A Proof of Concept and Dose-finding Study of XXB750 in Patients With Heart Failure

Study Overview
=================
Brief Summary
-----------------
This is a multicenter, randomized, placebo- and active-controlled, parallel-group, 24-week trial to investigate the efficacy, safety, and tolerability of XXB750 in participants with HFrEF/HFmrEF.

Detailed Description
-----------------
Eligible participants will be randomized to receive either subcutaneous (s.c.) XXB750 or placebo; or sacubitril/valsartan for 16 weeks, and then followed-up for 8 weeks

Official Title
-----------------
A Multi-center, Randomized, Placebo- and Active-controlled, Parallel-group, 24-week Proof of Concept and Dose-finding Study to Evaluate Efficacy, Safety, and Tolerability of XXB750 in Patients With Heart Failure

Conditions
-----------------
Heart Failure

Intervention / Treatment
-----------------
* Biological: Placebo
* Biological: XXB750 Low dose
* Biological: XXB750 Medium Dose
* Biological: XXB750 High Dose
* Drug: Sacubitril/valsartan


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Current symptom(s) of HF NYHA class II-III and LVEF < 50% Elevated NT-proBNP levels at screening. Receiving standard of care background HF therapy. Exclusion Criteria: Current acute decompensated HF or hospitalization for HF within 3 months prior to screening. Current symptomatic hypotension (for example dizziness/presyncope). K+ > 5.4 mmol/L at screening eGFR < 30 mL/min/1.73m2 at screening Other protocol-specific criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Arm 1<br>Placebo Treatment | Biological: Placebo<br>* S.C. Injection<br>|
| Experimental: Arm 2<br>XXB750 Low Dose | Biological: XXB750 Low dose<br>* S.C. Injection<br>|
| Experimental: Arm 3<br>XXB750 Medium Dose | Biological: XXB750 Medium Dose<br>* S.C. Injection<br>|
| Experimental: Arm 4<br>XXB750 High Dose | Biological: XXB750 High Dose<br>* S.C. Injection<br>|
| Active Comparator: Arm 5<br>Sacubitril/valsartan, open label tablet | Drug: Sacubitril/valsartan<br>* Tablet<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in log NT-proBNP from baseline to Week 16 | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in log NT-proBNP from baseline to Week 16 | To evaluate the efficacy of the highest and combined two highest XXB750 target dose levels compared to placebo and sacubitril/valsartan, respectively, in reducing NT-proBNP. | Baseline to Week 16 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Heart failure, randomized, double-blind, dose finding, XXB750