Personalized Theratyping Trial

The purpose of this study is to explore the use of off-label CFTR modulators that may affect CFTR function in patients with CFTR mutations that are not currently approved for these drugs.

Study Overview

• Status: Recruiting
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Symdeko

Detailed Description

The purpose of this study is to explore the use of off-label CFTR modulators that may affect CFTR function in patients with CFTR mutations that are not currently approved for these drugs. Symdeko (Tezacaftor/Ivacaftor), Orkambi (Ivacaftor and Lumacaftor), correctors of CFTR misfolding and Kalydeco (Ivacaftor), a potentiator of abnormal CFTR gating, will be explored as a treatment for patients with other CF mutations than those currently approved. Patients who have a mutation that responds to a CFTR corrector from in vitro study will be given Symdeko, or Orkambi, depending on the in vitro response pattern. Patients who have mutation response to a potentiator of CFTR function will be given Ivacaftor monotherapy. Patients with a mutation equivalent to wild type will be given Ivacaftor. If the patient is 6-12 years old, we will only study Orkambi or ivacaftor as symdeko is not yet FDA approved in this patient population.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Heather Hathorne, PhD; Phone Number: 205-638-9568; Email: hhathorne@peds.uab.edu

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • University of Alabama at Birmingham
      • Principal Investigator: George Solomon, MD
      • Contact: Heather Hathorne, PhD; Phone Number: 205-638-9568; Email: hhathorne@peds.uab.edu
      • Contact: Ginger Reeves, BS; Phone Number: 205-638-5970; Email: greeves@peds.uab.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of CF
• Age ≥6 y.o.
• CFTR mutation that may respond to approved correctors/potentiators in the opinion of the study investigators
• Informed Consent/Assent
• Stable CF pulmonary regimen

Exclusion Criteria:

• Exacerbation requiring antibiotic or steroids for >28 days before trial entry
• Ongoing participation in a CFTR modulator study
• Active smoking in the past 6 months
• History of solid organ transplant
• Any condition which precludes the use of CFTR modulators: e.g. advanced cirrhosis, End-stage Renal Disease (ESRD)
• Any condition that precludes the patient from participation in the opinion of the investigator
• Any meds that have significant drug-drug interactions or any other off label use of CFTR modulators

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Symdeko; Patients who have a mutation that responds to a CFTR corrector from in vitro study will be given Symdeko, depending on the in vitro response pattern	Drug: Symdeko; explore the use of off-label CFTR modulators that may affect CFTR function in patients with CFTR mutations that are not currently approved for these drugs.; Other Names: Orkambi; Ivacaftor
Experimental: Ivacaftor; Patients who have mutation response to a potentiator of CFTR function will be given Ivacaftor monotherapy.. Patients with a mutation equivalent to wild type will be given Ivacaftor.	Drug: Symdeko; explore the use of off-label CFTR modulators that may affect CFTR function in patients with CFTR mutations that are not currently approved for these drugs.; Other Names: Orkambi; Ivacaftor
Experimental: Orkambi; Patients who have a mutation that responds to a CFTR corrector from in vitro study will be given Orkambi, depending on the in vitro response pattern	Drug: Symdeko; explore the use of off-label CFTR modulators that may affect CFTR function in patients with CFTR mutations that are not currently approved for these drugs.; Other Names: Orkambi; Ivacaftor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
spirometry	change in lung function as measured via spirometry	32 weeks

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2019
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: July 3, 2018
• First Submitted That Met QC Criteria: July 3, 2018
• First Posted (Actual): July 16, 2018

Study Record Updates

• Last Update Posted (Actual): September 11, 2023
• Last Update Submitted That Met QC Criteria: September 8, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Cystic Fibrosis; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Chloride Channel Agonists; Ivacaftor
• Other Study ID Numbers: IRB-300001867

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No