days post-inclusion
Change in Length of Hospitalization
Tidsramme: 28 days post-inclusion
(e) Change of hospital length of hospitalization, quantified in days from study inclusion until hospital discharge (OUTCOME - Efficacy);
28 days post-inclusion
Change in frequency of nosocomial infection
Tidsramme: 28 days post-inclusion
(F) Change in the frequency of patients with nosocomial infection (OUTCOME - Efficacy);
28 days post-inclusion
Change in Lymphocyte cell count
Tidsramme: 28 days post-inclusion
(g) Change of absolute lymphocyte count (OUTCOME - Efficacy);
28 days post-inclusion
Change in viral RNA Negativization rate on nasopharyngeal swab test
Tidsramme: 7, 14, 21, and 28 days post-inclusion
(h) change in the proportion of patients with detected viral RNA and the viral RNA load, measured by quantitative reverse transcriptase polymerase chain reaction (RT-PCR), on day 7, 14, 21, and 28 (OUTCOME - Efficacy);
7, 14, 21, and 28 days post-inclusion
Description of adverse events type and frequency
Tidsramme: 28 days post-inclusion
(i) description of reported adverse events, discriminated by their severity, and classified according to MedDRA (OUTCOME - Safety).
28 days post-inclusion
Requirement of additional treatments for Adverse Drug reactions
Tidsramme: 28 days post-inclusion
(j) The number of subjects who required additional treatment as a consequence of reported adverse events in each therapeutic branch (OUTCOME - Safety)
28 days post-inclusion
Describe the AUC of purified F(ab')2 Anti-SARS-CoV-2
Tidsramme: Time 0 (Basal, prior to drug administration), hours 1, 3, 6, 24, 48, 49 and 96, days 7, 14, 21 and 28 days
(k1) Describe area under the curve (AUC) of the active drug, based on concentrations determined in plasma samples obtained from the first 20 patients
Time 0 (Basal, prior to drug administration), hours 1, 3, 6, 24, 48, 49 and 96, days 7, 14, 21 and 28 days
Describe the Cmax of purified F(ab')2 Anti-SARS-CoV-2
Tidsramme: Time 0 (Basal, prior to drug administration), hours 1, 3, 6, 24, 48, 49 and 96, days 7, 14, 21 and 28 days
(k2) Describe maximum plasma concentration (Cmax) of the active drug, based on concentrations determined in plasma samples obtained from the first 20 patients (at time Minute 0 min, hours 1, 3, 6, 24, 48, 49 and 96, day 7, 14, 21 and 28 days).
Time 0 (Basal, prior to drug administration), hours 1, 3, 6, 24, 48, 49 and 96, days 7, 14, 21 and 28 days
Describe the t1/2 of purified F(ab')2 Anti-SARS-CoV-2
Tidsramme: Time 0 (Basal, prior to drug administration), hours 1, 3, 6, 24, 48, 49 and 96, days 7, 14, 21 and 28 days
(k3) Describe plasma half life (t1/2) of the active drug, based on concentrations determined in plasma samples obtained from the first 20 patients (at time Minute 0 min, hours 1, 3, 6, 24, 48, 49 and 96, day 7, 14, 21 and 28 days).
Time 0 (Basal, prior to drug administration), hours 1, 3, 6, 24, 48, 49 and 96, days 7, 14, 21 and 28 days
Describe the Ke of purified F(ab')2 Anti-SARS-CoV-2
Tidsramme: Time 0 (Basal, prior to drug administration), hours 1, 3, 6, 24, 48, 49 and 96, days 7, 14, 21 and 28 days
(k4) Describe elimination constant (Ke) of the active drug, based on concentrations determined in plasma samples obtained from the first 20 patients (at time Minute 0 min, hours 1, 3, 6, 24, 48, 49 and 96, day 7, 14, 21 and 28 days).
Time 0 (Basal, prior to drug administration), hours 1, 3, 6, 24, 48, 49 and 96, days 7, 14, 21 and 28 days

Samarbeidspartnere og etterforskere

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

Sponsor

Administracion Nacional de Laboratorios e Institutos de Salud Dr. Carlos G. Malbran

Etterforskere

  • Hovedetterforsker: Guillermo A Keller, PhD, INPB - ANLIS Malbrán

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)

1. juni 2021

Primær fullføring (Forventet)

30. november 2021

Studiet fullført (Forventet)

31. desember 2021

Datoer for studieregistrering

Først innsendt

1. juni 2021

Først innsendt som oppfylte QC-kriteriene

2. juni 2021

Først lagt ut (Faktiske)

4. juni 2021

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

17. september 2021

Siste oppdatering sendt inn som oppfylte QC-kriteriene

11. september 2021

Sist bekreftet

1. september 2021

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • INPB001
  • PRIISA.BA 2578 (Registeridentifikator: PRIISA.BA)
  • RENIS IS003268 (Registeridentifikator: RENIS)
  • DI-2021-2196-APN-ANMAT#MS (Annen identifikator: Disposición ANMAT)

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

Ja

IPD-planbeskrivelse

Publication of the results of all data obtained is planned.

IPD-delingstidsramme

After completion of the study.

Tilgangskriterier for IPD-deling

By request to the Principal Investigator

IPD-deling Støtteinformasjonstype

  • Studieprotokoll
  • Statistisk analyseplan (SAP)
  • Informert samtykkeskjema (ICF)
  • Klinisk studierapport (CSR)
  • Analytisk kode

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Nei

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

produkt produsert i og eksportert fra USA

Nei

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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