A two-part study to assess the effectiveness, safety, and blood levels of repeat doses of inhaled ETD001 in people with cystic fibrosis

Phase 2

• Conditions: Cystic Fibrosis; Respiratory

• Registration Number: ISRCTN11798668
• Lead Sponsor: Enterprise Therapeutics Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-04-02
• Last Update Posted: 13 May 2024
• Study Completion: 2025-07-29

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 35

Inclusion Criteria

1. All genders = 18 years of age, who fit one of the following criteria: Women of childbearing potential who are willing and able to use contraception from a minimum of 28 days before receipt of the first dose of study medication until completion of the final follow up visit. Women of non-childbearing potential defined as being amenorrhoeic for >12 months with an appropriate clinical profile (e.g. age appropriate, menopausal symptoms). However, if indicated, this should be confirmed by follicle-stimulating hormone levels consistent with menopause (according to local laboratory ranges). Alternatively, women without a uterus or who have been permanently sterilised (e.g. hysterectomy, bilateral salpingectomy or bilateral oophorectomy, but not tubal ligation). Men who are willing and able to use one of the contraception methods from the time of the first dose, until completion of the final follow up visit
2. Have a confirmed diagnosis of CF [positive sweat chloride value = 60 mEq/L (by quantitative pilocarpine iontophoresis) and/or genotype with two identifiable mutations consistent with CF, accompanied by one or more clinical features consistent with the CF phenotype].
3. Have a FEV1 = 40% and = 90% of predicted normal for age, gender, and height using Global Lung Function Initiative (GLI) standards.
4. Be able to reproducibly perform spirometry manoeuvres (i.e., able to perform at least three acceptable forced expiratory curves based on the investigator’s assessment).
5.Clinically stable CF lung disease, defined as no documented decrease in FEV1 > 10%, or signs and symptoms of acute pulmonary exacerbation such as: increased cough, change in sputum (volume or consistency), change in respiratory examination and respiratory rate, decreased appetite or weight loss, chest pain, hemoptysis, decreased lung function, fever defined as temperature > 38°C (100.4°F) within 28 days prior to Visit 1.
6. Routine CF therapy (bronchodilator, anti-inflammatory, inhaled corticosteroid, physiotherapy technique/schedule (including use of vibrating vests etc.) has not changed (in dose or medication) within 28 days prior to Visit 1.
7. Provided written informed consent.
8. Be able and willing to follow instructions and complete study procedures and be willing to comply with the study protocol and study drug use.
9. Females must have a negative serum ß human chorionic gonadotropin (ß-hCG) at Visit 1
10. Be able to use a nebuliser.
11. Body mass index (BMI) > 16 and < 30 kg/m²

Exclusion Criteria

1. Abnormal liver function defined as any 2 or more of the following: =3 × upper limit of normal (ULN) aspartate aminotransferase (AST), =3 × ULN alanine aminotransferase (ALT), =3 × ULN gamma-glutamyl transpeptidase (GGT), =3 × ULN alkaline phosphatase (ALP), or =2 × ULN total bilirubin
2. Abnormal renal function defined as glomerular filtration rate =50 mL/min/1.73 m²
3. People with a history of any solid organ transplantation
4. Have a historical chest x-ray (anterior/posterior view) within the past 12 months with abnormalities suggesting unstable pulmonary disease other than CF
5. Received CFTR modulator therapy in the 60 days before Visit 1
6. Have changes in bronchodilator, corticosteroid or other anti-inflammatory medications 14 days prior to and inclusive of Visit 1
7. Be unable to withhold use of long-acting bronchodilators 24 hours prior to spirometry or unable to withhold short-acting bronchodilator within 6 hours prior to spirometry
8. Be unable to withhold use of anti-cholinergics within 24 hours of spirometry
9. Have started using dornase alfa, hypertonic saline, or other airway clearing therapy less than 28 days prior to Visit 1
10. Using inhaled antibiotics for less than 2 complete cycles and unable to complete the entire study during the off or on cycle
11. Have changes in inhaled or oral antibiotic use within 14 days prior to and inclusive of Visit 1
12. Be taking oral corticosteroids (prednisone equivalents) within 14 days prior to and inclusive of Visit 1, exceeding 10 mg per day or 20 mg every other day
13. Used diuretics, or renin-angiotensin aldosterone system antihypertensive drugs (spironolactone, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin receptor blockers (ARB)), drospirenone, or trimethoprim in the 28 days prior to Visit 1, or an anticipated need for any of these medications during the study
14. Presence of co-morbidities and medical history listed below, or in the opinion of the investigator, may pose additional risk by participating in the study, or may confound the results of the study:
14.1. Cirrhosis with portal hypertension (e.g., splenomegaly, oesophageal varices)
14.2. Past or present positive sputum culture for organisms that are often associated with a faster decline in pulmonary status is allowed if, in the opinion of the investigator, clinical stability has not been adversely affected. Subjects with these organisms can remain on chronic treatment for them if applicable, as long as the medications are not prohibited in this study. To assure clinical stability, treatment for these organisms should start at least 8 weeks before screening, and the subjects will be expected to continue the treatment through the final study visit.
14.3. History of malignancy within past 5 years (except for excised basal cell carcinoma of the skin with no recurrence, or treated carcinoma in situ of the cervix with no recurrence).
14.4. Abuse or suspected abuse of alcohol, medications, or illicit drugs within 1 year before Screening, per the investigator.
14.5. Psychiatric condition that makes it unlikely that the course of treatment or follow-up will be completed.
14.6. Smoking or vaping tobacco or cannabis products within 1 year before Screening.
14.7. Need for supplemental oxygen while awake, or > 2 L/minute while sleeping.
14.8. Recent significant weight loss, defined as 2 kg loss within the 4 weeks prior to screening.
14.9. Severe CF related diabetes mellitus with poor glucose control, microvascu

Study & Design

• Study Type: Interventional
• Study Design: Not specified