Clinical trial NCT03125395: A Rollover Safety Study of Lumacaftor/Ivacaftor in Subjects Aged 2 Years and Older With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation
Official title: A Phase 3, Rollover Study to Evaluate the Safety of Long-term Treatment With Lumacaftor/Ivacaftor Combination Therapy in Subjects Aged 2 Years and Older With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2017-04-24
Enrollment: 57
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A Rollover Safety Study of Lumacaftor/Ivacaftor in Subjects Aged 2 Years and Older With Cystic Fibrosis, Homozygous for F508del.


Eligibility criteria: Inclusion Criteria:

Subjects entering the Treatment Cohort must meet the following criteria:

* Completed 24 weeks of LUM/IVA treatment and the Safety Follow-up Visit in Study VX15-809-115 Part B (Study 115B, NCT02797132)
* Willing to remain on a stable CF medication regimen through the Safety Follow-up Visit

Subjects entering the Observational Cohort must meet 1 of the following criteria:

* Completed 24 weeks of LUM/IVA treatment and the Safety Follow-up Visit in Study 115B, but do not want to enroll in the Treatment Cohort.
* Received at least 4 weeks of LUM/IVA treatment and completed visits up to Week 24 and the Safety Follow-up Visit, if required, of Study 115B but are not taking LUM/IVA at the end of the Study 115B Treatment Period (i.e., Week 24) because of a drug interruption and either did not receive Vertex approval to enroll in the Treatment Cohort or do not want to enroll in the Treatment Cohort.
* Permanently discontinued LUM/IVA in Study 115B after receiving at least 4 weeks of treatment and remained in the study from the time of treatment discontinuation through the Week 24 Visit and Safety Follow-up Visit, if required.

Exclusion Criteria (Treatment Cohort Only):

* Prematurely discontinued LUM/IVA treatment in Study 115B.
* History of any comorbidity or laboratory abnormality that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering LUM/IVA to the subject
* History of drug intolerance or other serious reactions to LUM/IVA in Study 115B that would pose an additional risk to the subject in the opinion of investigator, and which should be discussed with the Vertex medical monitor.
* Subjects with a history of allergy or hypersensitivity to LUM/IVA.
* Liver function test (LFT) abnormality meeting criteria for LUM/IVA treatment interruption at the completion of Study 115B, for which no convincing alternative etiology is identified.
* QTc value at the completion of Study 115B that would pose an additional risk to the subject in the opinion of investigator, and which should be discussed with the Vertex medical monitor
* History of poor compliance with LUM/IVA and/or procedures in Study 115B as deemed by the investigator.
* Participation in an investigational drug trial (including studies investigating LUM and/or IVA) other than Study 115B.

Primary outcomes:
measure: Safety as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 up to Week 98
Secondary outcomes:
measure: Absolute Change in Sweat Chloride
timeFrame: From Parent Study 115B Baseline at Week 96
measure: Absolute Change in Body Mass Index (BMI)
timeFrame: From Parent Study 115B Baseline at Week 96
measure: Absolute Change in BMI-for-age Z-score
timeFrame: From Parent Study 115B Baseline at Week 96
measure: Absolute Change in Weight
timeFrame: From Parent Study 115B Baseline at Week 96
measure: Absolute Change in Weight-for-age Z-score
timeFrame: From Parent Study 115B Baseline at Week 96
measure: Absolute Change From Baseline in Stature (Height)
timeFrame: From Parent Study 115B Baseline at Week 96
measure: Absolute Change in Stature-for-age Z-score
timeFrame: From Parent Study 115B Baseline at Week 96
measure: Time-to-first Pulmonary Exacerbation
timeFrame: From Parent Study 115B Baseline through Week 96
measure: Number of Pulmonary Exacerbations (PEx)
timeFrame: From Parent Study 115B Baseline through Week 96
measure: Number of Cystic Fibrosis (CF) Related Hospitalizations
timeFrame: From Parent Study 115B Baseline through Week 96
measure: Absolute Change in Fecal Elastase-1 (FE-1) Levels
timeFrame: From Parent Study 115B Baseline at Week 96
measure: Absolute Change in Immunoreactive Trypsinogen (IRT) Serum Levels
timeFrame: From Parent Study 115B Baseline at Week 96
measure: Number of Participants With Microbiology Culture Status (Positive or Negative)
timeFrame: Week 96
measure: Absolute Change in Lung Clearance Index (LCI) 2.5
timeFrame: From Parent Study 115B Baseline at Week 96
measure: Absolute Change in Lung Clearance Index (LCI) 5.0
timeFrame: From Parent Study 115B Baseline at Week 96
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Chicago
country: United States
facility: Ann & Robert Lurie Children's Hospital of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children at Indiana University Health
state: Indiana
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: Children's Respiratory and Critical Care Specialists, P.A., Children's Hospitals and Clinics of Minn
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Buffalo
country: United States
facility: The Lung & Cystic Fibrosis Center at Women's & Children's Hospital of Buffalo
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Hospitals
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center/Rainbow Babies and Children's Hospital
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Norfolk
country: United States
facility: Children's Hospital of the King's Daughters
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Vancouver
country: Canada
facility: British Columbia's Children's Hospital
state: British Columbia
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Centre, Glen Site, Montreal Children's Hospital
state: Quebec
Study officials:
References:
citation: Hoppe JE, Chilvers M, Ratjen F, McNamara JJ, Owen CA, Tian S, Zahigian R, Cornell AG, McColley SA. Long-term safety of lumacaftor-ivacaftor in children aged 2-5 years with cystic fibrosis homozygous for the F508del-CFTR mutation: a multicentre, phase 3, open-label, extension study. Lancet Respir Med. 2021 Sep;9(9):977-988. doi: 10.1016/S2213-2600(21)00069-2. Epub 2021 May 6.