Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000468628
Ethics application status
Approved
Date submitted
6/04/2023
Date registered
5/05/2023
Date last updated
15/05/2023
Date data sharing statement initially provided
5/05/2023
Type of registration
Retrospectively registered

Titles & IDs
Public title
A study to compare the pharmacokinetics and pharmacodynamics of the free base form of PRTX007, the hydrochloride salt form of PRTX007 and the hydrochloride salt form of PRTX007 in combination with probenecid in healthy adults
Scientific title
A Phase 1, Randomised, Double-blind, Three-Period Crossover Study to Compare the Pharmacokinetics and Pharmacodynamics of a Single 400mg Dose of the Free Base Form of PRTX007, A Single Dose of the Hydrochloride Salt Form of PRTX007 and a Single 200mg Dose of the Hydrochloride Salt Form of PRTX007 Administered with a Single 500mg Dose of Probenecid.
Secondary ID [1] 309396 0
Protocol PRTX007-001
Universal Trial Number (UTN)
Trial acronym
Linked study record
This study is an additional cohort that was added via amendment to the parent study ACTRN12621000468820.

Health condition
Health condition(s) or problem(s) studied:
COVID-19 329626 0
Condition category
Condition code
Infection 326551 326551 0 0
Other infectious diseases
Respiratory 326552 326552 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Approximately 18 healthy men or women will be enrolled in this study. Subjects will be randomized to one of three drug sequences: A-B-C, B-C-A or C-A-B, where A is a single, oral 400mg dose of the free base form of oral PRTX007 and B is a single, oral 400mg dose of the hydrochloride salt form of PRTX007 and C is a single, oral 200mg dose of the hydrochloride salt form of PRTX007 administered with a single, oral 500mg dose of Probenecid. PRTX007 free base and hydrochloride salt forms will be given in the form of 200mg capsules. Probenecid will be given as a 500mg tablet. Subjects will receive a single dose of study drug on Day1, Day 5 and Day 9 per the sequence to which they were randomized. All doses will be administered under direct supervision in the Phase 1 unit and subjects will remain in the clinical research unit (CRU) in between doses and through the completion of the 24-hour post dose assessments on Day 10.
Intervention code [1] 325831 0
Treatment: Drugs
Comparator / control treatment
Free base form of PRTX007
Control group
Active

Outcomes
Primary outcome [1] 334392 0
Compare the pharmacokinetic profile of the free base form of PRTX007, the hydrochloride salt form of PRTX007 and the hydrochloride salt form of PRTX007 administered with Probenecid through the measurement of the plasma concentrations of PRTX007 and its active metabolite PRX034. PK parameters to be determined from plasma concentrations include Cmax (maximum observed concentration), Tmax (time to Cmax), AUClast (area under the concentration-time curve from time 0 to last measurable concentration), AUC0-12 (area under the concentration- time curve from time 0 to 12 hours post-dose), ?z (terminal elimination rate constant), t1/2 (apparent terminal half-life), AUCinf (area under the concentration-time curve extrapolated to infinite time).
Timepoint [1] 334392 0
On Day 1, Day 5 and Day 9, plasma will be collected pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours post dose. A 24 hour post dosing sample will be collected on Day 2, Day 6 and Day 10.
Secondary outcome [1] 420490 0
Compare the pharmacodynamic effects of the free base form of PRTX007, the hydrochloride salt form of PRTX007 and the hydrochloride salt form of PRTX007 administered with Probenecid through the measurement of multiple mRNA sequences in blood.
Timepoint [1] 420490 0
Samples will be collected on Day 1, Day 5 and Day 9 at pre-dose and 2, 6 and 12 hours post-dose. A 24-hour post dose sample will be collected on Day 2, Day 6 and Day 10 respectively. A 48-hour post-dose sample will be collected on Day 3 and Day 7. A 72-hour post dose sample will be collected on Day 4 and Day 8.
Secondary outcome [2] 420491 0
Compare the pharmacodynamic effects of the free base form of PRTX007, the hydrochloride salt form of PRTX007 and the hydrochloride salt form of PRTX007 administered with Probenecid through the measurement of cytokines and chemokines in blood. This will include polysubtype IFN alphas, IL-1RA, IL-6, IP-10, MCP-1, TNF-alpha, IL-1B.
Timepoint [2] 420491 0
Samples will be collected on Day 1, Day 5 and Day 9 at pre-dose and 2, 6 and 12 hours post-dose. A 24-hour post dose sample will be collected on Day 2, Day 6 and Day 10 respectively. A 48-hour post-dose sample will be collected on Day 3 and Day 7. A 72-hour post dose sample will be collected on Day 4 and Day 8.

Eligibility
Key inclusion criteria
1. Male or female and meet the following conditions:
a. Female participants must be of non-childbearing potential, defined as absence of menses for at least 1 year prior to dosing (without an alternative medical condition); and FSH levels less than or equal to 40 mIU/mL at screening; or,
b. If of childbearing potential, be non-pregnant or lactating and agree to use highly effective contraception from screening through 30 days post dose.
c. Male participants, if not surgically sterilized, and if engaging in sexual intercourse with a female partner of childbearing potential, must be willing to use highly effective contraception from screening through 90 days post dose and agree not to donate sperm during this period.
d. Highly effective contraception involves the use of a condom for the male, plus one of the following for the female:
i. Oral, injectable, implantable, intravaginal, or transdermal hormonal contraceptives, or
ii. Intrauterine device or intrauterine hormone-releasing system
e. Participants who do not engage in heterosexual intercourse will be considered abstinent and do not require contraception. Abstinence must be an ongoing and usual lifestyle of
the participant and complete abstinence must be maintained from screening through 30 days post dose.
2. Is judged to be in good health based on medical history, physical examination, vital sign measurements, and laboratory safety tests performed at the screening visit and/or before the first dose of study drug.
3. Weigh at least 45kg at the time of screening
4. Have a body mass index (BMI) greater than or equal to 18.0 and less than or equal to 32.0 kg/m2 at the time of screening
5. Negative SARS-CoV2 test per site standards
6. Agrees to be available for all study visits and cooperate fully with the requirements of the study protocol, including the schedule of assessments
7. Willing to refrain from over-the-counter (OTC) or prescription medications or herbal, nutritional or dietary supplements from 7 days before first dose through the final follow-up visit, except for limited use of acetyl-para-aminophenol (APAP) or in the case of necessary treatment of adverse events (AEs). Limited use of APAP is defined as less than 3g/day. These limits do not apply to its use for the necessary medical treatment of adverse events.
8. Willing to refrain from alcohol and caffeine from 48 hours before first dose through the last dose of study drug
9. Subjects who smoke no more than 2 cigarettes or equivalent per week can be included in the study but must be willing to abstain from smoking during the confinement period.
10. Willing and able to provide written informed consent
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Has an active malignancy, or history of malignancy, excluding basal or squamous cell carcinoma of the skin, within 2 years prior to screening
History of cardiovascular, cerebrovascular, or peripheral vascular disease, including, but not limited to, unstable angina, myocardial infarction, congestive heart failure, cardiac arrhythmia, hypertension, hypotension, or tachycardia. Clinically significant screening values measured after 5 minutes of rest in a supine position include:
a. Abnormal systolic blood pressure (<90 or > 150 mmHg)
b. Abnormal diastolic blood pressure (<40 or > 95 mmHg)
c. Abnormal respiratory rate (<10 or > 22 bpm)
3. Has a clinically significant history or presence of electrocardiogram (ECG) findings as judged by the PI or designee at screening, including:
a. Abnormal sinus rhythm (heart rate <40 bpm or > 100 bpm);
b. Average QT interval corrected using Fridericia’s formula (QTcF) interval duration >
450 msec for males and > 470 msec for females;
c. Average QRS interval > 120 msec after being confirmed by manual over-read
d. Average PR interval > 220 msec
4. Has clinically significant laboratory abnormalities including:
a. Impaired renal function (serum creatinine levels >106 µmol/L) at screening.
b. Alanine aminotransaminase (ALT) or aspartate aminotransaminase (AST) laboratory
values >1.5X upper normal limits.
c. Subject has an estimated creatinine clearance of <80 mL/min as determined by the
Cockcroft-Gault equation
Laboratory screening can be repeated upon investigator discretion.
5. History of prescription drug abuse or illicit drug use within 6 months prior to screening
6. History of moderate or severe psychiatric illness, based on physician’s judgement
7. History of alcohol abuse defined as an average daily intake >3 units, or an average weekly intake >21 units, where 1 unit is equivalent to 1 can or bottle (355mL) of beer, or 1 measure (25mL) of spirits, or 1 glass (175 mL) of wine within 5 years prior to screening
8. Positive alcohol breath test or urine test for drugs of abuse
9. Positive test results for hepatitis B surface antigen, hepatitis B core antibodies, hepatitis C virus antigen, and anti-human immunodeficiency virus (HIV) type 1 antibody
10. Has received treatment with another investigational drug, investigational device, or approved therapy for investigational use within 30 days or 5 half-lives (whichever is longer) prior to dosing; prior participation at any time in non-invasive methodology trials in which no drugs were given is acceptable. Receipt of the COVID-19 vaccine will be allowed up to 14 days prior to the first dose of study drug. Subjects will not be allowed to receive the COVID-19 vaccine from 14 days prior to the first dose through to 7 days after the last dose of study drug.
11. Has prior exposure to PRTX007
12. Has donated blood or plasma within 30 days prior to screening, or had a loss of whole blood of more than 500 mL within the 30 days prior to screening, or receipt of a blood transfusion within one year prior to screening
13. Has experienced symptoms of acute illness or chronic disease within 14 days prior to screening, or any disease or condition (medical or surgical) that, by the determination of the PI, might compromise interpretation of safety or PK data, or would place the subject at risk as a result of participation in the study
14. Is unable to cooperate fully with the requirements of the study protocol, including the schedule of assessments, or likely to be non-compliant with any study requirements
15. Other unspecified reasons that, in the opinion of the PI or Sponsor, make the subject unsuitable for enrollment.

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 opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated simple randomisation sequence
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
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis
This is an exploratory study and therefore it is not powered for inferential statistical analyses. It is anticipated that approximately 18 healthy male or female subjects will be enrolled and that this sample size is commonly used in studies of this design to obtain sufficient information on the comparability of pharmacokinetic and pharmacodynamic parameters between unique forms of the same compound.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
18/05/2022
Date of last participant enrolment
Anticipated
Actual
15/06/2022
Date of last data collection
Anticipated
15/06/2023
Actual
1/07/2022
Sample size
Target
18
Accrual to date
Final
18
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 24482 0
Scientia Clinical Research - Randwick
Recruitment postcode(s) [1] 40066 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 313590 0
Commercial sector/Industry
Name [1] 313590 0
Primmune Therapeutics Australia Pty Ltd
Country [1] 313590 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Primmune Therapeutics Australia Pty Ltd
Address
Suite 5.02, Level 5
139 Macquarie Street
Sydney NSW 2000
Country
Australia
Secondary sponsor category [1] 315376 0
None
Name [1] 315376 0
Address [1] 315376 0
Country [1] 315376 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312768 0
Alfred Hospital Human Research Ethics Committee
Ethics committee address [1] 312768 0
Ethics committee country [1] 312768 0
Australia
Date submitted for ethics approval [1] 312768 0
23/04/2021
Approval date [1] 312768 0
11/05/2021
Ethics approval number [1] 312768 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 125842 0
Dr Charlotte Lemech
Address 125842 0
Scientia Clinical Research Ltd.
Levels 5 and 6, Bright Building, Corner High and Avoca Sts, Randwick, NSW 2031
Country 125842 0
Australia
Phone 125842 0
+61 293 825 807
Fax 125842 0
Email 125842 0
[email protected]
Contact person for public queries
Name 125843 0
Puja Motwani
Address 125843 0
Scientia Clinical Research Ltd.
Levels 5 and 6, Bright Building, Corner High and Avoca Sts, Randwick, NSW 2031
Country 125843 0
Australia
Phone 125843 0
+61 293 825 800
Fax 125843 0
Email 125843 0
[email protected]
Contact person for scientific queries
Name 125844 0
Richard Daniels
Address 125844 0
Primmune Therapeutics, Inc. 2333 State St, Suite 203, Carlsbad, CA 92008
Country 125844 0
United States of America
Phone 125844 0
+1 760 330 7295
Fax 125844 0
Email 125844 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
Only aggregate participant data will be available from this study


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.