Safety, Tolerability, and Pharmacokinetics of SPL84 in Healthy Volunteers

A Phase 1, Randomized, Placebo-Controlled, Double Blind Single Ascending Dose Study in Healthy Volunteers to Evaluate the Safety, Tolerability, and Pharmacokinetics of SPL84

This Phase 1 study evaluated the safety, tolerability, and pharmacokinetics of SPL84 single ascending doses (SAD) in healthy volunteers (HV)

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: SPL84; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Israel
  • Jerusalem, Israel
    • Hadassah Ein Kerem Hospital Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria:

• Male adults 18 to 50 years old
• Considered healthy based on medical history, physical examination, 12-lead ECG and clinical laboratory results
• Body Mass Index (BMI) 19.0-30.0 kg/m2
• Subjects who have no difficulties in receiving drugs by inhalation

Key Exclusion Criteria:

• A major surgical procedure or significant traumatic injury within 28 days prior to study intervention administration
• Recent diagnosis of lung disease (< 12 weeks from planned enrollment)
• Any acute illness (e.g. acute infection) within 48 hours prior to the study intervention administration, which is considered of clinical significance by the Investigator.
• Chronic respiratory disease including but not limited to obstructive airway disease such as asthma or chronic obstructive pulmonary disease (COPD); restrictive disease such as idiopathic pulmonary fibrosis (IPF); or pulmonary vascular disease such as pulmonary arterial hypertension (PAH).
• History of adverse reactions during aerosol delivery of any medicinal product.
• Total body weight ≤50 kg at screening.
• Abnormal forced expiratory volume at one second (FEV1) at screening.
• Oxygen saturation ≤95% at screening.
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), alkaline phosphatase (ALP) and bilirubin (total and direct) above upper limit of normal (ULN) at screening and clinically significant
• Supine systolic blood pressure <90 or >140 mmHg, supine diastolic blood pressure <50 or >90 mmHg, heart rate <45 or >100 beats per minute (bpm), or elevated body temperature (>38ºC) at screening
• Clinically significant ECG abnormalities at screening
• Positive for SARS-CoV-19 at screening or Day -1 (baseline).
• Positive serology tests for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) antibody at screening.
• Positive urine drug, tobacco, and breath alcohol test result at screening or Day -1 (baseline).
• Use of any prescription or over-the-counter (OTC) medications, including vitamins and herbal or dietary supplements within 14 days prior to dosing.
• Subjects who have received any vaccines within 4 weeks prior to study intervention administration.
• History or current drug/alcohol abuse (excluding use of medicinal cannabis for pain management).
• History of smoking or vaping within 180 days (6 months) of screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Placebo solution for nebulization
Active Comparator: SPL84	Drug: SPL84; SPL84 solution for nebulization

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability of SPL84 as evaluated by number of subjects with at least one treatment-related adverse event (AE) or serious adverse event (SAEs)	Incidence, nature, and severity of AEs and SAEs	Day 1 through Day 31
Safety and Tolerability of SPL84 as assessed by number of participants with abnormal heart rate		Day 1 through Day 31
Safety and Tolerability of SPL84 as assessed by number of participants with abnormal respiratory rate		Day 1 through Day 31
Safety and Tolerability of SPL84 as assessed by number of participants with abnormal systolic and diastolic blood pressure		Day 1 through Day 31
Safety and Tolerability of SPL84 as assessed by number of participants with abnormal oximetry		Day 1 through Day 31
Safety and Tolerability of SPL84 as assessed by number of participants with abnormal temperature		Day 1 through Day 31
Safety and Tolerability of SPL84 as assessed by number of participants with abnormal hematology lab test results		Day 1 through Day 31
Safety and Tolerability of SPL84 as assessed by number of participants with abnormal biochemistry lab test results		Day 1 through Day 31
Safety and Tolerability of SPL84 as assessed by number of participants with abnormal urinalysis lab test results		Day 1 through Day 31
Safety and Tolerability of SPL84 as assessed by number of participants with abnormal electrocardiogram (ECG) parameters	using an ECG machine that automatically calculates heart rate and measure PR, QRS, QT, and QTc intervals	Day 1 through Day 31
Safety and Tolerability of SPL84 as assessed by number of participants with abnormal physical examination findings	Complete physical examinations include general appearance, head, ears, eyes, nose, throat, dentition, thyroid, chest (heart, lungs), abdomen, skin, neurological, extremities, back, neck, musculoskeletal, and lymph nodes.	Day 1 through Day 31
Safety and Tolerability of SPL84 as assessed by number of participants with abnormal Pulmonary function tests results	Pulmonary function tests will be performed according to the ATS/ERS and FEV1, FVC, and FEF25-75 will be measured	Day 1 through Day 31

Secondary Outcome Measures

Outcome Measure	Time Frame
Characterization of PK of SPL84: maximum serum concentration (Cmax)	Predose and 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours postdose, Day 7 and Day 31.
Characterization of PK of SPL84: Time to Cmax (Tmax)	Predose and 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours postdose, Day 7 and Day 31.
Characterization of PK of SPL84: terminal elimination half-life (t1/2)	Predose and 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours postdose, Day 7 and Day 31.
Characterization of PK of SPL84: Area under the curve to the final sample (AUC0-t)	Predose and 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours postdose, Day 7 and Day 31.
Characterization of PK of SPL84: Area under the curve to infinity (AUC0-∞)	Predose and 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours postdose, Day 7 and Day 31.
Characterization of PK of SPL84: Apparent clearance (CL/F)	Predose and 1, 2, 4, 6, 8, 12, 24, 48 and 72 hours postdose, Day 7 and Day 31.

Collaborators and Investigators

• Sponsor: SpliSense Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2023
• Primary Completion (Actual): August 6, 2023
• Study Completion (Actual): August 6, 2023

Study Registration Dates

• First Submitted: February 7, 2023
• First Submitted That Met QC Criteria: January 11, 2024
• First Posted (Estimated): January 23, 2024

Study Record Updates

• Last Update Posted (Estimated): January 23, 2024
• Last Update Submitted That Met QC Criteria: January 11, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Cystic Fibrosis
• Other Study ID Numbers: SPL84-CL-001-P

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No