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.

Study Overview

• Status: Completed
• Conditions: Coronavirus Disease 2019
• Intervention / Treatment: Drug: Interferon-Alpha2B; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 173
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Chile
  • RM
    • Santiago, RM, Chile, 8330033
      • Red de Salud UC Christus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Phase 1 stage:

Inclusion criteria:

1. Male subjects aged 18-50 years;
2. In good state of health, determined by medical history, physical exam, and normal laboratory tests at screening;
3. Are able to provide informed consent for participation;
4. Are able and willing to comply with the study schedule and procedures.

Exclusion Criteria

1. Active SARS-CoV-2 infection demonstrated by positive polymerase chain reaction (PCR) at enrollment;
2. Requiring CPAP for sleep apnea;
3. Pre-existing pulmonary disease;
4. 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;
5. 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;
6. Are legally incompetent and unable to understand the study's purpose, significance, and consequences, and to make decisions accordingly;
7. Have known hypersensitivity to interferon alpha or any component of the study drug or placebo control.

Phase 2 stage:

Inclusion criteria:

1. Active SARS-CoV-2 infection demonstrated by positive polymerase chain reaction (PCR) ≤ 5 days at enrollment;
2. 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;
3. Age ≥ 18 years;
4. Are able to provide informed consent for participation;
5. Are able and willing to comply with the study schedule and procedures.

Exclusion Criteria

1. Patients requiring CPAP for sleep apnea.
2. Patients with pre-existing pulmonary disease requiring chronic O2 supplementation.
3. Patients with known infection with Influenza A or B;
4. In the opinion of the Investigator, should undergo ventilatory (CPAP, mechanical ventilation, etc.) or circulatory support within 24 hours of study enrollment;
5. 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;
6. 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;
7. Are legally incompetent and unable to understand the study's purpose, significance, and consequences, and to make decisions accordingly;
8. Women who are pregnant or breast-feeding, or planning to conceive in the next 30 days;
9. Have known hypersensitivity to interferon alpha or any component of the study drug or placebo control.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1a: Interferon alpha 2b 2.5 MIU; Nebulized interferon alpha 2b 2.5 MIU every 12 hours during 10 days (20 doses total)	Drug: Interferon-Alpha2B; Nebulized interferon alpha 2B; Other Names: AP-003
Experimental: Part 1b: Interferon alpha 2b 5 MIU; Nebulized interferon alpha 2b 5 MIU every 12 hours during 10 days (20 doses total)	Drug: Interferon-Alpha2B; Nebulized interferon alpha 2B; Other Names: AP-003
Placebo Comparator: Part 1: Placebo; Nebulized placebo every 12 hours during 10 days (20 doses total)	Drug: Placebo; Nebulized placebo
Experimental: 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)	Drug: Interferon-Alpha2B; Nebulized interferon alpha 2B; Other Names: AP-003
Placebo Comparator: Part 2: Placebo; Nebulized placebo every 12 hours during 10 days (20 doses total)	Drug: Placebo; Nebulized placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-emergent adverse events in healthy subjects	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	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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum levels of interferon alpha 2b	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	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	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	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)	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	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	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	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	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	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	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	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	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	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	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)

Collaborators and Investigators

• Sponsor: Pontificia Universidad Catolica de Chile
• Collaborators: Altum Pharmaceuticals INC
• Investigators: Study Director: Arturo Borzutzky, M.D., Pontificia Universidad Catolica de Chile; Principal Investigator: Diego García-Huidobro, M.D., Ph.D., Pontificia Universidad Catolica de Chile; Principal Investigator: Carolina Iturriaga, R.N., Pontificia Universidad Catolica de Chile; Principal Investigator: Jose A Castro-Rodríguez, M.D., Ph.D., Pontificia Universidad Catolica de Chile; Principal Investigator: Eleanor Fish, Ph.D., University Health Network, Toronto, Canada

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2021
• Primary Completion (Actual): April 15, 2022
• Study Completion (Actual): July 28, 2022

Study Registration Dates

• First Submitted: July 22, 2021
• First Submitted That Met QC Criteria: August 1, 2021
• First Posted (Actual): August 3, 2021

Study Record Updates

• Last Update Posted (Actual): August 5, 2022
• Last Update Submitted That Met QC Criteria: August 3, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: COVID-19; Interferon alpha 2b
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Coronavirus Infections; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Immunologic Factors; Interferons; Interferon-alpha; Interferon alpha-2
• Other Study ID Numbers: 210224003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Available upon reasonable request.
• IPD Sharing Time Frame: Data will become available 1 year after study completion during 5 years upon reasonable request.
• IPD Sharing Access Criteria: Available upon reasonable request.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No