## Protocol Section
### Identification Module
**NCT ID:** NCT06429176

**Brief Title:** Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of SPL84 in Patients With Cystic Fibrosis

**Official Title:** A Phase 2a, Randomized, Placebo-Controlled, Double Blind Multiple Ascending Dose Study in Patients With Cystic Fibrosis Carrying the 3849 +10 Kb C->T Mutation to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of SPL84

#### Organization Study ID Info
**ID:** SPL84-002
#### Organization
**Class:** INDUSTRY
**Full Name:** SpliSense Ltd.
#### Secondary ID Infos
**ID:** 2024-511184-28
**Type:** EUDRACT_NUMBER
### Status Module
#### Completion Date
**Date:** 2025-12-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-24

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-20

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2025-10-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-07-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-24
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-15
**Study First Submit QC Date:** 2024-05-20
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** SpliSense Ltd.

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

### Description Module

**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.

The purpose of this research study is to:

* test the safety and effectiveness of multiple doses of the study drug, SPL84
* test how multiple doses of the drug are processed by the body

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.

Participants will:

Take drug SPL84 or a placebo by inhalation every week for 9 weeks months Visit the clinic approximately 14 times over 17.5 weeks for checkups and tests

### Conditions Module

**Conditions:**

- Cystic Fibrosis

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** SEQUENTIAL

##### Masking Info

**Masking:** DOUBLE

**Who Masked:**

- PARTICIPANT

- INVESTIGATOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 24

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Intervention Names:**

- Drug: SPL84

**Label:** SPL84

**Type:** ACTIVE_COMPARATOR

#### Arm Group 2

**Intervention Names:**

- Other: Placebo

**Label:** Placebo

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- SPL84

**Description:** SPL84 solution for nebulization

**Name:** SPL84

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Placebo

**Description:** Placebo solution for nebulization

**Name:** Placebo

**Type:** OTHER

### Outcomes Module

#### Primary Outcomes

**Description:** Incidence, nature, and severity of AEs and SAEs

**Measure:** 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)

**Time Frame:** Day 1 through Day 87

**Measure:** Safety and Tolerability of SPL84 as assessed by number of participants with abnormal heart rate

**Time Frame:** Day 1 through Day 87

**Measure:** Safety and Tolerability of SPL84 as assessed by number of participants with abnormal respiratory rate

**Time Frame:** Day 1 through Day 87

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

**Time Frame:** Day 1 through Day 87

**Measure:** Safety and Tolerability of SPL84 as assessed by number of participants with abnormal oximetry

**Time Frame:** Day 1 through Day 87

**Measure:** Safety and Tolerability of SPL84 as assessed by number of participants with abnormal temperature

**Time Frame:** Day 1 through Day 87

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

**Time Frame:** Day 1 through Day 87

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

**Time Frame:** Day 1 through Day 87

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

**Time Frame:** Day 1 through Day 87

**Description:** using an ECG machine that automatically calculates heart rate and measure PR, QRS, QT, and QTc intervals

**Measure:** Safety and Tolerability of SPL84 as assessed by number of participants with abnormal electrocardiogram (ECG) parameters

**Time Frame:** Day 1 through Day 87

**Description:** 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.

**Measure:** Safety and Tolerability of SPL84 as assessed by number of participants with abnormal physical examination findings

**Time Frame:** Day 1 through Day 87

**Description:** 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

**Measure:** Safety and Tolerability of SPL84 as assessed by number of participants with abnormal pulmonary function tests results

**Time Frame:** Day 1 through Day 87

**Description:** Sputum microbiology will be performed with a microbiology based assay; organism growth will be identified.

**Measure:** Safety and Tolerability of SPL84 as assessed by number of participants with abnormal sputum microbiology results results

**Time Frame:** Day 1 through Day 87

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

**Measure:** Safety and Tolerability of SPL84 as assessed by number of participants with abnormal immunogenicity results

**Time Frame:** Day 1 through Day 87

#### Secondary Outcomes

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

**Time Frame:** 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

**Measure:** Characterization of PK of SPL84: Time to Cmax (Tmax)

**Time Frame:** 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

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

**Time Frame:** 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

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

**Time Frame:** 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

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

**Time Frame:** 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

**Measure:** Characterization of PK of SPL84: Apparent clearance (CL/F)

**Time Frame:** 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

**Measure:** Characterization of excretion of SPL84: concentration of SPL84 in urine

**Time Frame:** Day 1 through Day 87

**Description:** Pulmonary function tests will be performed according to the ATS/ERS

**Measure:** Preliminary efficacy of SPL84 as assessed by change from baseline in percent predicted FEV1

**Time Frame:** Day 1 through Day 87

**Description:** The score for is standardized on a 0- to 100-point scale on which higher scores represent a higher quality of life

**Measure:** Preliminary efficacy of SPL84 as assessed by change from baseline in Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Score

**Time Frame:** Day 1 through Day 87

**Measure:** Preliminary efficacy of SPL84 as assessed by change from baseline in body weight

**Time Frame:** Day 1 through Day 87

**Measure:** Preliminary efficacy of SPL84 as assessed by change from baseline of antibiotic treatment

**Time Frame:** Day 1 through Day 87

### Eligibility Module

**Eligibility Criteria:** 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.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Birmingham

**Contacts:**

***Contact 1:***

- **Email:** kathrynmonroe@uabmc.edu

- **Name:** Kathryn Monroe

- **Phone:** 205-638-5599

- **Role:** CONTACT

**Country:** United States

**Facility:** University of Alabama at Birmingham

**State:** Alabama

**Status:** RECRUITING

**Zip:** 35233

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000010335

- Term: Pathologic Processes

- ID: D000010182

- Term: Pancreatic Diseases

- ID: D000004066

- Term: Digestive System Diseases

- ID: D000008171

- Term: Lung Diseases

- ID: D000012140

- Term: Respiratory Tract Diseases

- ID: D000030342

- Term: Genetic Diseases, Inborn

- ID: D000007232

- Term: Infant, Newborn, Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC06

- Name: Digestive System Diseases

- Abbrev: BC08

- Name: Respiratory Tract (Lung and Bronchial) Diseases

- Abbrev: BC16

- Name: Diseases and Abnormalities at or Before Birth

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M8485

- Name: Fibrosis

- Relevance: HIGH

- As Found: Fibrosis

- ID: M6755

- Name: Cystic Fibrosis

- Relevance: HIGH

- As Found: Cystic Fibrosis

- ID: M13102

- Name: Pancreatic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M8883

- Name: Gastrointestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M7255

- Name: Digestive System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M11168

- Name: Lung Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14977

- Name: Respiratory Tract Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M23686

- Name: Genetic Diseases, Inborn

- Relevance: LOW

- As Found: Unknown

- ID: M10276

- Name: Infant, Newborn, Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T1710

- Name: Cystic Fibrosis

- Relevance: HIGH

- As Found: Cystic Fibrosis

### Condition Browse Module - Meshes

- ID: D000003550

- Term: Cystic Fibrosis

- ID: D000005355

- Term: Fibrosis

### Intervention Browse Module - Browse Branches

- Abbrev: PhSol

- Name: Pharmaceutical Solutions

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M21860

- Name: Pharmaceutical Solutions

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
