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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Splisense Ltd.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

23 Oct 2024 → ongoing

Decision date (initial)

2024-08-20

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Splisense Ltd.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others

To evaluate the safety and tolerability of multiple ascending doses of SPL84 administered by inhalation and identify the MTD in participants with CF.

Secondary objectives 2

1. To characterize the PK and excretion of multiple ascending doses of SPL84 administered by inhalation in participants with CF
2. To assess preliminary efficacy of multiple ascending doses of SPL84 administered by inhalation in participants with CF

Conditions and MedDRA coding

Cystic fibrosis

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Male and female adults aged 18 and above at the time of consent.
2. 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.
3. Body mass index (BMI) of ≥ 17 kg/m2.
4. FEV1 40-90% predicted at screening.
5. 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.
6. Non-smokers or vapers for at least 180 days (6 months) prior to screening, per participant report.

Exclusion criteria 8

1. Use of Kalydeco, Orkambi, Symdeko/Symkevi or Trikafta/Kaftrio within 30 days of first dose with study intervention.
2. 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.
3. 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.
4. 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.
5. 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.
6. Liver disease characterized by clinically significant cirrhosis and/or documented portal hypertension.
7. History of any organ transplantation.
8. Documented COVID-19 infection within 4 weeks prior to dosing.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Incidence, nature, and severity of adverse events (AEs), AEs of Special Interest (AESIs) and serious adverse events (SAEs)
2. Changes from baseline in vital signs, clinical laboratory values, electrocardiogram (ECG), physical examination, sputum microbiology, and pulmonary function.
3. Immunogenicity

Secondary endpoints 6

1. Characterize the PK parameters based on concentration in plasma
2. Measure the concentrations of SPL84 in urine
3. Spirometry: − Forced expiratory volume in 1 second (FEV1); − Forced vital capacity (FVC); − Forced mid-expiratory flow (FEF25-75).
4. Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Score (CFQ-R RSS)
5. Body weight
6. Change in antibiotic treatment

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Splisense Ltd.

Sponsor organisation

Splisense Ltd.

Address

Minrav Bldg, Floor 1st, Haddasah Ein Karem Floor 1st Haddasah Ein Karem

City

Jerusalem

Postcode

9112101

Country

Israel

Scientific contact point

Organisation

Splisense Ltd.

Contact name

Clinical Trial Info

Public contact point

Organisation

Splisense Ltd.

Contact name

Clinical Trial Info

Third parties 7

Locations

10 EU/EEA countries · 14 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 5 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 65 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications