Safety, Tolerability, and Pharmacokinetics of SPL84 in Healthy Volunteers

NCT06217952 | Completed Phase 1

• 1 other identifier: SPL84-CL-001-P
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (12)

• 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 Outcomes (6)

• 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.

Study Arms (2)

SPL84

ACTIVE COMPARATOR

Drug: SPL84

Placebo

PLACEBO COMPARATOR

Other: Placebo

Interventions

SPL84 DRUG

SPL84 solution for nebulization

SPL84

Placebo OTHER

Placebo solution for nebulization

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• SpliSense Ltd.: lead

Study Sites (1)

Hadassah Ein Kerem Hospital Clinical Research Center

Jerusalem, Israel

Location

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2023
• First Posted: January 23, 2024
• Study Start: February 5, 2023
• Primary Completion: August 6, 2023
• Study Completion: August 6, 2023
• Last Updated: January 23, 2024

Record last verified: 2024-01

Locations

IL (1)