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Inhaled Interferon α2b for the Treatment of Coronavirus Disease 19 (COVID-19) (IN2COVID)
A Phase I/II Randomized, Double-blind, Placebo-controlled Study of Inhaled Interferon α2b for the Treatment of Coronavirus Disease 19 (COVID-19)
The IN2COVID Study is a 2-staged phase I/II double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of AP-003 (Interferon α2b) when administered via inhalation twice daily for 10 days. Participants will have a final visit at Day 11.
A lead-in phase 1 substudy will be performed with at least 18 healthy adult male subjects to assess safety and tolerability of inhaled AP-003 compared to placebo for 10 days. Two cohorts of 9 subjects will be randomly assigned to receive two doses of inhaled AP-003 or placebo with an allocation ratio of 2:1. The first cohort will assess a dose of 2.5 MIU of inhaled AP-003. If no adverse events are observed, the second cohort will be conducted using a dose of 5 MIU of inhaled AP-003. Maximum tolerated dose will be determined in this phase 1 substudy.
After the completion of phase 1, the study will continue with a phase 2 treatment RCT in patients with COVID-19. In this phase, 150 adults with mild or moderate COVID-19 demonstrated by SARS-CoV-2 positive polymerase chain reaction (PCR) ≤ 5 days at enrollment will be randomized 1:1 (75 in each arm) to receive nebulized AP-003 or identical placebo twice daily during 10 days.
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 2
- Fase 1
Contacten en locaties
Studie Locaties
-
-
RM
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Santiago, RM, Chili, 8330033
- Red de Salud UC Christus
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-
Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
Phase 1 stage:
Inclusion criteria:
- Male subjects aged 18-50 years;
- In good state of health, determined by medical history, physical exam, and normal laboratory tests at screening;
- Are able to provide informed consent for participation;
- Are able and willing to comply with the study schedule and procedures.
Exclusion Criteria
- Active SARS-CoV-2 infection demonstrated by positive polymerase chain reaction (PCR) at enrollment;
- Requiring CPAP for sleep apnea;
- Pre-existing pulmonary disease;
- Have any serious acute concomitant illness that, in the opinion of the investigator, would interfere with evaluation of safety of AP-003, or put the participant at risk of harm from study participation;
- Are currently receiving an investigational agent, have participated in another study of an investigational agent within 30 days of enrollment, or were previously enrolled in the current study;
- Are legally incompetent and unable to understand the study's purpose, significance, and consequences, and to make decisions accordingly;
- Have known hypersensitivity to interferon alpha or any component of the study drug or placebo control.
Phase 2 stage:
Inclusion criteria:
- Active SARS-CoV-2 infection demonstrated by positive polymerase chain reaction (PCR) ≤ 5 days at enrollment;
- Symptomatic of mild or moderate COVID-19 for ≤ 5 days at enrollment. Symptoms can include fever, cough, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, chest pain, with or without shortness of breath on exertion/dyspnea;
- Age ≥ 18 years;
- Are able to provide informed consent for participation;
- Are able and willing to comply with the study schedule and procedures.
Exclusion Criteria
- Patients requiring CPAP for sleep apnea.
- Patients with pre-existing pulmonary disease requiring chronic O2 supplementation.
- Patients with known infection with Influenza A or B;
- In the opinion of the Investigator, should undergo ventilatory (CPAP, mechanical ventilation, etc.) or circulatory support within 24 hours of study enrollment;
- Have any serious acute concomitant illness that, in the opinion of the Investigator, would interfere with evaluation of safety or efficacy, or put the participant at risk of harm from study participation;
- Are currently receiving an investigational agent, have participated in another study of an investigational agent within 30 days of enrollment, or were previously enrolled in the current study;
- Are legally incompetent and unable to understand the study's purpose, significance, and consequences, and to make decisions accordingly;
- Women who are pregnant or breast-feeding, or planning to conceive in the next 30 days;
- Have known hypersensitivity to interferon alpha or any component of the study drug or placebo control.
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Verviervoudigen
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
|
Experimenteel: Part 1a: Interferon alpha 2b 2.5 MIU
Nebulized interferon alpha 2b 2.5 MIU every 12 hours during 10 days (20 doses total)
|
Nebulized interferon alpha 2B
Andere namen:
|
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Experimenteel: Part 1b: Interferon alpha 2b 5 MIU
Nebulized interferon alpha 2b 5 MIU every 12 hours during 10 days (20 doses total)
|
Nebulized interferon alpha 2B
Andere namen:
|
|
Placebo-vergelijker: Part 1: Placebo
Nebulized placebo every 12 hours during 10 days (20 doses total)
|
Vernevelde placebo
|
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Experimenteel: Part 2: Interferon alpha 2b 5 MIU (or maximum tolerated dose from part 1)
Nebulized interferon alpha 2b 5 MIU (or maximum tolerated dose from part 1) every 12 hours during 10 days (20 doses total)
|
Nebulized interferon alpha 2B
Andere namen:
|
|
Placebo-vergelijker: Part 2: Placebo
Nebulized placebo every 12 hours during 10 days (20 doses total)
|
Vernevelde placebo
|
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Treatment-emergent adverse events in healthy subjects
Tijdsspanne: At the end of Phase 1 (Phase 1 is 11 days)
|
Safety and tolerability of AP-003 as measured by subject incidence of treatment-emergent adverse events.
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At the end of Phase 1 (Phase 1 is 11 days)
|
|
Change in perception of health status measured by EQ VAS in COVID-19 patients
Tijdsspanne: At Day 5 of Phase 2 (Phase 2 is 28 days)
|
Changes from baseline evaluation in COVID-19(+) participants' perception of health status at Day 5 as measured by EQ VAS in AP-003 treated patients compared to placebo.
|
At Day 5 of Phase 2 (Phase 2 is 28 days)
|
Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Serum levels of interferon alpha 2b
Tijdsspanne: Up to Day 11 of Phase 1 (Phase 1 is 11 days)
|
Pharmacokinetics of nebulized AP-003 in healthy adults assessed by serial serum quantification of interferon alpha 2b
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Up to Day 11 of Phase 1 (Phase 1 is 11 days)
|
|
Expression of interferon-induced genes in blood sputum samples
Tijdsspanne: Up to Day 11 of Phase 1 (Phase 1 is 11 days)
|
Evaluation of interferon-induced biomarkers after treatment with AP-003 in blood and sputum of healthy adults to assess biological effect of Interferon
|
Up to Day 11 of Phase 1 (Phase 1 is 11 days)
|
|
Change in perception of health status measured by EQ VAS
Tijdsspanne: Day 10 of Phase 2 (Phase 2 is 28 days)
|
Changes in participants' perception of health status from baseline to Day 10 as measured by EQ VAS in AP-003 treated patients compared to placebo.
|
Day 10 of Phase 2 (Phase 2 is 28 days)
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|
Change in perception of health status measured by EQ VAS
Tijdsspanne: Day 28 of Phase 2 (Phase 2 is 28 days)
|
Changes in participants' perception of health status from baseline to Day 28 as measured by EQ VAS in AP-003 treated patients compared to placebo.
|
Day 28 of Phase 2 (Phase 2 is 28 days)
|
|
Change in EuroQoL Quality of Life instrument (EQ-5D-5L)
Tijdsspanne: Up to day 28 of Phase 2 (Phase 2 is 28 days)
|
Changes in participants' perception of health status from baseline to Day 5, from baseline to Day 10, and from baseline to Day 28 as measured by EuroQoL Quality of Life instrument (EQ-5D-5L).
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Up to day 28 of Phase 2 (Phase 2 is 28 days)
|
|
Change in Ordinal Scale for Clinical Improvement
Tijdsspanne: Up to day 28 of Phase 2 (Phase 2 is 28 days)
|
Changes in participants' overall health from baseline to Day 5, from baseline to Day 10, and from baseline to Day 28 as measured by Ordinal Scale for Clinical Improvement in AP-003 treated patients compared to placebo.
|
Up to day 28 of Phase 2 (Phase 2 is 28 days)
|
|
Improvement in clinical symptoms
Tijdsspanne: Up to day 28 of Phase 2 (Phase 2 is 28 days)
|
Changes in participant's improvement in clinical symptoms from baseline to Day 5, from baseline to Day 10, and from baseline to Day 28 as measured by a daily symptom diary in AP-003 treated patients compared to placebo.
|
Up to day 28 of Phase 2 (Phase 2 is 28 days)
|
|
Emergency department visits
Tijdsspanne: Up to day 28 of Phase 2 (Phase 2 is 28 days)
|
The proportion of participants attending an emergency department for COVID-19 by Day 28 in AP-003 treated patients compared to placebo.
|
Up to day 28 of Phase 2 (Phase 2 is 28 days)
|
|
Hospitalizations
Tijdsspanne: Up to day 28 of Phase 2 (Phase 2 is 28 days)
|
The proportion of participants hospitalized for COVID-19 by Day 28 in AP-003 treated patients compared to placebo.
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Up to day 28 of Phase 2 (Phase 2 is 28 days)
|
|
Duration of hospitalization
Tijdsspanne: Up to day 28 of Phase 2 (Phase 2 is 28 days)
|
For hospitalized participants, duration of hospitalization in AP-003 treated patients compared to placebo.
|
Up to day 28 of Phase 2 (Phase 2 is 28 days)
|
|
Time from consent to clinical deterioration
Tijdsspanne: Up to day 28 of Phase 2 (Phase 2 is 28 days)
|
Time from consent to clinical deterioration defined as requiring or recommended for ventilatory support (continuous positive airway pressure [CPAP] or ventilator), shock requiring vasopressor support, and/or heart failure (defined as left ventricular ejection fraction [LVEF] < 30%) in AP-003 treated patients compared to placebo.
|
Up to day 28 of Phase 2 (Phase 2 is 28 days)
|
|
Change in SARS CoV-2 viral load
Tijdsspanne: Up to day 28 of Phase 2 (Phase 2 is 28 days)
|
SARS CoV-2 viral load by quantitative PCR from baseline to Day 5, from baseline to Day 10, and from baseline to Day 28 in AP-003 treated patients compared to placebo.
|
Up to day 28 of Phase 2 (Phase 2 is 28 days)
|
|
Change in inflammatory parameters
Tijdsspanne: Up to day 28 of Phase 2 (Phase 2 is 28 days)
|
Changes in D dimer, CRP, Ferritin, Troponin, creatine phosphokinase (CPK), LDH, IL-6 from baseline through Day 28 in AP-003 treated patients compared to placebo.
|
Up to day 28 of Phase 2 (Phase 2 is 28 days)
|
|
Organ failure rate
Tijdsspanne: Up to day 28 of Phase 2 (Phase 2 is 28 days)
|
Organ failure, any organ, from consent through Day 28 in AP-003 treated patients compared to placebo.
|
Up to day 28 of Phase 2 (Phase 2 is 28 days)
|
|
Death rate
Tijdsspanne: Up to day 28 of Phase 2 (Phase 2 is 28 days)
|
Death, any cause, from consent through Day 28 in AP-003 treated patients compared to placebo.
|
Up to day 28 of Phase 2 (Phase 2 is 28 days)
|
Medewerkers en onderzoekers
Medewerkers
Onderzoekers
- Studie directeur: Arturo Borzutzky, M.D., Pontificia Universidad Católica de Chile
- Hoofdonderzoeker: Diego García-Huidobro, M.D., Ph.D., Pontificia Universidad Católica de Chile
- Hoofdonderzoeker: Carolina Iturriaga, R.N., Pontificia Universidad Católica de Chile
- Hoofdonderzoeker: Jose A Castro-Rodríguez, M.D., Ph.D., Pontificia Universidad Católica de Chile
- Hoofdonderzoeker: Eleanor Fish, Ph.D., University Health Network, Toronto, Canada
Studie record data
Bestudeer belangrijke data
Studie start (Werkelijk)
Primaire voltooiing (Werkelijk)
Studie voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
- Coronaviridae-infecties
- Nidovirales-infecties
- RNA-virusinfecties
- Virusziekten
- Infecties
- Luchtweginfecties
- Ziekten van de luchtwegen
- Longontsteking, viraal
- Longontsteking
- Longziekten
- COVID-19
- Coronavirus-infecties
- Fysiologische effecten van medicijnen
- Anti-infectieuze middelen
- Antivirale middelen
- Antineoplastische middelen
- Immunologische factoren
- Interferonen
- Interferon-alfa
- Interferon alfa-2
Andere studie-ID-nummers
- 210224003
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
Beschrijving IPD-plan
IPD-tijdsbestek voor delen
IPD-toegangscriteria voor delen
IPD delen Ondersteunend informatietype
- Leerprotocool
- Statistisch Analyse Plan (SAP)
- Formulier voor geïnformeerde toestemming (ICF)
- Klinisch onderzoeksrapport (CSR)
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
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