Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618001920280
Ethics application status
Approved
Date submitted
8/10/2018
Date registered
26/11/2018
Date last updated
30/11/2021
Date data sharing statement initially provided
26/11/2018
Date results information initially provided
30/11/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A Single Ascending Doses (SAD) of a Novel Engineered Cationic Peptide PLG0206 in Healthy Subjects.
Scientific title
Safety and Tolerability of Single Ascending Doses (SAD) of a Novel Engineered Cationic Peptide PLG0206 in Healthy Subjects
Secondary ID [1] 295773 0
018-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Microbial Infections 309667 0
Condition category
Condition code
Infection 308469 308469 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Dose: Proposed dose escalation scheme 0.05, 0.125, 0.25, 0.5, 1, 2, and 3 mg/kg.
Route of Administration: Intravenous infusion over 1 hour. There will be a minimum of 7 days between dose escalation within which the safety data will be evaluated at each dose level before escalation to the next dose level.
Subjects will be randomized to PLG0206 IV or Placebo IV group in a 3:1 ratio There will be a total of up to 56 subjects, divided into up to 7 sequential groups: Within each group (n=8 subjects), 2 subjects will receive placebo and 6 will receive PLG0206. At each dose level, there will be 2 sentinel subjects, (1 active, 1 placebo), who will be dosed at least 48 hours in advance of the other subjects in their respective group. There will be at least 7 day period after dosing each of the dose levels before dose escalation.
Intervention code [1] 312204 0
Treatment: Drugs
Comparator / control treatment
Placebo - Saline solution
Control group
Placebo

Outcomes
Primary outcome [1] 307484 0
Safety and Tolerability
Timepoint [1] 307484 0
Safety and Tolerability will be evaluated as follows: Blood samples will be tested for standard chemical and haematology analytes, as well as pharmacokinetic (PK) and possible immunogenecity testing. Blood samples will be collected to assay for PLG0206 at pre-dose, 0.5 -h after start of infusion, within 1 minute after the end-of-infusion and at 0.5, 1, 2, 4, 6, 8, 12, 20, 24, 36 and 48 hours after the end-of-infusion. Total urine will be collected between the intervals 0-8, 8-16, 16-24 and 24-48 hours post dose. Vital signs will be recorded within 60 minutes pre-dose and at 0.5, 1, 2, 3, 4, 6, 9, 12, 24 (Day 2) and 48 hours (prior to discharge on Day 3) post-infusion completion, after at least 3 minutes of rest in supine position. A 12-lead ECG will be performed on Day 1 (dosing day), within 60 minutes prior to start of infusion. ECGs will also be assessed at 0.5 hours after infusion start, at completion of infusion and at 0.5, 1, 2, 4, 6, 9, 12, 24 and 48 hours post-infusion completion. Continuous cardiac monitoring (Holter), will be performed on Day -1 for 12 hours starting at 24 hours prior to the start of infusion on Day 1. It will begin again from the start of infusion up to 24 hours after infusion. The PK parameters which will be analysed are as follows but not limited to the following: Primary PK parameters: Cmax, AUC0-t, AUC0-Inf Secondary PK parameters: Time Corresponding to Cmax (Tmax), Tlast, Terminal half-life ( T1/2), Terminal elimination rate, Apparent clearance (CL) and Apparent volume of distribution (Vz/F).
Secondary outcome [1] 352059 0
To characterize the pharmacokinetic (PK) profile of single doses of PLG0206.
Timepoint [1] 352059 0
Pharmacokinetic profile will be analysed as follows: Blood samples for PK assessment will be collected to assay for PLG0206 at pre-dose, 0.5 -h after start of infusion, within 1 minute after the end-of-infusion and at 0.5, 1, 2, 4, 6, 8, 12, 20, 24, 36 and 48 hours after the end-of-infusion. Batch Urine PK analysis will be performed, and samples will be collected at the following time points: 90 min prior to drug administration apart from urine PK samples which should be obtained 15 min prior to drug administration and between the intervals 0-8, 8-16, 16-24 and 24-48 hours post dose. The PK parameters which will be analysed are as follows but not limited to the following:
Primary PK parameters: Cmax, AUC0-t, AUC0-Inf
Secondary PK parameters: Time Corresponding to Cmax (Tmax), Tlast, Terminal half-life ( T1/2), Terminal elimination rate ( ?z), Apparent clearance (CL) and Apparent volume of distribution (Vz/F).

Eligibility
Key inclusion criteria
1. Male or female between 18 and 45 years of age (inclusive). Females of child bearing potential using oral contraceptives who agree to use two reliable methods of contraception (e.g., double-barrier condom plus diaphragm, condom or diaphragm along with stable dose of oral contraception) throughout the study perilod and until 3 months after receiving study drug. Women of childbearing potential will require compulsory pregnancy testing. A negative serum pregnancy test is required at screening, and a negative urine pregnancy test is required at Day -1 if Day -1 > 7 days from screening.
2. Healthy with no clinically significant medical problems.
3. BMI between 18 and 30 kg/m2 with weight between 45 and 100 kg (both inclusive) at Day -1.
4. No history of alcohol or drug abuse (Barbiturates, Benzodiazepines, Cocaine, Methadone, Amphetamines, Methamphetamines, Opiates, Phencyclidine, Tetrahydrocannabinol (cannabis), Tricyclic Antidepressants). Subjects should be enrolled only after passing the urine drug screen.
5. Non-smokers or light smokers (less than 5 cigarettes per week) by history and planned during study.
6. No history of significant allergies such as urticaria, angioedema or anaphylaxis.
7. No prior exposure to PLG0206.
8. Willing and able to sign written, informed consent.
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Any significant past or current cardiac, pulmonary, hepatic, renal or other medical condition which in the opinion of the investigator would make participation of the subject in this study medically unsafe or compromise the accuracy of assessment of the study.
2. Subjects who have safety laboratory values outside the local laboratory reference ranges considered clinically significant as per Principal Investigator’s (PI’s) discretion (can be repeated once at screening as per PI’s discretion).
3. Current use of any prescription medications, except oral contraceptives.
4. Use of non-prescription medications including vitamins, antacids, herbal and
dietary supplements including St John’s Wort within 7 days (or 14 days if the
drug is a potential enzyme inducer) or 5 half-lives whichever is longer, prior to
the first dose of study medication.
5. Subjects with past medical history of malignancy except basal cell or squamous cell carcinoma of the skin who have had curative surgical treatment and at least 6 months has elapsed since the procedure.
6. A value outside the specified range of 90 mm Hg – 140 mm Hg for systolic blood pressure (BP) and 50 mm Hg –90 mm Hg for diastolic BP (both inclusive) at screening (can be repeated once at screening as per PI’s discretion).
7. History of clinically significant acute bacterial, viral, or fungal systemic infections in the last 4 weeks prior to screening.
8. Clinical or laboratory evidence of an active infection at the time of screening.
9. Serological evidence of human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or antihepatitis C virus (Anti-HCV) at screening.
10. QTcF > 450 msec
11. Vaccination within 3 months of screening for the study or requiring vaccination during the study or within 3 months after completion of the study.
12. Females who are pregnant or nursing.
13. Participation in any other investigational medicinal product study within 8
weeks or 5 half-lives of the study drug, whichever is longer, prior to screening.
14. Unable or unwilling to comply with the protocol requirements for study visits and procedures.
15. Subjects who do not have good venous access for infusion of study drug or for blood sampling.
16. History of hypersensitivity to diphenhydramine or paracetamol.
17. History of any other hypersensitivity reaction as deemed clinically significant by the Principal Investigator.
18. Any significant clinical finding or history that in the opinion of the investigator could affect study results or be associated with higher risk for the subject.
19. Blood donation during the period of study from screening visit to termination visit at Day 7.
20. Any condition that may prevent the patient to receive the PLG0206 or may interfere with the PK of PLG0206.

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

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
1/12/2018
Actual
25/11/2019
Date of last participant enrolment
Anticipated
5/06/2020
Actual
10/11/2020
Date of last data collection
Anticipated
18/06/2020
Actual
24/11/2020
Sample size
Target
56
Accrual to date
Final
44
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 11944 0
CMAX Clinical Research Pty Ltd - Adelaide
Recruitment postcode(s) [1] 24090 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 300364 0
Commercial sector/Industry
Name [1] 300364 0
Peptilogics, Inc.
Country [1] 300364 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Peptilogics, Inc.
Address
2730 Sidney Street
Suite 300
Pittsburgh, PA 15203
United States of America
Country
United States of America
Secondary sponsor category [1] 299808 0
None
Name [1] 299808 0
Address [1] 299808 0
Country [1] 299808 0
Other collaborator category [1] 280319 0
Commercial sector/Industry
Name [1] 280319 0
Novotech (Australia) Pty Limited
Address [1] 280319 0
Level 3, 235 Pyrmont Street, Pyrmont NSW 2009
Country [1] 280319 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301176 0
Bellberry Human Research Ethics Committee D
Ethics committee address [1] 301176 0
129 Glen Osmond Road, Eastwood, SA, 5063
Ethics committee country [1] 301176 0
Australia
Date submitted for ethics approval [1] 301176 0
25/07/2018
Approval date [1] 301176 0
12/09/2018
Ethics approval number [1] 301176 0

Summary
Brief summary
This is a single centre, first in human, SAD, randomized, double-blind, placebo-controlled clinical trial of PLG0206, an engineered cationic antibiotic peptide (eCAP) or matching placebo, administered to healthy subjects. There will be a total of up to 56 subjects, divided into up to 7 sequential groups.
Subjects who are eligible for enrolment after screening testing will return to the study centre on Day -2 for confinement at the study site. Subjects will be discharged on Day 3 (48 hours post dose), after recording vital signs and the 12-lead ECG and obtaining safety bloods (haematology and chemistries). Serial blood samples for PK evaluations will be obtained. For each subject, the total duration of the study will be 1 week after dosing.
A Safety Review Committee (SRC) comprising of relevant site investigators, the medical monitor and sponsor representative will oversee safety, Cohort evaluation and dose-escalation for the study. A formal charter will be established to include the rules, meeting frequency and scope of responsibilities of the SRC for the conduct of the SRC.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 86106 0
Dr Angela Molga
Address 86106 0
CMAX Clinical Research, Level 5, 18a North Terrace, Adelaide, SA 5000
Country 86106 0
Australia
Phone 86106 0
+61 8 7088 7900
Fax 86106 0
Email 86106 0
[email protected]
Contact person for public queries
Name 86107 0
Dr Jonathan Steckbeck, PhD
Address 86107 0
Chief Executive Officer and Founder, Peptilogics, Inc., 2730 Sidney Street, Suite 300, Pittsburgh, PA 15203, United States of America
Country 86107 0
United States of America
Phone 86107 0
+1 408 689 4588
Fax 86107 0
Email 86107 0
[email protected]
Contact person for scientific queries
Name 86108 0
Dr Jonathan Steckbeck, PhD
Address 86108 0
Chief Executive Officer and Founder, Peptilogics, Inc., 2730 Sidney Street, Suite 300, Pittsburgh, PA 15203, United States of America
Country 86108 0
United States of America
Phone 86108 0
+1 408 689 4588
Fax 86108 0
Email 86108 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
SourceTitleYear of PublicationDOI
Dimensions AIHow to Combat Gram-Negative Bacteria Using Antimicrobial Peptides: A Challenge or an Unattainable Goal?2021https://doi.org/10.3390/antibiotics10121499
N.B. These documents automatically identified may not have been verified by the study sponsor.