Hyperpolarized Imaging for New Treatments

• Status: Recruiting
• Trial end date: 2025-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The introduction of triple combination CFTR modulator therapy for patients with Cystic Fibrosis (CF) with at least one copy of the deltaF508 mutation is expected to provide major health benefits, but will also require novel outcome measures that can detect CF lung disease at an early stage, capture the efficacy of new therapies when disease manifestations are limited, as well as determine whether stopping existing chronic maintenance therapies does not have negative effects.

In the past decade, research has focused on the multiple breath washout (MBW) test, as a sensitive outcome measure, especially if highly-effective modulator therapies are initiated in early childhood. Even LCI, however, may not adequately capture early lung function changes, thus warranting investigation of even more sensitive outcome measures.

Magnetic resonance imaging (MRI) has the advantage of being a radiation-free modality, making it more suitable for assessing response to therapy in a shorter time frame with repeated imaging. Inhalation of a hyperpolarized gas enables the visualization and quantification of regional ventilation in the lung and can be combined with structural MRI to assess both structure and function in parallel.

The main Investigator and others have recently formed an international consortium (the 129Xe MRI Clinical Trial Consortium), comprised of both imaging experts and pulmonary clinicians to standardize imaging procedures, thus facilitating multi-site implementations. Data from this proposed study (HyPOINT; Hyperpolarized Imaging for New Treatments) will inform the future utility of MRI for both longitudinal studies to track disease progression over time as well as for future interventional trials. Further, the current study could inform the design of future trials of interventions of patients for whom currently no effective CFTR modulator therapy is available and for patients with rare genotypes thus laying the groundwork for a more personalized medicine approach in the near-term future.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Children's Hospital Medical Center, Cincinnati
• Collaborators: The Hospital for Sick Children; University of Virginia; University of Wisconsin, Madison

Criteria

Inclusion Criteria:

1. Written informed consent (and assent when applicable) obtained from subject or subject's legal representative.

2. Willingness and ability to adhere to the study visit schedule and other protocol requirements.

3. Documentation of a CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and one or more of the following criteria:

1. Sweat chloride equal to or greater than 60 mEq/liter by quantitative pilocarpine iontophoresis test

2. Two well-characterized mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene

4. Phase 1 only: Age 6 to 18 years, inclusive, at the time of consent.

5. Phase 2 only: Ages 9 to 18 years, inclusive, at the time of consent.

6. Clinically stable with no acute antibiotic usage in the 14 days prior to the first visit.

7. Genotype with F508del on at least one allele.

8. No change in chronic pulmonary medications or therapies in the 28 days prior to the first visit.

9. Stable CFTR modulator therapy (TEZ/IVA or LUM/IVA) for at least 28 days prior to the first visit or currently not receiving CFTR modulator therapy.

10. Ability to cooperate with MRI procedures.

11. Phase 1 only: FEV1 greater than or equal to 80% predicted based on GLI reference equations.

Exclusion Criteria:

1. Standard MRI exclusions (Metal implants, claustrophobia).

2. For females of childbearing potential: Positive urine pregnancy test at Screening or Visit 1 or Lactating.

3. Any other condition that, in the opinion of the Site Investigator/designee, would preclude informed consent or assent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.