Inhaled Interferon α2b for the Treatment of Coronavirus Disease 19 (COVID-19)

NCT04988217 | Completed Phase 1 DMC

• 1 other identifier: 210224003
• Study Type: interventional
• Target: 173
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Coronavirus Disease 2019

Keywords

Interferon alpha 2b; COVID-19

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (15)

• Serum levels 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

  Up to Day 11 of Phase 1 (Phase 1 is 11 days)

• Change in perception of health status measured by EQ VAS

  Day 10 of Phase 2 (Phase 2 is 28 days)

• Change in perception of health status measured by EQ VAS

  Day 28 of Phase 2 (Phase 2 is 28 days)

• Change in EuroQoL Quality of Life instrument (EQ-5D-5L)

  Up to day 28 of Phase 2 (Phase 2 is 28 days)

Study Arms (5)

Part 1a: Interferon alpha 2b 2.5 MIU

EXPERIMENTAL

Nebulized interferon alpha 2b 2.5 MIU every 12 hours during 10 days (20 doses total)

Drug: Interferon-Alpha2B

Part 1b: Interferon alpha 2b 5 MIU

EXPERIMENTAL

Nebulized interferon alpha 2b 5 MIU every 12 hours during 10 days (20 doses total)

Drug: Interferon-Alpha2B

Part 1: Placebo

PLACEBO COMPARATOR

Nebulized placebo every 12 hours during 10 days (20 doses total)

Drug: Placebo

Part 2: Interferon alpha 2b 5 MIU (or maximum tolerated dose from part 1)

EXPERIMENTAL

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

Part 2: Placebo

PLACEBO COMPARATOR

Nebulized placebo every 12 hours during 10 days (20 doses total)

Drug: Placebo

Interventions

Interferon-Alpha2B DRUG

Nebulized interferon alpha 2B

Also known as: AP-003

Part 1a: Interferon alpha 2b 2.5 MIU; Part 1b: Interferon alpha 2b 5 MIU; Part 2: Interferon alpha 2b 5 MIU (or maximum tolerated dose from part 1)

Placebo DRUG

Nebulized placebo

Part 1: Placebo; Part 2: Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• 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.
• Patients requiring CPAP for sleep apnea.
• Patients with pre-existing pulmonary disease requiring chronic O2 supplementation.

Sponsors & Collaborators

• Pontificia Universidad Catolica de Chile: lead
• Altum Pharmaceuticals INC: collaborator

Study Sites (1)

Red de Salud UC Christus

Santiago, RM, 8330033, Chile

Location

Related Publications (1)

• Garcia-Huidobro D, Iturriaga C, Perez-Mateluna G, Fajuri P, Severino N, Urzua M, Fraga JP, de la Cruz J, Poli C, Castro-Rodriguez JA, Fish E, Borzutzky A; IN(2)COVID Research Team. Safety, Tolerability, Bioavailability, and Biological Activity of Inhaled Interferon-alpha2b in Healthy Adults: The IN2COVID Phase I Randomized Trial. Clin Drug Investig. 2023 Jun;43(6):447-461. doi: 10.1007/s40261-023-01278-3. Epub 2023 Jun 22.

  PMID: 37347370 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

Interferon-alpha2b

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Arturo Borzutzky, M.D.

  Pontificia Universidad Catolica de Chile

  STUDY DIRECTOR

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2021
• First Posted: August 3, 2021
• Study Start: September 15, 2021
• Primary Completion: April 15, 2022
• Study Completion: July 28, 2022
• Last Updated: August 5, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data will become available 1 year after study completion during 5 years upon reasonable request.
• Access Criteria: Available upon reasonable request.

Locations

CL (1)