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

Recruiting now · Phase 2 · Has a placebo group

Conditions studied: Heart Failure With Reduced Ejection Fraction

In brief

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.

Key facts

Study ID

NCT07695090

Run by

Qanatpharma AG

People needed

60

Starts

2026-07-01

Expected to finish

2027-09-01

Last updated by the study team

2026-07-17

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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.
• Females taking oral or transdermal hormonal contraceptives within 30 days prior to first study drug administration
• Female participants who are currently breastfeeding or planning to breastfeed
• Any malignancy not considered cured (except basal cell carcinoma of the skin). A participant is considered cured if there has been no evidence of cancer recurrence for the 5 years prior to screening
• Unstable coronary syndromes
• Moderate or severe valvular disease
• Body mass index >40 kg/m2
• Estimated glomerular filtration rate (eGFR) of <30 ml/m2
• Participants with a ferro-magnetic aneurysm clip or vascular clamp that is non-MRI compatible
• Claustrophobia or inability to undergo MRI without sedation
• Any other recognized CMRI contraindication as per local guidelines

Where it is running

• St. Michael's Hospital — Toronto, Ontario, Canada (enrolling)
• University Health Network (UHN) Peter Munk Cardiac Centre — Toronto, Ontario, Canada

Full record on ClinicalTrials.gov

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