E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Cystic fibrosis (CF) is a life-threatening genetic disorder that results in the accumulation of thick, sticky mucus in the lungs, clogging airways and leading to infection and chronic inflammation.
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011762 |
E.1.2 | Term | Cystic fibrosis |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety and tolerability of multiple ascending doses (MAD) of inhaled SNSP113 administered once-daily for 28 days to adult Cystic Fibrosis (CF) subjects.
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject voluntarily agrees to participate in this study, is able and willing to comply with the protocol and signs a written Ethics Committee (EC) approved informed consent prior to study-specific screening procedures being performed; 2. Male and female subjects 18 to 65 years of age (inclusive), on the day of signing informed consent; 3. Documented and confirmed diagnosis of pulmonary CF as defined by CF signs and symptoms AND genotype with two identifiable mutations consistent with CF, accompanied by one or more clinical features consistent with the CF phenotype; or sweat chloride >60 mEq/L; 4. Body mass index (BMI) of ≥18.0 kg/m2; 5. Spirometry at Screening demonstrating a forced expiratory volume in 1 second (FEV1) of ≥40% and ≤90% of predicted normal for age, sex, and height; 6. Stable pulmonary symptoms associated with CF for 28 days prior to Screening and between the Screening visit and Day 1 as determined by Investigator; 7. Fulfilling the following laboratory criteria at Screening or results that are considered not clinically significant by the Investigator: a) hepatic function tests (alkaline phosphatase [ALP], alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyl transaminase [GGT], bilirubin) ≤3 x upper limit of normal (ULN); b) hemoglobin ≥10 g/dL, platelets ≥75,000/mm3, neutrophils ≥1.0 x 109/L; c) serum creatinine ≤2.0 mg/dL (177 µmol/L); 8. Results of ECG recording at Screening are within normal limits or deemed to be not clinically significant by the Investigator; 9. Able and willing to comply with scheduled visits, treatment plan, study restrictions, spirometry laboratory tests, contraceptive guidelines, and other study procedures as determined by the Investigator; 10. Female subjects of child-bearing potential must either be sexually inactive (abstinent) from Day -28 until 28 days after the last dose of study product (SNSP113 or placebo) or be willing to use highly effective methods of birth control from Day -14 until 28 days after the last dose of study product. For the purpose of this study highly effective contraception is defined as: a) oral, intravaginal, or transdermal combined (estrogen and progestogen containing) hormonal methods of contraception; OR b) oral, injected or implanted (progestogen only) hormonal methods of contraception (e.g., Depo-Provera®, Implanon®); OR c) placement of an intrauterine device (IUD) or intrauterine system (IUS). 11. Females of non-childbearing potential must be postmenopausal with documented amenorrhea for at least 1 year prior to dosing and follicle-stimulating hormone (FSH) serum levels consistent with postmenopausal status OR undergone sterilization procedures at least 6 months prior to dosing such as: a) hysteroscopic sterilization; b) bilateral tubal ligation or salpingectomy; c) hysterectomy; d) bilateral oophorectomy. 12. All male subjects must either be sexually inactive (abstinent) or be willing to use a condom with spermicide during the study from Day 1 until 28 days after the last dose of study product. |
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E.4 | Principal exclusion criteria |
1. Subjects with significant clinical/laboratory/radiological/spirometry sign(s) within 28 days prior to Screening or between the Screening visit and Day 1 that, in the opinion of the Investigator, is indicative of unstable respiratory disease; 2. Positive screening tests for hepatitis B surface antigen (HBsAG), anti-hepatitis C virus (HCV) antibodies and anti-Human Immunodeficiency Virus (HIV) 1 and 2 antibodies; positive laboratory-confirmed SARS-CoV-2 (COVID-19) infection as determined by RT-PCR, or other commercial or public health assay in any specimen < 72 hours prior to randomization; 3. Any active infection including acute upper respiratory or lower respiratory infections, pulmonary exacerbation (PEx), changes in therapy for pulmonary disease, or any non-CF-related illness which results in the initiation of any new therapy within 28 days prior to Screening; 4. Changes (e.g., dose, frequency, addition of, discontinuation) in the CF baseline therapies within 28 days prior to Screening; 5. Regular use (>3 times per week) of a high-dose NSAID (e.g., >1.6 g ibuprofen/day) within 28 days prior to Screening or at any time between the Screening visit and Day 1; 6. Current or former regular smoker (tobacco, e-cigarette, or cannabis products) within the last 6 months; 7. Not willing to abstain from use of cannabis products for the duration of the study; 8. History of alcohol or substance abuse in the past 12 months and/or positive drug test at Screening. Presence of drug(s) administered for known conditions are permitted with concurrence from the Sponsor’s medical monitor (e.g., benzodiazepine); 9. Participation in an interventional clinical trial involving the receipt of an investigational product or device within the 28 days prior to Screening or 6 half-lives of an investigational product, whichever is longer; 10. Female subjects who are pregnant, have a positive serum pregnancy test at Screening, are lactating or who plan to become pregnant during the study and/or within 90 days after receiving the study product; 11. History of organ transplantation or listed for organ transplantation; 12. Subjects requiring supplemental oxygen; 13. Subjects with previous or current pneumothorax within 3 months or any other condition that would contraindicate the performance of spirometry in the judgement of the Investigator; 14. Hemoptysis more than 30 mL over 24 h at any time within 28 days prior to Screening or at any time between Screening visit and Day 1; 15. History of malignancy <5 years prior to signing the informed consent, except for treated basal cell or squamous cell skin cancer or in situ cervical cancer; 16. Subjects who, per Investigator's judgment, are not ideal clinical trial candidates due to personal reasons (e.g., perceived willingness or ability to comply with protocol and study procedures) that would likely impede the subject's successful study completion. 17. Sexually active male subjects with female partners of child-bearing potential not willing to use effective methods of birth control during the study from Day -14 until 28 days after the last dose of study product. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Vital signs (blood pressure, heart rate, respiratory rate) • Clinical laboratory evaluations (hematology included complete blood cell count (CBC) with differential and platelet count, serum biochemistry including blood urea nitrogen and creatinine, liver function tests, coagulation profile, and urinalysis) • ECG parameters • Pulmonary function assessed by spirometry, pulse oximetry • PE |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Visit 1 through study completion |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 1 |