Lumacaftor Yields Reversal of Impaired Cerebral Blood Flow in Heart Failure Patients

NCT07695090 | Recruiting Phase 2 DMC

• 1 other identifier: QP586-A01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief Summary

Cognitive impairment (CI) is highly prevalent in patients with heart failure with reduced ejection fraction (HFrEF), which has significant implications for disease management, quality of life and clinical outcomes. Currently, there are no specific treatments for CI aside from the current standard of care therapy for HF, making this a high unmet medical need. Impaired cerebral autoregulation is a proposed mechanistic factor that leads to cerebral hypoperfusion, ischemic damage and the development for CI. Preclinical data indicates that restoring CFTR-protein expression normalizes cerebral microvascular function and cerebral blood flow (CBF) in models of HF. The purpose of this study is to investigate whether CFTR-targeting therapy enhances cerebral perfusion and cognitive function in heart failure patients using the CFTR-corrector Lumacaftor.

Conditions

Heart Failure With Reduced Ejection Fraction

Keywords

Heart Failure with Reduced Ejection Fraction; Cognitive Impairment; Cerebral Blood Flow; CFTR; Microvascular

Outcome Measures

Primary Outcomes (1)

• Efficacy of lumacaftor treatment in increasing cerebral blood flow versus placebo in HFrEF patients.

  Change from baseline in global cerebral blood flow at 1 month using treatment or placebo as assessed by perfusion weighted MRI.

  Baseline and 1 month

Secondary Outcomes (10)

• Rate of treatment-emergent adverse events as assessed by MedDRA.

  Baseline up to Day 90

• Number of participants with clinically significant changes from baseline in physical examinations findings at 1 week, 1 month and 3 months.

  Baseline, 1 week, 1 month and 3 months

• Number of participants with clinically significant changes from baseline in vital signs at 1 week, 1 month and 3 months.

  Baseline, 1 week, 1 month and 3 months

• Number of participants with clinically significant changes from baseline in electrocardiograms (ECGs) at 1 week, 1 month and 3 months.

  Baseline, 1 week, 1 month and 3 months

• Number of participants with clinically significant changes from baseline in laboratory test results at 1 week, 1 month and 3 months.

  Baseline, 1 week, 1 month and 3 months

Study Arms (2)

Lumacaftor

EXPERIMENTAL

Participants receive 1 tablet of Lumacaftor 200 mg twice daily for 30 days.

Drug: Lumacaftor 200 MG

Placebo

PLACEBO COMPARATOR

Participants receive 1 tablet of Lumacaftor placebo tablet twice daily for 30 days.

Drug: Placebo

Interventions

Lumacaftor 200 MG DRUG

Lumacaftor 200 mg q12

Lumacaftor

Placebo DRUG

Identical placebo

Placebo

Eligibility Criteria

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

You may qualify if:

• Participants screened for enrolment must meet all of the following criteria to be eligible for study participation:
• Provide written informed consent
• Aged 18 years or older with stable heart failure NYHA class II-III, with reduced cardiac output and an EF of \<40% on optimal goal directed medical therapy as per CCS Guidelines and the AHA/ACC/HFSA Guidelines for the Management of Heart Failure
• No hospital admissions for inpatient care in 3 months prior to study
• CBF at screening of ≤45 mL/100g/min
• Able to comply with study procedures
• Female participants must fulfill at least one of the following:
• Negative serum pregnancy (β-hCG) test at screening if participant is of childbearing potential (defined as having gone through menarche and not postmenopausal)
• Post-menopausal for a minimum of 1 year (defined as 12 consecutive months with no menses without an alternative medical cause) Be surgically sterile for a minimum of 6 months (achieved through partial/total hysterectomy, bilateral oophorectomy, or bilateral salpingectomy; note that tubal ligation is not considered a method of permanent sterilization)
• Agree to avoid pregnancy and be willing to use medically acceptable methods of contraception for the duration of study and for 1 month after the last dose of the IMP (for females) and for 3 months after the last dose (for males)

You may not qualify if:

• Participants screened for enrolment, meeting any of the following criteria are not eligible for study participation:
• Participants with symptomatic HF who have non-MRI compatible cardiac implantable electronic devices (CIEDs), such as a cardiac defibrillator or pacemaker, or in whom this is required within 3 months of the study
• Those requiring coronary revascularisation in 6 months following the study
• Participants with cystic fibrosis (CF) or any other condition that may require use of CFTR modulating agents
• Participants using antiallergics (e.g., montelukast), antibiotics (e.g., clarithromycin), anticoagulants (e.g., warfarin), anticonvulsants (e.g., carbamazepine), antidepressants (e.g., citalopram), antifungals (e.g., fluconazole), anti-mycobacterials (e.g., rifabutin), barbituates, benzodiazepines (e.g., midazolam), immunosuppressants (e.g., cyclosporine), proton pump inhibitors (e.g., esomeprazole) within 30 days of trial start
• A history of or known seropositivity for human immunodeficiency virus (HIV) and active hepatitis B and/or C infection
• Participants with moderate or severe hepatic disease (such as cirrhosis), or impaired liver function tests defined as serum ALT and/or AST \>3 x the upper limit of normal (ULN) or total bilirubin \>2 x ULN
• Resting heart rate of \>100 bpm
• Symptomatic blood pressure \<90 mmHg systolic
• Any major deviation in clinical lab values and/or electrocardiograms deemed clinically significant at baseline that in the opinion of the investigator would compromise the outcome of the trial as it relates to the active therapy
• Any clinically significant abnormalities in physical examination, neurological examination, vital signs, safety laboratory tests, and/or electrocardiograms that may impact the safety of the participant, in the opinion of the investigator
• Any suicidal behaviour in the past 2 years (i.e., actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behaviour), or any suicidal ideation (type 4 or 5) in the last 6 months (i.e., active suicidal thought with intent but without specific plan, or active suicidal thought with plan and intent), as defined by the C-SSRS
• Participants currently experiencing any clinically significant or unstable medical condition that in the opinion of the investigator might limit their ability to complete the study, or to comply with the requirements of the protocol, including dermatologic disease, haematological disease, pulmonary disease, kidney disease, hepatic disease, gastrointestinal disease, genitourinary disease, endocrine disease, neurological disease, and psychiatric disease
• Participants with severe chronic obstructive pulmonary disease (COPD), or demonstrating a significant degree of pulmonary obstruction with a forced expiratory volume in the first second (FEV1) or forced vital capacity (FVC) that is \<70% of the predicted normal value, or FEV/FVC ratio that is \<65%
• Females having used implanted, injected, intravaginal, or intrauterine hormonal contraceptive within 6 months prior to first study drug administration.

Sponsors & Collaborators

• Qanatpharma AG: lead
• Qanatpharma Canada LTD: collaborator

Study Sites (2)

St. Michael's Hospital

Toronto, Ontario, M5B 1M8, Canada

RECRUITING

University Health Network (UHN) Peter Munk Cardiac Centre

Toronto, Ontario, M5G2N2, Canada

NOT YET RECRUITING

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

lumacaftor

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Kim Connelly

  Unity Health Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Qanatpharma Clinical Program Manager

CONTACT

1-877-308-4220; info@qanatpharma.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2025
• First Posted: July 10, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: July 17, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: 12 months after article publication and for up to 36 months following article publication.
• Access Criteria: Data sharing requests can be made by qualified researchers for approved proposals under the terms of a Data Use Agreement.

Locations

CA (2)