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

Prior treatment

• Unstable adherence to standard use of CF medications, e.g. inhaled antibiotics, dornase alfa (Pulmozyme), hypertonic saline and physiotherapy in the period of 30 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.
• Previous participation in active arm of SPL84-002 study (Cohort 1-3)
• 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.
• Unstable adherence to standard use of CF medications, e.g. inhaled antibiotics, dornase alfa (Pulmozyme), hypertonic saline and physiotherapy in the period of 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 30 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.
• Documented COVID-19 infection within 4 weeks prior to dosing.

Other illness

• Liver disease characterized by clinically significant cirrhosis and/or documented portal hypertension.
• History of any organ transplantation.
• Abnormal vital signs at screening or Day 1 pre-dose: heart rate > 120 bpm at rest; systolic blood pressure > 150 or < 90 mmHg; respiration rate > 24 bpm; and oxygen screening < 92% at rest.

Other

• Use of Kalydeco, Orkambi, Symdeko/Symkevi or Trikafta/Kaftrio within 30 days of first dose with study intervention.

• Male and female adults aged 18 and above at the time of consent.
• Diagnosis of CF and two CF causing mutations; 3849+10 Kb C->T mutation on one allele in the 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.
• Stable lung functions as defined at screening FEV1 not more than 20% lower than the highest absolute FEV1 (in liters) within 120 days prior to Day 1. If adequate documentation of prior spirometry is not available, determination of stable lung function per the treating physician is acceptable, provided the FEV1 at Day 1 is within 20% of the FEV1 at screening.
• Non-smokers or vapers for at least 180 days (6 months) prior to screening, per participant report.
• FEV1 40-80% predicted at screening, during the run-in period, and Day 1 pre-dose, performed in accordance with GLI and ATS standards.
• 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.
• Stable lung function; defined as screening ppFEV1 not more than 10 units lower (absolute change) than the ppFEV1 measured at least 90 days prior to screening.