An investigational study to assess the effect of GS-5745 on adult patients with Cystic Fibrosis

• Register: EUCTR
• Last refreshed on: 30 April 2018
• Main ID: EUCTR2015-002192-23-BE
• Date of registration: 18/05/2016
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences, Inc.
• Public title: An investigational study to assess the effect of GS-5745 on adult patients with Cystic Fibrosis
• Scientific title: A Phase 2b, Dose-Ranging Study of the Effect of GS-5745 on FEV1 in Adult Subjects with Cystic Fibrosis
• Date of first enrolment: 18/07/2016
• Target sample size: 150
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-002192-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Canada, France, Germany, Ireland, Spain, United Kingdom, United States

Contacts

• Name: Clinical Trials Mailbox
• Affiliation: Gilead Sciences International Ltd.

• Name: Clinical Trials Mailbox
• Affiliation: Gilead Sciences International Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects must meet all of the following inclusion criteria to be eligible for participation in this study.
1) Male or female 18 years of age or older
2) Confirmed diagnosis of CF as determined by the 2008 Cystic Fibrosis Foundation Consensus Report [Farrell et al., J Pediatr 2998; 153:S4-14] criteria
3) Subjects must be able to perform acceptable and reproducible spirometry as per the American Thoracic Society (ATS) Guidelines
4) Must have a body weight of > 40 kg (88.2 lbs) at study Screening
5) Subjects must be a never-smoker or an ex-smoker with < 5 pack-year history of smoking and be smoke-free (including marijuana or e-cigarettes/vaping) for 12 months prior to Screening
6) Pre-bronchodilator FEV1 = 40% and = 80% of predicted at Screening
7) Two pre-bronchodilator spirometry measures taken at least 4 days apart (one during Screening, one at Baseline) using the sponsor provided central spirometry equipment must meet the following 2 criteria:
- The relative difference of FEV1(L), calculated as the absolute value of [(first FEV1 – second FEV1) / first FEV1 ] x 100 should be < 12% AND
- The absolute difference in FEV1 should be < 200 ml
8) Negative Investigation/History of Important Bacteria Inclusions:
Tuberculosis (TB):
- A negative QuantiFERON-TB Gold test during Screening
Non-Tuberculous Mycobacteria species (NTM):
- All sputum cultures for ANY Mycobacterium spp. performed 24 months prior to Screening must be negative. If only 1 NTM culture was performed 24 months prior to Screening, that NTM culture and the most recent NTM culture obtained >24 months prior to Visit 1 must both be negative AND
- A negative sputum culture < 12 months prior to Screening for any Mycobacterium
spp. AND
- No current treatment for active NTM during Screening
Burkholderia spp.
- All sputum/throat cultures for ANY Burkholderia spp. performed 24 months prior to Screening must be negative. If only 1 Burkholderia culture was performed 24 months prior to Screening, that Burkholderia spp. culture and the most recent Burkholderia spp. culture obtained >24 months prior to Screening were both negative AND
- A negative culture for Burkholderia spp. during Screening AND
- No current treatment for Burkholderia spp. during Screening
9) Clinically stable with no evidence of significant respiratory symptoms that would require administration of (IV) antibiotics, oxygen supplementation, or hospitalization within 30 days of Baseline.
10) A chest radiograph, computed tomography (CT) or magnetic resonance imaging (MRI) within 90 days of Baseline, interpreted as showing no acute findings such as infiltrates [lobar or diffuse interstitial], pleural effusion, or pneumothorax, and no significant intercurrent illness; chronic, stable findings (eg chronic scarring or atelectasis) are allowed. If not available then a chest radiograph at Screening will be obtained and should be interpreted as above.
11) On stable CF chronic medical regimen for at least 30 days prior to Baseline and expected to remain stable through the completion of the study. This includes but is not limited to: chronic azithromycin use, inhaled bronchodilators, inhaled corticosteroids, inhaled dornase alpha, inhaled hypertonic saline, inhaled mannitol, ivacaftor, and/or ivacaftor/lumacaftor.
- Inhaled antibiotics (ie, tobramycin, aztreonam, colistin) should be stable for 2 “on-treatment cycles” to be considered a stable CF medication (ie, approximately 2 months if they are taken as continuous inhaled antibi
Exclusion criteria:
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
1) Concurrent use of oral antibiotics (excluding chronic azithromycin use) or IV antibiotics
within 30 days of Baseline
2) Hospitalization for a respiratory event within 30 days of Baseline
3) Active allergic bronchopulmonary aspergillosis (ABPA) requiring treatment; previous history of ABPA without current ABPA anti-fungal prophylaxis is acceptable
4) Any acute “non-CF related” illness within 2 weeks prior to Baseline (eg, gastroenteritis)
5) Current use of systemic immunosuppressive drugs including oral corticosteroids within 30 days of Baseline
6) Current requirement for daily continuous oxygen supplementation or requirement (medically necessary) of more than 2 L/minute at night (subject would not meet this exclusion criterion if supplemental oxygen is used for comfort only)
7) History of anaphylaxis requiring the use of epinephrine
8) History of solid organ (including lung) or hematologic transplant, or currently on a transplant waiting list
9) History of lung resection
10) History of HIV, hepatitis B, or hepatitis C
11) History of malignancy in the last 5 years except for subjects who have been successfully treated for non-melanoma skin cancer or cervical cancer
12) History of alcohol or drug abuse in the past year, including but not limited to cannabis, cocaine, opiates, as determined by the investigator
13) Laboratory parameters at screening:
- Abnormal liver function tests defined as > 3 times the upper limit of normal (ULN) of any of the following: serum aspartate transaminase (AST), serum alanine transaminase (ALT), gamma-glutamyl transpetidase (GGT) and serum alkaline phosphatase.
- Total Bilirubin > 2 times the ULN
- Hemoglobin < 10 g/dL for females and < 11.5 g/dL for males at screening
- Serum creatinine > 2 times the ULN
14) Clinically significant abnormal ECG at screening; abnormalities considered not clinically significant, per investigator, are not exclusionary
15) Known hypersensitivity to the investigational medicinal product or formulation excipient
16) Presence of any condition or abnormality that would compromise subject safety or the quality of data, or any serious or active medical or psychiatric illness, which in the opinion of the investigator, would interfere with subject treatment, assessment, or compliance with the protocol
17) Receipt of any investigational non-biological drug therapy within 30 days of enrollment OR receipt of any marketed or investigational biologic within 4 months prior to enrollment


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Cystic Fibrosis
MedDRA version: 19.0 Level: PT Classification code 10011762 Term: Cystic fibrosis System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Product Code: GS-5745
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: GS-5745
Current Sponsor code: GS-5745
Other descriptive name: GS-5745
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 8

Primary end point(s): The absolute change in pre-bronchodilator FEV1 percent predicted from Baseline to Week 8

Secondary Objective: To assess safety, tolerability, and pharmacokinetics (PK) of GS-5745 in subjects with CF
To evaluate the effect of GS-5745 on post-bronchodilator forced expiratory volume in 1 second (FEV1) in subjects with CF after 8 weeks of treatment

Main Objective: To evaluate the effect of GS-5745 on pre-bronchodilator forced expiratory volume in 1 second (FEV1) in subjects with cystic fibrosis (CF) after 8 weeks of treatment

Secondary Outcome(s)

Secondary end point(s): - The safety evaluation will be assessed by AEs, concomitant medications, clinical laboratory tests, vital signs and ADA data.
- Primary PK parameters will include Cmax, Tmax, Clast, Tlast, and AUClast (as applicable)
- The absolute change in post-bronchodilator FEV1 percent predicted from Baseline to Week 8
- The relative change in pre-bronchodilator FEV1 percent predicted from Baseline to Week 8
- The relative change in post-bronchodilator FEV1 percent predicted from Baseline to Week 8

Timepoint(s) of evaluation of this end point: week 8

Secondary ID(s)

2015-002192-23-DE

GS-US-404-1808

Source(s) of Monetary Support

Gilead Sciences, Inc.