A Single Ascending Doses (SAD) of a Novel Engineered Cationic Peptide PLG0206 in Healthy Subjects.
Safety and Tolerability of Single Ascending Doses (SAD) of a Novel Engineered Cationic Peptide PLG0206 in Healthy Subjects
Peptilogics, Inc.
56 participants
Nov 25, 2019
Interventional
Conditions
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.
Eligibility
Inclusion Criteria8
- 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.
- Healthy with no clinically significant medical problems.
- BMI between 18 and 30 kg/m2 with weight between 45 and 100 kg (both inclusive) at Day -1.
- 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.
- Non-smokers or light smokers (less than 5 cigarettes per week) by history and planned during study.
- No history of significant allergies such as urticaria, angioedema or anaphylaxis.
- No prior exposure to PLG0206.
- Willing and able to sign written, informed consent.
Exclusion Criteria24
- 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.
- 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).
- Current use of any prescription medications, except oral contraceptives.
- 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.
- 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.
- 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).
- History of clinically significant acute bacterial, viral, or fungal systemic infections in the last 4 weeks prior to screening.
- Clinical or laboratory evidence of an active infection at the time of screening.
- Serological evidence of human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or antihepatitis C virus (Anti-HCV) at screening.
- QTcF > 450 msec
- Vaccination within 3 months of screening for the study or requiring vaccination during the study or within 3 months after completion of the study.
- Females who are pregnant or nursing.
- 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.
- Unable or unwilling to comply with the protocol requirements for study visits and procedures.
- Subjects who do not have good venous access for infusion of study drug or for blood sampling.
- History of hypersensitivity to diphenhydramine or paracetamol.
- History of any other hypersensitivity reaction as deemed clinically significant by the Principal Investigator.
- 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.
- Blood donation during the period of study from screening visit to termination visit at Day 7.
- Any condition that may prevent the patient to receive the PLG0206 or may interfere with the PK of PLG0206.
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Interventions
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.
Locations(1)
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ACTRN12618001920280