Safety and Efficacy of Inhaled XW001 For Hospitalized COVID-19 Patients Requiring Oxygen Therapy

Safety and Efficacy of Inhaled XW001 (Interleukin 29 Analog for Nebulization) For Hospitalized COVID-19 Patients Requiring Oxygen Therapy: A Multiregional, Randomized, Double-blind, Placebo-controlled Study

This is a multiregional, randomized, double-blind, placebo-controlled Phase 2 study in patients with confirmed symptomatic COVID-19, designed to evaluate the safety, tolerability, efficacy, and PK of XW001 (IL-29 analog) inhalation solution. The purpose of this study is to evaluate whether treatment with XW001 reduces the likelihood of worsening disease in patients with severe COVID-19. Hospitalized patients on oxygen therapy by mask or nasal prongs (WHO-OSCI score 4) will be enrolled.

Study Overview

• Status: Withdrawn
• Conditions: COVID-19 Acute Respiratory Distress Syndrome
• Intervention / Treatment: Drug: XW001; Drug: Placebo

Detailed Description

Treatment arm patients will receive inhaled XW001 1 mg and placebo arm patients will receive volume-matching placebo 1 mL, once daily, using a commercially available nebulizer for up to 14 days. Treatment should be continued until discharge or progression to score 6 or higher but maximum up to 14 days. Dosing must be started within 48 hours of hospitalization. In addition, both the treatment groups will receive SoC.

The present study is a pilot in the development phase and comprising approximately 120 patients. An independent, external Data Monitoring Committee (DMC) will review all the preliminary clinical data available, including safety, tolerability, efficacy, and PK for the first 20 patients. The decision to recruit the subsequent 100 patients will solely depend on safety and tolerability.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Bs AS
    • Caba, Bs AS, Argentina, 1430
      • Hospital Pirovano
• Peru
  • Lima, Peru, 511
    • Hospital Nacional Arzobispo Loayza

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or nonpregnant or nonlactating female, aged 18 to 70 years at the time of consenting
2. Hospitalized due to infection with SARS-CoV-2 confirmed on validated local RT-PCR or other equivalent assays within 48 hours prior to screening and within 96 hours prior to randomization
3. Assessed to be hospitalized cases (rated at WHO-OSCI score 4 [on oxygen therapy by mask or nasal prongs]) within 24 hours prior to randomization

4. Admitted to hospital as clinically indicated for management of severe COVID-19 defined by the following criteria:

   • Positive RT-PCR test for SARS-CoV-2 or an equivalent test
   • Symptom suggestive of severe systemic illness with COVID-19, which could include any symptom of moderate illness or shortness of breath at rest, or respiratory distress

   • Clinical signs indicative of severe illness with COVID-19, being given oxygenation and meeting one of the following:

     • Respiratory rate ≥30 breaths per minute
     • Heart rate ≥125 beats per minute
     • Oxygen saturation (SpO2) <94% on room air at sea level
     • Arterial partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) <300 mmHg or SpO2/FiO2 <315 mmHg
     • Lung infiltrates >50%
   • No criteria for critical severity
5. Female of childbearing potential must be postmenopausal for 1 year or longer, surgically sterile or having used a medically effective method of contraception for at least 3 months prior to hospitalization
6. Willing and able to provide a signed and dated or electronic informed consent for participation in this study.

Exclusion Criteria:

Patients will be excluded from the study if they satisfy any of the following criteria at the screening visit unless otherwise stated:

1. Having become symptomatic (fever, cough, and other likely symptoms) or positive on virologic test for more than 8 days prior to hospitalization
2. Diagnosed with SARS-CoV-2 confirmed more than 48 hours prior to hospitalization, otherwise reconfirmed positive on repeated RT-PCR (local laboratory) or other equivalent assays within 48 hours prior to randomization
3. Having been hospitalized for more than 48 hours, or showing a worsening medical condition within 48 hours after hospitalization in the opinion of the investigator
4. Known to have received any approved or investigational COVID-19 vaccines within 6 months prior to randomization. Vaccination records can be self-reported by the patient if there is no recorded history
5. Known to have received any approved or investigational therapeutic agents against SARS-CoV-2 including convalescent plasma, monoclonal antibodies, except for remdesivir, dexamethasone, or IL-6 inhibitors as a part of SoC
6. Having received any investigational medicinal products within 90 days of randomization
7. On noninvasive ventilation, eg, continuous positive airway pressure or bilevel positive airway pressure or high-flow oxygen therapy (at WHO-OSCI score 5)
8. Intubated, ventilated (invasively), on any advanced organ/life support (pressors, renal replacement therapy, ECMO), or remaining in the intensive care unit (at WHO-OSCI score 6 and 7)
9. Known to be hypersensitive or allergic to any natural or recombinant protein products
10. Inability to utilize nebulized drugs, or history of bronchospasm with inhaled medications
11. Patients with cardiac disease (New York Heart Association III/IV), liver cirrhosis (>5 x upper limit of normal [ULN]), on chemotherapy, dialysis patients with estimated glomerular filtration rate <30 mL/min/1.73m2, or have other debilitating condition or any other clinically significant medical condition or laboratory abnormality that, in the opinion of the investigator, would jeopardize the safety of the patient or non- COVID-19 irreversible underlying condition with projected fatal course within 6 months or with high-risk of mortality
12. Female patients are pregnant or lactating, or male or female patients have a childbearing plan within 30 days prior to randomization until 90 days after the last dosing.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: XW001; Treatment arm patients will receive inhaled XW001 1 mg, once daily, using a commercially available nebulizer (Aerogen Solo, Aerogen Ireland) for up to 14 days. Treatment should be continued until discharge or progression to score 6 or higher but maximum up to 14 days. Dosing must be started within 48 hours of hospitalization.	Drug: XW001; It is anticipated that inhalation of 1 mg XW001 solution up to 14 days will result in a relatively lower systemic exposure in COVID-19 patients on oxygen therapy compared to that in healthy participants as COVID-19 patients tend to have impaired lung function of diffusive, restrictive, obstructive, or mixed origins.; Other Names: IL-29 analog
Placebo Comparator: Placebo; Placebo arm patients will receive volume-matching placebo 1 mL, once daily, using a commercially available nebulizer (Aerogen Solo, Aerogen Ireland) for up to 14 days. Treatment should be continued until discharge or progression to score 6 or higher but maximum up to 14 days. Dosing must be started within 48 hours of hospitalization.	Drug: Placebo; It is anticipated that inhalation of 1 mg Placebo solution up to 14 days will result in a relatively lower systemic exposure in COVID-19 patients on oxygen therapy compared to that in healthy participants as COVID-19 patients tend to have impaired lung function of diffusive, restrictive, obstructive, or mixed origins.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent adverse events (TEAEs)	Incidence of treatment-emergent adverse events (TEAEs), grade ≥3 TEAEs, SAEs, TEAEs leading to premature discontinuation of study treatment, TEAEs leading to study discontinuation, and TEAEs leading to deaths	35 days
Change from the baseline in clinical laboratory results	Percentage of the lab results change	35 days
Incidence of clinically significant laboratory findings	Percentage of the lab results change	35 days
Change from the baseline in vital signs results	Vital signs will be recorded twice daily while the patient is hospitalized. Vital signs may also be performed at other times if judged clinically appropriate or if the ongoing review of the data suggests a more detailed assessment of vital signs is required.	35 days
Change from the baseline in electrocardiogram (ECG) findings	A 12-lead ECG is to be performed at screening in the supine position and at rest for at least 5 minutes. Additionally, a 12-lead ECG will be performed if QT abnormality is noted or early termination while the patient is hospitalized or at the discretion of the investigator.	35 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to clinical improvement from the time of randomization.	Time to clinical improvement is defined as the time (in days) from the randomization date to the first day on which a patient satisfies a score of 0, 1, 2, or 3 on the 9-point WHO-OSCI and maintains a score ≤3 at least 48 hours (initial improvement) and maintains this up to the 28-day timeframe (sustained improvement)	28 days
Time to hospital discharge from the time of randomization	At or below WHO-OSCI score 2 from the time of randomization	28 days
Time to clinical recovery from the time of randomization	Time of clinical recovery (in days) will be calculated using the WHO-OSCI from the randomization date to the first day on which the patient satisfies a score of 0 or 1 on the 9-point WHO-OSCI and remains at 0 or 1 until Day 28 (has no subsequent readmission for COVID-19 signs or symptoms)	28 days
Time to viral clearance	targeted not detected on real-time quantitative polymerase chain reaction [qPCR] assay) from the time of randomization	28 days
Viral load kinetics on real-time qPCR assay	A real-time qPCR will be done to determine the viral load kinetics in positive RT-PCR samples.	28 days
Proportions of patients experiencing clinical improvement, hospital discharge, clinical recovery, and viral clearance	The proportions of patients will be compared using the logistic regression.	28 days
Proportion of patients experiencing clinical progression from the time of randomization	The proportions of patients will be compared using the logistic regression.	35 days
Proportion of patients progressing to on noninvasive ventilation or high-flow oxygen from the time of randomization	The proportions of patients will be compared using the logistic regression.	35 days
Proportion of patients progressing to on intubation with ventilation from the time of randomization	The proportions of patients will be compared using the logistic regression.	35 days
Proportion of patients progressing to death from the time of randomization	Proportion of patients progressing to death (WHO-OSCI score 8) within the 35-day timeframe from the time of randomization	35 days
Changes from the baseline in the BCSS total score and breathlessness and cough subscores	Change from the baseline in the BCSS scores will also be evaluated daily. A physical examination including height and weight will be measured. Height will be measured at screening only. If a patient is not able to stand easily, the patient may provide height.	35 days
Changes from the baseline in the NEWS2	Change from the baseline in the NEWS2 scores will also be evaluated daily. A physical examination including height and weight will be measured. Height will be measured at screening only. If a patient is not able to stand easily, the patient may provide height.	35 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum XW001 concentration and appropriate serum XW001	PK parameters determined via the noncompartmental analysis (intensive PK cohort only) or a population PK analysis approach	35 days
Proportions of patients with newly emerging serum anti-XW001 antibody	Proportions of anti-XW001 antibody after the randomization compared to the baseline (at the time of randomization).	35 days

Collaborators and Investigators

• Sponsor: Sciwind Biosciences APAC CO Pty. Ltd.
• Collaborators: Hangzhou Sciwind Biosciences Co., Ltd.; Sciwind Biosciences USA Co., Ltd.
• Investigators: Principal Investigator: Eddie Angles, Hospital Nacional Arzobispo Loayza; Principal Investigator: Ricardo Teijeiro, Hospital Pirovano

Study record dates

Study Major Dates

• Study Start (Estimated): October 30, 2021
• Primary Completion (Estimated): March 10, 2022
• Study Completion (Estimated): April 10, 2022

Study Registration Dates

• First Submitted: October 17, 2021
• First Submitted That Met QC Criteria: October 17, 2021
• First Posted (Actual): October 19, 2021

Study Record Updates

• Last Update Posted (Actual): August 21, 2023
• Last Update Submitted That Met QC Criteria: August 17, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Respiratory Distress Syndrome
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; COVID-19; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: SCW1201-3121

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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