AP01 Heart Failure (AHF) Study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ananda Pharma GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Decision date (initial)

2024-03-04

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Sponsor: Ananda Pharma; partly funded by a national grant: ILB/BIG-FuE: 80178335

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Safety, Therapy, Efficacy

• Metabolism of the cardiomyocytes:
a) Reduction of lactate during 90 minutes after first dose (AUC)
b) Reduction of NT- proBNP after 72 hours

Secondary objectives 1

1. • Symptomatic and clinical improvement: a) Echocardiography (Visit 1 compared to Visit 6) b) Kansas City Cardiomyopathy Questionnaire (KCCQ-23) (Visit 1 compared to Visit 10 and 11)

Conditions and MedDRA coding

Acute Heart Failure

Study design 1 period

Regulatory references

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Provide written informed consent according to local regulations. 2. Males and females aged > 18 years. 3. Unplanned hospitalization or emergency department visit for AHF. Acute HF is defined as including all of the following criteria: • Dyspnoea at rest in a recumbent sitting position (30 to 45 degrees), which has worsened within the past week. • Radiological evidence of HF on a chest X-ray (if an appropriate chest computerized tomography scan is done the X-ray need not be performed). • Brain natriuretic peptide (BNP) >500 pg/mL or NT-pro BNP >2000 pg/mL. 4. Serum lactate level above or equal to 18.0 mg/dl (≥ 1.99 mmol/L). 5. Ejection Fraction (EF) < 40% (echocardiography). 6. Ability to start the study drug administration within 12 h after initial clinical assessment. 7. Systolic blood pressure ≥ 90 mmHg and ≤ 165 mmHg at the time of initial clinical assessment.

Exclusion criteria 1

1. 1. Women of child-bearing potential (i.e., pre-menopausal women) and breast-feeding women without documentation of a negative blood pregnancy assay within 12 h prior to randomization. 2. Patients with Heart Failure NYHA I and II. 3. Known active myocarditis, obstructive hypertrophic cardiomyopathy, congenital heart disease, restrictive cardiomyopathy, constrictive pericarditis, uncorrected clinically significant primary valvular disease. 4. Serum lactate level below 18.0 mg/dl < 1.99 mmol/L. 5. Clinical diagnosis of acute coronary syndrome meeting any 2 of the following 3 criteria: • Prolonged chest pain at rest, or an accelerated pattern of angina • Electrocardiogram changes indicative of ischemia or myocardial injury defined as: a new ST elevation at the J point of two anatomically contiguous leads with the cut-off points: ≥0.2 mV in men ≥40 years (>0.25 mV in men <40 years) or ≥0.15 mV in women in leads V2-V3 and/or ≥0.1 mV in other leads; or ST depression and T wave changes. New horizontal or down sloping ST depression ≥0.05 mV in two contiguous leads; and/or new T inversion ≥0.3 mV in two contiguous leads. • Serum troponin >3 times upper limit of normal. 6. Terminal illness other than congestive HF with expected survival <180 days. 7. Clinically suspected acute mechanical cause of ADHF (e.g., papillary muscular rupture). The diagnosis need not be confirmed by imaging or cardiac catheterization. 8. Body temperature ≥ 38°C just prior to randomization. 9. Acute or chronic respiratory disorder (e.g., severe chronic obstructive pulmonary disease) or primary pulmonary hypertension sufficient to cause dyspnea at rest, which may interfere with the ability to interpret dyspnea assessments or hemodynamic measurements. 10. Creatinine clearance <25 mL/min/1.73m² (as measured by the MDRD formula) at the time of screening. 11. Anemia (hemoglobin <9 g/dL or a hematocrit <25%) 12. Patients with severe hepatic impairment. 13. Current drug abuse or chronic alcoholism sufficient to impair participation and compliance to the study protocol. 14. Known vasculitis, active infective endocarditis, or suspected infections, e.g., pneumonia, acute hepatitis, systemic inflammatory syndrome, or sepsis. 15. Participation in an investigational clinical drug study within 30 days prior to randomization. 16. Males and females aged < 18 years. 17. Missing informed consent. 18. Any condition that, in the Investigator's opinion, makes the patient unsuitable for study participation.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Reduction of lactate during 90 minutes after first dose, reported as area under the curve. Reduction of NT-proBNP 72 hours after first dose.

Secondary endpoints 1

1. Symptomatic and clinical improvement: a) Echocardiography (Visit 1 compared to Visit 6) b) Kansas City Cardiomyopathy Questionnaire (KCCQ-23): Visit 1 compared to Visit 10 and 11. Symptomatic and clinical improvement: Outcome differences NYHA III compared to NYHA IV, Duration of hospital stay, Mortality and Rate of Re-Hospitalisation

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ananda Pharma GmbH

Sponsor organisation

Ananda Pharma GmbH

Address

Karl-Liebknecht-Strasse 94, Babelsberg Nord Babelsberg Nord

City

Potsdam

Postcode

14482

Country

Germany

Scientific contact point

Organisation

Ananda Pharma GmbH

Contact name

Clinical Trials Unit

Public contact point

Organisation

Ananda Pharma GmbH

Contact name

Clinical Trials Unit

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Application history

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