Coronavirus Disease 2019
Conditions
Keywords
Interferon alpha 2b, COVID-19
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.
Interventions
Nebulized interferon alpha 2B
DRUGPlacebo
Nebulized placebo
Sponsors
Altum Pharmaceuticals INC
Pontificia Universidad Catolica de Chile
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-emergent adverse events in healthy subjects | 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. |
| Change in perception of health status measured by EQ VAS in COVID-19 patients | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in perception of health status measured by EQ VAS | 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. |
| Change in EuroQoL Quality of Life instrument (EQ-5D-5L) | 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). |
| Change in Ordinal Scale for Clinical Improvement | 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. |
| Improvement in clinical symptoms | 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. |
| Emergency department visits | 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. |
| Hospitalizations | 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. |
| Serum levels of interferon alpha 2b | 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 |
| Time from consent to clinical deterioration | 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. |
| Change in SARS CoV-2 viral load | 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. |
| Change in inflammatory parameters | 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. |
| Organ failure rate | 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. |
| Death rate | 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. |
| Duration of hospitalization | 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. |
| Expression of interferon-induced genes in blood sputum samples | 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 |
Countries
Chile
Outcome results
None listed