A First in Human Study of the Safety, Tolerability and Pharmacokinetics of PRV-002 in Healthy Volunteers

NCT05033444 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: PRV-002-AU-01PRV-002-AUU-01
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the safety, tolerability, and pharmacokinetics of different dose levels of PRV-002 in Health Volunteers

Conditions

Traumatic Brain Injury (TBI)

Keywords

Safety; Tolerability; Pharmacokinetics; PRV-002

Outcome Measures

Primary Outcomes (43)

• Safety endpoint - Evaluation of the Incidence, severity, and relationship of AEs/SAEs (or ADEs/SADEs) (including withdrawals due to AEs (or ADEs)).

  AEs/SAEs (or ADEs/SADEs) to be recorded as written descriptions on case report forms

  Baseline pre-intervention (Day -28 to Day -2 and Day -1); during intervention and immediately afterwards (Day 1); Day 2; and through Day 5.

• Safety endpoint - Change from baseline in physical examination findings (Full)

  Full physical exam including general appearance, head, ears, eyes, nose and throat, neck (including thyroid and lymph nodes), respiratory system, cardiovascular system, gastrointestinal system, renal system, neurological condition, musculoskeletal system, skin and any other focused assessments suggested by the presence of specific symptoms and measured by written descriptions.

  Baseline pre-intervention Day -28 to -2.

• Safety endpoint - Change from baseline in physical examination findings (symptom directed)

  Symptom-directed physical examination (focused assessments suggested by the presence of specific symptoms) will be performed if clinically indicated, as determined by the Investigator. The pre-dose physical examination assessment should be performed on the scheduled day, at any time prior to dosing. All other physical examinations will be performed within ± 1 hour of the nominated timepoint. Measured by written descriptions.

  Baseline pre-intervention Day -1 and and Day 1; Day 2

• Safety endpoint - Change from baseline in vital signs (including changes from baseline in SpO2).

  SpO2 measured as percent of oxygen (%)

  Baseline pre-intervention between Day -28 to -2; Day 1 pre-intervention; Day 1 at 0.5hr, 1hr, 2hr, 6hr; Day 2 at 24 hr post intervention; Day 5

• Safety endpoint - Change from baseline in vital signs (including changes from baseline in blood pressure).

  Blood pressure measured for systolic and diastolic pressure as mm of mercury.

  Baseline pre-intervention between Day -28 to -2; Day 1 pre-intervention; Day 1 at 0.5hr, 1hr, 2hr, 6hr; Day 2 at 24 hr post intervention; Day 5

• Safety endpoint - Change from baseline in vital signs (including changes from baseline in heart rate).

  Heart rate measured as beats per minute (BPM)

  Baseline pre-intervention between Day -28 to -2; Day 1 pre-intervention; Day 1 at 0.5hr, 1hr, 2hr, 6hr; Day 2 at 24 hr post intervention; Day 5

• Safety endpoint - Change from baseline in vital signs (including changes from baseline in respiration rate).

  Respiration rate measured as breaths per minute

  Baseline pre-intervention between Day -28 to -2; Day 1 pre-intervention; Day 1 at 0.5hr, 1hr, 2hr, 6hr; Day 2 at 24 hr post intervention; Day 5

• Safety endpoint - Change from baseline in vital signs (including changes from baseline in body temperature).

  Body temperature measured as degrees Celsius (C)

  Baseline pre-intervention between Day -28 to -2; Day 1 pre-intervention; Day 1 at 0.5hr, 1hr, 2hr, 6hr; Day 2 at 24 hr post intervention; Day 5

• Safety endpoint - Changes from baseline in lung spirometry.

  Lung spirometry measured as the ratio of forced expiratory value (FEV1)/ forced vital capacity (FVC) and reported as percentage (%)

  Baseline pre-intervention between Day -28 to -2; Day 1 pre-intervention; Day 1 at 0.25hr, 1hr, 10hr; Day 2 at 24 hr post intervention; Day 5

• Safety endpoint - Change from baseline in ECG parameters of heart rate

  Heart ratel measured beats per minute (BPM)

  Baseline pre-intervention; during intervention and immediately afterwards (Day 1); Day 2; and through Day 5.

• Safety endpoint - Change from baseline in ECG parameters of PR interval, QRS interval, and QT interval

  PR interval, QRS interval, and QT interval as measured in milliseconds (ms)

  Baseline pre-intervention between Day -28 to -2; Day -1; Day 1 pre-intervention; Day 1 at 0.5hr, 2hr, 6hr; 12hr; Day 2 at 24 hr post intervention; Day 5

• Safety endpoint - Change from baseline in hematocrit values

  Hematocrit measured as the percentage of red blood cells in whole blood (%)

  Baseline pre-intervention between Day -28 to -2; Day -1; Day 1 at 6hr; Day 2 at 24 hr post intervention; Day 5

• Safety endpoint - Change from baseline in hemoglobin values

  Hemoglobin measured as the amount of hemoglobin in whole blood measured as grams per deciliter (g/dL)

  Baseline pre-intervention between Day -28 to -2; Day -1; Day 1 at 6hr; Day 2 at 24 hr post intervention; Day 5

• Safety endpoint - Change from baseline in Red Blood Cell (RBC) indices

  RBC measured as the number of million RBCs per microliter (mcL) of blood

  Baseline pre-intervention between Day -28 to -2; Day -1; Day 1 at 6hr; Day 2 at 24 hr post intervention; Day 5

• Safety endpoint - Change from baseline in Thrombocyte Count (Platelets); White Blood Cells (WBC); Basophils; Eosinophils; Lymphocytes; Monocytes; and Neutrophils.

  Platelets measured as the number of cells per microliter (mcL) of blood

  Baseline pre-intervention between Day -28 to -2; Day -1; Day 1 at 6hr; Day 2 at 24 hr post intervention; Day 5

• Safety endpoint - Change from baseline in the blood hormone level of Dehydroepiandrosterone-sulfate (DHEAS)

  Dehydroepiandrosterone sulfate (DHEAS) measured as the number of micrograms per deciliter (µg/dL) of blood

  Baseline pre-intervention Day -1; Day 1 at 6hr; Day 2 at 24 hr; Day 5

• Safety endpoint - Change from baseline in the blood hormone level of dihydrotestosterone (DHT)

  Dihydrotestosterone (DHT) measured as the number of nano moles per liter (nmol/L) of blood

  Baseline pre-intervention Day -1; Day 1 at 6hr; Day 2 at 24 hr; Day 5

• Safety endpoint - Change from baseline in the blood hormone level of luteinizing hormone (LH)

  Luteinizing hormone (LH) measured as the number of International units per liter (IU/L)

  Baseline pre-intervention Days -28 to -2

• Safety endpoint - Change from baseline in the blood hormone level of dehydroepiandrosterone sulfate (DHEAS)

  Dehydroepiandrosterone sulfate (DHEAS) measured as the number of micrograms per deciliter (mcg/dL)

  Baseline pre-intervention Day -1; Day 1 at 6hr; Day 2 at 24 hr; Day 5

• Safety endpoint - Change from baseline in the blood hormone level of thyroid stimulating hormone (TSH)

  Thyroid stimulating hormone (TSH) measured as the number of milli-international units per liter (mIU/L)

  Baseline pre-intervention Day -1; Day 1 at 6hr; Day 2 at 24 hr; Day 5

• Safety endpoint - For postmenopausal women only, change from baseline in the blood hormone level of follicle-stimulating hormone (FSH) and human chorionic gonadotropin (hGH)

  Follicle-stimulating hormone (FSH) and human chorionic gonadotropin (hGH) measured as the number of milli-international units per milliliter (mIU/mL)

  Baseline pre-intervention Day -1; Day 1 at 6hr; Day 2 at 24 hr; Day 5

• Safety endpoint - Change from baseline in the blood hormone level of free thyroxine (FT4), testosterone, and dihydrotestosterone (DHT)

  Free thyroxine (FT4), testosterone, and dihydrotestosterone (DHT) measured as the number of nanograms per deciliter (ng/dL)

  Baseline pre-intervention Day -1; Day 1 at 6hr; Day 2 at 24 hr; Day 5

• Safety endpoint - Change from baseline in the blood hormone level of progesterone

  Progesterone measured as the number of nanograms per miiliiliter (ng/mL)

  Baseline pre-intervention Day -1; Day 1 at 6hr; Day 2 at 24 hr; Day 5

• Safety endpoint - Change from baseline in the blood hormone level of estradiol (E2) and free trilodothyronine (FT3)

  Estradiol (E2) and free trilodothyronine (FT3) measured as the number of picograms per milliliter (pg/mL)

  Baseline pre-intervention Day -1; Day 1 at 6hr; Day 2 at 24 hr; Day 5

• Safety endpoint Change in baseline in clotting factors Partial thromboplastin time (aPTT) and Prothrombin time (PT)

  Partial thromboplastin time (aPTT) and Prothrombin time (PT) measured as time to clot in seconds (sec)

  Baseline pre-intervention between Day -28 to -2; Day -1; Day 1 at 6hr; Day 2 at 24 hr post intervention; Day 5

• Safety endpoint - Change from baseline in the clotting factor Fibrinogen

  Fibrinogen measured as the number of milligrams per deciliter (mg/dL)

  Baseline pre-intervention between Day -28 to -2; Day -1; Day 1 at 6hr; Day 2 at 24 hr post intervention; Day 5

• Safety endpoint - Change from baseline in the clotting factor International Normalized Ratio (INR)

  International Normalized Ratio (INR) measured as the ratio of patient PT/control PT

  Baseline pre-intervention between Day -28 to -2; Day -1; Day 1 at 6hr; Day 2 at 24 hr post intervention; Day 5

• Safety endpoint - Change from baseline in urinalysis parameters bilirubin, blood, glucose, nitrites, protein, and urobilinogen

  Bilirubin, blood, glucose, nitrites, protein, and urobilinogen measured as the number of milligrams per deciliter (mg/dL)

  Post dose Day 1 at 0 to 6hr, 6 to 12hr, and 12 to 24hr

• Safety endpoint - Change from baseline in urinalysis parameter ketones

  Ketones measured as the number of millimoles per liter (mmol/L)

  Post dose Day 1 at 0 to 6hr, 6 to 12hr, and 12 to 24hr

• Safety endpoint - Change from baseline in urinalysis parameter leukocyte esterase

  Leukocyte esterase measured as negative or positive; number of WBCs per high power field

  Post dose Day 1 at 0 to 6hr, 6 to 12hr, and 12 to 24hr

• Safety endpoint - Change from baseline in urinalysis parameter pH

  pH measured as pH units

  Post dose Day 1 at 0 to 6hr, 6 to 12hr, and 12 to 24hr

• Safety endpoint - Change from baseline in urinalysis parameter specific gravity

  Specific gravity measured as specific gravity units as a ratio of density of urine/density of water

  Post dose Day 1 at 0 to 6hr, 6 to 12hr, and 12 to 24hr

• Safety endpoint - Change from baseline in serum chemistry parameters globulin, protein, and albumin

  Globulin, protein, and albumin measured as grams per deciliter (g/dL)

  Baseline pre-intervention Days -28 to -2; Day -1; Day 1 at 6hr; Day 2 at 24hr; Day 5.

• Safety endpoint - Change from baseline in serum chemistry parameter alkaline phosphatase

  Alkaline phosphatase measured as International units per liter (IU/L)

  Baseline pre-intervention Days -28 to -2; Day -1; Day 1 at 6hr; Day 2 at 24hr; Day 5.

• Safety endpoint - Change from baseline in serum chemistry parameters bicarbonate, chloride, sodium, and magnesium

  Bicarbonate, chloride, sodium, and magnesium measured as milliequivalents per liter (mEq/L)

  Baseline pre-intervention Days -28 to -2; Day -1; Day 1 at 6hr; Day 2 at 24hr; Day 5.

• Safety endpoint - Change from baseline in serum calcium, glucose, phosphate, creatinine, urea, uric acid, bilirubin (conjugated and unconjugated), high density lipoproteins, low density lipoproteins, total bilirubin, total cholesterol

  Calcium, glucose, phosphate, creatinine, urea, uric acid, bilirubin (conjugated and unconjugated), high density lipoproteins, low density lipoproteins, total bilirubin, total cholesterol, triglycerides measured as milligrams per deciliter (mg/dL)

  Baseline pre-intervention Days -28 to -2; Day -1; Day 1 at 6hr; Day 2 at 24hr; Day 5.

• Safety endpoint - Change from baseline in serum chemistry parameters potassium

  Potassium measured as millimoles per liter (mmol/L)

  Baseline pre-intervention Days -28 to -2; Day -1; Day 1 at 6hr; Day 2 at 24hr; Day 5.

• Safety endpoint - Change from baseline in serum chemistry parameters lipase, creatine kinase, lactate dehydrogenase, aspartate aminotransferase, gamma-glutamyl transferase, alanine aminotransferase, and amylase

  Lipase, creatine kinase, lactate dehydrogenase, aspartate aminotransferase, gamma-glutamyl transferase, alanine aminotransferase, and amylase measured as Units per liter (U/L)

  Baseline pre-intervention Days -28 to -2; Day -1; Day 1 at 6hr; Day 2 at 24hr; Day 5.

• Safety endpoint - Change from baseline in virology parameters HIV-1/-2; HBsAg; HCV; SARS-COV-2

  HIV-1/-2; HBsAg; HCV; SARS-COV-2 test results measured as negative or positive

  Baseline pre-intervention Day -28 to -2

• Safety endpoint - Change from baseline in drug screen findings for alcohol

  Alcohol test results measured as percentage (%)

  Baseline pre-intervention Day -28 to -2; Day -1

• Safety endpoint - Change from baseline in urine drug screen findings for amphetamines, barbiturates, benzodiazepines, cocaine, cotinine, methamphetamines, opiates, phencyclidine, THC, and tricyclic antidepressants

  Urine amphetamines, barbiturates, benzodiazepines, cocaine, cotinine, methamphetamines, opiates, phencyclidine, THC, and tricyclic antidepressants test results measured as nanograms per milliliter (ng/mL)

  Baseline pre-intervention Day -28 to -2; Day -1

• Safety endpoint - Change from baseline for pregnancy test for serum hCG and urine hCG

  Serum hCG and Urine hCG levels measured in milli-international units per liter (mIU/L)

  Serum pregnancy test Days -28 to -2 and on Day 5; Urine pregnancy test Day -1

• Safety endpoint - Change from baseline for confirmation of postmenopausal status test for FSH

  FSH levels measured in milli-international units per liter (mIU/L)

  Baseline pre-intervention on Days -28 to -2

Secondary Outcomes (10)

• Plasma pharmacokinetics - Cmax

  Samples collected on Day 1 pre-dose and at 0.25, 0.5, 1, 1.5, 2. 3, 4, 6, 10, 12hrs; Day 2 at 24 hr; Day 5.

• Plasma pharmacokinetics - Tmax

  Samples collected on Day 1 pre-dose and at 0.25, 0.5, 1, 1.5, 2. 3, 4, 6, 10, 12hrs; Day 2 at 24 hr; Day 5.

• Plasma pharmacokinetics - area under the curve

  Samples collected on Day 1 pre-dose and at 0.25, 0.5, 1, 1.5, 2. 3, 4, 6, 10, 12hrs; Day 2 at 24 hr; Day 5.

• Plasma pharmacokinetics - area under the concentration-time curve

  Samples collected on Day 1 pre-dose and at 0.25, 0.5, 1, 1.5, 2. 3, 4, 6, 10, 12hrs; Day 2 at 24 hr; Day 5.

• Plasma pharmacokinetics - apparent terminal elimination half-life t1/2)

  Samples collected on Day 1 pre-dose and at 0.25, 0.5, 1, 1.5, 2. 3, 4, 6, 10, 12hrs; Day 2 at 24 hr; Day 5.

Other Outcomes (2)

• Exploratory endpoints - PRV-002 metabolites in plasma

  Samples collected on Day 1, 2, and 5

• Nasal Spray Attributes Questionnaire

  Nasal spray attributes questionare completed on Day 1 at 15 minutes post dose

Study Arms (2)

PRV-002

EXPERIMENTAL

PRV-002 active formulation

Drug: PRV-002

Placebo comparator

PLACEBO COMPARATOR

Placebo used is hydroxypropyl beta cyclodextrin (HPβCD)

Drug: Placebo

Interventions

PRV-002 DRUG

SAD portion: Eligible participants will be randomized to receive a single ascending dose of PRV-002 on study Day 1. Dose escalation will be conducted in a total of 3 cohorts. Within each cohort, 6 participants will be randomized to receive a single dose of PRV-002. The starting dose, dose increments and dose range to be evaluated are based on available nonclinical data. PRV-002 dose levels in the range of 0.133 to 0.533 mg/kg (based on a 60kg participant) will be investigated. MAD portion: Eligible participants will be randomized to receive a multiple (one dose per day for 5 consecutive days). Dose escalation will be conducted in a total of 2 cohorts. Within each cohort, 6 participants will be randomized to receive of PRV-002. The starting dose, dose increments and dose range to be evaluated are based on available nonclinical data. PRV-002 dose levels in the range of 0.133 to 0.266 mg/kg (based on a 60kg participant) will be investigated.

Also known as: Experimental drug

PRV-002

Placebo DRUG

Placebo used is hydroxypropyl beta cyclodextrin (HPβCD)

Also known as: Placebo control

Placebo comparator

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects.
• Adult males and females, 18 to 55 years of age (inclusive) at screening.
• Body mass index (BMI) ≥ 18.0 and ≤ 30.0 kg/m2, with a body weight (to 1 decimal place) ≥ 50 kg at screening.
• Be non-smokers (including tobacco, e-cigarettes and marijuana) for at least 3 months prior to first study drug administration.
• Have a negative test for cotinine at the screening visit and at check-in on Day -1.
• Medically healthy without clinically significant abnormalities (in the opinion of the Investigator) at the screening visit in the Schedules of
• Assessments (SoA), including:
• Physical examination without any clinically significant findings
• Systolic BP in the range of 90 to 160 mmHg (inclusive) and diastolic BP in the range of 50 to 95 mmHg (inclusive) after 5 minutes in supine position
• Heart rate in the range of 40 to 100 bpm (inclusive) after 5 minutes rest in supine position
• Body temperature (tympanic or oral) in the range 35.5°C to 37.7°C (inclusive)
• No clinically significant findings in serum chemistry, haematology, coagulation, and urinalysis tests
• Triplicate 12-lead ECG (taken after the volunteer has been supine for at least 5 minutes) with a QTcF ≤ 450 msec for males and ≤ 470 msec for females and no clinically significant abnormalities
• Pulmonary assessments must be within the normal range (forced expiratory volume in 1 second \[FEV1\], forced vital capacity \[FVC\] and FEV1/FVC ratio ≥ 80% of normal values; f forced expiratory flow over the middle one half of the FVC \[FEF25-75%\] \> 75% of predicted)
• Oxygen saturation (SpO2) monitor ≥ 95%.

You may not qualify if:

• History or presence of significant cardiovascular disease
• History or presence of significant pulmonary disease
• History or presence of significant hepatic disease
• History or presence of significant renal disease
• History or presence of significant haematological disease
• History or presence of significant gastrointestinal disease
• History or presence of significant disease
• History or presence of significant endocrine disease
• History or presence of significant immunologic disease
• History or presence of significant dermatologic disease
• History or presence of significant or neurological disease
• No major surgery within the past 3 months determined by the PI to be clinically significant.
• Absence of any acute illness.
• Current infection that requires systemically absorbed antibiotic.
• Current infection that requires systemically absorbed antifungal.

Sponsors & Collaborators

• Odyssey Group International, Inc.: lead
• Avance Clinical Pty Ltd.: collaborator

Study Sites (1)

Nucleus Network Pty Ltd,

Melbourne, Victoria, 3004, Australia

Location

Related Links

• Related Info

MeSH Terms

Conditions

Brain Injuries, Traumatic

Interventions

Drugs, Investigational

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations

Study Officials

• Philip Ryan, Dr.

  Nucleus Network

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants will be randomized in a 3:1 ratio of PRV-002 and Placebo. The following controls will be employed to maintain the double-blind status of the study: Nasal Spray containing active drug and placebo will be indistinguishable in appearance Randomization list will be provided to the study center pharmacist for dispensing purposes and kept in the pharmacy, accessible to the pharmacist and authorized personnel only PK results for the SRC between cohorts will be presented in a blinded fashion.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind, placebo-controlled, single ascending dose, multi-cohort study.

Study Record Dates

• First Submitted: August 12, 2021
• First Posted: September 2, 2021
• Study Start: February 9, 2022
• Primary Completion: October 1, 2022
• Study Completion: September 13, 2024
• Last Updated: November 4, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)