The Topic Trial - Study to Determine the Safety and Efficacy of Ivacaftor

NCT03085485 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: F1609200091R34HL127166-01
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The study is a Phase 2 Study to establish the safety and efficacy of a drug called Ivacaftor (VX-770) in patients with chronic obstructive pulmonary disease (COPD), chronic bronchitis, and acquired CFTR dysfunction as detected by sweat chloride analysis. The design is a pilot, randomized (3:1, active:placebo), double-blind, placebo-controlled study. Approximately 40 subjects with COPD will be randomized.

Conditions

Chronic Obstructive Pulmonary Disease; Chronic Bronchitis

Keywords

COPD; CFTR; ivacaftor; topic trial

Outcome Measures

Primary Outcomes (4)

• Safety of Ivacaftor - Number of Participants With Adverse Events

  Safety of ivacaftor will be determined by number of participants with adverse events (including serious adverse events).

  From Screening to Day 98

• Safety of Ivacaftor - Number of Participants With Abnormal Serum Chemistry

  Number of participants with abnormal serum chemistry values compared to screening values will also be used to determine safety of ivacaftor.

  From Screening to Day 98

• Safety of Ivacaftor - Number of Participants With Abnormal Hematology

  Safety of ivacaftor will also be determined by number of participants with abnormal changes in their screening hematology values.

  From Screening to Day 98

• Safety of Ivacaftor - Number of Participants With Abnormal ECG (Prolonged QT Intervals)

  Number of participants with abnormal changes in their screening ECGs is another factor that will be used to evaluate the safety of ivacaftor.

  From Screening to Day 98

Secondary Outcomes (7)

• Central CFTR Activity Measured by Mucociliary Clearance (MCC) Percentage Clearance at 60 Mins

  From Screening to Day 84

• Peripheral CFTR Activity Measured by Change in Sweat Chloride

  From Screening to Day 84

• Indicators of Respiratory Function and COPD Health : Change in FEV1 Predict %

  From Screening to Day 84

• San Diego Shortness of Breath Questionnaire (SOBQ)

  From D1 to Day 84

• Breathlessness, Cough, and Sputum Scale (BCSS)

  From D1 to Day 84

Study Arms (2)

Ivacaftor

ACTIVE COMPARATOR

Ivacaftor, 150 mg PO every 12 hrs for 84 days

Drug: Ivacaftor 150 MG

Placebo

PLACEBO COMPARATOR

matching placebo

Drug: Placebo

Interventions

Ivacaftor 150 MG DRUG

Ivacaftor is a CFTR potentiator

Also known as: KALYDECO

Ivacaftor

Placebo DRUG

placebo pills

Placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or Female age 40-80
• A Clinical diagnosis of COPD as defined by GOLD
• At Least a 10 pack year smoking history
• Exhibit symptoms of chronic bronchitis as defined by the Medical Research Council
• FEV1% predicted ≥ 35% and ≤70% Post Bronchodilator
• Clinically stable in the last 4 weeks with no evidence of COPD exacerbation
• Weight of 40 kg-120 kg
• Willingness to use at least one form of acceptable birth control including abstinence, condom with spermicide, or hormonal contraceptives from time of signing ICF through study follow up visit
• Willing to monitor blood glucose if known history of diabetes mellitus requiring insulin or medical therapy
• Element of CFTR Dysfunction, as defined by Sweat Chloride \> 30 mEq/L)

You may not qualify if:

• Current Diagnosis of Asthma
• Known Diagnosis of Cystic Fibrosis
• Use of Continuous Oxygen Therapy of greater than 2 liters per minute - patients on 2 liters of Oxygen or less will be excluded if they have been hospitalized for COPD in the prior year or had more than 2 exacerbations requiring steroids and/or antibiotics in the prior year.
• Documented history of drug abuse within the last year
• Subjects should not have a pulmonary exacerbation or changes in therapy for pulmonary disease within 28 days before receiving the first dose of study drug.
• Cirrhosis or elevated liver transaminases \> 3X ULN
• GFR \< 50 estimated by Cockroft-Gault
• Any illness or abnormal lab finding 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.
• Pregnant or Breastfeeding
• Subjects taking moderate or strong inhibitors or inducers of CYP3A4, including certain herbal medications and grapefruit juice. (Excluded medications and foods including the drugs and foods listed in the IRB HSP application.)
• Uncontrolled Diabetes
• Recent (e.g 1year) arterial thrombotic events (peripheral arterial disease, thrombotic stroke)
• Clinically significant arrhythmias requiring anti-arrhythmic agent(s) or conduction abnormalities that in the opinion of the investigator that affect patient safety such as the abnormalities listed below (patients with stable coronary artery disease are eligible) : (1) Angina symptoms (2) History of MI (3) Revascularization procedure in the last year prior to screening (4) Clinically significant congestive heart failure (known LVEF \<= 45%, cor pulmonale, diastolic heart failure, etc)

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Vertex Pharmaceuticals Incorporated: collaborator

Study Sites (1)

UAB Lung Health Center

Birmingham, Alabama, 35294, United States

Location

Related Publications (1)

• Vijaykumar K, Solomon GM, Guimbellot J, Acosta EP, Bhambhavni PG, White S, Kim H, Raju SV, Rasmussen LW, Harris N, Liu B, Hathorne H, Rowe SM, Dransfield MT. Ivacaftor for Chronic Obstructive Pulmonary Disease: Results from a Phase 2, Randomized Controlled Trial. Am J Respir Crit Care Med. 2025 May;211(5):823-831. doi: 10.1164/rccm.202407-1302OC.

  PMID: 39316773 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Bronchitis, Chronic

Interventions

ivacaftor

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bronchitis; Respiratory Tract Infections; Infections; Bronchial Diseases

Results Point of Contact

• Title: Bo Liu
• Organization: University of Alabama at Birmingham

boliu@uabmc.edu

(205) 975-7868

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: The design is a pilot, randomized (3:1, active:placebo), double-blind, placebo-controlled study

Study Record Dates

• First Submitted: February 16, 2017
• First Posted: March 21, 2017
• Study Start: March 16, 2017
• Primary Completion: September 30, 2022
• Study Completion: September 30, 2022
• Last Updated: December 12, 2024
• Results First Posted: December 21, 2023

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)