XXB750 for Heart Failure

Recruiting at 8 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Novartis Pharmaceuticals

Must be taking: Beta blockers, ACE inhibitors, ARBs, Sacubitril/valsartan

Must not be taking: ACE inhibitors, ARBs, Sacubitril/valsartan

Disqualifiers: Severe pulmonary disease, eGFR <45, others

Compensation: Varies

Number of Visits: Unknown

Duration: 13 weeks for Cohort 1, 146 days for Cohort 2

27 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new medication, XXB750, in patients with certain types of heart failure. It aims to see if the drug can improve heart function and be safely used alongside other treatments.

Will I have to stop taking my current medications?

The trial requires participants to be on a stable dose of certain medications. If you are in Cohort 1, you must be on a stable dose of a beta blocker and an ACE inhibitor or ARB. If you are in Cohort 2, you must be on a stable dose of a beta blocker and sacubitril/valsartan. You may need to stop taking sacubitril/valsartan if you are in Cohort 1 or ACE inhibitor/ARB if you are in Cohort 2, at least 4 weeks before screening.

What data supports the effectiveness of the drug XXB750 for heart failure?

The research highlights that placebo treatments in heart failure can lead to improvements in exercise duration and symptoms, suggesting that the supportive environment and repeated assessments in clinical trials can enhance patient outcomes. This implies that any observed benefits of XXB750 should be carefully evaluated against these placebo effects to determine its true effectiveness. ^{1 2 3 4 5}

How does the drug XXB750 differ from other heart failure treatments?

XXB750 is unique because it is being compared to a placebo, which has shown significant improvements in exercise duration and symptoms in heart failure patients, highlighting the importance of the placebo effect in treatment outcomes. ^{1 2 4 6 7}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

This trial is for adults with heart failure who have a left ventricular ejection fraction (LVEF) of 50% or less. They must have stable blood pressure and heart rate, be on certain heart medications, and not severely overweight. Excluded are those with severe lung disease, recent acute heart failure or cardiovascular events, significant valve disease, recent device implantation in the heart, or poor kidney function.

Inclusion Criteria

Your heart's pumping ability is less than 50% as shown in recent tests.

Your blood pressure is between 110-160 mmHg for cohort 1 or 105-160 mmHg for cohort 2, and your heart rate is between 50-90 beats per minute.

You have heart problems that affect your ability to do regular activities.

Exclusion Criteria

You have a history of serious lung disease needing ongoing oxygen therapy or medicine for high blood pressure in the lungs.

Other protocol-specific criteria may apply

You had severe heart failure in the last 3 months before the screening.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Cohort 1 receives a single dose of XXB750 or placebo, followed by a domiciling period. Cohort 2 receives three doses of XXB750 or placebo, each followed by a domiciling period.

13 weeks for Cohort 1, 146 days for Cohort 2

Follow-up

Participants are monitored for safety, tolerability, and pharmacokinetics after treatment

13 weeks for Cohort 1, 13 weeks for Cohort 2

Treatment Details

Interventions

• Placebo
• XXB750

Trial Overview The study tests the safety and tolerability of a new medication called XXB750 compared to a placebo in patients with reduced (HFrEF) or mildly reduced (HFmrEF) ejection fraction. Participants will receive either XXB750 or placebo without knowing which one they get while researchers monitor their reactions over time.

Participant Groups

Group I: XXB750 Cohort 2 Experimental Treatment 1 Intervention

XXB750, multiple doses

Group II: XXB750 Cohort 1 Experimental Treatment 1 Intervention

XXB750, single dose

Group III: Placebo Cohort 1 Placebo Group 1 Intervention

Placebo, single dose

Group IV: Placebo Cohort 2 Placebo Group 1 Intervention

Placebo, multiple doses

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Findings from Research

In a study of 5050 patients with heart failure, vericiguat did not significantly improve health status outcomes measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) compared to placebo, indicating it may not enhance quality of life despite its use.

However, vericiguat effectively reduced the risk of cardiovascular death or heart failure hospitalization across different baseline health statuses, suggesting it is beneficial for clinical outcomes in heart failure patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vericiguat and Health-Related Quality of Life in Patients With Heart Failure With Reduced Ejection Fraction: Insights From the VICTORIA Trial. Butler, J., Stebbins, A., Melenovský, V., et al.[2022]

The Heart Failure Collaboratory gathered a diverse group of stakeholders to discuss the need for standardizing background therapies in clinical trials for heart failure, particularly for patients with reduced ejection fraction.

The paper emphasizes the importance of establishing a common background therapy to improve the comparability and reliability of results in future heart failure treatment studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal Background Pharmacological Therapy for Heart Failure Patients in Clinical Trials: JACC Review Topic of the Week. Fiuzat, M., Hamo, CE., Butler, J., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Vericiguat and Health-Related Quality of Life in Patients With Heart Failure With Reduced Ejection Fraction: Insights From the VICTORIA Trial. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Placebo treatment in congestive heart failure. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Optimal Background Pharmacological Therapy for Heart Failure Patients in Clinical Trials: JACC Review Topic of the Week. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

The placebo effect in heart failure. [2019]

5. England pubmed.ncbi.nlm.nih.gov

A putative placebo analysis of the effects of LCZ696 on clinical outcomes in heart failure. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Adverse effects of enalapril in the Studies of Left Ventricular Dysfunction (SOLVD). SOLVD Investigators. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Quality of life among 5,025 patients with left ventricular dysfunction randomized between placebo and enalapril: the Studies of Left Ventricular Dysfunction. The SOLVD Investigators. [2019]