A Rollover Safety Study of Lumacaftor/Ivacaftor in Subjects Aged 2 Years and Older With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation

Cystic Fibrosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03125395
• Other study ID #: VX16-809-116
• Secondary ID: 2019-003112-31
• Status: Completed
• Phase: Phase 3
• Start date: May 12, 2017
• Est. completion date: July 17, 2019

Study information

• Verified date: July 2020
• Source: Vertex Pharmaceuticals Incorporated
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: July 17, 2019
• Est. primary completion date: July 17, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• LUM/IVA
Participants received LUM/IVA every q12h.

Locations

Country	Name	City	State
Canada	McGill University Health Centre, Glen Site, Montreal Children's Hospital	Montreal	Quebec
Canada	The Hospital for Sick Children	Toronto	Ontario
Canada	British Columbia's Children's Hospital	Vancouver	British Columbia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Boston Children's Hospital	Boston	Massachusetts
United States	The Lung & Cystic Fibrosis Center at Women's & Children's Hospital of Buffalo	Buffalo	New York
United States	University of North Carolina Hospitals	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Ann & Robert Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	University Hospitals Cleveland Medical Center/Rainbow Babies and Children's Hospital	Cleveland	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Texas Children's Hospital	Houston	Texas
United States	Riley Hospital for Children at Indiana University Health	Indianapolis	Indiana
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	Children's Respiratory and Critical Care Specialists, P.A., Children's Hospitals and Clinics of Minn	Minneapolis	Minnesota
United States	Children's Hospital of the King's Daughters	Norfolk	Virginia
United States	Stanford University	Palo Alto	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Seattle Children's Hospital	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)		Day 1 up to Week 98
Secondary	Absolute Change in Sweat Chloride	Sweat samples were collected using an approved collection device.	From Parent Study 115B Baseline at Week 96
Secondary	Absolute Change in Body Mass Index (BMI)	BMI was defined as weight in kilogram (kg) divided by height in square meter (m^2).	From Parent Study 115B Baseline at Week 96
Secondary	Absolute Change in BMI-for-age Z-score	BMI was defined as weight in kilograms divided by height in m^2. z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean.	From Parent Study 115B Baseline at Week 96
Secondary	Absolute Change in Weight		From Parent Study 115B Baseline at Week 96
Secondary	Absolute Change in Weight-for-age Z-score	Z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean.	From Parent Study 115B Baseline at Week 96
Secondary	Absolute Change From Baseline in Stature (Height)		From Parent Study 115B Baseline at Week 96
Secondary	Absolute Change in Stature-for-age Z-score	Z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean.	From Parent Study 115B Baseline at Week 96
Secondary	Time-to-first Pulmonary Exacerbation	Pulmonary exacerbation was defined as new or changed treatment with oral, inhaled, or intravenous antibiotics and fulfillment of pre-specified protocol-defined criteria.	From Parent Study 115B Baseline through Week 96
Secondary	Number of Pulmonary Exacerbations (PEx)	Pulmonary exacerbation was defined as new or changed treatment with oral, inhaled, or intravenous antibiotics and fulfillment of pre-specified protocol-defined criteria.	From Parent Study 115B Baseline through Week 96
Secondary	Number of Cystic Fibrosis (CF) Related Hospitalizations		From Parent Study 115B Baseline through Week 96
Secondary	Absolute Change in Fecal Elastase-1 (FE-1) Levels		From Parent Study 115B Baseline at Week 96
Secondary	Absolute Change in Immunoreactive Trypsinogen (IRT) Serum Levels		From Parent Study 115B Baseline at Week 96
Secondary	Number of Participants With Microbiology Culture Status (Positive or Negative)	Following microbial tests were performed: Burkholderia, Methicillin Resistant Staphylococcus Aureus (MRSA), Methicillin Susceptible Staphylococcus Aureus (MSSA), Pseudomonas Aeruginosa Mucoid (P. Aeruginosa Mucoid), P. Aeruginosa Non-Mucoid, P. Aeruginosa Small Colony Variant and Stenotrophomonas Maltophilia.	Week 96
Secondary	Absolute Change in Lung Clearance Index (LCI) 2.5	LCI 2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.	From Parent Study 115B Baseline at Week 96
Secondary	Absolute Change in Lung Clearance Index (LCI) 5.0	LCI 5.0 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/20th of its starting value.	From Parent Study 115B Baseline at Week 96