Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000981527p
Ethics application status
Submitted, not yet approved
Date submitted
16/07/2024
Date registered
12/08/2024
Date last updated
12/08/2024
Date data sharing statement initially provided
12/08/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1, Randomized Double-Blind, Placebo-Controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of an Intermittent Consecutive Day Dosing Regimen of PRTX007 in Healthy Adults
Scientific title
A Phase 1, Randomized Double-Blind, Placebo-Controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of an Intermittent Consecutive Day Dosing Regimen of PRTX007 in Healthy Volunteers
Secondary ID [1] 312414 0
PRTX007-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lassa Virus 334233 0
Condition category
Condition code
Infection 330899 330899 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a Phase 1, single-centre, prospective, randomised, double-blind study examining an intermittent consecutive day dosing regimen of PRTX007 administered orally to healthy male and female volunteers.

Fifteen healthy volunteers will be randomised to receive either a 750 mg oral dose of PRTX007 capsules or matching placebo capsules on Day 1 through Day 3, Day 8 through Day 10 and on Day 15 (7 total doses).

Adherence to the study intervention will be done via supervised drug administration.
Intervention code [1] 328920 0
Treatment: Drugs
Comparator / control treatment
Placebo - Capsules containing microcrystalline cellulose and identical in appearance to the study intervention will be used in this study.
Control group
Placebo

Outcomes
Primary outcome [1] 338657 0
To assess the safety and tolerability of PRTX007 given on consecutive day dosing in healthy volunteers.
Timepoint [1] 338657 0
Adverse events will be graded for severity using the terms: Mild, Moderate, or Severe to describe the maximum intensity of the AE and assessed continuously as they are reported or observed and reviewed daily from Day -1 until Day 30 (End of Study/Early Termination Visit [EOS/ETV}).
Vital signs - Blood pressure and heart rate is measured using sphygmomanometer, respiratory rate by manual breath count and temperature by thermometer. Assessed at Screening, Day -1, pre-dose Day 1, 2 and Day 3 and then 1, 2, 3, 4, 6 hrs post-dose, Day 4 post-dose, Day 5 post-dose, Day 6 post-dose, pre-dose Day 8, and Day 10 then 1, 2, 3, 4, 6 hrs post-dose, Day 12, 13, 14, 15, 16 and Day 30 post-dose (End of Study/Early Termination Visit [EOS/ETV}).
Clinical laboratory evaluations - blood and urine samples will be collected from Screening, Day -1, Day 4 post-dose, pre-dose Day 8, Day 11 post-dose, pre-dose Day 15, Day 16 and Day 30 post-dose (End of Study/Early Termination Visit [EOS/ETV}).
Electrocardiogram (ECG) - 12-lead ECG recordings will be obtained in triplicate at screening and Day 30 (End of Study/Early Termination Visit [EOS/ETV}) only, then single recordings obtained at Day -1, pre-dose Day 1 2 hrs post-dose, Day 2 2 hrs post-dose, Day 3 2 hrs post-dose, Day 8 2 hrs post-dose, Day 9 2 hrs post-dose, Day 10 2 hrs post-dose and Day 15 hrs post-dose.
Complete physical examination to include assessments of the overall general appearance as well as dermatologic, head, eyes, nose and throat (HEENT), lymphatic, cardiovascular, respiratory, gastrointestinal, musculoskeletal, and neurological systems will be performed at Screening and Day 30 post-dose (End of Study/Early Termination Visit [EOS/ETV}). Height (only at screening) and weight (both performed per site SOP) and Body Mass Index (BMI) will also be recorded.
A focused physical examination includes assessments of the chest (heart, lungs), abdomen, skin, neurological, and musculoskeletal examinations will be performed on admission on Day -1 and at the time of clinic discharge on Day 16.
Secondary outcome [1] 436876 0
To assess the pharmacokinetic (PK) characteristics of PRTX007 and PRX034, the active metabolite of prodrug PRTX007

This outcome is a composite outcome of the plasma concentrations of PRTX007 and its key metabolite PRX034 after intermittent consecutive day doses of PRTX007.

PK parameters to be determined from plasma concentrations include maximum observed concentration (Cmax), time to Cmax (Tmax), AUClast, AUC from time 0 to 12 hours post-dose (AUC0-12), terminal elimination rate constant ( ?z), apparent terminal half-life (t1/2), AUC extrapolated to infinite time ( AUCinf).
Timepoint [1] 436876 0
Pharmacokinetic Assessments:
Pharmacokinetics will be determined by analyzing plasma samples for concentrations of PRTX007 and PRX034 with a validated LC-MS/MS assay.
Blood (plasma) PK samples will be collected from all subjects at the following timepoints:
• On Day 1 and Day 15, plasma will be collected for PK analyses pre-dose (within 60 minutes prior) at 30, 60, and 90 minutes (all ± 5 minutes), and 2, 3, 4, 6, 8, and 12 hours (all ± 15 minutes) after dosing. A 24 hour (± 1 hour) post dosing trough sample will be collected on Days 2 and 16 respectively.


• On Day 3, Day 8 and Day 10 plasma will be collected for PK analyses pre-dose (within 60 minutes prior) and at 2 and 6 hours (all ± 15 minutes) after dosing.
Secondary outcome [2] 436877 0
To assess the pharmacodynamics (PD) of PRTX007 given on consecutive days in normal healthy volunteers, including reproducibility of key immune response markers
Timepoint [2] 436877 0
Pharmacodynamic Assessments:
• Cytokines/Chemokines
- On Day 1, Day 2, Day 3, Day 8, Day 9, Day 10 and Day 15 blood will be collected for cytokine and chemokine analysis pre-dose (within 60 minutes prior) and then at 2, 6, and 12 hours (all ± 10 minutes) after dosing. A 24 hour (± 1 hour) post-dose sample will be collected on Day 4 and Day 11 respectively.
• mRNA, neopterin
- On Day 1, Day 2, Day 3, Day 8, Day 9, Day 10 and Day 15 blood will be collected for mRNA and neopterin analysis pre-dose (within 60 minutes prior) and then at 2, 6, and 12 hours (all ± 10 minutes) after dosing. A 24 hour (± 1 hour) post-dose sample will be collected on Day 4 and Day 11 respectively.
• Cellular assays (FACS)
- On Day 1, Day 3, Day 8, Day 10 and Day 15 blood will be collected for cellular assays (FACS) pre-dose (within 60 minutes prior) and then at 6 hours (± 10 minutes) after dosing. A single sample will be collected on Day 30 as part of the safety follow-up assessment.

Eligibility
Key inclusion criteria
- Aged between 18 and 65 years of age at time of consent
- Male or female and meet the following conditions:
a. Female participants must be of non-child-bearing potential, defined as absence of
menses for at least 1 year prior to dosing (without an alternative medical condition); and
FSH levels greater than or equal to 40 mIU/mL at screening; or,
b. If of child-bearing potential, be non-pregnant or lactating and agree to use highly
effective contraception from screening through 30 days post final dose.
c. Male participants, if not surgically sterilized, and if engaging in sexual intercourse with
a female partner of child-bearing potential, must be willing to use highly effective
contraception from screening through 90 days post final 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 final dose.
- 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.
- Weigh at least 45kg at the time of screening
- 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
- Have suitable venous access for blood sampling
- Negative SARS-CoV2 test if required per site standards
- Agrees to be available for all study visits and cooperate fully with the requirements of the
study protocol, including the schedule of assessments
- Willing to refrain from over-the-counter (OTC) or prescription medications or herbal,
nutritional or dietary supplements from 7 days or 5 half-lives of the drug (whichever is
longer) before first dose through the final follow-up visit, except for limited use of
paracetamol (up to 2g per day for no more than 3 consecutive days), ibuprofen (up to
1.2g per day for no more than 3 consecutive days), oral all forms of contraceptive
medication or in the case of necessary treatment of adverse events (AEs). These limits
do not apply to its use for the necessary medical treatment of adverse events.
- Willing to refrain from alcohol and caffeine from 48 hours before first dose through the
last dose of study drug
- Subjects who smoke no more than 5 cigarettes or equivalent per week can be included
in the study but must be willing to abstain from smoking during the confinement period.
- 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
- 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 or semi-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)
The resting time may be extended as needed to accommodate clinical activities and may be repeated twice.
- 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
c. Average QRS interval > 120 msec after being confirmed by manual over-read
d. Average PR interval > 220 msec
- 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.
- History of prescription drug abuse or in the opinion of the investigator illicit drug use
within 6 months prior to screening
- Use of any vaccines within 14 days prior to first dose administration on Day 1.
- History of moderate or severe psychiatric illness, based on physician’s judgment
- History of alcohol abuse defined as 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]) within 5 years prior to
screening
- Positive alcohol breath test or urine test for drugs of abuse. May be repeated at the
investigator’s discretion.
- 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
- 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.
- 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
- 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
- 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
- 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)
Participants who meet the study eligibility criteria will be assigned a randomization number pre-dose on Day -1 or Day 1, which corresponds to a study treatment (PRTX007 or placebo). The randomization schedule will be stored in a secure, restricted access area. Sealed participant-specific code break envelopes will be produced by the unblinded statistician(s) 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)
The allocation to PRTX007 or placebo will be performed using a block randomization algorithm and will be documented in the study randomization schedule.
Masking / blinding
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
15/10/2024
Actual
Date of last participant enrolment
Anticipated
15/10/2024
Actual
Date of last data collection
Anticipated
14/11/2024
Actual
Sample size
Target
15
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 316827 0
Commercial sector/Industry
Name [1] 316827 0
Primmune Therapeutics, Inc.
Country [1] 316827 0
United States of America
Primary sponsor type
Government body
Name
United States Defense Threat Reduction Agency (DTRA)
Address
Country
United States of America
Secondary sponsor category [1] 319055 0
Commercial sector/Industry
Name [1] 319055 0
Avance Clinical Pty Ltd
Address [1] 319055 0
Country [1] 319055 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 315595 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 315595 0
Ethics committee country [1] 315595 0
Australia
Date submitted for ethics approval [1] 315595 0
31/07/2024
Approval date [1] 315595 0
Ethics approval number [1] 315595 0

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

Contacts
Principal investigator
Name 135186 0
Dr Christopher Argent
Address 135186 0
Scentia Clinical Research, Ltd., Levels 5 and 6, Bright Building, Corber High and Avoca Streets, Randwick, NSW 2031
Country 135186 0
Australia
Phone 135186 0
+61 2 9382 5844
Fax 135186 0
Email 135186 0
[email protected]
Contact person for public queries
Name 135187 0
Ms. Puja Motwani
Address 135187 0
Scentia Clinical Research, Ltd., Levels 5 and 6, Bright Building, Corber High and Avoca Streets, Randwick, NSW 2031
Country 135187 0
Australia
Phone 135187 0
+61 293 825 800
Fax 135187 0
Email 135187 0
[email protected]
Contact person for scientific queries
Name 135188 0
Dr Curtis Scribner
Address 135188 0
Primmune Therapeutics, Inc., 2333 State Street, Suite 203, Carlsbad, CA, 92008
Country 135188 0
United States of America
Phone 135188 0
+1 510 914 8368
Fax 135188 0
Email 135188 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


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.