Chronic Stable Heart FailurePhase 2NCT02696967
A Study of CLR325 in Chronic Stable Heart Failure Patients.
A Phase 2 study testing CLR325 in people with Chronic Stable Heart Failure, run by Novartis Pharmaceuticals at 11 sites in 5 countries.
Trial summary
The purpose of this study was to determine the safety and tolerability of CLR325 intravenous (i.v.) infusion in patients with stable heart failure to determine if further clinical development of the drug in this indication was warranted. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Stable Heart Failure
- What is being tested?
- CLR325
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 11 sitesin 5 countries
- Study dates
- 17 May 2016to 14 Jan 2019
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female patients >18 years of age
- Body weight between 50 kg and 140 kg
- Cardiac ejection fraction of ≤ 45% assessed within the last 6 months
- For PA catheter cohorts, patients who are planned to have a clinically indicated pulmonary artery catheter in place prior to randomization
- In the opinion of the investigator, heart failure patients who do not require a change in their dose of acetylcholinesterase (ACE), angiotensin receptor blocker (ARB), β-blocker, mineralocorticoid receptor antagonist, or diuretic for 24 h after randomization.
- At Baseline, vital signs (systolic and diastolic blood pressure and pulse rate) assessment in the supine position after the subject has rested for at least five minutes.
Who cannot join
- Impaired renal function as indicated by clinically significant abnormal creatinine values (Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2 calculated using the Modification of Diet in Renal Disease Study (MDRD) equation)
- History of chronic hepatitis of any non-cardiac etiology
- History of any active or clinically significant cardiac tachyarrhythmia (such as recurrent atrial fibrillation with rapid ventricular response within the last year) and patients with chronic atrial fibrillation with a pulse rate ≤ 100 bpm
- Patients who received an i.v. infusion of a cardiac inotrope (e.g., dobutamine or milrinone) in the last 24 h prior to randomization
- Patients with any significant change in their dose of their ACE, ARB, mineralocorticoid receptor antagonist, diuretic, or β-blocker within the last 12 h
- Patients with known significant valvular heart diseases indicated by the following:
Show all 11Show fewer
- severe aortic stenosis (aortic valve area < 1.0 cm2 or peak gradient > 50 mm Hg as determined by echocardiography)
- severe mitral stenosis
- History of acute coronary syndrome within the last 60 days as determined by both clinical and enzymatic criteria
- For echocardiography-based cohorts only, patients admitted to an inpatient setting for acute decompensated heart failure within the last 30 days
- For PA catheter cohorts, patients with a pulmonary capillary wedge pressure of <10 mm Hg at Baseline. For echocardiographic cohorts, patients with a lateral E/E' ratio of < 7 on their baseline echocardiogram. For patients in whom a lateral E/E' ratio cannot be determined (e.g., patients in atrial fibrillation), a central venous pressure of < 5 mm Hg on baseline echocardiogram as determined by inferior vena cava criteria.
Trial locations and contacts
11 sites in 5 countries.
11 sites in 5 countries
United States6 sites
Novartis Investigative Site
Chicago, Illinois, 60611
Novartis Investigative Site
Cleveland, Ohio, 44195
Novartis Investigative Site
Houston, Texas, 77030
Novartis Investigative Site
Philadelphia, Pennsylvania, 19104
Novartis Investigative Site
St Louis, Missouri, 63110
Novartis Investigative Site
Tacoma, Washington, 98405
Germany2 sites
Novartis Investigative Site
Greifswald, 17475
Novartis Investigative Site
Regensburg, Bavaria, 93053
About this study
Official title: A Randomized, Subject and Investigator-blind, Placebo-controlled Study of CLR325 in Chronic Stable Heart Failure Patients
The purpose of this study was to determine the safety and tolerability of CLR325 intravenous (i.v.) infusion in patients with stable heart failure to determine if further clinical development of the drug in this indication was warranted.
- Conditions
- Chronic Stable Heart Failure
- Being tested
- CLR325, Placebo
- Keywords
- Apelin, CLR325, Chronic heart failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CLR325Drug
CLR325 Concentrate for solution for infusion
PlaceboOther
Normal saline
| Study group | Role | What they receive |
|---|---|---|
| CLR325 | Experimental | Patients were assigned to one of the 2 treatment arms in fixed randomization ratio. Patients randomized to this arm received single dose of CLR325 (i.v.) in double blind manner. Receives: Drug: CLR325 |
| Placebo | Placebo comparator | Patients were assigned to one of the 2 treatment arms in fixed randomization ratio. Patients randomized to this arm received single dose of placebo (i.v.) in double blind manner. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With Adverse Events, Serious Adverse Events and Death
Analysis of absolute and relative frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC) in each treatment arm to demonstrate that CLR325 is safe for the treatment of chronic stable heart-failure patients through the monitoring of relevant clinical and laboratory safety parameters.
Measured: Day 1 to 28
Secondary outcomes (12)
Pharmacokinetic of CLR325 and CQJ295: Area Under the Plasma Concentration-time Curve From Time Zero to 18 Hours (AUC0-18hr)
AUC0-18hr is the area under the plasma concentration-time curve from time zero to 18 hours after the start of CLR325 infusion. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Only descriptive analysis performed.
Measured: 0, 0.5, 3, 5, 8, 10, 12, and 18 hours post start of CLR325 infusion on Day 1
Pharmacokinetic of CLR325 and CQJ295: Area Under the Plasma Concentration-time Curve From From Time Zero to 28 Hours (AUC0-28hrs)
AUC0-28hr is the area under the plasma concentration-time curve from time zero to 28 hours after the start of CLR325 infusion. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Only descriptive analysis performed.
Measured: 0, 0.5, 3, 5, 8, 10, 12, 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1
Pharmacokinetic of CLR325 and CQJ295: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf)
AUCinf is the area under the plasma concentration-time curve from time zero to infinity. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Only descriptive analysis performed.
Measured: 0, 0.5, 3, 5, 8, 10, 12, 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1
Pharmacokinetic of CLR325 and CQJ295: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast)
AUClast is the area under the plasma concentration-time curve from time zero to the last measurable concentration sampling time. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Only descriptive analysis performed.
Measured: 0, 0.5, 3, 5, 8, 10, 12, 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1
Pharmacokinetic of CLR325: Clearance From Plasma (CL) Following Drug Administration
CL is the systemic (or total body) clearance from plasma following CLR325 infusion. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Only descriptive analysis performed.
Measured: 0, 0.5, 3, 5, 8, 10, 12, 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1
Pharmacokinetic of CLR325 and CQJ295: Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax,ss)
Cmax,ss is the observed maximum plasma concentration following drug administration at steady state. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Only descriptive analysis performed.
Measured: 0, 0.5, 3, 5, 8, 10, 12, 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1
Pharmacokinetic of CLR325 and CQJ295: Terminal Elimination Half-life (T1/2)
T^1/2 is the elimination half-life associated with the terminal slope of a semi logarithmic concentration-time curve. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Only descriptive analysis performed.
Measured: 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1
Pharmacokinetic of CLR325 and CQJ295: Time to Reach the Maximum Concentration After Drug Administration (TMax)
Tmax is the time to reach maximum plasma concentration after single dose administration. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Only descriptive analysis performed.
Measured: 0, 0.5, 3, 5, 8, 10, 12, 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1
Pharmacokinetic of CLR325: Volume of Distribution at Steady State Following Intravenous Administration (Vss)
Vss is the volume of distribution at steady state following intravenous administration. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Only descriptive analysis performed.
Measured: 0, 0.5, 3, 5, 8, 10, 12, 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1
Pharmacokinetic of CLR325 and CQJ295: Amount of Drug (or Defined Metabolite) Excreted Into the Urine From Time (Ae 0-28 Hours)
Ae 0-28 hours is the amount of drug (or defined metabolite) excreted into the urine from time zero to 28 hours after the start of CLR325 infusion. The urine PK parameters were measured using an non-compartmental methods. Only descriptive analysis performed.
Measured: 0-28 hours on Day 1
Pharmacokinetic of CLR325 and CQJ295: Renal Clearance From Plasma (CLr) Following Drug Administration
CLr is the renal clearance from urine following CLR325 infusion. The urine PK parameters were measured using an non-compartmental methods. Only descriptive analysis performed.
Measured: 0-28 hours on Day 1
Number of Patients With Increase in Anti-CLR325 and Anti-apelin Antibodies in Serum
Anti-CLR325 anti-apelin antibodies in serum were analyzed predose, Day 10 and Day 28 to determine the immunogenicity of an 18-hour i.v. infusion of CLR325 in heart failure patients.
Measured: Baseline (BL), Day 10 (D10) and Day 28 (D28)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2016 (estimated)
- Study start17 May 2016
- Primary completion14 Jan 2019
- Study completion14 Jan 2019
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.
- Other trials for Chronic Stable Heart FailureStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02696967
- Sponsor's protocol ID
- CCLR325X2202
- Other IDs
- 2016-001387-12, 2016
- Status last verified
- Sep 2020
- First submitted
- 26 Feb 2016
- Last updated
- 5 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Subject and Investigator-blind, Placebo-controlled Study of CLR325 in Chronic Stable Heart Failure Patients
- ClinicalTrials.gov ID
- NCT02696967
- Acronym / sponsor ID
- CCLR325X2202
- Conditions
- Chronic Stable Heart Failure
- Keywords
- Apelin, CLR325, Chronic heart failure
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 17 May 2016 (actual)
- Primary completion
- 14 Jan 2019 (actual)
- Study completion
- 14 Jan 2019 (actual)
- First posted
- 2 Mar 2016 (estimated)
- Results
- Posted 4 Mar 2020
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 was to determine the safety and tolerability of CLR325 intravenous (i.v.) infusion in patients with stable heart failure to determine if further clinical development of the drug in this indication was warranted.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CLR325 | Experimental | Drug: CLR325Patients were assigned to one of the 2 treatment arms in fixed randomization ratio. Patients randomized to this arm received single dose of CLR325 (i.v.) in double blind manner. |
| Placebo | Placebo comparator | Other: PlaceboPatients were assigned to one of the 2 treatment arms in fixed randomization ratio. Patients randomized to this arm received single dose of placebo (i.v.) in double blind manner. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male and female patients >18 years of age
- Body weight between 50 kg and 140 kg
- Cardiac ejection fraction of ≤ 45% assessed within the last 6 months
- For PA catheter cohorts, patients who are planned to have a clinically indicated pulmonary artery catheter in place prior to randomization
- In the opinion of the investigator, heart failure patients who do not require a change in their dose of acetylcholinesterase (ACE), angiotensin receptor blocker (ARB), β-blocker, mineralocorticoid receptor antagonist, or diuretic for 24 h after randomization.
Key exclusion criteria (11 listed)
- Impaired renal function as indicated by clinically significant abnormal creatinine values (Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2 calculated using the Modification of Diet in Renal Disease Study (MDRD) equation)
- History of chronic hepatitis of any non-cardiac etiology
- History of any active or clinically significant cardiac tachyarrhythmia (such as recurrent atrial fibrillation with rapid ventricular response within the last year) and patients with chronic atrial fibrillation with a pulse rate ≤ 100 bpm
- Patients who received an i.v. infusion of a cardiac inotrope (e.g., dobutamine or milrinone) in the last 24 h prior to randomization
- Patients with any significant change in their dose of their ACE, ARB, mineralocorticoid receptor antagonist, diuretic, or β-blocker within the last 12 h
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 |
|---|---|---|
| CLR325CLR325 Concentrate for solution for infusion | Drug | CLR325 |
| PlaceboNormal saline | Other | Placebo |
Primary outcome
Number of Patients With Adverse Events, Serious Adverse Events and Death
Time frame: Day 1 to 28
Analysis of absolute and relative frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC) in each treatment arm to demonstrate that CLR325 is safe for the treatment of chronic stable heart-failure patients through the monitoring of relevant clinical and laboratory safety parameters.
12 secondary outcomes
Pharmacokinetic of CLR325 and CQJ295: Area Under the Plasma Concentration-time Curve From Time Zero to 18 Hours (AUC0-18hr)
Time frame: 0, 0.5, 3, 5, 8, 10, 12, and 18 hours post start of CLR325 infusion on Day 1
Pharmacokinetic of CLR325 and CQJ295: Area Under the Plasma Concentration-time Curve From From Time Zero to 28 Hours (AUC0-28hrs)
Time frame: 0, 0.5, 3, 5, 8, 10, 12, 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1
Pharmacokinetic of CLR325 and CQJ295: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf)
Time frame: 0, 0.5, 3, 5, 8, 10, 12, 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1
Pharmacokinetic of CLR325 and CQJ295: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast)
Time frame: 0, 0.5, 3, 5, 8, 10, 12, 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1
Pharmacokinetic of CLR325: Clearance From Plasma (CL) Following Drug Administration
Time frame: 0, 0.5, 3, 5, 8, 10, 12, 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1
Pharmacokinetic of CLR325 and CQJ295: Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax,ss)
Time frame: 0, 0.5, 3, 5, 8, 10, 12, 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1
Pharmacokinetic of CLR325 and CQJ295: Terminal Elimination Half-life (T1/2)
Time frame: 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1
Pharmacokinetic of CLR325 and CQJ295: Time to Reach the Maximum Concentration After Drug Administration (TMax)
Time frame: 0, 0.5, 3, 5, 8, 10, 12, 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1
Pharmacokinetic of CLR325: Volume of Distribution at Steady State Following Intravenous Administration (Vss)
Time frame: 0, 0.5, 3, 5, 8, 10, 12, 18, 20, 24, and 28 hours post start of CLR325 infusion on Day 1
Pharmacokinetic of CLR325 and CQJ295: Amount of Drug (or Defined Metabolite) Excreted Into the Urine From Time (Ae 0-28 Hours)
Time frame: 0-28 hours on Day 1
Pharmacokinetic of CLR325 and CQJ295: Renal Clearance From Plasma (CLr) Following Drug Administration
Time frame: 0-28 hours on Day 1
Number of Patients With Increase in Anti-CLR325 and Anti-apelin Antibodies in Serum
Time frame: Baseline (BL), Day 10 (D10) and Day 28 (D28)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- A Plain Language Trial Summary is available on novartisclinicatrials.comLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
11 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 CLR325 in people with Chronic Stable Heart Failure, run by Novartis Pharmaceuticals at 11 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 6 inclusion and 11 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 5 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Germany, Belgium, Netherlands, Singapore. 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 4 Mar 2020). 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?
Number of Patients With Adverse Events, Serious Adverse Events and Death (time frame: Day 1 to 28). 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 5 Jan 2021.