Safety and Efficacy of AT-001 in Patients With Diabetic Cardiomyopathy
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| ClinicalTrials.gov Identifier: NCT04083339 |
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Recruitment Status :
Active, not recruiting
First Posted : September 10, 2019
Last Update Posted : December 8, 2022
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Sponsor:
Applied Therapeutics, Inc.
Information provided by (Responsible Party):
Applied Therapeutics, Inc.
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Brief Summary:
This is a multicenter, randomized, placebo-controlled, 2-part study to evaluate the safety and efficacy of AT-001 in adult patients (N=675) with Diabetic Cardiomyopathy at high risk of progression to overt heart failure.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Diabetic Cardiomyopathies | Drug: AT-001 Drug: Placebo | Phase 3 |
The study consists of two consecutive parts: Part A and Part B. Part A will evaluate the safety and efficacy of two doses of AT-001 vs placebo. The primary objective of Part A is to demonstrate that AT-001 improves or prevents the decline of functional capacity in patients with Diabetic Cardiomyopathy. Part B is an extension of at least 12 months that will evaluate the safety and efficacy of chronic administration of AT-001 vs placebo in the same patients who had previously been evaluated in Part A. Assessments in Part B will include safety endpoints and exploratory clinical efficacy endpoints, i.e. death and hospitalization due to a cardiac event.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 675 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure (ARISE-HF): A Multicenter, Randomized, Placebo-Controlled Study to Evaluate the Safety and Efficacy of AT-001 in Patients With Diabetic Cardiomyopathy |
| Actual Study Start Date : | September 20, 2019 |
| Estimated Primary Completion Date : | December 2023 |
| Estimated Study Completion Date : | December 2025 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: AT-001 High dose
The total daily doses will be of 3g. The dose selection and the frequency of dosing was based on the results of the phase 1/2 study demonstrating that 3g/day of AT-001 is capable of producing the maximum inhibition of the production of sorbitol (a pharmacodynamic biomarker of biological activity).
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Drug: AT-001
AT-001 will be administered as 3 capsules twice daily, before breakfast and before dinner. At present AT001 is the sole name for the active substance. No INN/genetic name is available to date |
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Experimental: AT-001 Low Dose
The total daily doses will be of 2g. The dose selection and the frequency of dosing was based on the results of the phase 1/2 study demonstrating that 2g/day of AT-001 is capable of producing a sufficient inhibition of the production of sorbitol (a pharmacodynamic biomarker of biological activity).
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Drug: AT-001
AT-001 will be administered as 3 capsules twice daily, before breakfast and before dinner. At present AT001 is the sole name for the active substance. No INN/genetic name is available to date |
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Placebo Comparator: Placebo Comparator
Placebo capsules will be used as comparator
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Drug: Placebo
Matching placebo will be administered as 3 capsules twice daily, before breakfast and before dinner |
Primary Outcome Measures :
- Peak VO2 during cardio-pulmonary exercise test (CPET); [ Time Frame: 15 months after randomization] ]Changes in Peak VO2 during cardio-pulmonary exercise test (CPET) from baseline to approximately Month 15 (15-18 months). A CPET may be repeated at approximately Month 27 (27-30 months).
Secondary Outcome Measures :
- Progression to overt heart failure (Stage C Heart Failure) [ Time Frame: 27 months after randomization ]Defined by the occurrence of one of the following events: cardiovascular death, hospitalization for heart failure, urgent heart failure visit, new diagnosis of heart failure
- Changes in NT-proBNP [ Time Frame: 27 months after randomization ]Changes in NT-proBNP may reflect worsening of cardiomyopathy over time
- Changes in the modified Kansas City Cardiomyopathy Questionnaire (KCCQ) score [ Time Frame: 27 months after randomization ]Changes in the modified KCCQ may reflect deterioration of clinical status over time
Other Outcome Measures:
- Worsening of diabetic cardiomyopathy [ Time Frame: 15 and 27 months after randomization ]Defined by either ≥ 20% increase in NT-proBNP or ≥ 5 point decrease in the mKCCQ score
- Changes in echocardiographic parameters [ Time Frame: 27 months after randomization ]Changes assessed on cardiac ultra-sound from baseline
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| Ages Eligible for Study: | 40 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Type 2 Diabetes Mellitus
- Diabetic cardiomyopathy
- Peak VO2 < 75% of predicted normal value based on age and gender
Exclusion Criteria:
- Prior diagnosis or signs/symptoms of overt/symptomatic heart failure / stage C heart failure
- Prior echocardiogrphic measurement of ejection fraction (EF) < 40%
- Prior acute coronary syndrome (ACS), coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), coronary artery disease (CAD) or stroke
- Severe or moderate cardiac valve disease requiring intervention
- Clinically significant arrhythmia
- Prior diagnosis of congenital, infective, toxic, infiltrative, post-partum, or hypertrophic cardiomyopathy
- Blood pressure > 140 mmHg (systolic) or > 90 mmHg (diastolic) at screening
- HbA1c >8.5% at screening
- Severe disease that would impact the performance of a cardio-pulmonary exercise test
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04083339
Locations
Show 79 study locations
Sponsors and Collaborators
Applied Therapeutics, Inc.
Investigators
| Study Chair: | James L Januzzi, MD | Harvard Medical School (HMS and HSDM) |
| Responsible Party: | Applied Therapeutics, Inc. |
| ClinicalTrials.gov Identifier: | NCT04083339 |
| Other Study ID Numbers: |
AT-001-2001 |
| First Posted: | September 10, 2019 Key Record Dates |
| Last Update Posted: | December 8, 2022 |
| Last Verified: | December 2022 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Applied Therapeutics, Inc.:
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Type 2 Diabetes Aldose Reductase Inhibitor Stage B Heart Failure Stage C Heart Failure Cardiopulmonary Exercise Test |
Additional relevant MeSH terms:
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Cardiomyopathies Diabetic Cardiomyopathies Heart Diseases Cardiovascular Diseases |
Diabetes Complications Diabetes Mellitus Endocrine System Diseases |