Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of SPL84 in Patients With Cystic Fibrosis

NCT06429176 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: SPL84-0022024-511184-28
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 3

Brief Summary

The goal of this clinical trial is to learn if drug SPL84 is safe for adult patients with cystic fibrosis (CF). It will also learn if the drug works to treat works to treat CF with a specific mutation (3849 +10kb C--\>T). The purpose of this research study is to test the safety and effectiveness of multiple doses of the study drug, SPL84. Researchers will compare drug SPL84 to a placebo (a look-alike substance that contains no drug) to see if drug SPL84 is safe and if it works to treat CF. In cohorts 1-3, SPL84 will be tested as a monotherapy, and in Cohort 4, SPL84 will be tested in participants who are already stable on CFTR modulator therapy. Participants will take drug SPL84 or a placebo by inhalation every week for 9 weeks (cohorts 1-3) or 12 weeks (cohort 4) and visit the clinic approximately weekly for checkups and tests.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (13)

• 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 87 (Cohort 1-3) or 108 (Cohort 4)

• Safety and Tolerability of SPL84 as assessed by number of participants with abnormal heart rate

  Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)

• Safety and Tolerability of SPL84 as assessed by number of participants with abnormal respiratory rate

  Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)

• Safety and Tolerability of SPL84 as assessed by number of participants with abnormal systolic and diastolic blood pressure

  Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)

• Safety and Tolerability of SPL84 as assessed by number of participants with abnormal oximetry

  Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)

• Safety and Tolerability of SPL84 as assessed by number of participants with abnormal temperature

  Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)

• Safety and Tolerability of SPL84 as assessed by number of participants with abnormal hematology lab test results

  Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)

• Safety and Tolerability of SPL84 as assessed by number of participants with abnormal biochemistry lab test results

  Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)

• Safety and Tolerability of SPL84 as assessed by number of participants with abnormal urinalysis lab test results

  Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)

• 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 87 (Cohort 1-3) or 108 (Cohort 4)

• 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, thyroid, chest (heart, lungs), abdomen, skin, neurological, extremities, back, neck, musculoskeletal, and lymph nodes.

  Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)

• 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 American Thoracic Society (ATS)/European Respiratory Society (ERS) and forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and forced mid-expiratory flow (FEF25-75) will be measured

  Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)

• Safety and Tolerability of SPL84 as assessed by number of participants with abnormal immunogenicity results

  assessment of anti-SPL84 antibodies will be performed both in serum and sputum

  Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)

Secondary Outcomes (14)

• Characterization of pharmacokinetics (PK) of SPL84: maximum serum concentration (Cmax)

  Cohort 1-3: Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87; Cohort 4: Predose and 1, 3, and 6 hours post dose on Days 1 and 78

• Characterization of PK of SPL84: Time to Cmax (Tmax)

  Cohort 1-3: Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87; Cohort 4: Predose and 1, 3, and 6 hours post dose on Days 1 and 78

• Characterization of PK of SPL84: terminal elimination half-life (t1/2)

  Cohort 1-3: Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87; Cohort 4: Predose and 1, 3, and 6 hours post dose on Days 1 and 78

• Characterization of PK of SPL84: Area under the curve to the final sample (AUC0-t)

  Cohort 1-3: Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87; Cohort 4: Predose and 1, 3, and 6 hours post dose on Days 1 and 78

• Characterization of PK of SPL84: Area under the curve to infinity (AUC0-∞)

  Cohort 1-3: Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87; Cohort 4: Predose and 1, 3, and 6 hours post dose on Days 1 and 78

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: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of CF and two CF causing mutations; 3849+10 Kb C-\>T mutation on one allele in the CF transmembrane conductance regulator (CFTR) gene (homozygote or compound heterozygote). Source documentation from a certified genetic laboratory is required.
• Body mass index (BMI) of ≥ 17 kg/m2.
• FEV1 40-90% predicted at screening.
• Non-smokers or vapers for at least 180 days (6 months) prior to screening, per participant report.

You may not qualify if:

• Use of Kalydeco, Orkambi, Symdeko/Symkevi or Trikafta/Kaftrio within 30 days of first dose with study intervention.
• Use of any investigational drug (other than SPL84) or device within 30 days of first dose with study intervention.
• Use of systemic steroids over 3 consecutive months in the last 6 months prior to screening, or use of systemic steroids in the last month prior to screening. Use of inhaled steroids above 1 mg.
• Use of CF medications, e.g. inhaled antibiotics, dornase alfa (Pulmozyme), hypertonic saline and physiotherapy should be on stable regimen for the period 28 days prior to screening; those participants taking inhaled antibiotics for prophylaxis must be on a stable regimen of these drugs for at least 90 days prior to first dose with study intervention.
• Any acute infection including acute upper respiratory or lower respiratory infections, pulmonary exacerbation, changes in therapy for pulmonary disease, or any non CF-related illness which results in the initiation of any new therapy within 14 days prior to first dose with study intervention.
• Hemoptysis of greater than 30 mL within 90 days prior to Day 1, or hospitalization for hemoptysis within 6 months of first dose with study intervention.
• Liver disease characterized by clinically significant cirrhosis and/or documented portal hypertension.
• History of any organ transplantation.
• Documented coronavirus disease (COVID-19) infection within 4 weeks prior to dosing.
• Cohort 4:
• Diagnosis of CF and two CF causing mutations; 3849+10 Kb C-\>T mutation on one allele in the CF transmembrane conductance regulator (CFTR) gene (homozygote or compound heterozygote). Source documentation from a certified genetic laboratory is required.
• Body mass index (BMI) of ≥ 17 kg/m2.
• FEV1 40-80% predicted at screening.
• Non-smokers or vapers for at least 180 days (6 months) prior to screening, per participant report.
• Stable adherence to standard use of Trikafta/Kaftio or Alyftrek for at least 3 months, or Alyftrek for 1 month after switching from Trikafta/Kaftio, according to prescribing information.

Sponsors & Collaborators

• SpliSense Ltd.: lead

Study Sites (3)

University of Southern California

Los Angeles, California, 90033, United States

RECRUITING

National Jewish Health

Denver, Colorado, 80206, United States

RECRUITING

Boston Children'S Hospital

Boston, Massachusetts, 02115, United States

NOT YET RECRUITING

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 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2024
• First Posted: May 24, 2024
• Study Start: June 24, 2024
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: May 14, 2026

Record last verified: 2026-05

Locations

US (3)