Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000704897
Ethics application status
Approved
Date submitted
7/05/2021
Date registered
8/06/2021
Date last updated
6/12/2022
Date data sharing statement initially provided
8/06/2021
Date results information initially provided
6/12/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Study to evaluate the safety, tolerability, and efficacy of enoxaparin for inhalation alone and in combination with N-acetylcysteine in healthy volunteers and hospitalised COVID-19 patients
Scientific title
A four-part study to evaluate the safety, tolerability, and efficacy of enoxaparin for inhalation, alone and in combination with N-acetylcysteine in healthy volunteers and hospitalised COVID-19 patients
Secondary ID [1] 302860 0
AT-H201-AU-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 319855 0
COVID-19 321937 0
Condition category
Condition code
Respiratory 317787 317787 0 0
Other respiratory disorders / diseases
Infection 319663 319663 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a Phase I/IIa, double-blind, placebo-controlled study which is subdivided into 4 parts. Parts A-C will be conducted in healthy adult participants and Part D will be conducted in hospitalised COVID-19 patients with moderate illness.
Part A (Cohorts 1-4) will be conducted as a single ascending dose (SAD) study, whereby healthy volunteers will be enrolled to receive a single dose of inhaled enoxaparin (or placebo). Three dose levels of inhaled enoxaparin will be explored in Part A (0.25, 0.5, 1 or 2 mg/kg/dose). Sentinel dosing will be employed for all dose level cohorts for Part A.

Part B (Cohorts 5-6) will be conducted as a multiple ascending dose (MAD) study, whereby healthy volunteers will be enrolled to receive multiple doses of inhaled enoxaparin (or placebo) every 12 hours (q12h) for 7 days. Two dose levels of inhaled enoxaparin will be explored in Part B (0.5 or 1 mg/kg/dose).

In Part C (Cohorts 7-8), healthy volunteers will be enrolled to receive MADs of inhaled enoxaparin (or placebo) in combination with fixed doses of inhaled N-acetylcysteine. Two dose levels of inhaled enoxaparin will be explored in Part C (0.5 or 1 mg/kg/dose). Each dose of inhaled N-acetylcysteine will be 600 mg.Sentinel dosing will be employed for all dose level cohorts for Part C.
Dosing in part C is as follows:
• Participants will receive a single dose of inhaled N-acetylcysteine on study Day 1.
• Participants will receive a single dose of inhaled enoxaparin (or placebo) on study Day 2.
• Participants will receive a single dose each of inhaled enoxaparin (or placebo) and inhaled N-acetylcysteine on study Day 3.
• Participants will receive inhaled enoxaparin (or placebo) q12h plus inhaled N-acetylcysteine every 6 hours (q6h) for 7 days starting on study Day 4.

In Part D (Cohort 9), COVID-19 patients will be enrolled to receive inhaled enoxaparin (or placebo) in combination with inhaled N-acetylcysteine (multiple dosing schedule), plus best supportive care treatment for COVID-19. The dose level of inhaled enoxaparin to be evaluated in Part D will be based on safety and tolerability data obtained in Part C, or placebo. Each dose of inhaled N-acetylcysteine will be 600 mg.

The subjects will be confined to the clinical trial unit throughout the treatment period and dosing will be witnessed by the site staff, the schedule of assessments will include safety assessments as required.
Intervention code [1] 319146 0
Treatment: Drugs
Comparator / control treatment
Part A: Saline 0.9% solution for nebulization
Part B: Saline 0.9% solution for nebulization
Part C: Saline 0.9% solution for nebulization in combination with inhaled N-acetylcysteine (600 mg per dose)
Part D: Saline 0.9% solution for nebulization in combination with inhaled N-acetylcysteine (600 mg per dose)
Control group
Placebo

Outcomes
Primary outcome [1] 325810 0
Part A &B
• To evaluate the safety and tolerability of enoxaparin administered via inhalation (IH) using a single and multiple ascending dose schedule in healthy adult volunteers.
Timepoint [1] 325810 0
Part A & B
Safety and tolerability endpoints/outcome assessments include:
• Incidence, type and severity of AEs
• Changes from baseline in vital sign measurements
• Changes from baseline in clinical laboratory parameters (Hematology, Coagulation, Biochemistry and Urinalysis)
• Changes from baseline in electrocardiogram (ECG) parameters
• Changes from baseline in physical examination findings including auscultation
• Changes from baseline in oxygen saturation (SpO2)
• Changes from baseline in lung spirometry

Part A outcomes will be measured at the following timepoints: Baseline, Day 1,2, Day 3-7, Day 8.
Part B outcomes will be measured at the following timepoints: Baseline, Day 1,2,3,4,5,6,7 Day 8-13, Day 14.
Primary outcome [2] 327534 0
Part C
• To evaluate the safety and tolerability of inhaled enoxaparin administered in healthy volunteers using a multiple dose schedule in combination with inhaled N-acetylcysteine (NAC) treatment.
Timepoint [2] 327534 0
Part C
Safety and tolerability endpoints/outcome assessments include:
• Incidence, type and severity of AEs
• Changes from baseline in vital sign measurements
• Changes from baseline in clinical laboratory parameters (Hematology, Coagulation, Biochemistry and Urinalysis)
• Changes from baseline in electrocardiogram (ECG) parameters
• Changes from baseline in physical examination findings including auscultation
• Changes from baseline in oxygen saturation(SpO2)
• Changes from baseline in lung spirometry

Part C outcomes will be measured at the following timepoints: Baseline, Day 1,2,3,4,5,6,7,8,9,10,11, Day 12-16, Day 17.
Primary outcome [3] 327535 0
Part D
• To evaluate the safety and tolerability of inhaled enoxaparin when administered as an adjunct to inhaled N-acetylcysteine therapy in COVID-19 patients with moderate illness.
Timepoint [3] 327535 0
Part D
Safety and tolerability endpoints/outcome assessments include:
• Incidence, type and severity of AEs
• Changes from baseline in vital sign measurements
• Changes from baseline in clinical laboratory parameters (Hematology, Coagulation, Biochemistry and Urinalysis)
• Changes from baseline in electrocardiogram (ECG) parameters
• Changes from baseline in physical examination findings including auscultation
• Changes from baseline in oxygen saturation
• Changes from baseline in lung spirometry


Part D outcomes will be measured at the following timepoints: Baseline, Day 1,2,3,4,5,6,7,8, Day 9-14, Day 15, Days 16-28,Day 29.
Secondary outcome [1] 389209 0

To assess the pharmacokinetics (PK) of inhaled enoxaparin administered using a single and multiple ascending dose schedule in healthy adult volunteers.(Part A & B)
Timepoint [1] 389209 0
Part A,& B
• PK parameters calculated include (but are not limited to):
o Maximum observed concentration (Cmax)
o Time to Cmax (Tmax)
o Area under the concentration time curve (AUC0-t)
o Apparent terminal elimination half-life (t½)

PK assessment will occur at the following timepoints:
Part A: 5 min, 10 min, 15 min, 30 min, 45 min, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr, 24 hr
Part B: Day 1 (5 min, 10 min, 15 min, 30 min, 45 min, 1 hr,2 hr, 4 hr, 6 hr, 8 hr, 12 hr) , Day 7 ( min, 10 min, 15 min, 30 min, 45 min, 1 hr,2 hr, 4 hr, 6 hr, 8 hr, 12 hr) , Day 8
Secondary outcome [2] 395637 0

To assess the PK of inhaled enoxaparin and inhaled N-acetylcysteine when administered alone and in combination in healthy adult volunteers.(Part C)
Timepoint [2] 395637 0
Part C
• PK parameters calculated include (but are not limited to):
o Maximum observed concentration (Cmax)
o Time to Cmax (Tmax)
o Area under the concentration time curve (AUC0-t)
o Apparent terminal elimination half-life (t½)

PK assessment will occur at the following timepoints:
Day 1 (5 min, 10 min, 15 min, 30 min, 45 min, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr), Day 2 , Day 3 (5 min, 10 min, 15 min, 30 min, 45 min, 1 hr , 2 hr, 4 hr, 6 hr, 8 hr, 12 hr), Day 4, Day 10 ( 5 min, 10 min, 15 min, 30 min, 45 min, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr), Day 11
Secondary outcome [3] 395638 0

To assess the incidence and severity of local irritation associated with inhaled enoxaparin administered with inhaled N-acetylcysteine, using a combination treatment schedule in COVID-19 patients with moderate illness. (Part D) Assessed by clinical examination and participant self-report.
Timepoint [3] 395638 0
Part D
Incidence and severity of local irritation observed for a period of 24 hours following each dose of study drug.
Secondary outcome [4] 396146 0
To assess the incidence and severity of local irritation associated with single and multiple ascending doses of IH enoxaparin administration in healthy volunteers. (Part A & B). Assessed by clinical examination and participant self-report.
Timepoint [4] 396146 0
Incidence and severity of local irritation observed for a period of 24 hours following each dose of study drug.
Secondary outcome [5] 396147 0
To assess the incidence and severity of bronchospasm following administration of single and multiple ascending doses of inhaled enoxaparin in healthy volunteers.(Part A & B). Assessed by clinical observation of breathing difficulty (including wheezing), with RR > 30/min.
Timepoint [5] 396147 0
Incidence and severity of bronchospasms observed for a period of 24 hours following each dose of study drug.
Secondary outcome [6] 396182 0
To assess the incidence and severity of local irritation associated with multiple ascending doses of inhaled enoxaparin administered in combination with inhaled N-acetylcysteine treatment in healthy volunteers (Part C). Assessed by clinical examination and participant self-report.
Timepoint [6] 396182 0
Incidence and severity of local irritation observed for a period of 24 hours following each dose of study drug.
Secondary outcome [7] 396183 0
To assess the incidence and severity of bronchospasm associated with multiple ascending doses of inhaled enoxaparin administered in combination with inhaled N-acetylcysteine treatment in healthy volunteers.(Part C). Assessed by clinical observation of breathing difficulty (including wheezing), with RR > 30/min.
Timepoint [7] 396183 0
Incidence and severity of bronchospasms observed for a period of 24 hours following each dose of study drug.
Secondary outcome [8] 396188 0
To assess the incidence and severity of bronchospasm associated with inhaled enoxaparin administered with inhaled N-acetylcysteine, using a combination treatment schedule in COVID-19 patients with moderate illness.(Part D). Assessed by clinical observation of breathing difficulty (including wheezing), with RR > 30/min.
Timepoint [8] 396188 0
Incidence and severity of bronchospasms observed for a period of 24 hours following each dose of study drug.
Secondary outcome [9] 396191 0
To evaluate the efficacy of inhaled enoxaparin (at study Days 8, 15 and 29) when administered with inhaled N-acetylcysteine using a combination treatment schedule, in COVID-19 patients with moderate illness. (Part D), composite assessments include assessments include Chest X-Rays, NIAID score, SOFA score,duration of hospitalisation assessed by data-linkage to medical records.
Timepoint [9] 396191 0
• Efficacy endpoints/outcome assessments include:
o Changes from baseline in chest x-ray findings at Day 29 post-first intervention dose.
o Changes from baseline in National Institute of Allergy and Infectious Diseases (NIAID) assessment of breathlessness score at Day 8, Day 15 and Day 29 post-first intervention dose.
o Changes from baseline in Sequential Organ Failure Assessment (SOFA) score at Day 8, Day 15 and Day 29 post-first intervention dose.
o Number of days free of supplemental oxygen at Day 8, Day 15 and Day 29 post-first intervention dose (greater than or equal to status 5 on the NIAID 8-point ordinal scale)
o Duration of hospitalisation at Day 15 and Day 29 post-first intervention dose.
o Survival (based on all-cause mortality) at Day 29 post-first intervention dose.

Eligibility
Key inclusion criteria
Part A, B & C
1. Volunteers must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects.
2. Adult males and females, 18 to 64 years of age (inclusive) at the screening visit.
3. Be non-smokers (including tobacco, e-cigarettes and marijuana) for a minimum of 3 months prior to participation in the study. Non-smokers with a significant history of smoking (> 5 pack years) are not eligible.
4. Have no history or presence of tuberculosis, asthma, chronic obstructive pulmonary disease or major pulmonary airway disease (participants with history of childhood asthma but no subsequent episodes are eligible).
5. Body Mass Index (BMI) within the range of 18.5 to 30.0 kg/m2 inclusive at the screening visit, and on Day -1, prior to dosing.
6. Medically healthy without clinically significant abnormalities at the screening visit and Day -1, including:
a. Physical examination without any clinically relevant findings.
b. Systolic blood pressure in the range of 90 to 160 mm Hg (inclusive) and diastolic
blood pressure in the range of 50 to 95 mm Hg (inclusive) after 5 minutes in
supine position.
c. Heart rate in the range of 45 to 100 beats/min (inclusive) after 5 minutes rest in
supine position at the screening visit.
d. Body temperature, between 35.5°C and 37.7°C (inclusive).
e. The screening 12-lead electrocardiogram (ECG) must be within normal range
corrected QT interval [QTc] males less than or equal to 450 msec; females less than or equal to 470 msec) or with
abnormalities, which are deemed not clinically significant according to the opinion
of the Investigator at the screening visit.
f. No clinically relevant findings in serum chemistry, haematology, coagulation and
urinalysis examinations as judged by the Investigator at screening.
g. Pulmonary assessments must be within the normal range at the screening visit
and on Day -1, prior to dosing (forced expiratory volume in 1 second [FEV1], forced
vital capacity [FVC] and FEV1/FVC ratio greater than or equal to 80% of normal values; forced expiratory
flow over the middle one half of the FVC [FEF25-75%] > 75% of predicted;
h. oxygen saturation monitor greater than or equal to 95%).
7. Normal chest x-ray indicating no significant anomaly at the screening visit.
8. Negative cotinine, drug and alcohol tests at screening and Day -1.
9. Female volunteers must:
a. Be of non-child-bearing potential i.e. surgically sterilised (hysterectomy, bilateral
salpingectomy, bilateral oophorectomy at least 6 weeks before the screening visit) or
postmenopausal (where postmenopausal is defined as no menses for 12 months
without an alternative medical cause and a follicle-stimulating hormone level > 40
IU/L at the screening visit), or
b. If of childbearing potential, must have a negative pregnancy test at Screening and before the first study drug administration (Day -1). They must agree not to attempt to become pregnant must not donate ova, and must agree to use 2 forms of a highly effective contraceptive method
for penile-vaginal intercourse between signing consent, during the study, and at least 30 days
after the last dose of study therapy
10. Male volunteers must agree not to donate sperm and if engaging in sexual intercourse with a female partner who could become pregnant, must agree to use a condom in addition to having the female partner use a highly effective contraceptive method between signing consent, during the study, and at least 90 days after the last dose of study therapy.
11. Willingness to cooperate with the researcher and comply with all study requirements.
12. Have suitable venous access for blood sampling.

Part D
1. Hospitalised males or non-pregnant, non-lactating females greater than or equal to 18 years of age at the screening visit with SARS-CoV-2 infection that is documented by an authorised diagnostic RT-PCR test (a) at or within 72 hours of screening or (b) on Day 1, prior to dose administration.
2. Must meet the NIH COVID-19 definition of moderate illness (“Individuals who have evidence of lower respiratory disease by clinical assessment or imaging and a saturation of oxygen (SpO2) greater than or equal to 94% on room air at sea level).”
3. Negative drug and alcohol tests at screening and on Day 1, prior to first dose administration (excludes cotinine). Exceptions may be made for prescribed concomitant medications, at the discretion of the Investigator.
4. Female volunteers must:
a. Be of non-child-bearing potential i.e. surgically sterilised (hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least 6 weeks before the Screening visit) or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause and an FSH level > 40 IU/L at screening), or
b. If of childbearing potential, must have a negative pregnancy test at Screening and before the first study drug administration (Day 1). They must agree not to attempt to become pregnant, must not donate ova, and must agree to use 2 forms of a highly effective contraceptive method for penile-vaginal intercourse between signing consent, during the study, and at least 30 days after the last dose of study therapy.
5. Male volunteers must agree not to donate sperm and if engaging in sexual intercourse with a female partner who could become pregnant, must agree to use a condom in addition to having the female partner use a highly effective contraceptive method between signing consent, during the study, and at least 90 days after the last dose of study therapy.
6. The patient or a legally authorised representative has provided written informed consent.
7. The patient or the authorised representative is aware of the investigational nature of this study and willing to comply with protocol treatments, blood tests, and other evaluations listed in the informed consent form (ICF).
Minimum age
18 Years
Maximum age
64 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Part A, B & C
1. History or presence of significant cardiovascular, hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological or psychiatric disease, including any acute illness or surgery within the past three months determined by the Investigator to be clinically relevant.
2. History or presence of obstructive pneumonia, severe pulmonary interstitial fibrosis, alveolar proteinosis and allergic alveolitis caused by lung tumour.
3. Any history or presence of:
a. Coagulation abnormalities
b. Significant bleeding disorder
4. Known allergy to low molecular weight heparin (LMWH) or heparin, or heparin-induced thrombocytopenia.
5. Positive heparin-induced thrombocytopenia Platelet Factor 4 (PF4) antibody test at the screening visit.
6. Known allergy or sensitivity to N-acetylcysteine (NAC)(Part C only).
7. Females who are currently breastfeeding.
8. Positive serum pregnancy test for women of child-bearing potential at the screening visit or positive urine pregnancy test with confirmatory serum pregnancy test on Day -1.
9. Liver function test results (i.e., aspartate aminotransferase [AST], alanine aminotransferase [ALT], and gamma-glutamyl transferase [GGT]) and total bilirubin elevated >1.2 fold above the normal limits at the screening visit.
10. Positive testing for active human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies at the screening visit.
11. Positive testing for SARS-CoV-2 viral RNA prior to check-in on Day -1 (the test should be performed between Day -3 and Day -2, with the results to be reviewed by the PI prior to check-in.
12. Donation of blood or plasma within 30 days prior to randomisation, or loss of whole blood of more than 500 mL within 30 days prior to randomisation, or receipt of a blood transfusion within 1 year of study enrolment.
13. Participation in another investigational clinical trial within 30 days or 5 half-lives (whichever is longer) prior to the first drug administration.
14. Any other condition or prior therapy, which, in the opinion of the Investigator, would make the volunteer unsuitable for this study, including unable to cooperate fully with the requirements of the study protocol or likely to be non-compliant with any study requirements.

Part D
1. Participation in any other clinical trial of an experimental treatment for COVID-19, with the exception of emergency access treatments.
2. Concurrent treatment with other agents with actual or possible direct acting antiviral activity against SARS-CoV-2 < 24 hours prior to study drug dosing except for remdesivir and azithromycin..
3. Uncontrolled hypertension (systolic blood pressure (BP) > 150 mm Hg and/or diastolic BP > 100 mmHg), unstable angina, congestive heart failure (CHF) of any New York Heart Association (NYHA) classification, serious cardiac arrhythmia requiring treatment (exceptions: atrial fibrillation, paroxysmal supraventricular tachycardia), history of myocardial infarction within 12 months of enrolment.
4. Hypotension requiring vasoactive peptides, such as dopamine, norepinephrine, epinephrine, or dobutamine.
5. Renal function impairment with Creatinine >2 mg/dL.
6. Liver function impairment with Bilirubin >2 mg/dL.
7. Platelet count <50,000/µL.
8. Multi-organ failure.
9. Documented active infection with a bacterial pathogen requiring parenteral systemic antibiotics.
10. Bacterial or fungal sepsis.
11. History of an allergic reaction or hypersensitivity to the study drug or any component of the study drug formulation.
12. Current use of anti-inflammatory treatments
o Exceptions: Steroids (e.g. complement inhibitor, anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody, anti-interleukin [IL]-6 antibody) and non-steroidal anti-inflammatory drugs (NSAIDs) are allowed.
o Additional exceptions: Antibiotics and some antiviral drugs (remdesivir, azithromycin) are allowed; Systemic corticosteroids are allowed.
13. Females who are currently breastfeeding.
14. Positive pregnancy test for WOCBP at screening or on Day 1, prior to dose administration.
15. Positive testing for active HIV, HBsAg or HCV antibodies at screening.
16. Presence of any uncontrolled concomitant illness, serious illness, medical conditions, or other medical history, including laboratory results, which, in the Investigator’s opinion, would be likely to interfere with their participation in the study.
17. Major surgical procedure, open biopsy, within 4 weeks prior to Screening, anticipation of need for major surgical procedure during the course of the study.
18. Any other condition or prior therapy, which, in the opinion of the Investigator, would make the patient unsuitable for this study, including unable to cooperate fully with the requirements of the study protocol or likely to be non-compliant with any study requirements.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Sealed participant-specific code break envelopes will be produced by the Sponsor (or a Sponsor delegate) and will be retained at the clinical facility in a secure, accessible location.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Block randomisation algorithm
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Observed values and changes from baseline in clinical laboratory parameters, vital signs, ECG parameters and SpO2 levels will be summarised at each protocol scheduled timepoint. Physical examination data (including auscultation findings) will be listed by participant.
Adverse events will be coded using the latest version of Medical Dictionary for regulatory Activities (MedDRA). Adverse events will be grouped by system organ class and preferred term and summarised, by treatment arm at the time of onset of the AE. The incidence and severity of AEs of special interest (AESIs) will be summarised and listed separately.
Mean and individual plasma concentrations of enoxaparin (Parts A-C) and N-acetylcysteine (Part C only) will be presented graphically with concentration displayed on a linear and logarithmic scale. Plasma concentration data at each timepoint will be summarised for each dose level using descriptive statistics. Pharmacokinetic parameters will be determined using non-compartmental methods and summarised by cohort using descriptive statistics. Analyses using linear models will be performed to assess dose proportionality (both single dose and multiple dose), time dependence, accumulation, and attainment of steady state (multiple dose).
For time-to-event outcomes in Part D, Kaplan-Meier (K-M) estimates will be computed and presented in tabular and graphical form for each treatment group and will include identification and incorporation of censored observations. The median time-to-event, standard error and 95% confidence intervals for each treatment group will be estimated from the K-M estimates determined. Comparison of the study arms will be based on the log-rank test. For other endpoints determined over time, a generalised linear model will be employed to examine all time points simultaneously between the study groups. In addition, differences between the groups at specific time points can be evaluated by univariate statistics such as t-tests or Wilcoxon tests. All statistical calculations will be performed using an appropriately chosen software package.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Sponsor have decided not to proceed to Part D as the change in COVID-19 treatment options have changed and they are reviewing alternate indications for the study drug
Date of first participant enrolment
Anticipated
15/09/2021
Actual
30/09/2021
Date of last participant enrolment
Anticipated
15/09/2022
Actual
13/07/2022
Date of last data collection
Anticipated
Actual
29/07/2022
Sample size
Target
60
Accrual to date
Final
41
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 18086 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 32075 0
5000 - Adelaide
Recruitment outside Australia
Country [1] 23119 0
United States of America
State/province [1] 23119 0
To be confirmed

Funding & Sponsors
Funding source category [1] 307279 0
Commercial sector/Industry
Name [1] 307279 0
Atossa Therapeutics, Inc.
Country [1] 307279 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Atossa Genetics Aus Pty Ltd
Address
Level 16, Tower 2 Darling Park,
201 Sussex Street, Sydney NSW
2000, Australia
Country
Australia
Secondary sponsor category [1] 309318 0
Commercial sector/Industry
Name [1] 309318 0
Avance Clinical Pty Ltd
Address [1] 309318 0
Level 1, 2 Ann Nelson Drive
Thebarton SA 5031
Country [1] 309318 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307377 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 307377 0
123 Glen Osmond Road, Eastwood SA 5063
Ethics committee country [1] 307377 0
Australia
Date submitted for ethics approval [1] 307377 0
03/12/2020
Approval date [1] 307377 0
01/07/2021
Ethics approval number [1] 307377 0

Summary
Brief summary
This is a Phase I/IIa, double-blind, placebo-controlled study which is subdivided into 4 parts. Parts A-C will be conducted in healthy adult participants and Part D will be conducted in hospitalised COVID-19 patients with moderate illness.
Part A (Cohorts 1-4) will be conducted as a single ascending dose (SAD) study, whereby healthy volunteers will be enrolled to receive a single dose of inhaled enoxaparin (or placebo). Three dose levels of inhaled enoxaparin will be explored in Part A (0.25, 0.5, 1 or 2 mg/kg/dose). Sentinel dosing will be employed for all dose level cohorts for Part A.
Part B (Cohorts 5-6) will be conducted as a multiple ascending dose (MAD) study, whereby healthy volunteers will be enrolled to receive multiple doses of inhaled enoxaparin (or placebo). Two dose levels of inhaled enoxaparin will be explored in Part B (0.5 or 1 mg/kg/dose).
In Part C (Cohorts 7-8), healthy volunteers will be enrolled to receive MADs of inhaled enoxaparin (or placebo) in combination with fixed doses of inhaled N-acetylcysteine . Two dose levels of inhaled enoxaparin will be explored in Part C (0.5 or 1 mg/kg/dose). Each dose of inhaled N-acetylcysteine will be 600 mg.Sentinel dosing will be employed for all dose level cohorts for Part C.
In Part D (Cohort 9), COVID-19 patients will be enrolled to receive inhaled enoxaparin (or placebo) in combination with inhaled N-acetylcysteine (multiple dosing schedule), plus best supportive care treatment for COVID-19. The dose level of inhaled enoxaparin to be evaluated in Part D will be based on safety and tolerability data obtained in Part C, or placebo. Each dose of inhaled N-acetylcysteine will be 600 mg.
Dosing in each cohort Part A-C will occur in a sequential manner. The decision to escalate between dose levels and proceed to the next cohort will be based on a review of the available safety and PK data by the Safety Review Committee (SRC). The SRC will consist of (at a minimum), the PI, an independent Medical Monitor and a Sponsor’s medical representative. Other individuals (e.g. medical experts) may be invited to participate at the discretion of the SRC.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 107014 0
Dr Emir Redzepagic
Address 107014 0
CMAX Clinical Research Pty Ltd
Level 5, 18a North Terrace
Adelaide
South Australia
5000
Country 107014 0
Australia
Phone 107014 0
+61 0413 231 264
Fax 107014 0
Email 107014 0
[email protected]
Contact person for public queries
Name 107015 0
Dr B. Heather Fraser, PhD
Address 107015 0

Atossa Therapeutics Inc.
107 Spring St
Seattle, WA 98104
Country 107015 0
United States of America
Phone 107015 0
+1 650 996 2622
Fax 107015 0
Email 107015 0
[email protected]
Contact person for scientific queries
Name 107016 0
Dr Steven C Quay, MD, PhD, FACS
Address 107016 0

Atossa Therapeutics Inc.
107 Spring St
Seattle, WA 98104
Country 107016 0
United States of America
Phone 107016 0
+1 206 419 4873
Fax 107016 0
Email 107016 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The individual participant clinical trial data and metadata arising from this study are considered confidential, commercial trade secret information which is subject to subsequent product development and potential patent filings relating to the formulation of the investigational product.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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