Safety and Tolerability Study of AZD4831 in Patients With Heart Failure.

NCT03756285 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: D6580C00003
• Study Type: interventional
• Target: 41
• Locations: 5 countries
• Sites: 13

Brief Summary

A randomized, double-blind, placebo-controlled, parallel group, multicentre study in patients with Heart Failure with preserved Ejection Fraction (HFpEF). The study will be conducted at approximately 15 sites in 5 countries. Approximately 96 patients will be randomized to AZD4831 or placebo (treatment duration 90 days).

Conditions

Heart Failure

Keywords

Heart Failure with Ejection Fraction

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in MPO Specific Activity

  To compare the effect of AZD4831 to placebo on Target engagement, defined as ex vivo zymozan stimulated Myeloperoxidase (MPO) specific activity

  Measurements on day 0, 10, 30 and 90. Change reported from day 0 to day 90.

Secondary Outcomes (2)

• Change From Baseline in CFVR Measured in the Mid-distal Segment of the Left Anterior Descending (LAD) Coronary Artery Under Adenosine Infusion Measured by Transthoracic Doppler Echocardiography (TDE).

  Measurement on day 0 and 90.

• Change From Baseline in Walking Distance

  Measurement on day 0, 30 and 90. Change reported from day 0 to day 90.

Study Arms (2)

AZD4831

EXPERIMENTAL

AZD4831 tablets taken orally for for 90 days.

Drug: AZD4831

Placebo

PLACEBO COMPARATOR

Placebo tablets taken orally for 90 days.

Drug: Placebo

Interventions

AZD4831 DRUG

AZD4831 tablet taken orally for 90 days.

AZD4831

Placebo DRUG

Placebo tablet taken orally for 90 days.

Placebo

Eligibility Criteria

• Age: 45 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this CSP
• Provision of signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses
• Age
• Patient must be 45 to 85 years of age inclusive, at the time of signing the informed consent form
• Type of patient and disease characteristics
• Signs and symptoms of HF in judgement of Investigator AND
• Stable NYHA II-IV and
• Ejection fraction (EF) ≥ 40 % and
• Elevated NT-proBNP or BNP in the last 1 year defined as:
• o Measured as out-patient: NT-proBNP ≥125 ng/L or BNP≥35 ng/L with sinus rhythm, NT-proBNP ≥750 ng/L or BNP ≥200 ng/L with atrial fibrillation (AF),
• o Measured when hospitalized acutely: NT-proBNP ≥500 (ng/L) or BNP ≥125 ng/L with sinus rhythm, NT-proBNP ≥1250 (ng/L) or BNP ≥350 ng/L with AF
• And at least one of the following:
• Hospitalization with HF as primary cause in last 12 months
• Structural heart disease on echo according to ESC guidelines i.e. either enlarged Left atrial volume index (LAVI \> 34 ml/m2) or increased LVM (LVM index \> 95 g/m2 in women and \> 115 g/m2 in men)

You may not qualify if:

• Creatinine clearance by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR \<30 ml/min/1.73m2 or dialysis
• Life expectancy \< 3 years due to other reasons than cardiovascular disease
• Any ongoing skin disorder, history of or ongoing clinically significant allergy/hypersensitivity.
• Current decompensated HF
• Primary cardiomyopathy (e.g. constrictive, restrictive, infiltrative, toxic, hypertrophic, congenital or any primary cardiomyopathy) in judgment of investigator
• Current hemodynamically significant valve disease in opinion of investigator
• EF ever documented \< 40%
• Any current life-threatening dysrhythmia
• Probable alternative primary reason for patient's symptoms in judgment of investigator, including but not limited to:
• Isolated pulmonary arterial hypertension or right ventricular (RV) failure; in the absence of left-sided HF
• Anaemia: Hb \<100 mg/L (10g/dL)
• Severe chronic obstructive pulmonary disease (COPD) or lung disease (chronic O2, nebulizer or oral steroid therapy)
• Cardiac surgery, acute coronary syndrome (ACS), or non-elective percutaneous coronary intervention (PCI) \< 3 months
• Known or clinically judged significant macrovascular coronary artery disease (CAD) that has not been revascularized
• Heart transplantation or left ventricular assist device ever

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (13)

Research Site

Chicago, Illinois, 60611, United States

Location

Research Site

Boston, Massachusetts, 02115, United States

Location

Research Site

Aarhus N, 8200, Denmark

Location

Research Site

Herlev, 2730, Denmark

Location

Research Site

Hvidovre, 2650, Denmark

Location

Research Site

Odense C, 5000, Denmark

Location

Research Site

Turku, 20520, Finland

Location

Research Site

Deventer, 7416 SE, Netherlands

Location

Research Site

Dordrecht, 3318 AT, Netherlands

Location

Research Site

Groningen, 9713 GZ, Netherlands

Location

Research Site

Gothenburg, 41345, Sweden

Location

Research Site

Lund, 22242, Sweden

Location

Research Site

Stockholm, 171 76, Sweden

Location

Related Publications (1)

• Lam CSP, Lund LH, Shah SJ, Voors AA, Erlinge D, Saraste A, Pirazzi C, Grove EL, Barasa A, Schou M, Aziz A, Svedlund S, Wijngaarden JV, Lindstedt EL, Gustavsson A, Nelander K, Garkaviy P, Gan LM, Gabrielsen A. Myeloperoxidase Inhibition in Heart Failure With Preserved or Mildly Reduced Ejection Fraction: SATELLITE Trial Results. J Card Fail. 2024 Jan;30(1):104-110. doi: 10.1016/j.cardfail.2023.04.003. Epub 2023 Apr 16.

  PMID: 37072105 DERIVED

Related Links

• Redacted CSP
• Redacted SAP

MeSH Terms

Conditions

Heart Failure

Interventions

AZD4831

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Limitations and Caveats

Due to premature study termination, the statistical assumptions for the study design according to the Clinical Study Protocol could not be fulfilled, therefore, no statistical conclusions can be made based on primary or secondary efficacy objectives. Statistical significance could not be evaluated for any efficacy objectives and the p-values presented are viewed as nominal.

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2018
• First Posted: November 28, 2018
• Study Start: December 11, 2018
• Primary Completion: May 7, 2020
• Study Completion: May 7, 2020
• Last Updated: July 19, 2021
• Results First Posted: July 19, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

FI (1); NL (3); SE (3); US (2); DK (4)