SPL84 for Cystic Fibrosis

Recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: SpliSense Ltd.

Must not be taking: Kalydeco, Orkambi, Symdeko, Trikafta

Disqualifiers: Organ transplantation, Liver disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 14

Duration: 9 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, SPL84, to determine its safety and effectiveness in treating cystic fibrosis (CF) in adults. Researchers aim to discover if SPL84 can alleviate CF symptoms, especially for those with a specific gene mutation. Participants will receive either SPL84 or a placebo (a treatment with no active ingredients) to compare results. This trial suits adults with CF who have a specific gene mutation and have not smoked or vaped in the last six months. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

You may need to stop taking certain medications like Kalydeco, Orkambi, Symdeko/Symkevi, or Trikafta/Kaftrio at least 30 days before starting the trial. Other CF medications should be on a stable regimen for at least 28 days before screening, and inhaled antibiotics for prophylaxis should be stable for at least 90 days before the trial.

Is there any evidence suggesting that SPL84 is likely to be safe for humans?

Research has shown that SPL84 is generally safe for humans. In earlier studies, participants inhaled single doses of SPL84 up to 160 mg, and they tolerated it well with minimal effects on the rest of the body. This indicates that SPL84 did not cause significant problems at these doses. Additionally, tests on mice and monkeys demonstrated the drug's safety at certain dose levels.

These results are promising and suggest that SPL84 might be safe for people with cystic fibrosis. However, ongoing research is crucial to confirm its safety for individuals with this condition. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

SPL84 is unique because it targets the underlying cause of cystic fibrosis rather than just managing symptoms. Unlike standard treatments like CFTR modulators, antibiotics, and mucus thinners, SPL84 has a novel mechanism of action that aims to enhance the defective protein function directly. This targeted approach could potentially reduce lung infections and improve lung function more effectively. Researchers are excited because if successful, SPL84 could offer a more comprehensive treatment option for individuals with cystic fibrosis, improving their quality of life significantly.

What evidence suggests that SPL84 might be an effective treatment for cystic fibrosis?

Research has shown that SPL84, which participants in this trial may receive, may help treat cystic fibrosis, especially in patients with a certain genetic mutation. In earlier studies, up to 70% of patients showed improved lung function, as measured by ppFEV1, a test that checks lung performance. SPL84 was generally safe and well-tolerated, with no serious side effects reported. Researchers will compare participants taking SPL84 in this trial to those receiving a placebo to assess improvements in lung function. These findings suggest that SPL84 might help people with this genetic type of cystic fibrosis breathe more easily. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

Adults with cystic fibrosis can join this trial. They'll use an inhaler to take SPL84 or a placebo weekly for over two months and visit the clinic about 14 times in that period. The study will check if they have a specific CF mutation.

Inclusion Criteria

FEV1 40-90% predicted at screening.

I have cystic fibrosis with a specific genetic mutation.

Body mass index (BMI) of ≥ 17 kg/m2.

Exclusion Criteria

I have not taken Kalydeco, Orkambi, Symdeko/Symkevi, or Trikafta/Kaftrio in the last 30 days.

I have been on a stable CF treatment plan for at least 28 days.

I have not coughed up more than 30 mL of blood in the last 3 months or been hospitalized for coughing up blood in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive SPL84 or placebo by inhalation every week for 9 weeks

9 weeks

14 visits (in-person) over 17.5 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• SPL84

Trial Overview The trial is testing SPL84, a new drug for cystic fibrosis, against a placebo (a substance with no active drug). It aims to determine the safety of multiple doses and how well it treats CF when taken by inhalation.

How Is the Trial Designed?

Group I: SPL84 Active Control 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

SPL84 is already approved in United States for the following indications:

Approved in United States as SPL84 for:

• Cystic fibrosis with the 3849+10 kilobase (Kb) C->T splicing mutation

Who Is Running the Clinical Trial?

SpliSense Ltd.

Lead Sponsor

Trials

2

Recruited

60+

Published Research Related to This Trial

In a study involving 19 adults with cystic fibrosis carrying the deltaF508 mutation, the drug 4-Phenylbutyrate (Buphenyl) was found to be safe and well-tolerated, with a maximum tolerated dose established at 20 g due to minimal adverse reactions.

Buphenyl treatment resulted in a statistically significant increase in chloride transport in nasal epithelia, demonstrating its potential to improve the function of the defective CFTR protein in cystic fibrosis patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence of CFTR function in cystic fibrosis after systemic administration of 4-phenylbutyrate. Zeitlin, PL., Diener-West, M., Rubenstein, RC., et al.[2022]

The triple combination therapy of elexacaftor-tezacaftor-ivacaftor has shown significant efficacy in improving lung function and survival rates in cystic fibrosis patients, particularly those with the p.Phe508del mutation, which is associated with poorer outcomes.

This review highlights the safety and effectiveness of these CFTR modulators, which work by correcting the misfolding of the CFTR protein, and discusses their regulatory approval and potential future research directions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elexacaftor-tezacaftor-ivacaftor: The new paradigm to treat people with cystic fibrosis with at least one p.Phe508del mutation. Gramegna, A., Contarini, M., Bindo, F., et al.[2022]

The study of 186 cystic fibrosis patients found that specific polymorphisms in the IL8 gene, particularly rs2227307, are linked to the severity and early onset of the disease, suggesting a genetic influence on disease progression.

Pulmonary function markers, such as oxygen saturation and spirometric variables, were associated with IL8 gene polymorphisms, indicating that these genetic variations may contribute to the variability in lung disease severity and overall clinical outcomes in cystic fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL8 gene as modifier of cystic fibrosis: unraveling the factors which influence clinical variability. Furlan, LL., Marson, FA., Ribeiro, JD., et al.[2019]

A new strategy using a cocktail of antisense oligonucleotides (ASOs) successfully skips exon 23 of the CFTR gene, leading to increased production of a functional CFTR protein in cells with the W1282X mutation, which is associated with severe cystic fibrosis.

This approach enhances CFTR-mediated chloride current in human bronchial epithelial cells, suggesting a promising avenue for developing targeted therapies for patients with the W1282X mutation, overcoming limitations of current treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exon-skipping antisense oligonucleotides for cystic fibrosis therapy. Kim, YJ., Sivetz, N., Layne, J., et al.[2022]

The study successfully identified and characterized the cystic fibrosis transmembrane conductance regulator (CFTR) protein in T84 colonocyte cells, confirming its presence as a 170-kDa protein that behaves similarly to CFTR found in human pancreas and colon.

CFTR was localized to the apical region of T84 cells, indicating that these cells express sufficient levels of CFTR for further immunochemical studies, which could aid in understanding its role in cystic fibrosis and related conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of the cystic fibrosis transmembrane conductance regulator in a colonocyte cell line. Cohn, JA., Nairn, AC., Marino, CR., et al.[2019]

Mutations in the ATP8B1 gene, which causes Progressive familial intrahepatic cholestasis type 1 (PFIC1), lead to significantly reduced levels of the CFTR protein in the apical membrane of intestinal and pulmonary cells, which is crucial for proper function.

The study demonstrates that ATP8B1 is essential for the correct localization of CFTR, suggesting that the extrahepatic symptoms seen in PFIC1 patients, similar to those in cystic fibrosis, may be due to impaired CFTR function caused by ATP8B1 deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The phospholipid flippase ATP8B1 mediates apical localization of the cystic fibrosis transmembrane regulator. van der Mark, VA., de Jonge, HR., Chang, JC., et al.[2018]

SPL84, an inhaled antisense oligonucleotide for cystic fibrosis, showed no adverse effects in preclinical safety studies conducted on mice and monkeys, indicating a strong safety profile.

The no observed adverse effect level (NOAEL) was established at the highest doses tested, providing a safety margin of approximately 40 times the proposed starting clinical dose, which supports its progression to clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and toxicity profile of SPL84, an inhaled antisense oligonucleotide for treatment of cystic fibrosis patients with the 3849 +10kb C->T mutation, supports a Phase 1/2 clinical study. Friedman, L., Avitzur, OB., Galai, EO., et al.[2023]

Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) significantly improves lung function and quality of life in cystic fibrosis patients, as shown in a systematic review of 9 clinical trials and 16 observational studies involving participants aged 6-11 and older with specific genetic mutations.

The treatment has a favorable safety profile, with mostly mild to moderate side effects, although its effects on cystic fibrosis-related diabetes remain unclear and further research is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Elexacaftor-Tezacaftor-Ivacaftor in the Treatment of Cystic Fibrosis: A Systematic Review. Kapouni, N., Moustaki, M., Douros, K., et al.[2023]

SPL84, an inhaled antisense oligonucleotide (ASO) drug for cystic fibrosis, shows broad distribution and effective penetration into lung epithelial cells and nuclei in both mouse and monkey models, indicating its potential efficacy.

The drug demonstrated stability in CF patient-derived mucus and successfully navigated through thick mucus, suggesting it could effectively restore cystic fibrosis transmembrane conductance regulator (CFTR) channel activity, making it a promising treatment option for CF patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delivery Characterization of SPL84 Inhaled Antisense Oligonucleotide Drug for 3849 + 10 kb C- > T Cystic Fibrosis Patients. Ozeri-Galai, E., Friedman, L., Barchad-Avitzur, O., et al.[2023]

A splice-switching antisense oligonucleotide (ASO) targeting the common CFTR splicing mutation (c.3718-2477C>T) effectively blocks abnormal splicing in primary bronchial epithelial cells from cystic fibrosis patients, leading to long-term improvements in CFTR activity.

The ASO treatment resulted in better recovery of chloride secretion compared to ivacaftor, a current treatment option, suggesting that ASOs could be a promising therapeutic strategy for correcting CFTR function in cystic fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antisense oligonucleotide-mediated correction of CFTR splicing improves chloride secretion in cystic fibrosis patient-derived bronchial epithelial cells. Michaels, WE., Bridges, RJ., Hastings, ML.[2020]

Early diagnosis of cystic fibrosis (CF) in newborns can significantly enhance both the quality and quantity of life for patients.

Interventions such as improved nutrition, management of infections, diabetes care, and early treatment with dornase alfa are crucial for better health outcomes in CF patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence-based medicine in cystic fibrosis: how should practice change? Conway, SP.[2008]

Citations

1. splisense.com splisense.com/wp-content/uploads/2025/09/SpliSense-Reports-Positive-Results-from-Phase-2-Study-of-SPL84.pdf

SpliSense Reports Positive Results from Phase 2 Study of ... No treatment related Severe Adverse Events (SAEs) were observed. •. Efficacy – Improvement in lung function (ppFEV1) was observed in up to 70% ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1569199324017983

A phase I study assessing the safety and tolerability of ... SPL84 was safe and well-tolerated when administered as a single inhaled dose to HVs at doses up to 160 mg, with minimal systemic exposure.

3. cysticfibrosisnewstoday.com cysticfibrosisnewstoday.com/news/spl84-shows-signs-improving-lung-function-cf-patients/

SPL84 shows signs of improving lung function in CF patients SPL84, an investigational inhalation therapy designed to treat CF caused by a specific mutation, was well-tolerated in a Phase 2 trial.

4. firstwordpharma.com firstwordpharma.com/story/5994402

SpliSense touts early cystic fibrosis data for inhaled ASO Patients who received SPL84 had an estimated mean absolute change in ppFEV1 of 10 compared with placebo. SpliSense said no safety signals were ...

5. oindpnews.com oindpnews.com/2025/09/splisense-reports-data-from-ongoing-phase-2-trial-of-spl84-inhaled-antisense-oligonucleotide-for-cf/

SpliSense reports data from ongoing Phase 2 trial ... Hart added, “The favorable safety and efficacy profile emerging from our SPL84 program provides clinical validation of our ASO platform.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39500647/

A phase I study assessing the safety and tolerability of ... SPL84 was safe and well-tolerated when administered as a single inhaled dose to HVs at doses up to 160 mg, with minimal systemic exposure.

7. cysticfibrosisjournal.com cysticfibrosisjournal.com/article/S1569-1993(23)00390-9/fulltext

P014 Safety and toxicity profile of SPL84, an inhaled ... The NOAEL for mice and monkeys was 54.4 and 20.8 mg/kg/week, respectively, resulting in sufficient safety margins. These results supported initiation of a Phase ...

8. tandfonline.com tandfonline.com/doi/abs/10.1080/17425255.2023.2266361

The safety and toxicity profile of SPL84, an inhaled ... These successful results supported the initiation of a phase 1/2 clinical study of SPL84 (ongoing), assessing the safety, tolerability, and pharmacokinetics of ...