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CompletedNCT03277196Updated Oct 23, 2024Results posted

A Study to Evaluate the Safety of Long-term Ivacaftor Treatment in Participants With Cystic Fibrosis Who Are Less Than 24 Months of Age at Treatment Initiation and Have an Approved Ivacaftor-Responsive Mutation

A Phase 3 interventional study of IVA in Cystic Fibrosis, sponsored by Vertex Pharmaceuticals Incorporated. Completed at 29 sites in 6 countries. Open to participants aged 0 Months to 24 Months. Per ClinicalTrials.gov, last updated 2024-10-23.

Sponsored by Vertex Pharmaceuticals Incorporated · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
86
Allocation
Non-randomized
Ages
0 Months to 24 Months
Sex
All
01

Study summary

This is a Phase 3, 2-arm, multicenter study with an open-label ivacaftor arm and an observational arm to evaluate the safety and efficacy of long-term ivacaftor treatment in participants with cystic fibrosis (CF) who are \<24 months of age at treatment initiation and have an approved Ivacaftor-Responsive mutation.

02

Conditions studied

  • Cystic Fibrosis
03

Who can participate

Ages eligible
0 Months to 24 Months
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

Ivacaftor Arm: Participants From Study 124 (NCT02725567 ) Part B:

  • Participants transitioning from Study 124 Part B must have completed the last study visit of Study 124 Part B.
  • As judged by the investigator, parent or legal guardian must be able to understand protocol requirements, restrictions, and instructions; and must sign the informed consent form (ICF).

Ivacaftor Arm: Participants Not From Study 124 Part B:

  • Confirmed diagnosis of CF, or 2 CF-causing mutations.
  • An ivacaftor- responsive CFTR mutation on at least 1 allele. Participants will be eligible in countries/regions where ivacaftor is approved for use in participants 2 years of age and older.
  • As judged by the investigator, parent or legal guardian must be able to understand protocol requirements, restrictions, and instructions; and must sign the ICF.

Observational Arm:

  • Received ivacaftor treatment in Study 124 Part B and elected not to enroll or ineligible to enroll in the ivacaftor arm of Study 126.

Exclusion criteria

Exclusion Criteria:

Ivacaftor Arm: Participants From Study 124 Part B:

  • History of any illness or condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering ivacaftor to the participant.
  • Participants receiving commercially available ivacaftor treatment

Ivacaftor Arm: Participants Not From Study 124 Part B:

  • History of any illness or condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering ivacaftor to the participant
  • An acute upper or lower respiratory infection, or pulmonary exacerbation, or changes in therapy for pulmonary disease within 4 weeks of Day 1
  • Abnormal liver function at screening
  • Hemoglobin \<9.5 g/dL at screening
  • History of solid organ or hematological transplantation
  • Use of any moderate or strong inducers or inhibitors of CYP3A within 2 weeks of Day 1

Observational Arm:

  • Receiving ivacaftor treatment

Other protocol defined Inclusion/Exclusion criteria may apply.

04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
86 participants (actual)

Study arms

  • Experimental
    Ivacaftor Arm

    Participants less than (\<) 24 months of age and weighing 5 to less than (\<) 7 kilogram (kg) received 25 mg IVA every 12 hours (q12h), 7 to \<14 kg received 50 mg IVA q12h, and those weighing 14 to \<25 kg received 75 mg IVA q12h. Participants more than or equal (\>=) 24 months of age and weighing \<14 kg received 50 mg IVA q12h, and those weighing more than or equal to (\>=)14 kg received 75 mg IVA q12h in the treatment period for up to 96 weeks. Doses were determined based on safety and pharmacokinetic (PK) data from parent study, age and weight.

    Drug: IVA

  • No intervention
    Observational Arm

Interventions

  • DrugIVA

    Granules for oral administration.

    Also known as: VX-770, ivacaftor

05

What researchers measure

Primary outcomes

  1. Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs

    Time frame: Day 1 up to Week 120

Secondary outcomes

  1. Absolute Change in Sweat Chloride

    Sweat samples were collected using an approved collection device.

    Time frame: From Baseline at Week 96

06

Results

Posted Oct 23, 2024

Participant flow

This study was planned to include 2 arms: an ivacaftor (IVA) arm (open-label, 96-week treatment period) and an observational arm. However, there were no participants enrolled in the observational arm. A total of 86 participants enrolled in the Ivacaftor arm.

Participant flow — Overall Study
MilestoneIvacaftor Treatment
Started86
Rollover participants38
Iva-naïve participants48
Completed58
Not completed28
Withdrew: Commercial drug is available for participants20
Withdrew: Lost to follow-up3
Withdrew: Withdrawal of consent (not due to ae)3
Withdrew: Other2

Outcome measures

PrimarySafety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
Time frame:
Day 1 up to Week 120
Reported as:
Count of participants · Participants
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
ParticipantsIvacaftor Treatment
Participants with TEAEs85
Participants with SAEs21
SecondaryAbsolute Change in Sweat Chloride

Sweat samples were collected using an approved collection device.

Time frame:
From Baseline at Week 96
Reported as:
Mean · millimole per liter (mmol/L)
Absolute Change in Sweat Chloride
millimole per liter (mmol/L)Ivacaftor Treatment
Absolute Change in Sweat Chloride-55.3 ± 25.0

Adverse events

Collected over Day 1 up to Week 120. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Ivacaftor Arm0/86 (0%)21/86 (24.4%)83/86 (96.5%)
Most frequent serious events
Showing 10 of 23
Most frequent serious events
EventIvacaftor Arm
Infective pulmonary exacerbation of cystic fibrosisInfections and infestations9/86
ConstipationGastrointestinal disorders2/86
Pseudomonas test positiveInvestigations2/86
Adrenocortical insufficiency acuteEndocrine disorders1/86
Distal intestinal obstruction syndromeGastrointestinal disorders1/86
PyrexiaGeneral disorders1/86
BronchiolitisInfections and infestations1/86
BronchitisInfections and infestations1/86
GastroenteritisInfections and infestations1/86
Gastroenteritis viralInfections and infestations1/86
Most frequent other events
Showing 10 of 28
Most frequent other events
EventIvacaftor Arm
CoughRespiratory, thoracic and mediastinal disorders60/86
PyrexiaGeneral disorders34/86
RhinorrhoeaRespiratory, thoracic and mediastinal disorders33/86
Upper respiratory tract infectionInfections and infestations24/86
VomitingGastrointestinal disorders22/86
RashSkin and subcutaneous tissue disorders21/86
Ear infectionInfections and infestations19/86
DiarrhoeaGastrointestinal disorders15/86
ConstipationGastrointestinal disorders13/86
Infective pulmonary exacerbation of cystic fibrosisInfections and infestations13/86

Baseline characteristics

Baseline data was analyzed on safety Set which is defined as all participants who received at least 1 dose of study drug.

Age, Continuous
Age, Continuous(months)Ivacaftor Treatment
Mean10.2 ± 5.19
Sex: Female, Male
Sex: Female, Male(Participants)Ivacaftor Treatment
Female40
Male46
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Ivacaftor Treatment
Hispanic or Latino2
Not Hispanic or Latino79
Not collected per local regulations5
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Ivacaftor Treatment
White82
Asian1
Not collected per local regulations3
07

Study locations

29 sites
  • University of Alabama at Birmingham
    Birmingham, Alabama 35233, United States
  • Stanford University
    Palo Alto, California 94034, United States
  • Alfred I DuPont Hospital for Children
    Wilmington, Delaware 19803, United States
  • Nemours Children's Hospital
    Orlando, Florida 32827, United States
  • Center for Advanced Pediatrics
    Atlanta, Georgia 30329, United States
  • Northwestern University
    Chicago, Illinois 60611, United States
  • Riley Hospital for Children at Indiana University Health
    Indianapolis, Indiana 46202, United States
  • John Hopkins Hospital
    Baltimore, Maryland 21287, United States
  • Boston Children's Hospital
    Boston, Massachusetts 02115, United States
  • Childrens's Hospitals and Clinics of Minnnesota
    Minneapolis, Minnesota 55404, United States
  • Children's Mercy Hospital
    Kansas City, Missouri 64108, United States
  • Billings Clinic Hospital
    Billings, Montana 59101, United States
  • Nationwide Children's Hospital
    Columbus, Ohio 43205, United States
  • Children's Hospital of Philadelphia
    Philadelphia, Pennsylvania 19104, United States
  • Texas Children's Hospital
    Houston, Texas 77030, United States
  • Seattle Children's Hospital
    Seattle, Washington 98105, United States
  • University of Wisconsin
    Madison, Wisconsin 53792, United States
  • Queensland Children's Hospital
    South Brisbane, Australia
  • The Hospital for Sick Children
    Toronto, Ontario, Canada
  • Universitaetsklinikum Heidelberg, Zenter fuer Kinder-und Jugendmedizin
    Heidelberg, Germany
  • Children's Health Ireland at Crumlin
    Dublin, Ireland
  • Children's University Hospital Temple Street
    Dublin, Ireland
  • University Hospital Limerick
    Limerick, Ireland
  • Paediatric Clinical Research Facility
    Edinburgh, United Kingdom
  • Alder Hey Children's Alder Hey Children's NHS Foundation Trust
    Liverpool, United Kingdom
  • Great Ormond Street Hospital for Sick Children
    London, United Kingdom
  • Royal Brompton & Harefield NHS Founcation Trust, Royal BromptonHospital
    London, United Kingdom
  • Royal Manchester Children's Hospital
    Manchester, United Kingdom
  • Oxford University Hospitals NHS Trust, John Radcliffe Hospital
    Oxford, United Kingdom
08

References and documents

Study documents

  • Study protocol · Oct 5, 2017
  • Statistical analysis plan · Apr 25, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No — Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/independent-research/clinical-trial-data-sharing

09

Registry details

Key details

Study ID
NCT03277196
Lead sponsor
Vertex Pharmaceuticals Incorporated
Responsible party
Sponsor
First posted
Sep 8, 2017
Start date
Aug 16, 2017
Primary completion
Oct 2, 2023
Completion
Oct 2, 2023
Results posted
Oct 23, 2024
Last update
Oct 23, 2024

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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