Heart FailurePhase 1ANX-042 Aim 1NCT03019653
Safety and Efficacy of ANX-042 in Human Cardiorenal Syndrome
A Phase 1 study testing ANX-042 in people with Heart Failure and Cardiorenal Disease, run by Mayo Clinic at 1 site in United States.
Trial summary
The purpose of this study is to look at kidney function and hormonal function in patients with a history of heart failure and kidney dysfunction, and to see how the use of a new drug, ANX-042, affects those functions. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Heart Failure, Cardiorenal Disease, Renal Disfunction
- What is being tested?
- ANX-042
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2017to 13 Sep 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Left ventricular ejection fraction of equal or less than 40% assessed by echocardiography, nuclear scan, MRI or left ventriculogram within the past 48 months. If assessment is greater than 12 months old, hand-held echocardiogram (ECHO) determination will be performed at consent visit once enrolled.
- Stable New York Heart Association (NYHA) class II and III symptoms as defined by: no change in NYHA symptoms over the past 3 months, on stable doses of furosemide, angiotensin-converting enzyme (ACE) inhibitor or angiotensin II type 1 (AT1) blocker, beta blocker, or aldosterone antagonist over the last 4 weeks and no episode of decompensated Congestive Heart Failure (CHF) over the past 6 months.
- Calculated creatinine clearance of equal or less than 89 ml/min and greater than 20 ml/min, using the Modification of Diet in Renal Disease (MDRD) formula assessed within the past 48 months and a confirmatory calculated creatinine clearance equal or less than 89 ml/min and greater than 20 ml/min at the time of enrollment.
- Digoxin, antiarrhythmic medications and other vasodilators will be allowed; however, all medications must be at stable doses 4 weeks prior to enrollment. Subjects taking non-steroidal anti-inflammatory drugs (NSAIDs), except aspirin, will not be able to increase their medication dose for the duration of the study.
Who cannot join
- Prior diagnosis of intrinsic renal diseases, such as glomerular nephritis or polycystic kidney disease, including renal artery stenosis of > 50% (unless revascularized)
- Peritoneal or hemodialysis within 90 days or anticipation that dialysis or ultrafiltration of any form will be required during the study period
- Hospitalization for decompensated CHF during the past 6 months
- Myocardial infarction within 6 months of screening
- Unstable angina within 6 months of screening, or any evidence of acute myocardial ischemia
- Significant valvular stenosis (greater than moderate in severity) , hypertrophic, restrictive or obstructive cardiomyopathy, constrictive pericarditis, primary pulmonary hypertension, or biopsy proven active myocarditis
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- Severe congenital heart diseases
- Sustained ventricular tachycardia or ventricular fibrillation within 14 days of screening
- Second or third degree heart block without a permanent cardiac pacemaker
- Stroke within 3 months of screening, or other evidence of significantly compromised central nervous system (CNS) perfusion
- Alanine transaminase (ALT) >2 times the upper limit of normal
- Serum sodium of < 125 milliequivalent/dL (mEq/dL) or > 160 mEq/dL
- Serum potassium of < 3.0 mEq/dL or > 5.7 mEq/dL
- Hemoglobin < 8.5 gm/dl
- Other acute or chronic medical conditions or laboratory abnormality which may increase the risks associated with study participation or may interfere with interpretation of the data
- Have received an investigational drug within 1 month prior to dosing
- Patients with an allergy to iodine
- Female subject who is pregnant or breastfeeding
- In the opinion of the investigator, is unlikely to comply with the study protocol or is unsuitable for any reasons
- Documented systolic blood pressure less than 90 mmHg at consent visit
Trial locations and contacts
1 site in 1 country.
United States1 site
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
Official title: A Phase Ib, Double-Blind, Placebo-Controlled, Single-site Trial to Determine the Safety and Efficacy of a Novel Renal-Specific Peptide, ANX-042, in Enhancing GFR Without Significant Hypotension in Human Cardiorenal Syndrome (CRS): ANX-042 Aim #1
The purpose of this study is to look at kidney function and hormonal function in patients with a history of heart failure and kidney dysfunction, and to see how the use of a new drug, ANX-042, affects those functions.
Read the detailed description
Subjects will have a choice of admitting the night prior to renal clearance study day or the day of. Subjects will admit (fasting) to the Clinical Research and Trials Unit, after 3 weeks of diet compliance, the morning of the first renal clearance study day. They will avoid taking any sulfa containing medications and Probenecid for 72 hours prior to Visit Two and Visit Three. They will complete a 24-hour urine collection which will be assessed for creatinine clearance, microalbumin and sodium concentration and excretion. A pregnancy test will be performed, if necessary. Their first urine void after admitting will be collected for protein analysis. Brief physical exam (same as at Visit 1) will be performed by a qualified Study Team Member. Their usual morning dose of medications will be held until given initial water load prior to start of renal clearance infusion. Echocardiogram to determine systolic, diastolic function and cardiac output will be performed prior to the start of study drug infusion. A bladder ultrasound will be performed after their first void. If subject is unable to sufficiently empty their bladder, a urinary catheter will be placed with their permission. The subjects will be placed in the supine position for 1 hour. During the first 15 minutes, two standard intravenous (IV) catheters will be placed (one in each arm). One catheter will be used for infusion and the other (in the contralateral arm) for blood sampling. Subjects will be asked to drink 5 mL/Kg of water initially and then drink an amount equal to the urine output, and blood drawn, after each clearance period to ensure sufficient urinary flow. A priming dose (calculated according to body size) of iothalamate (0.06 mg/Kg) to measure glomerular filtration rate (GFR) will be infused, followed by a constant rate IV sustaining dose (calculated according to estimated kidney function) of iothalamate to achieve steady-state plasma concentrations of 15 to 20 mg/L. The subjects will be asked to empty their bladder spontaneously at the end of each clearance period.
After an equilibration period of 45 minutes, urine and blood samples will be collected at 30-minutes to determine the baseline GFR and urinary sodium excretion (UNaV). Blood pressure will be measured at 20-minute intervals for the first 2 hours, then every 30 minutes, by using automatic blood pressure cuff. Heart rate will be continuously monitored by electrocardiography. Urinary samples for determination of volume, sodium, potassium, and iothalamate will be obtained at the end of each clearance period. Venous blood samples for iothalamate and sodium will be obtained at the middle of each clearance period. During the first clearance, venous blood samples for renin, aldosterone, angiotensin II, AnxA1, Atrial Natriuretic Peptide (ANP), Brain natriuretic peptide (BNP) and cGMP will be obtained and urine samples for Annexin A1(AnxA1) and cyclic guanosine monophosphate (cGMP) will also be obtained. Buffy coat from Ethylenediaminetetraacetic acid (EDTA) vacutainer tubes will be saved for possible future DNA analysis.
After the baseline renal clearance, subjects will be randomized to receive infusion of active study drug or placebo for 8 hours. The research pharmacist will prepare the study drug or placebo infusion, thus both the patients and investigators will be blinded. Renal clearance and blood draws will be carried out every 2 hours during the infusion as described above (4 times), and blood draw for assays at the end of 4 and 8 hours infusion as listed above. Another echocardiogram will be repeated after 4 hour of drug infusion. Subjects will be given 3 meals throughout the day. Dismissal will occur after one hour of post-infusion monitoring.
- Conditions
- Heart Failure, Cardiorenal Disease, Renal Disfunction
- Being tested
- ANX-042, Placebo
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ANX-042Drug
The first 20 subjects will receive a dose 0.003 µg/kg/min by infusion, the next 20 subjects will receive a dose of 0.006 µg/kg/min, then the next 20 subjects will receive 0.01 µg/kg/min.
PlaceboDrug
The pharmacy created a placebo for this study is sterile Dextrose (5%) solution (D5W) 0.9% Sodium Chloride for intravenous administration to match study drug.
| Study group | Role | What they receive |
|---|---|---|
| ANX-042 first, then Placebo | Active comparator | In the first intervention period the subjects will receive an infusion of ANX-042. There will be a 3 week washout period. In the second intervention period, the subjects will receive an infusion of placebo Receives: Drug: ANX-042; Drug: Placebo |
| Placebo first, then ANX-042 | Active comparator | In the first intervention period the subjects will receive placebo. There will be a 3 week washout period. In the second intervention period, the subjects will receive an infusion of ANX-042. Receives: Drug: ANX-042; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Glomerular Filtration Rate
Measured: baseline to 3 weeks
Secondary outcomes (6)
Change in Sodium Excretion
Measured: baseline to 3 weeks
Change in Urine Flow
Measured: baseline to 3 weeks
Change in Blood Pressure
Measured: baseline to 3 weeks
Change in Renin-angiotensin-aldosterone system (RAAS)
Measured: baseline to 3 weeks
Change in Urine Annexin A1 (AnxA1) Protein Levels
Measured: baseline to 3 weeks
Number of Subjects with Hypotension
Measured: 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2017 (estimated)
- Study startJan 2017
- Primary completion13 Sep 2024
- Study completion13 Sep 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe 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 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Paul M. McKie, M.D., Mayo Clinic
- Investigators
- Paul M McKie, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03019653
- Sponsor's protocol ID
- 16-001847
- Other IDs
- R01HL084155-06A1
- Acronym
- ANX-042 Aim 1
- Status last verified
- Nov 2024
- First submitted
- 11 Jan 2017
- Last updated
- 15 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib, Double-Blind, Placebo-Controlled, Single-site Trial to Determine the Safety and Efficacy of a Novel Renal-Specific Peptide, ANX-042, in Enhancing GFR Without Significant Hypotension in Human Cardiorenal Syndrome (CRS): ANX-042 Aim #1
- ClinicalTrials.gov ID
- NCT03019653
- Acronym / sponsor ID
- ANX-042 Aim 1 / 16-001847
- Conditions
- Heart Failure, Cardiorenal Disease, Renal Disfunction
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Jan 2017 (actual)
- Primary completion
- 13 Sep 2024 (actual)
- Study completion
- 13 Sep 2024 (actual)
- First posted
- 12 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to look at kidney function and hormonal function in patients with a history of heart failure and kidney dysfunction, and to see how the use of a new drug, ANX-042, affects those functions.
Detailed description
Subjects will have a choice of admitting the night prior to renal clearance study day or the day of. Subjects will admit (fasting) to the Clinical Research and Trials Unit, after 3 weeks of diet compliance, the morning of the first renal clearance study day. They will avoid taking any sulfa containing medications and Probenecid for 72 hours prior to Visit Two and Visit Three. They will complete a 24-hour urine collection which will be assessed for creatinine clearance, microalbumin and sodium concentration and excretion. A pregnancy test will be performed, if necessary. Their first urine void after admitting will be collected for protein analysis. Brief physical exam (same as at Visit 1) will be performed by a qualified Study Team Member. Their usual morning dose of medications will be held until given initial water load prior to start of renal clearance infusion. Echocardiogram to determine systolic, diastolic function and cardiac output will be performed prior to the start of study drug infusion. A bladder ultrasound will be performed after their first void. If subject is unable to sufficiently empty their bladder, a urinary catheter will be placed with their permission. The subjects will be placed in the supine position for 1 hour. During the first 15 minutes, two standard intravenous (IV) catheters will be placed (one in each arm). One catheter will be used for infusion and the other (in the contralateral arm) for blood sampling. Subjects will be asked to drink 5 mL/Kg of water initially and then drink an amount equal to the urine output, and blood drawn, after each clearance period to ensure sufficient urinary flow. A priming dose (calculated according to body size) of iothalamate (0.06 mg/Kg) to measure glomerular filtration rate (GFR) will be infused, followed by a constant rate IV sustaining dose (calculated according to estimated kidney function) of iothalamate to achieve steady-state plasma concentrations of 15 to 20 mg/L. The subjects will be asked to empty their bladder spontaneously at the end of each clearance period.
After an equilibration period of 45 minutes, urine and blood samples will be collected at 30-minutes to determine the baseline GFR and urinary sodium excretion (UNaV). Blood pressure will be measured at 20-minute intervals for the first 2 hours, then every 30 minutes, by using automatic blood pressure cuff. Heart rate will be continuously monitored by electrocardiography. Urinary samples for determination of volume, sodium, potassium, and iothalamate will be obtained at the end of each clearance period. Venous blood samples for iothalamate and sodium will be obtained at the middle of each clearance period. During the first clearance, venous blood samples for renin, aldosterone, angiotensin II, AnxA1, Atrial Natriuretic Peptide (ANP), Brain natriuretic peptide (BNP) and cGMP will be obtained and urine samples for Annexin A1(AnxA1) and cyclic guanosine monophosphate (cGMP) will also be obtained. Buffy coat from Ethylenediaminetetraacetic acid (EDTA) vacutainer tubes will be saved for possible future DNA analysis.
After the baseline renal clearance, subjects will be randomized to receive infusion of active study drug or placebo for 8 hours. The research pharmacist will prepare the study drug or placebo infusion, thus both the patients and investigators will be blinded. Renal clearance and blood draws will be carried out every 2 hours during the infusion as described above (4 times), and blood draw for assays at the end of 4 and 8 hours infusion as listed above. Another echocardiogram will be repeated after 4 hour of drug infusion. Subjects will be given 3 meals throughout the day. Dismissal will occur after one hour of post-infusion monitoring.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ANX-042 first, then Placebo | Active comparator | Drug: ANX-042, Drug: PlaceboIn the first intervention period the subjects will receive an infusion of ANX-042. There will be a 3 week washout period. In the second intervention period, the subjects will receive an infusion of placebo |
| Placebo first, then ANX-042 | Active comparator | Drug: ANX-042, Drug: PlaceboIn the first intervention period the subjects will receive placebo. There will be a 3 week washout period. In the second intervention period, the subjects will receive an infusion of ANX-042. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Left ventricular ejection fraction of equal or less than 40% assessed by echocardiography, nuclear scan, MRI or left ventriculogram within the past 48 months. If assessment is greater than 12 months old, hand-held echocardiogram (ECHO) determination will be performed at consent visit once enrolled.
- Stable New York Heart Association (NYHA) class II and III symptoms as defined by: no change in NYHA symptoms over the past 3 months, on stable doses of furosemide, angiotensin-converting enzyme (ACE) inhibitor or angiotensin II type 1 (AT1) blocker, beta blocker, or aldosterone antagonist over the last 4 weeks and no episode of decompensated Congestive Heart Failure (CHF) over the past 6 months.
- Calculated creatinine clearance of equal or less than 89 ml/min and greater than 20 ml/min, using the Modification of Diet in Renal Disease (MDRD) formula assessed within the past 48 months and a confirmatory calculated creatinine clearance equal or less than 89 ml/min and greater than 20 ml/min at the time of enrollment.
- Digoxin, antiarrhythmic medications and other vasodilators will be allowed; however, all medications must be at stable doses 4 weeks prior to enrollment. Subjects taking non-steroidal anti-inflammatory drugs (NSAIDs), except aspirin, will not be able to increase their medication dose for the duration of the study.
Key exclusion criteria (20 listed)
- Prior diagnosis of intrinsic renal diseases, such as glomerular nephritis or polycystic kidney disease, including renal artery stenosis of > 50% (unless revascularized)
- Peritoneal or hemodialysis within 90 days or anticipation that dialysis or ultrafiltration of any form will be required during the study period
- Hospitalization for decompensated CHF during the past 6 months
- Myocardial infarction within 6 months of screening
- Unstable angina within 6 months of screening, or any evidence of acute myocardial ischemia
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 |
|---|---|---|
| ANX-042The first 20 subjects will receive a dose 0.003 µg/kg/min by infusion, the next 20 subjects will receive a dose of 0.006 µg/kg/min, then the next 20 subjects will receive 0.01 µg/kg/min. | Drug | ANX-042 first, then Placebo, Placebo first, then ANX-042 |
| PlaceboThe pharmacy created a placebo for this study is sterile Dextrose (5%) solution (D5W) 0.9% Sodium Chloride for intravenous administration to match study drug. | Drug | ANX-042 first, then Placebo, Placebo first, then ANX-042 |
Primary outcome
Change in Glomerular Filtration Rate
Time frame: baseline to 3 weeks
6 secondary outcomes
Change in Sodium Excretion
Time frame: baseline to 3 weeks
Change in Urine Flow
Time frame: baseline to 3 weeks
Change in Blood Pressure
Time frame: baseline to 3 weeks
Change in Renin-angiotensin-aldosterone system (RAAS)
Time frame: baseline to 3 weeks
Change in Urine Annexin A1 (AnxA1) Protein Levels
Time frame: baseline to 3 weeks
Number of Subjects with Hypotension
Time frame: 3 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2024.
- Individual participant dataSharing planned: No
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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.
Paul M McKie, MD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ANX-042 in people with Heart Failure and Cardiorenal Disease, run by Mayo Clinic at 1 site in United States.
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 4 inclusion and 20 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: finished, as of the sponsor's last update on 15 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 in Glomerular Filtration Rate (time frame: baseline to 3 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Nov 2024.