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Trial registered on ANZCTR


Registration number
ACTRN12624000650594p
Ethics application status
Submitted, not yet approved
Date submitted
7/05/2024
Date registered
21/05/2024
Date last updated
21/05/2024
Date data sharing statement initially provided
21/05/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A Randomised, Double-Blind, Placebo-Controlled, Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Single Dose of EMP-012 for Injection Administered Subcutaneously to Healthy Volunteers
Scientific title
A Randomised, Double-Blind, Placebo-Controlled, Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Single Dose of EMP-012 for Injection Administered Subcutaneously to Healthy Volunteers
Secondary ID [1] 311713 0
EMP-012-1
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Lung Disease 333191 0
Condition category
Condition code
Respiratory 329879 329879 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a randomised, double-blind, placebo-controlled single ascending dose study conducted in healthy adult volunteers.

Approximately 40 participants will be enrolled across a total of 4 cohorts. Each cohort will enrol up to 10 participants with 6 participants randomized to receive EMP-012 for Injection and 4 participants randomised to receive placebo in a double blinded manner.

Participants will receive a single dose of EMP-012 for Injection administered subcutaneously (SC) or placebo (according to their randomisation) on Day 1 at the following nominal dose levels:
• Cohort 1: 25 mg
• Cohort 2: 50 mg
• Cohort 3: 100 mg
• Cohort 4: 200 mg

Participants will be dosed while in a supine or semi-supine position, and administration of study drug will be performed in the clinical trial facility by an appropriately qualified staff member who is trained on the procedure(s) of administering each of the study treatments. The exact dates and times of study drug administration will be recorded in the eCRF.

The decision to escalate between dose levels will be based upon review of blinded available safety data from each cohort, by a Safety Review Committee (SRC ). Sentinel dosing will be employed, whereby the first two participants in each cohort (1 randomised to EMP-012 and the other randomised to placebo) will be dosed at last 48 hours ahead of the remaining participants.
Intervention code [1] 328330 0
Treatment: Drugs
Comparator / control treatment
Placebo (normal saline for SC injection) will be administered as a single dose on Day 1.
Control group
Placebo

Outcomes
Primary outcome [1] 337862 0
To evaluate the safety and tolerability of single ascending doses of EMP-012 for Injection in healthy volunteers.
Timepoint [1] 337862 0
Adverse events - will be graded using a three-point severity scale (mild, moderate, severe) and assessed continuously as they are reported or observed and reviewed daily from Screening until Day 172 (End of Study/Early Termination [EOS/ET]).

Local tolerability and injection site reactions of pain, tenderness, erythema/redness and induration/swelling will be graded as per the FDA Guidance for Industry document entitled Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (2007) pre-dose Day 1, 0.25 hr, 0.5 hr, 1 hr, 2 hrs, 6 hrs, 8 hrs post-dose, Day 2 24 hrs post-dose, Day 3 48 hrs post-dose, Day 8 and Day 15.

Clinical Laboratory Assessments (haematology, clinical chemistry, coagulation and urinalysis) blood and urine will be collected at Screening, Day -1, Day 2 24 hrs post-dose, Day 3 48 hrs (+/- 6 hrs) post-dose, Day 8, Day 15, Day 22, Day 29, Day 36, Day 64, Day 92, Day 120, Day 148 and Day 172 (EOS/ET).

Vital signs - Blood pressure and heart rate is measured using sphygmomanometer, respiratory rate by manual breath count, temperature by tympanic or infrared thermometer, pulse rate and oxygen saturation by pulse oximeter. Measured from Screening, Day -1, pre-dose Day 1 - 0.25hr, 0.5 hr, 1 hr, 2 hrs, 6 hrs, 8 hrs post-dose, Day 2 24 hrs post-dose, Day 3 48 hrs post-dose, Day 8, Day 15, Day 22, Day 29, Day 36, Day 50, Day 64, Day 78, Day 92, Day 120, Day 148, and Day 172 (EOS/ET).

Electrocardiogram (ECG) 12-lead ECG recordings will be obtained in triplicate at Screening and Day -1 to be conducted within 5 minutes with each recording at least 1 minute apart, single recordings then taken Day 1 - 0.25hr, 0.5 hr, 1 hr, 2 hrs, 6 hrs, 8 hrs post-dose, Day 2 24 hrs post-dose, Day 3 48 hrs post-dose, Day 8, Day 15, Day 22, Day 29, Day 36, Day 50, Day 64, Day 78, Day 92, Day 120, Day 148, and Day 172 (EOS/ET).
Secondary outcome [1] 433495 0
To evaluate the pharmacokinetics (PK) of EMP-012 for Injection in plasma following single dose administration in healthy volunteers.
Timepoint [1] 433495 0
Blood plasma samples will be collected pre-dose Day 1 - 0.25 hr, 0.5 hr, 1 hr, 2 hrs, 6 hrs, 8 hrs post-dose, Day 2 24 hrs post-dose and Day 3 48 hrs post-dose.

Eligibility
Key inclusion criteria
1. Must have given written informed consent before any study-related activities are performed and must be able to understand the full nature and purpose of the study, including possible risks and adverse effects.
2. Adult males and females, 18 to 65 years of age (inclusive) at screening.
3. Body mass index (BMI) greater than or equal to 18.0 and less than or equal to 32.0 kg/m2, with a body weight less than or equal to 100 kg at screening.
4. Medically healthy (in the opinion of the PI or delegate), as determined by pre-study medical history, and without clinically significant (CS) abnormalities including the following:
a. Physical examination without any CS findings.
b. Systolic blood pressure (BP) in the range of 90 to 140 mmHg and diastolic BP in the range of 60 to 90 mmHg after resting for 5 minutes in a supine or semi-supine position.
c. Pulse rate in the range of 50 to 100 bpm after 5 minutes resting in a supine or semi-supine position.
d. Body temperature (tympanic or infrared), between 35.5°C and 37.7°C.
e. Electrocardiogram without clinically significant abnormalities including QT interval corrected for Fredericia (QTcF) <450 msec for male participants and <470 msec for female participants.
f. No CS findings in clinical chemistry, haematology, coagulation, and urinalysis tests.
5. Female volunteers:
a. Must 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 (FSH) level consistent with postmenopausal status [>40 U/L], per local laboratory guidelines), or
b. If of child-bearing potential, must:
i. Have a negative pregnancy test at the screening visit and on admission to the study site on Day-1.
ii. Agree not to attempt to become pregnant or donate ova from signing the consent form until at least 6 months after the last dose of study drug.
iii. Agree to use adequate contraception (defined as use of a condom by the male partner combined with use of a highly effective method of contraception from one month prior to screening until at least 6 months after the last dose of study drug, if not exclusively in a same-sex relationship or abstinent as a committed lifestyle.
6. Male volunteers, must:
a. Agree not to donate sperm from signing the consent form until at least 6 months after the last dose of study drug.
b. If engaging in sexual intercourse with a female partner who could become pregnant, agree to use adequate contraception (defined as use of a condom combined with use of a highly effective method of contraception from signing the consent form until at least 6 months after the last dose of study drug.
c. If engaging in sexual intercourse with a female partner who is not of childbearing potential or a same-sex partner, agree to use a condom from signing the consent form until at least 6 months after the last dose of study drug.
7. Have suitable venous access for blood sampling.
8. Willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Known hypersensitivity to the study drug or any of the study drug ingredients.
2. History of anaphylaxis or other significant allergy which, in the opinion of the PI (or delegate), would interfere with the volunteer’s ability to participate in the study.
3. History or presence of CS cardiovascular, pulmonary, hepatic, renal, haematological, gastrointestinal (GI), endocrine, immunologic, dermatologic, psychiatric, or neurological disease/disorder, including any acute illness, within the past 3 months determined by the PI (or delegate) to be clinically relevant.
4. History of surgery or hospitalization within 3 months prior to screening, or surgery planned during the study.
5. Any history of malignant disease in the last 10 years (excludes surgically resected skin squamous cell or basal cell carcinoma).
6. Presence of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia.
7. History of risk factors for torsade de pointes (including a family history of long QT syndrome or sudden cardiac death) or a known arrythmia.
8. Presence or having sequelae of GI, liver (including Gilbert’s syndrome), kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs. Note: history of cholecystectomy is permitted.
9. Liver function test results elevated >1.5-fold above the ULN for gamma glutamyl transferase (GGT), bilirubin (total, conjugated and unconjugated), ALP, AST or ALT. Volunteers with ALP and/or ALT/AST above the limits specified may be included, at the discretion of the PI (or delegate), if the levels are unaccompanied by clinical signs and are determined to be normal variants.
10. Haemoglobin A1c (HbA1c) >7.0% at Screening.
11. Haemoglobin <120 g/L for females and <130 g/L for males or haematocrit outside the upper or lower limits of the normal range per reference laboratory at both Screening and Day -1.
12. Participants with history or pre-existing renal disease, as defined below:
a. Estimated glomerular filtration rate (eGFR) < 80 mL/min/1.73 m2 at Screening and Day -1 (calculated using the Chronic Kidney Disease Epidemiology Collaboration formula). Note: one retest of the exclusionary eGFR value is allowed at the discretion of the PI (or delegate).
b. Urinary albumin-to-creatinine ratio > 10 mg/µmol (100 mg/g).
13. Suspicion of, or known Gilbert’s syndrome.
14. A history of, or positive test results for human immunodeficiency virus (HIV-1 or HIV-2), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies at the screening visit.
15. Positive drugs of abuse test, cotinine test or alcohol breath test results at the screening visit and/or on admission to the study site on Day 1.
16. Regular consumption of more than 10 standard alcoholic drinks/week and/or more than 4 standard alcoholic drinks on any one day, where 1 standard drink is 10 g of pure alcohol and is equivalent to 285 mL beer [4.9% Alc/Vol], 100 mL wine [12% Alc/Vol], or 30 mL spirit [40% Alc/Vol]).
17. Volunteer smokes more than 5 cigarettes or equivalent nicotine-containing products per week, and/or the volunteer is unwilling to abstain from smoking or the use of nicotine-containing products for 72 hours prior to check-in on Day -1 and throughout the confinement period at the study site.
Note: 1 average cigar equals approx. 5 average cigarettes; 1 average pipe session equals approx. 5 average cigarettes; 1 average nicotine liquid vape session equals 1 average e-cigarette equals 1 average cigarette.
18. Females who are breastfeeding or planning to breastfeed.
19. Presence or evidence of recent sunburn, scar tissue, tattoos, or open sores that, in the opinion of the PI (or delegate), would interfere with evaluation of the participant’s response to the study drug.
20. Use of any prescription or over-the-counter (OTC) medication within 14 days or 5 half-lives of the medication (whichever is longer) prior to the first dose of study drug, except use of contraceptives, the use of paracetamol (up to 2 g per day) for no more than 3 consecutive days and the use of ibuprofen (up to 1.2 g per day) for no more than 3 consecutive days.
21. Use of herbal products, diet aids, vitamins, and/or hormone supplements within 7 days prior to the first dose of study drug.
22. Current infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medication within 10 days prior to study drug administration.
23. Unwillingness or inability to refrain from receiving a vaccine both 28 days prior to and 28 days after study drug administration.
24. Donation of blood or plasma within 30 days prior to study drug administration, or loss of whole blood of more than 500 mL within 30 days prior to study drug administration, or receipt of a blood transfusion within 1 year of study drug administration.
25. Participation in another clinical study of an investigational drug or investigational device within 30 days or 5 half-lives of the investigational drug (whichever is longer) prior to screening.
26. Any other condition or prior therapy that in the opinion of the PI (or delegate) would make the volunteer unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance 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)
All study participants who sign an informed consent form (ICF) will receive a unique sequential number (i.e., a screening number). Participants who meet the study eligibility criteria will be assigned a randomisation number prior to dose administration on Day 1, which corresponds to a study treatment (EMP-012 or placebo). Sealed participant-specific code break envelopes will be produced by the Clinical Research Organisation (CRO) unblinded statistician(s) and will be retained at the study site in a secure, accessible location.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The allocation to EMP-012 or placebo will be performed using a block randomisation algorithm and will be documented in the study randomisation schedule. Randomisation numbers assigned will be in accordance with this randomisation schedule.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
12/07/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 26359 0
Nucleus Network Brisbane Clinic - Herston
Recruitment postcode(s) [1] 42331 0
4006 - Herston

Funding & Sponsors
Funding source category [1] 316042 0
Commercial sector/Industry
Name [1] 316042 0
Empirico Inc
Country [1] 316042 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Empirico Inc
Address
Country
United States of America
Secondary sponsor category [1] 318204 0
Commercial sector/Industry
Name [1] 318204 0
Avance Clinical Pty Ltd
Address [1] 318204 0
Country [1] 318204 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 314864 0
Bellberry Human Research Ethics Committee A
Ethics committee address [1] 314864 0
https://bellberry.com.au/
Ethics committee country [1] 314864 0
Australia
Date submitted for ethics approval [1] 314864 0
08/05/2024
Approval date [1] 314864 0
Ethics approval number [1] 314864 0

Summary
Brief summary
This is a randomised, double-blind, placebo-controlled, ascending dose study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of EMP-012, and how this drug acts in the body in healthy volunteers. EMP-012 may be indicated for use in patients with Chronic Lung Disease, but a trial of the drug in healthy volunteers is needed before trials in Chronic Lung Disease patients can proceed.

Who is it for?
You may be eligible for this study if you are aged 18 to 65 years and are in good general health without a clinically significant medical history.

Study details
All healthy volunteer participants who choose to enrol in this study will be assigned by chance to receive either a single dose of EMP-012 or placebo. All participants will have their vital signs checked (heart rate, blood pressure, temperature, etc), and will provide blood and urine samples for testing.
It is hoped this research will determine the maximum dose of EMP-012 that can be administered safely without causing severe reactions. Once the dose of EMP-012 has been determined in healthy volunteers, a trial investigating the efficacy of EMP-012 as a treatment for patients with Chronic Lung Disease may proceed.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 132974 0
Dr Gloria Wong
Address 132974 0
Nucleus Network, Level 5, 300 Herston Road, Herston, QLD 4006
Country 132974 0
Australia
Phone 132974 0
+61 430 891 636
Fax 132974 0
Email 132974 0
g.wong@nucleusnetwork.com.au
Contact person for public queries
Name 132975 0
Gloria Wong
Address 132975 0
Nucleus Network, Level 5, 300 Herston Road, Herston, QLD 4006
Country 132975 0
Australia
Phone 132975 0
+61 430 891 636
Fax 132975 0
Email 132975 0
g.wong@nucleusnetwork.com.au
Contact person for scientific queries
Name 132976 0
Gloria Wong
Address 132976 0
Nucleus Network, Level 5, 300 Herston Road, Herston, QLD 4006
Country 132976 0
Australia
Phone 132976 0
+61 430 891 636
Fax 132976 0
Email 132976 0
g.wong@nucleusnetwork.com.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.