Lumacaftor/Ivacaftor Combination Therapy in Subjects With Cystic Fibrosis Who Have an A455E-CFTR Mutation

• Register: EUCTR
• Last refreshed on: 29 January 2018
• Main ID: EUCTR2016-001585-29-NL
• Date of registration: 18/07/2016
• Prospective Registration: Yes
• Primary sponsor: Vertex Pharmaceuticals Incorporated
• Public title: Lumacaftor/Ivacaftor Combination Therapy in Subjects With Cystic Fibrosis Who Have an A455E-CFTR Mutation
• Scientific title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Efficacy of Lumacaftor/Ivacaftor Combination Therapy in Subjects With Cystic Fibrosis Who Have an A455E-CFTR Mutation
• Date of first enrolment: 21/12/2016
• Target sample size: 20
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001585-29
• 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: yes; 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

Netherlands

Contacts

• Name: Clinical Trials and Medical Info
• Affiliation: Vertex Pharmaceuticals Incorporated

• Name: Clinical Trials and Medical Info
• Affiliation: Vertex Pharmaceuticals Incorporated

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female with confirmed diagnosis of CF. The subject must have both of the following:
- One or more characteristic phenotypic features, such as chronic cough and sputum production, persistent chest radiograph abnormalities, or airway obstruction manifested by wheezing and air trapping; or a history of CF in a sibling; or a positive newborn screening test result;
-An increased sweat chloride concentration by pilocarpine iontophoresis on two or more occasions; or identification of two CF mutations; or demonstration of abnormal nasal epithelial ion transport.
2. Age 12 years or older on the date of informed consent.
3. All subjects must have an A455E mutation on at least 1 CFTR allele.
4. Forced expiratory volume in one second (FEV1) =30% of predicted and =90% of predicted at the Screening Visit, based on the Global Lung Function Initiative (GLI)-012 multi-ethnic all-age reference equations.24
5. Stable CF disease as judged by the investigator.
6. Willing to remain on a stable medication regimen for CF from 4 weeks before Day 1 through the Follow-up Visit.
7. Willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.
8. Subject (or subject’s legally appointed and authorized representative) will sign and date an informed consent form (ICF), and where appropriate, assent form.
Are the trial subjects under 18? yes
Number of subjects for this age range: 5
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. History of any comorbidity reviewed at the Screening Visit that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject. For example:
- A history of cirrhosis with portal hypertension.
- An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 28 days before Day 1 (the first dose of study drug).
2. A G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R, or R117H mutation on at least one CFTR allele.
3. Ongoing or prior participation in an investigational drug study (including studies investigating LUM/IVA or IVA) within 30 days before the Screening Visit.
- A washout period of 5 terminal half-lives of the previous investigational study drug or 30 days, whichever is longer, must elapse before the Screening Visit. The duration of the elapsed time may be longer if required by local regulations.
- Subjects who participated in Vertex Study VX14-661-108 may not be enrolled.
- Ongoing participation in a noninterventional study (including observational studies) is permitted.
4. Pregnant or breastfeeding.
5. Any of the following abnormal laboratory values at the Screening Visit: ? -Hemoglobin <10 g/dL
Any 2 or more of the following:
- aspartate aminotransferase (AST) =3 × upper limit of normal (ULN)
- alanine aminotransferase (ALT) =3 × ULN
- gamma-glutamyl transpeptidase (GGT) =3 × ULN
- alkaline phosphatase =3 × ULN
ALT or AST >5 × ULN
Bilirubin >2 × ULN
Glomerular filtration rate =45 mL/min/1.73 m2 (calculated by the Counahan-Barratt equation).
6. History of cataract/lens opacity, or evidence of cataract/lens opacity determined to be clinically significant by the ophthalmologist or optometrist during the ophthalmologic examination at the Screening Visit (if applicable).
7. Use of strong inhibitors or strong inducers of CYP3A, including consumption of certain herbal medications (e.g., St. John’s Wort) and certain fruit and fruit juices, within 14 days before Day 1 (the first dose of study drug).
8. Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements outlined in Section 11.6.5.


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

Health Condition(s) or Problem(s) studied

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

Cystic fibrosis
MedDRA version: 20.0 Level: PT Classification code 10011762 Term: Cystic fibrosis System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Trade Name: Orkambi 200 mg/125 mg film-coated tablets

Product Name: LUM/IVA fixed-dose combination
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: LUMACAFTOR
Current Sponsor code: VX-809
Other descriptive name: LUMACAFTOR
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
INN or Proposed INN: IVACAFTOR
CAS Number: 873054-44-5
Current Sponsor code: VX-770
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 125-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: To explore the association between LUM/IVA-induced CFTR function in in vitro organoid-based measurements and clinical response to LUM/IVA in subjects with CF 12 years of age and older who have at least one A455E mutation.

To explore the effect of LUM/IVA on glucose tolerance and insulin secretion in subjects with CF 12 years of age and older who have at least one A455E mutation.

Main Objective: To evaluate the efficacy of LUM/IVA in subjects with CF 12 years of age and older who have at least one A455E mutation.

Primary end point(s): Absolute change from baseline in percent predicted forced expiratory volume in 1 second (ppFEV1) through 8 weeks of treatment.

Timepoint(s) of evaluation of this end point: through 8 weeks of treatment

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. through 8 weeks of treatment
2. at 8 weeks of treatment
4. after approximately 8 weeks of treatment

Secondary end point(s): 1. Change from baseline in sweat chloride through 8 weeks of treatment.
2. Change from baseline in the Cystic Fibrosis Questionnaire Revised (CFQ-R) at 8 weeks of treatment.
3. Organoid-based measurements of LUM/IVA-induced CFTR function in vitro versus clinical outcomes.
4. Change from baseline in glucose and insulin levels during the OGTT after approximately 8 weeks of treatment.

Secondary ID(s)

VX15-809-111

Source(s) of Monetary Support

Vertex Pharmaceuticals Incorporated