- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT04988217
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.
Studieoversigt
Status
Betingelser
Intervention / Behandling
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 2
- Fase 1
Kontakter og lokationer
Studiesteder
-
-
RM
-
Santiago, RM, Chile, 8330033
- Red de Salud UC Christus
-
-
Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
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.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Firedobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: 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
Andre navne:
|
|
Eksperimentel: 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
Andre navne:
|
|
Placebo komparator: Part 1: Placebo
Nebulized placebo every 12 hours during 10 days (20 doses total)
|
Forstøvet placebo
|
|
Eksperimentel: 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
Andre navne:
|
|
Placebo komparator: Part 2: Placebo
Nebulized placebo every 12 hours during 10 days (20 doses total)
|
Forstøvet placebo
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Treatment-emergent adverse events in healthy subjects
Tidsramme: 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.
|
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
Tidsramme: 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)
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Serum levels of interferon alpha 2b
Tidsramme: 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
|
Up to Day 11 of Phase 1 (Phase 1 is 11 days)
|
|
Expression of interferon-induced genes in blood sputum samples
Tidsramme: 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
Tidsramme: 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)
|
|
Change in perception of health status measured by EQ VAS
Tidsramme: 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)
Tidsramme: 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).
|
Up to day 28 of Phase 2 (Phase 2 is 28 days)
|
|
Change in Ordinal Scale for Clinical Improvement
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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.
|
Up to day 28 of Phase 2 (Phase 2 is 28 days)
|
|
Duration of hospitalization
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)
|
Samarbejdspartnere og efterforskere
Samarbejdspartnere
Efterforskere
- Studieleder: Arturo Borzutzky, M.D., Pontificia Universidad Católica de Chile
- Ledende efterforsker: Diego García-Huidobro, M.D., Ph.D., Pontificia Universidad Católica de Chile
- Ledende efterforsker: Carolina Iturriaga, R.N., Pontificia Universidad Católica de Chile
- Ledende efterforsker: Jose A Castro-Rodríguez, M.D., Ph.D., Pontificia Universidad Católica de Chile
- Ledende efterforsker: Eleanor Fish, Ph.D., University Health Network, Toronto, Canada
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Coronaviridae infektioner
- Nidovirales infektioner
- RNA-virusinfektioner
- Virussygdomme
- Infektioner
- Luftvejsinfektioner
- Luftvejssygdomme
- Lungebetændelse, viral
- Lungebetændelse
- Lungesygdomme
- COVID-19
- Coronavirus infektioner
- Lægemidlers fysiologiske virkninger
- Anti-infektionsmidler
- Antivirale midler
- Antineoplastiske midler
- Immunologiske faktorer
- Interferoner
- Interferon-alfa
- Interferon alfa-2
Andre undersøgelses-id-numre
- 210224003
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
IPD-planbeskrivelse
IPD-delingstidsramme
IPD-delingsadgangskriterier
IPD-deling Understøttende informationstype
- Studieprotokol
- Statistisk analyseplan (SAP)
- Formular til informeret samtykke (ICF)
- Klinisk undersøgelsesrapport (CSR)
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
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