New inhaled therapy targets Hard-to-Treat cystic fibrosis mutation

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Cohort 1-3: Inclusion Criteria: * 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. Exclusion Criteria: * 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: Inclusion Criteria: * 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. Exclusion Criteria: * Previous participation in active arm of SPL84-002 study (Cohort 1-3) * 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.