Heart FailurePhase 2SATELLITENCT03756285

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

A Phase 2 study testing AZD4831 in people with Heart Failure, run by AstraZeneca at 13 sites in 5 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Trial 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. Read more about this study

Who is it for?: Ages 45 to 85 years
Conditions the study is for: Heart Failure
What is being tested?: AZD4831
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 41 participants
Where: 13 sitesin 5 countries
Study dates: 11 Dec 2018to 7 May 2020
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 45 to 85 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Show all 27Show fewer

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),
or
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)
Pulmonary capillary wedge pressure (PCWP) at rest >15 mmHg or >25 mmHg at exercise
Spectral tissue Doppler echocardiography - E/e' ratio ≥13 at rest
Weight
Body Mass Index (BMI) range 18-40kg/m2
Sex
Male or female of nonchildbearing potential
Reproduction
Female patients must be 1 year post-menopausal or surgically sterile
Male patients must be surgically sterile or using an acceptable method of contraception (defined as barrier methods in conjunction with spermicides) for the duration of the study (from the time they sign consent) and for 3 months after the last dose of AZD4831/matching placebo to prevent pregnancy in a partner. Male patients must not donate or bank sperm during this same time period
Genetic sampling
For inclusion in this genetic research, patients must fulfil all of the inclusion criteria described above and provide informed consent for the genetic sampling and analysis

Who cannot join

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

Show all 18Show fewer

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
Patients with uncontrolled or clinically significant thyroid disease as judged by the investigator.
Alanine transaminase (ALT) or aspartate aminotransferase (AST) ≥2 x upper limit of normal (ULN). Resampling will not be allowed during the same screening period if detected abnormal values do not have reasonable explanation and are not expected to return to normal level within few days.
Known positive HIV, hepatitis C antibody, hepatitis B virus surface antigen or hepatitis B virus core antibody, at screening

Trial locations and contacts

13 sites in 5 countries.

Country

City, postcode or hospital

13 sites in 5 countries

Denmark4 sites

Research Site
Aarhus N, 8200
Research Site
Herlev, 2730
Research Site
Hvidovre, 2650
Research Site
Odense C, 5000

Other trials in Denmark

Netherlands3 sites

Research Site
Deventer, 7416 SE
Research Site
Dordrecht, 3318 AT
Research Site
Groningen, 9713 GZ

Other trials in Netherlands

Sweden3 sites

Research Site
Gothenburg, 41345
Research Site
Lund, 22242
Research Site
Stockholm, 171 76

Other trials in Sweden

United States2 sites

Research Site
Boston, Massachusetts, 02115
Research Site
Chicago, Illinois, 60611

Other trials in United States

Finland1 site

Research Site
Turku, 20520

Other trials in Finland

About this study

Official title: A Randomized, Double Blind, Placebo-controlled, Parallel Group, Multicentre, Phase 2a Study to Assess Target Engagement, Safety and Tolerability of AZD4831 in Patients With Heart Failure With Preserved Ejection Fraction (HFpEF)

Read the detailed description

This is a randomized, double-blind, placebo controlled, parallel group, multicentre study in patients with Heart Failure with preserved Ejection Fraction (HFpEF) and mid-range Ejection Fraction (HRmrEF). The study will be conducted at approximately 15 sites in 5 countries (USA, Sweden, Denmark, Finland, Netherlands). Patients suitable for the study will be checked for eligibility, signing the informed consent and enrolled to the study at visit 1. The study will be divided into two parts, Part A and Part B. In part A 37 patients will be randomized at visit 2 in a 2:1 ratio to once daily dosing of AZD4831 or matching placebo for approximately 90 days. After approximately 30 days of treatment, an interim analysis will be done to analyse the safety, tolerability and target engagement. After the evaluation, the randomization to Part B may proceed. In Part B the approximate 59 remaining patients will be randomized and treated for approximately 90 days.

Conditions: Heart Failure
Being tested: AZD4831, Placebo
Keywords: Heart Failure with Ejection Fraction
Medical subject headings: Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AZD4831Drug
AZD4831 tablet taken orally for 90 days.
PlaceboDrug
Placebo tablet taken orally for 90 days.

Study groups in NCT03756285
Study group	Role	What they receive
AZD4831	Experimental	AZD4831 tablets taken orally for for 90 days. Receives: Drug: AZD4831
Placebo	Placebo comparator	Placebo tablets taken orally for 90 days. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 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).
To compare the effect of AZD4831 to placebo on coronary flow velocity reserve (CFVR) measured in the mid-distal segment of the left anterior descending (LAD) coronary artery under adenosine infusion measured by Transthoracic Doppler Echocardiography (TDE).
Measured: Measurement on day 0 and 90.
Change From Baseline in Walking Distance
To compare the effect of AZD4831 to placebo on 6 minutes walking test (6MWT)
Measured: Measurement on day 0, 30 and 90. Change reported from day 0 to day 90.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

11 Dec 20187 May 2020

First posted28 Nov 2018
Study start11 Dec 2018
Primary completion7 May 2020
Study completion7 May 2020

Why it stopped: A decision was made to stop the study early when AstraZeneca evaluated the available data and it was considered that completing the study would provide limited additional information and unlikely to change the study conclusions.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Heart FailureStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 41 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03756285
Sponsor's protocol ID: D6580C00003
Acronym: SATELLITE
Status last verified: Jun 2021
First submitted: 19 Nov 2018
Last updated: 19 Jul 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Publications

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.
PubMed 37072105

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life(COREVIVE-HFrEF)
Heart Failure With Reduced Ejection Fraction, Iron Deficiency
Not yet recruitingPhase 2
A Study of Bimagrumab in Participants With HFpEF
Heart Failure, Diastolic, Diastolic Heart Failure
Recruiting
Evaluation of a French Hospital Discharge Therapeutic Education Program by Nurses for Heart Failure Patient (EduSor)
Heart Failure
Active, not recruiting
Assessment of Combined CCM and ICD Device in HFrEF
Heart Failure, Heart Failure With Reduced Ejection Fraction
Not yet recruiting
RELIEVE-HFrEF TRIAL: REducing Lung congestIon Symptoms Using the v-wavE Shunt in adVancEd Heart Failure With Reduced EF
Heart Failure and Reduced Ejection Fraction, Heart Failure Chronic

All Heart Failure trials

Study at a glance

From the registry record, last updated by the sponsor on 19 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double Blind, Placebo-controlled, Parallel Group, Multicentre, Phase 2a Study to Assess Target Engagement, Safety and Tolerability of AZD4831 in Patients With Heart Failure With Preserved Ejection Fraction (HFpEF)
ClinicalTrials.gov ID: NCT03756285
Acronym / sponsor ID: SATELLITE / D6580C00003
Conditions: Heart Failure
Keywords: Heart Failure with Ejection Fraction
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: A decision was made to stop the study early when AstraZeneca evaluated the available data and it was considered that completing the study would provide limited additional information and unlikely to change the study conclusions.
Enrolment: 41 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: 11 Dec 2018 (actual)
Primary completion: 7 May 2020 (actual)
Study completion: 7 May 2020 (actual)
First posted: 28 Nov 2018 (actual)
Results: Posted 19 Jul 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
AZD4831	Experimental	Drug: AZD4831AZD4831 tablets taken orally for for 90 days.
Placebo	Placebo comparator	Drug: PlaceboPlacebo tablets taken orally for 90 days.

Who may qualify

Ages: 45 to 85 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (27 listed)

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

Key exclusion criteria (18 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AZD4831AZD4831 tablet taken orally for 90 days.	Drug	AZD4831
PlaceboPlacebo tablet taken orally for 90 days.	Drug	Placebo

Primary outcome

Change From Baseline in MPO Specific Activity
Time frame: Measurements on day 0, 10, 30 and 90. Change reported from day 0 to day 90.
To compare the effect of AZD4831 to placebo on Target engagement, defined as ex vivo zymozan stimulated Myeloperoxidase (MPO) specific activity

2 secondary outcomes

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).
Time frame: Measurement on day 0 and 90.
Change From Baseline in Walking Distance
Time frame: Measurement on day 0, 30 and 90. Change reported from day 0 to day 90.

Results and safety

Results posted to the registry on 19 Jul 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
AZD4831	27	24
Placebo	14	9

Primary outcome: Change From Baseline in MPO Specific Activity

Time frame: Measurements on day 0, 10, 30 and 90. Change reported from day 0 to day 90.. Geometric least squares mean (95% Confidence Interval). Unit: Ratio

Measure	AZD4831 n = 20	Placebo n = 14
Value	0.547 (0.379 to 0.790)	2.177 (1.168 to 4.058)

AZD4831 vs Placebo: Least Square Means Ratio: 0.25 (95% CI 0.12 to 0.52), p <0.001, Mixed Models Analysis

Population analysed: 20 of 27 patients in AZD4831 and 14 of 14 patients in placebo with evaluable measurements for analysis

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse Events will be collected from the time of the first dose throughout the treatment period and including the follow-up period, up to 124 days. Serious Adverse Events will be recorded from the time of signing the informed consent form through follow-up period, up to 124 days.. Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
AZD4831	2 of 27 (7.4%)	21 of 27 (77.8%)	0 of 27
Placebo	2 of 14 (14.3%)	9 of 14 (64.3%)	0 of 14

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Jul 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 37072105Lam 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.
Redacted CSPLink provided by the sponsor.
Redacted SAPLink provided by the sponsor.
Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Related trials for Heart Failure

RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life(COREVIVE-HFrEF)
Heart Failure With Reduced Ejection Fraction, Iron Deficiency
Not yet recruitingPhase 2
A Study of Bimagrumab in Participants With HFpEF
Heart Failure, Diastolic, Diastolic Heart Failure
Recruiting
Evaluation of a French Hospital Discharge Therapeutic Education Program by Nurses for Heart Failure Patient (EduSor)
Heart Failure
Active, not recruiting
Assessment of Combined CCM and ICD Device in HFrEF
Heart Failure, Heart Failure With Reduced Ejection Fraction
Not yet recruiting
RELIEVE-HFrEF TRIAL: REducing Lung congestIon Symptoms Using the v-wavE Shunt in adVancEd Heart Failure With Reduced EF
Heart Failure and Reduced Ejection Fraction, Heart Failure Chronic

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

13 sites in 5 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing AZD4831 in people with Heart Failure, run by AstraZeneca at 13 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 19 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Denmark, Netherlands, Sweden, United States, Finland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in MPO Specific Activity (time frame: Measurements on day 0, 10, 30 and 90. Change reported from day 0 to day 90.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03756285, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jul 2021.