Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001313820
Ethics application status
Approved
Date submitted
25/07/2021
Date registered
27/09/2021
Date last updated
2/03/2023
Date data sharing statement initially provided
27/09/2021
Date results information initially provided
2/03/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
An Ascending-dose, Randomized, Placebo-controlled, Parallel, Double-blind, Single-dose, First-in-Human Study to Evaluate the Safety and Pharmacokinetics of RECCE®327 in Healthy Male Subjects
Scientific title
An Ascending-dose, Randomized, Placebo-controlled, Parallel, Double-blind, Single-dose, First-in-Human Study to Evaluate the Safety and Pharmacokinetics of RECCE®327 in Healthy Male Subjects
Secondary ID [1] 304855 0
RECCE327-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Serious/life-threatening bacterial infections 322957 0
Condition category
Condition code
Infection 320533 320533 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
(1) A sterilized mixture of copolymer of acrolein polyethylene-polyacrolein copolymers in the presence of polyethylene glycol and water (RECCE®327) will be administered in a double blind manner, as a single intravenous 1-hour infusion, in sequential cohorts:
• Cohort 1: 50 mg
• Cohort 2: 150 mg
• Cohort 3: 500 mg
• Cohort 4: 1,000 mg
• Cohort 5: 2,000 mg
• Cohort 6: 4,000 mg
• Cohort 7: 6,000 mg
• Cohort 8: 3,000 mg
(2) cetirizine (Zyrtec®) 10 mg oral tablet, given once, 10 hours prior to starting the intravenous infusion of study drug or placebo
(3) 0.9% aqueous saline 3-mL, intravenous catheter flush, given once immediately prior to and once immediately following study drug administration
Intervention code [1] 321245 0
Treatment: Drugs
Comparator / control treatment
Placebo, consisting of the same formulation as the investigational product but without the active ingredient, will be administered in a double blind manner, as a single intravenous 1-hour infusion, in sequential cohorts.
Control group
Placebo

Outcomes
Primary outcome [1] 328357 0
Safety and tolerability of RECCE®327 administered as a 1-hour intravenous infusion in healthy male subjects. Safety assessments will include the nature, frequency and severity of adverse events by treatment, laboratory safety parameters (serology, haematology, biochemistry, and urinalysis), blood pressure, and other vital signs (heart rate, respiration, and temperature), physical examination, and 12 lead electrocardiogram (ECG). Continuous cardiac telemetry will be used to monitor cardiac function.
Timepoint [1] 328357 0
Safety evaluations will be collected from the time of screening through completion of the end-of-study visit, or until all safety evaluations return to baseline or are considered stable and not requiring further follow up.

Adverse events as documented in the medical record will be collected from Screening through completion of the end-of-study visit, or until all safety evaluations return to baseline or are considered stable and not requiring further follow up.

A 12-lead ECG will be obtained from each subject at Screening, at check-in on Day -1, at Baseline (predose) and at 1, 2 and 4 hours postdose on Day 1, and at 24 hours on Day 2, and at the Day 7 EOS visit.

Vital signs will be measured with subject in supine position (for at least 5 minutes) at Screening, Check-in on Day -1, and Baseline (within 30 minutes prior to dosing). Additionally, blood pressure and heart rate measurements will be obtained at the following times:
Day 1: every 15 minutes (± 5 minutes) for the first 2 hours postdose, then every 30 minutes (± 5 minutes) from 2 to 6 hours postdose, then at 8 and 12 hours postdose (±10 minutes); Day 2: 24 hours (±10 minutes) postdose; and Day 7 (EOS visit).

Physical examination will be performed at Screening, Day-1 prior to dosing, Day 2, and Day 7 (EOS visit).

Clinical laboratory samples will be collected at Screening, Day -1 prior to dosing, Day 2, and Day 7 (EOS visit).

Cardiac telemetry will be performed on Day 1, from 1 hour predose to 7 hours post beginning of infusion.

Local infusion site pain and tolerability plus study staff assessment of the infusion site will be assessed using a visual pain scale and standardized template for marking the infusion site, at the following times postdose: 0.25, 0.5 and 1 hour (± 5 minutes), and 12 and 24 hours (± 15 minutes).
Secondary outcome [1] 398702 0
Pharmacokinetics (PKs) of RECCE327 administered as a 1-hour intravenous infusion in healthy male subjects.

The following individual PK parameters will computed: maximum plasma concentration (Cmax), time to Cmax, elimination rate constant, half-life, adjusted r2, AUC from dosing to infinity, AUC from time of dosing to last measurable concentration, percentage of area under the curve extrapolated beyond the last quantifiable plasma concentration, total body clearance, volume of distribution at steady state, mean residence time.

The following PK parameters will be determined for urine:
• Cumulative amount of drug excreted (Ae)
• Fraction of dose eliminated in urine (Furine)
• Urinary clearance
Timepoint [1] 398702 0
PK assessments will be obtained from all subjects who received either study drug or placebo on Day 1 and Day 2.

PK analysis will be completed only on the active treatment subjects.

PK analysis of drug plasma concentrations: Predose (0 hour; within 30 minutes prior to start of infusion), and at 5, 10, 15, 20, 30, 45 and 60 minutes (immediately prior to end of infusion), 65, 70, 75 and 80 minutes, and 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, and 24 hours post-dose.

PK analysis of drug urine concentrations: Predose (-8 to 0 hour) and then at the following intervals postdose: 0-4, 4-8, 8-12, 12-24 hours

Eligibility
Key inclusion criteria
To be eligible for enrollment, subjects must meet all of the following inclusion criteria:
1. Healthy male subjects between the ages of 18 and 55 years, inclusive, at Screening.
2. Willing and able to provide written informed consent prior to participating in the study.
3. Able to communicate clearly with the Investigator and staff; able to read, complete questionnaires, and understand study procedures.
4. Able to complete all Screening period evaluations, stay in the clinical research facility for the duration of the study, and attend scheduled follow-up visit on Day 7 (EOS). Additional visits may be required if there are any abnormalities that have not returned to Baseline by time of discharge from testing unit on Day 2 or by EOS visit on Day 7.
5. Body mass index (BMI) between 18 and 30 kg/m2, inclusive, and body weight not less than 50 kg.
6. In good general health, free from clinically significant medical or psychiatric illness or disease (in the opinion of the Investigator and as determined by medical/surgical history, physical examination, weight, 12-lead electrocardiogram (ECG), and clinical laboratory tests).
7. Vital signs at Screening must be within the following ranges and stable (measured in supine position after at least 5 minutes of rest):
• Systolic blood pressure (SBP) greater than or equal to 90 and less than or equal to 160 mmHg
• Diastolic blood pressure (DBP) greater than or equal to 50 and less than or equal to 95 mmHg
• Heart rate (HR) greater than or equal to 45 and less than or equal to 100 beats per minute (bpm)
• Note: If vital signs are out of range, the Investigator may obtain one additional reading, so that up to two consecutive assessments are made within 1 hour, and with the volunteer seated quietly during the 5 minutes preceding the assessment.
8. A 12-lead ECG consistent with normal cardiac conduction and function at Screening, including but not limited to: heart rate (HR) between 45 and 100 bpm; QTcF interval less than or equal to 450 ms; and morphology consistent with healthy cardiac conduction and function.
9. Nonsmoker within the previous 6 months (before Screening), and does not use tobacco-containing, or nicotine-containing products (including, but not limited to, cigarettes, pipes, cigars, chewing tobacco, e-cigarettes, nicotine patch, or nicotine gum).
10. Has clinical chemistry, hematology, coagulation, and complete urinalysis (fasted for at least 10 hours) results at Screening and at admission within 1.5 times the upper limit of normal (ULN) of the reference range for the testing laboratory. The following laboratory evaluations must be within the limits described below, at Screening and Baseline (admission):
• hemoglobin, hematocrit, reticulocyte count must be within normal limits (WNL);
• total white blood cell (WBC) count must not exceed the ULN; subjects with total WBC count below the lower limit of normal (LLN) may be enrolled at PI discretion (as athletic male healthy volunteers may have physiologically mildly low WBC counts);
• prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen must be WNL;
• blood urea and creatinine must be WNL;
• Glomerular Filtration Rate (GFR) must be greater than or equal to 80 mL/min [as calculated by Cockcroft and Gault formula];
• Urinalysis (UA) must be in range (or negative); abnormal UA results may be allowed upon agreement of PI (or Designee) and Sponsor.
11. Has a negative urine drug, urine cotinine, and breath alcohol Screen result at Screening and admission to clinical testing unit.
12. Male subjects who are non-sterilized must agree to be heterosexually abstinent or use highly effective contraception, defined as the use of a male condom and one other form of contraception by the female partner (e.g., oral contraceptive pill, hormonal implant, intrauterine device (IUD), intrauterine system (IUS), injectable contraceptive, or female partner is surgically sterile) from the time of Screening and for 3 months (90 days) after receiving the study drug.
13. Male subjects must agree to not donate sperm during the study and for 3 months (90 days) after receiving the study drug.
Minimum age
18 Years
Maximum age
55 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
Subjects meeting one or more of the following criteria will be excluded from the study:
1. Has a history of or current clinically significant medical illness including (but not limited to) pulmonary, cardiovascular, coagulation disorders, renal disorders, lipid abnormalities, gastrointestinal, immunologic, endocrine, neurologic, psychiatric, or thromboembolic disease, metabolic disturbances, or any other current physical condition that the Investigator (or Designee) considers should exclude the subject or that could interfere with the interpretation of the study results.
• Subjects with history of or current condition of any of the following will be excluded: Gilbert’s syndrome, asthma or reactive airway disease (any age), migraine;
• Subjects with history of cholecystectomy or splenectomy, or other completely resolved medical conditions may be included at the discretion of the Investigator (or Designee) and the Sponsor.
2. Has any clinically significant medical condition, physical examination finding, ECG abnormality, or clinically significant abnormal value for clinical chemistry, hematology, coagulation, or urinalysis at Screening or at admission to the study center, as deemed appropriate by the Investigator (or Designee).
3. Has had any history of clotting or coagulation disorder.
4. Has had any history of clinically significant renal disease.
5. History or presence of malignancy within the past 5 years, with the exception of adequately treated localized skin cancer (basal cell or squamous cell carcinoma), which is allowed.
6. Currently suffers from clinically significant systemic allergic disease, or has a history of significant drug allergies, including but not limited to:
• A history of anaphylactic reaction
• Allergic (histamine-like) reaction due to any drug that led to significant morbidity
• Known hypersensitivity to any component of the formulation of test article (RECCE®327), reference (placebo) article, or pretreatment article(s).
7. Has donated or intends to donate blood or blood products or has had an acute loss of blood (>500 mL) during the 3 months before study drug administration, or intends to donate blood or blood products within 3 months after the completion of the study.
8. Has had an acute, clinically significant illness within 30 days prior to Day 1, or has had a recent febrile illness with an abnormal body temperature within 72 hours prior to admission.
9. Has a history within the past 24 months before Screening of drug abuse (defined as any illicit drug use), or a history of alcohol abuse (defined as alcohol consumption exceeding 10 units per week). One unit of alcohol equals 360 mL (12 oz) of beer, 45 mL (1.5 oz) of liquor, or 150 mL (5 oz) of wine.
10. Has a positive test for alcohol or drugs of abuse at Screening or upon admittance to the testing facility, or is unwilling to abstain from alcohol and drugs of abuse throughout the study.
11. Has a smoking history during the past 6 months before Screening. This includes the use of any nicotine containing substances (e.g., nicotine patch or gum, chewing tobacco, e-cigarettes), or has a positive cotinine test at Screening or at admission, or is unwilling to abstain from these products for the duration of the study.
12. Has used any investigational compound, an experimental medical device, or participated in another clinical trial (randomized subjects only) within 3 months prior to receiving the study drug.
13. If the male subject intends to impregnate others or donate sperm within 90 days (3 months) after receiving the study drug.
14. Has inadequate venous access for the required blood draws for the study.
15. Is unable to meet or perform study requirements, or has a known or suspected inability to comply with the study protocol.
16. Is an immediate family member of the Investigator, or is an employee of the study center, or is in a dependent relationship with a study site employee who is involved in the conduct of this study (e.g., spouse, parent, child, sibling) or may consent under duress.
17. Use of a significantly abnormal diet (including keto diet) during the 4 weeks prior to receiving the study medication until the EOS visit.
18. Use of any over-the-counter (OTC) medication (including nutritional or dietary supplements, herbal preparations, or vitamins) within 14 days prior to receiving the study medication until the EOS visit.
19. Use of Vitamin K supplements or any drug which affects coagulation within 14 days prior to receiving the study medication until the EOS visit.
20. Use of any prescription medication from 14 days or 5 half-lives of the medication, whichever is longer, prior to receiving the study medication until the EOS visit.
21. Receipt of any vaccination within 14 days prior to receiving the study medication until the EOS visit.
22. Engagement in non-routine strenuous exercise or sunbathing from 48 hours prior to receiving the study medication until the EOS visit.
23. Consumption of beverages or foods that contain alcohol, grapefruit, poppy seeds, broccoli, Brussels sprouts, pomegranate, star fruit, char-grilled meat, or caffeine/xanthine from 3 days prior to admission until the EOS visit. Subjects will be instructed not to consume any of the above products; however, allowance for an isolated single incidental consumption may be evaluated and approved by the study Investigator based on the potential for interaction with the study drug.
24. Has a positive test for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus (HIV) at Screening or has been previously treated for hepatitis B, hepatitis C, or HIV infection.
25. Subjects who, in the opinion of the Investigator (or Designee), should not participate in this study.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
6/12/2021
Actual
16/12/2021
Date of last participant enrolment
Anticipated
Actual
7/12/2022
Date of last data collection
Anticipated
Actual
21/12/2022
Sample size
Target
80
Accrual to date
Final
75
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 309228 0
Commercial sector/Industry
Name [1] 309228 0
Recce Pharmaceuticals, Ltd.
Country [1] 309228 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Recce Pharmaceuticals, Ltd.
Address
Suite 10, 3 Brodie Hall Drive Technology Park
Bentley WA 6102
Country
Australia
Secondary sponsor category [1] 310196 0
None
Name [1] 310196 0
Address [1] 310196 0
Country [1] 310196 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309076 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 309076 0
123 Glen Osmond Road
Eastwood SA 5063
Ethics committee country [1] 309076 0
Australia
Date submitted for ethics approval [1] 309076 0
21/07/2021
Approval date [1] 309076 0
22/10/2021
Ethics approval number [1] 309076 0

Summary
Brief summary
This is a Phase 1, single-center, randomized, placebo controlled, single dose, double blind, parallel, pioneer-group, first-in-human (FIH) study to assess the safety, tolerability, and pharmacokinetics of RECCE®327 when administered as a single dose via a 1-hour IV infusion. All subjects will receive pretreatment with the antihistamine compound, cetirizine (Zyrtec®). Eight dose cohorts will be studied . An initial dose of 50 mg or placebo will comprise the 1st cohort of 10 subjects. The study will consist of a Screening period (up to 28 days), followed by Baseline assessments (Day -1), an in-patient Study Treatment Period (Day 1 and Day 2), and follow-up visit to the clinic at Day 7 (End of Study [EOS]).

After fulfilling Screening requirements, all subjects will check into the clinic in the afternoon of Day –1 for Baseline assessments. Subjects will be randomized on Day -1 to the sequence of RECCE®327 or placebo. Subjects will remain under observation at the investigational site for the duration of the study, from admission on Day –1 until discharge from clinic on Day 2. All subjects will return on Day 7 for a follow-up visit, or sooner as the Investigator deems necessary.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 112890 0
Dr Nicolas Farinola
Address 112890 0
CMAX Clinical Research
Level 5, 18a North Terrace Adelaide
South Australia 5000
Country 112890 0
Australia
Phone 112890 0
+61 421 570 586
Fax 112890 0
Email 112890 0
nicholas.farinola@sa.gov.au
Contact person for public queries
Name 112891 0
Ms Michele Dilizia
Address 112891 0
Recce Pharmaceuticals, Ltd.
Suite 10, 3 Brodie Hall Drive Technology Park
Bentley WA 6102
Country 112891 0
Australia
Phone 112891 0
+61 8 9362 9860
Fax 112891 0
Email 112891 0
michele.dilizia@recce.com.au
Contact person for scientific queries
Name 112892 0
Ms Michele Dilizia
Address 112892 0
Recce Pharmaceuticals, Ltd.
Suite 10, 3 Brodie Hall Drive Technology Park
Bentley WA 6102
Country 112892 0
Australia
Phone 112892 0
+61 8 9362 9860
Fax 112892 0
Email 112892 0
michele.dilizia@recce.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.