Evaluation of COR-1167 Sodium in Patients with Worsening Heart Failure: A Randomized, Placebo-Controlled, Dose-Response Study

The primary objective of the study is to evaluate the **dose-effect relationship** of three doses of COR-1167 compared to placebo, administered once daily subcutaneously for four weeks, in subjects with **Worsening Heart Failure** (WHF). The evaluation focuses on several clinical parameters: natriuresis, body weight, levels of N-terminal pro B-type natriuretic peptide (NT-proBNP), Kansas City Cardiomyopathy Questionnaire (KCCQ) Total Symptom Score (TSS), and Left Atrial Volume Index (LAVi). These parameters are clinically relevant as they provide insights into the therapeutic efficacy of COR-1167 in managing WHF, potentially improving patient outcomes by addressing fluid overload, cardiac function, and quality of life.

Secondary objectives include: - Evaluating the safety and tolerability of three subcutaneous doses of COR-1167 administered once daily for four weeks to subjects with WHF. - Assessing the potential immunogenicity of the same dosing regimen. These secondary objectives are crucial for understanding the overall risk-benefit profile of COR-1167, ensuring that the treatment is not only effective but also safe and well-tolerated by patients.

The clinical trial involves a total of **130 participants** diagnosed with **worsening heart failure**. The study population includes both male and female subjects, with age categories spanning from adults to the elderly. Participants were selected based on specific criteria, including a history of heart failure hospitalization within the past 12 months and the requirement for intravenous diuretics due to significant volume overload. All participants are prescribed an oral loop diuretic for at least one month prior to the index event. The trial also considers lifestyle factors such as the inability to procreate or the use of highly effective birth control methods. The study population includes a vulnerable group, ensuring comprehensive representation. Key inclusion criteria involve elevated levels of NT-proBNP or BNP, and the presence of clinical signs of congestion. Participants must have been admitted to the hospital no more than 48 hours before randomization and must continue to exhibit significant volume overload requiring additional intravenous loop diuretics.

The clinical trial is designed to evaluate the **dose-effect relationship** of three doses of COR-1167 versus placebo in subjects with **worsening heart failure**. This study is a randomized, double-blind, controlled trial, conducted over a period of four weeks. Participants will receive subcutaneous injections of either COR-1167 or a placebo solution, administered once daily. The trial aims to assess the effects on natriuresis, body weight, levels of N-terminal pro B-type natriuretic peptide (NT-proBNP), Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS), and Left Atrial Volume Index (LAVi). The primary endpoints focus on these individual assessments, while secondary endpoints include safety and tolerability, as well as anti-drug antibody determination after the 28-day treatment period.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility is confirmed based on criteria such as recent heart failure hospitalization, prescribed oral loop diuretics, and significant volume overload. Participants must also provide informed consent. Following randomization, participants will attend regular follow-up visits to monitor clinical safety laboratory parameters, vital signs, physical examinations, and 12-lead electrocardiograms. Adverse events will be documented throughout the study. The end-of-study visit will conclude the trial, with a final assessment of the primary and secondary endpoints.

Participant involvement is expected to last for the entire 28-day treatment period, with the possibility of early termination if significant adverse events occur or if the participant withdraws consent. The trial is scheduled to commence recruitment in July 2025, with an estimated completion date in October 2026. The study is not classified as low intervention and is categorized as a Phase IIb study, indicating its exploratory nature in assessing the efficacy and safety of the investigational product.

The clinical trial involves the administration of **COR-1167**, a synthetic protein-based investigational drug developed by Corteria Pharmaceuticals. **COR-1167** is formulated as a **solution for injection in a pre-filled syringe**. The active substance, **COR-1167 sodium**, is delivered via **subcutaneous injection**. The dosing regimen consists of once-daily administration for a period of four weeks. The pre-filled syringe is equipped with a safety device to minimize the risk of accidental needle sticks post-use. The trial aims to evaluate the dose-effect relationship of three different doses of **COR-1167** in subjects with worsening heart failure, focusing on parameters such as natriuresis, body weight, NT-proBNP levels, and other clinical endpoints.

The study also includes a **placebo solution for injection** that matches the appearance and administration route of **COR-1167**. The placebo is used as a comparator to assess the efficacy and safety of the investigational drug. The placebo is administered under the same conditions as **COR-1167**, ensuring blinding and maintaining the integrity of the trial design. The placebo does not contain any active pharmaceutical ingredients and serves to provide a baseline for evaluating the therapeutic effects of **COR-1167**.

The efficacy of the investigational product, COR-1167, in the treatment of worsening heart failure will be assessed through a series of primary endpoints. These endpoints include the evaluation of the dose-effect relationship of COR-1167 on **natriuresis**, body weight, levels of N-terminal pro B-type natriuretic peptide (NT-proBNP), Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS), and Left Atrial Volume Index (LAVi). These parameters will be measured to determine the therapeutic impact of the treatment over a 4-week period.

The collection and analysis of these efficacy parameters will be conducted at specified intervals throughout the trial. The assessments will be performed using validated scales and laboratory tests to ensure accuracy and reliability. The trial will involve the administration of three different doses of COR-1167, compared against a placebo, with the treatment being administered subcutaneously once daily. The data collected will be analyzed to establish the relationship between the dose and the observed effects on the primary endpoints.