Corticotrophin Releasing Factor 2 Agonist For the Treatment of Worsening Heart Failure (WHF) – The CRAFT-WHF Study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Corteria Pharmaceuticals

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

12 Nov 2025 → ongoing

Decision date (initial)

2025-07-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Corteria Pharmaceuticals

External identifiers

EU CT number

2024-518951-52-00

ClinicalTrials.gov

NCT06815471

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety

To evaluate the dose-effect relationship of 3 doses of COR-1167 versus placebo administered once daily (o.d.) subcutaneously (s.c.) for 4 weeks to subjects with worsening heart failure (WHF) on: 1) natriuresis; 2) body weight; 3) levels of N-terminal pro B-type natriuretic peptide (NT-proBNP); 4) Kansas City Cardiomyopathy Questionnaire (KCCQ) Total Symptom Score (TSS); and 5) Left Atrial Volume Index (LAVi).

Secondary objectives 2

1. To evaluate the safety and tolerability of 3 s.c. doses of COR-1167 administered o.d. for 4 weeks to subjects with WHF.
2. To evaluate the potential immunogenicity of 3 s.c. doses of COR-1167 administered o.d. for 4 weeks to subjects with WHF.

Conditions and MedDRA coding

Worsening Heart Failure

Regulatory references

Scientific advice from competent authorities

Medicines Evaluation Board

Plan to share IPD

No

IPD plan description

This is not a phase 3 trial that would benefit from IPD sharing.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 1) Heart failure hospitalization (HFH) during previous 12 months
2. 2) Prescribed an oral loop diuretic for at least 1 month preceding the index event
3. 3) NT-proBNP ≥1,000 pg/mL or B-type natriuretic peptide (BNP) ≥250 pg/mL
4. 4) Requires treatment with i.v. diuretics for volume overload (the index event) defined by the presence of a. clinically significant extravascular volume overload evidenced by pitting edema, ascites, or pleural effusion AND b. ≥1 of the following clinical signs and symptoms of congestion: i. Dyspnea at rest ii. Rales heard on auscultation iii. Pulmonary congestion identified by diagnostic imaging (e.g. interstitial or alveolar edema on chest X-ray or B lines on lung ultrasound) (pleural effusion does not affect the lung parenchyma and cannot be used as a sign of pulmonary congestion) iv. Jugular venous distention
5. 5) Risk factors for diuretic resistance
6. 6) Unable to procreate or must agree to use a highly effective form of birth control from screening through 30 days after the last dose of study treatment
7. 7) Signed written informed consent to participate in the study in accordance with local regulations
8. 8) Admitted to the hospital not more than 48 hours prior to randomization
9. 9) In the opinion of the investigator, participant continues to have significant volume overload (≥5 kg) requiring treatment with additional i.v. loop diuretics

Exclusion criteria 17

1. 1) Age <18 years (or legal age for the country of participation) or >85 years atscreening
2. 2) Index event primarily triggered by one of the following events: a. pulmonary embolism b. cerebrovascular accident c. acute myocardial infarction d. significant arrhythmia (e.g.,sustained ventricular tachycardia, or atrial fibrillation/flutter with sustained ventricular response >130 beats per minute, or bradycardia with sustained ventricular rate <45 beats per minute) e. infection (requiring intravenous antibiotics and/or with fever > 101.5 F / 38.5 C) f. severe anemia (hemoglobin <7g/dl) g. exacerbation of chronic obstructive pulmonary disease (COPD)
3. 3) Requirement for i.v. inotropic therapy or i.v. vasodilators (except for nitrates), mechanical ventilation, high-flow oxygen therapy, or noninvasive ventilation (NIV) (use of continuous positive airway pressure [CPAP] for obstructive sleep apnea is allowed)
4. 4) Requirement for, or planned use of left ventricular assist devices (LVADs), intra-aortic balloon pump (IABP), or any type of mechanical circulatory support (MCS)
5. 5) History of solid organ transplant or active on a transplant list
6. 6) Systolic blood pressure (SBP) <100 mmHg at randomization
7. 7) Estimated glomerular filtration rate (eGFR) < 20 mL/min/1.73 m2 at screening
8. 8) Coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), implantation of cardiac resynchronization therapy [CRT]), heart valve procedure or any cardiac surgery within 1 month prior to screening or planned during the study. Note: Remote monitoring devices such as cardioMEMS and implantable cardioverter-defibrillators (ICDs) are not an exclusion.
9. 9) Severe stenotic cardiac valvular disease
10. 10) Severe chronic pulmonary disease requiring chronic steroid therapy or chronic oxygen therapy (> 2 L/min)
11. 11) Uncorrected severe hyperthyroidism or hypothyroidism. Note: Severe hyperthyroidism refers to persistent symptomatology (e.g. tachycardia, weight loss, tremors, anxiety, sweating, goiter) despite treatment. Severe hypothyroidism refers to persistent symptomatology (e.g. extreme fatigue, weight gain, cold intolerance, constipation, hair loss, voice changes, depression, swelling around the eyes) despite treatment.
12. 12) Severe restrictive, obstructive, or infiltrative cardiomyopathy
13. 13) Body weight < 70 kg
14. 14) Use of any investigational drug(s) within 5 half-lives of screening
15. 15) At high risk of death (defined as life expectancy ≤1 year) from causes other than heart failure or any disease that, in the opinion of the Investigator, will preclude their safe participation in this study, and will make implementation of the protocol or interpretation of the study results difficult
16. 16) Presence of any other conditions actual or anticipated, that the Investigator feels would restrict or limit the subject’s participation or compliance with all study procedures
17. 17) Subject is the Investigator or any Sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoints are the individual assessments of the dose-effect relationship of COR-1167 on: • Natriuresis • Body weight • NT-proBNP • KCCQ-TSS • LAVi

Secondary endpoints 2

1. Safety and tolerability of 3 s.c. o.d. doses of COR-1167, as assessed by the following parameters: o Clinical safety laboratory parameters (hematology, chemistry, coagulation, urinalysis, eGFR) o Vital signs (blood pressure, heart rate, respiratory rate, and body temperature) o Physical examinations o 12-lead electrocardiogram (ECG) o Adverse events (AEs)
2. Anti-drug antibody (ADA) semi-quantitative determination after 28-day treatment with COR-1167

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Corteria Pharmaceuticals

Sponsor organisation

Corteria Pharmaceuticals

Address

128 Rue La Boetie

City

Paris

Postcode

75008

Country

France

Scientific contact point

Organisation

Corteria Pharmaceuticals

Contact name

Marie-Laure Ozoux

Public contact point

Organisation

Corteria Pharmaceuticals

Contact name

Philip Janiak

Third parties 5

Sponsor responsibilities

Article 77 compliance

Corteria Pharmaceuticals

Contact point sponsor

Corteria Pharmaceuticals

Article 77 implementation

Corteria Pharmaceuticals

Locations

5 EU/EEA countries · 42 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 5 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 44 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications