XXB750 for Heart Failure

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called XXB750 to determine its safety and tolerability for people with certain types of heart failure. The study includes two groups: one will receive a single dose, and the other will receive multiple doses of XXB750, with some participants receiving a placebo for comparison. It seeks participants who have been living with heart failure that affects their daily life, have had it for a while, and are already on stable heart medications. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that XXB750 has been tested for safety in people with heart failure. Previous studies found it generally well-tolerated. Some research examined different doses of XXB750 and found no severe side effects. However, like many treatments, some people might still experience mild reactions.

XXB750 is currently being tested for heart failure, but this is an early trial. The goal is to assess its safety and tolerability. While past trials provide promising data, more research is needed to fully understand its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for heart failure?

Unlike the standard treatments for heart failure, which often focus on easing symptoms or slowing progression, XXB750 is unique because it directly targets the underlying mechanisms of the condition. Researchers are particularly excited about XXB750 because it introduces a new active ingredient that could potentially improve heart function more effectively. Additionally, the treatment comes in two forms—single and multiple doses—offering flexibility that might lead to more personalized care for patients. This novel approach could represent a significant advancement in how we manage heart failure, potentially leading to better patient outcomes.

What evidence suggests that XXB750 might be an effective treatment for heart failure?

Research has shown that XXB750 might help people with heart failure who have a lower or slightly lower heart pumping ability. In some studies, patients taking XXB750 have exercised longer and felt better. Another study found that XXB750 lowered levels of NT-proBNP, a substance often high in people with heart failure, suggesting that the treatment could improve heart function. Although the research remains in the early stages, these initial results are promising for those considering this treatment. Participants in this trial will receive either XXB750 or a placebo, with some receiving a single dose and others multiple doses, to further evaluate its effectiveness. ^{1 3 6 7 8}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06142383

A Proof of Concept and Dose-finding Study of XXB750 in ...

To evaluate the efficacy and dose-response relationship of three XXB750 target dose levels compared to placebo in reducing NT-proBNP. Baseline to Week 16 ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05328752

Safety and Tolerability Study of XXB750 in Heart Failure ...

To evaluate the safety and tolerability of XXB750 in adult participants with chronic stable heart failure with reduced or mildly reduced ejection fraction ( ...

3.

withpower.com

withpower.com/trial/phase-1-heart-failure-3-2022-0b362

XXB750 for Heart Failure · Info for Participants

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 ...

4.

academic.oup.com

academic.oup.com/eurheartj/article/45/47/5087/7887814

Centrally adjudicated vs. investigator-reported outcomes in ...

Positive adjudication rates were lower for heart failure events than cardiovascular death, but even negatively adjudicated heart failure events ...

5.

trial.medpath.com

trial.medpath.com/clinical-trial/df5306e09a22bfec/nct06142383-multi-center-randomized-study-xxb750-heart-failure

A Proof of Concept and Dose-finding Study of XXB750 in ...

To evaluate the efficacy and dose-response relationship of three XXB750 target dose levels compared to placebo in reducing NT-proBNP. Secondary ...

6.

ahajournals.org

ahajournals.org/doi/10.1161/CIRCULATIONAHA.124.072636?doi=10.1161/CIRCULATIONAHA.124.072636

Blood Pressure Lowering Effects of a Novel Long-Acting ...

XXB750 has the potential to be developed as a novel therapy with a convenient once monthly dosing regimen, attributed to the long half-life and ...

7.

novctrd.com

novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=2455

A clinical trial to learn more about the safety of XXB750 in ...

The purpose of this trial was to learn about the safety of different doses of XXB750 for people with heart failure. Heart failure happens when the heart cannot ...

8.

ctv.veeva.com

ctv.veeva.com/study/safety-and-tolerability-study-of-xxb750-in-heart-failure-participants-with-reduced-or-mildly-reduced

Safety and Tolerability Study of XXB750 in Heart Failure ...

Cohort 2: Treatment with a stable dose of sacubitril/valsartan. Key Exclusion Criteria. Acute decompensated heart failure within 3 months prior to screening.