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| ID | Type | Description | Link |
|---|---|---|---|
| TR 000954 | Other Identifier | National Center for Advancing Translational Sciences |
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| Name | Class |
|---|---|
| Sanofi | INDUSTRY |
| National Institutes of Health (NIH) | NIH |
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The primary objective of the current study is to determine whether Ataciguat (HMR1766) slows progression of valve calcification in patients with moderate calcific aortic valve stenosis. Secondary and tertiary objectives are to determine whether Ataciguat slows progression of aortic valve function, reduces systemic inflammation, and prevents left ventricular dysfunction in patients with moderate calcific aortic valve stenosis.
Patients with Moderate Calcific Aortic Valve Stenosis may be eligible for enrollment in this study. Participation lasts 12 months, which includes a total of 3 study visits (baseline/screening visit, 6 month follow up visit and 12 month follow up visit). During each visit, a blood sample will be taken along with other research related tests (Orthostatic Tolerance Standing Test, CT Scan, Echocardiogram, DEXA Scan). Qualifying Participants will be supplied with 6 months worth of study medication or placebo during visits 1 (baseline/screening visit) and 2 (6 month follow up visit) in which they will take at home daily with food. On visit 3 (12 month follow up visit), any remaining study medication or placebo will be returned to study staff.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ataciguat (HMR1766) | Experimental | 200mg taken daily for 12 months |
|
| Matching Placebo | Placebo Comparator | Taken Daily for 12 months |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ataciguat (HMR1766) | Drug |
| ||
| Placebo Comparator: Matching Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in Aortic Valve Calcium Levels | This will be done using computed tomography (CT) scanning to evaluate aortic valve calcium levels, which is considered to be a "gold standard" for evaluating valvular calcium burden. As measured in Arbitrary Units (AU). | baseline, 6 mos |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Levels of Plasma Interleukin-6 | Determine whether long-term treatment with HMR1766 will result in sustained increases in systemic sGC signaling and reduce levels of circulating inflammatory cytokines in patients with mild to moderate CAVS. This will be done using ELISA-based measurements of interleukin-6 and tumor necrosis factor alpha in venous blood samples. Key comparisons will be between HMR1766-treated and placebo-treated groups, where we will examine the change in inflammatory cytokine levels from baseline in subjects receiving HMR1766 or placebo capsules. |
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Inclusion Criteria
Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| Jordan D Miller, PhD | Mayo Clinic | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic in Rochester | Rochester | Minnesota | 55905 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39989354 | Derived | Zhang B, Enriquez-Sarano M, Schaff HV, Michelena HI, Roos CM, Hagler MA, Zhang H, Casaclang-Verzosa G, Huang R, Bartoo A, Ranadive S, Joyner MJ, Pislaru S, Nkomo VT, Kremers WK, Araoz PA, Singh G, Walters MA, Hawkinson J, Cunningham KY, Sung J, Dunagan B, Ye Z, Miller JD. Reactivation of Oxidized Soluble Guanylate Cyclase as a Novel Treatment Strategy to Slow Progression of Calcific Aortic Valve Stenosis: Preclinical and Randomized Clinical Trials to Assess Safety and Efficacy. Circulation. 2025 Apr;151(13):913-930. doi: 10.1161/CIRCULATIONAHA.123.066523. Epub 2025 Feb 24. |
| Label | URL |
|---|---|
| Mayo Clinic Clinical Trials | View source |
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Patients were required to complete initial testing for valve calcium and function (in addition to other tests/screening characteristics) prior to enrollment.
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| ID | Title | Description |
|---|---|---|
| FG000 | Ataciguat (HMR1766) | 200mg taken daily for 6 months Ataciguat (HMR1766) |
| FG001 | Matching Placebo | Taken Daily for 6 months Placebo Comparator: Matching Placebo |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Ataciguat (HMR1766) | 200mg taken daily for 12 months Ataciguat (HMR1766) |
| BG001 | Matching Placebo | Taken Daily for 12 months Placebo Comparator: Matching Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Changes in Aortic Valve Calcium Levels | This will be done using computed tomography (CT) scanning to evaluate aortic valve calcium levels, which is considered to be a "gold standard" for evaluating valvular calcium burden. As measured in Arbitrary Units (AU). | Posted | Mean | Standard Error | Arbitrary Units | baseline, 6 mos |
|
Adverse event data were acquired during the periods of patient enrollment (from 6 months to a maximum of 12 months of treatment duration). The total study duration was 3 years.
Our definitions of AE and SAE do not differ from those provided on clinicaltrials.gov. For this study, adverse events were identified through regularly scheduled follow-up phone calls by study staff.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Ataciguat (HMR1766) | 200mg taken daily for 6 months Ataciguat (HMR1766) | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Elevated Liver Enzymes | Hepatobiliary disorders | Systematic Assessment | Elevated liver enzymes at 6 month follow-up with clinically-indicated testing showing hepatic inflammation. Resolved after discontinuation of study drug. Not definitive whether hepatotoxicity was due to study drug or other medications taken. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jordan D. Miller, Ph.D. | Mayo Clinic | 507-293-0813 | Miller.Jordan@mayo.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 8, 2014 | Jun 17, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D001024 | Aortic Valve Stenosis |
| D003251 | Constriction, Pathologic |
| D002114 | Calcinosis |
| ID | Term |
|---|---|
| D000082862 | Aortic Valve Disease |
| D006349 | Heart Valve Diseases |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| C515616 | 5-chloro-2-(5-chlorothiophene-2-sulfonylamino)-N-(4-(morpholine-4-sulfonyl)phenyl)benzamide |
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| Other |
|
| baseline, 6 mos |
| Change in Aortic Valve Function: Aortic Valve Area | Determine whether long-term treatment with HMR1766 will result in sustained increases in systemic sGC signaling slow progression of aortic valve dysfunction in patients with mild to moderate CAVS. This will be done using echocardiography-based measurements of aortic valve function. Key comparisons will be between HMR1766-treated and placebo-treated groups, where we will examine the change in:
| baseline, 6 mos |
| Change in Left Ventricular Function | Determine whether long-term treatment with HMR1766 will result in sustained increases in systemic sGC signaling slow progression of aortic valve dysfunction in patients with mild to moderate CAVS. This will be done using echocardiography-based measurements of aortic valve function. Key comparisons will be between HMR1766-treated and placebo-treated groups, where we will examine the change in: 1. Left ventricular systolic function (measured by echocardiographic measurement of left ventricular ejection fraction) and 2. Left ventricular diastolic function (measured using the E/A ratio derived from Doppler measurements). | baseline, 6 mos |
| Change in Plasma Tumor Necrosis Factor Alpha | Determine whether long-term treatment with ataciguat reduces levels of circulating inflammatory cytokines. | Baseline, 6 months |
| Change in Aortic Valve Function: Transvalvular Pressure Gradient | Determine whether long-term treatment with HMR1766 will result in sustained increases in systemic sGC signaling slow progression of aortic valve dysfunction in patients with mild to moderate CAVS. This will be done using echocardiography-based measurements of aortic valve function. Key comparisons will be between HMR1766-treated and placebo-treated groups, where we will examine the change in:
| baseline, 6 mos |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Region of enrollment was confined to patients able to travel to Mayo Clinic Rochester for a minimum of 2 visits (baseline/6mo and potentially 12mo) | Count of Participants | Participants |
|
| Units | Counts |
|---|
| Participants |
|
|
|
| Secondary | Change in Levels of Plasma Interleukin-6 | Determine whether long-term treatment with HMR1766 will result in sustained increases in systemic sGC signaling and reduce levels of circulating inflammatory cytokines in patients with mild to moderate CAVS. This will be done using ELISA-based measurements of interleukin-6 and tumor necrosis factor alpha in venous blood samples. Key comparisons will be between HMR1766-treated and placebo-treated groups, where we will examine the change in inflammatory cytokine levels from baseline in subjects receiving HMR1766 or placebo capsules. | One placebo sample was not obtained/available for analysis, thereby reducing the number of data points from 11 to 10. | Posted | Mean | Standard Error | pg/ml | baseline, 6 mos |
|
|
|
| Secondary | Change in Aortic Valve Function: Aortic Valve Area | Determine whether long-term treatment with HMR1766 will result in sustained increases in systemic sGC signaling slow progression of aortic valve dysfunction in patients with mild to moderate CAVS. This will be done using echocardiography-based measurements of aortic valve function. Key comparisons will be between HMR1766-treated and placebo-treated groups, where we will examine the change in:
| Posted | Mean | Standard Error | change in cm^2 | baseline, 6 mos |
|
|
|
|
| Secondary | Change in Left Ventricular Function | Determine whether long-term treatment with HMR1766 will result in sustained increases in systemic sGC signaling slow progression of aortic valve dysfunction in patients with mild to moderate CAVS. This will be done using echocardiography-based measurements of aortic valve function. Key comparisons will be between HMR1766-treated and placebo-treated groups, where we will examine the change in: 1. Left ventricular systolic function (measured by echocardiographic measurement of left ventricular ejection fraction) and 2. Left ventricular diastolic function (measured using the E/A ratio derived from Doppler measurements). | Posted | Mean | Standard Error | percent | baseline, 6 mos |
|
|
|
|
| Secondary | Change in Plasma Tumor Necrosis Factor Alpha | Determine whether long-term treatment with ataciguat reduces levels of circulating inflammatory cytokines. | One placebo sample was not obtained/available for analysis, thereby reducing the number of data points from 11 to 10. | Posted | Mean | Standard Error | pg/ml | Baseline, 6 months |
|
|
|
| Secondary | Change in Aortic Valve Function: Transvalvular Pressure Gradient | Determine whether long-term treatment with HMR1766 will result in sustained increases in systemic sGC signaling slow progression of aortic valve dysfunction in patients with mild to moderate CAVS. This will be done using echocardiography-based measurements of aortic valve function. Key comparisons will be between HMR1766-treated and placebo-treated groups, where we will examine the change in:
| Posted | Mean | Standard Error | change in mm Hg | baseline, 6 mos |
|
|
|
| 12 |
| 1 |
| 12 |
| 9 |
| 12 |
| EG001 | Matching Placebo | Taken Daily for 6 months Placebo Comparator: Matching Placebo | 0 | 12 | 1 | 12 | 10 | 12 |
|
| Hospitalization due progression of disease | Cardiac disorders | Systematic Assessment | Patient reported to the hospital with dyspnea and fatigue. Subsequent testing revealed that patient had progressed to severe aortic valve stenosis during the follow-up period and was deemed eligible for surgery. |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Dizziness/Lightheadedness | Nervous system disorders | Systematic Assessment |
|
| Nosebleed | Blood and lymphatic system disorders | Systematic Assessment |
|
| Rash/Dry Skin | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Bradycardia | Cardiac disorders | Systematic Assessment |
|
| Tired/Fatigue | Nervous system disorders | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Odor in urine | Gastrointestinal disorders | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | Systematic Assessment |
|
| Chest Pain/Tightness | Cardiac disorders | Systematic Assessment |
|
| Lower back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Mood Changes | Nervous system disorders | Systematic Assessment |
|
| Ankle Edema | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Fall (study unrelated) | Musculoskeletal and connective tissue disorders | Systematic Assessment | Subject tripped and fell. No sustained injuries as a result. |
|
| Runny Nose (Common Cold) | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Hot Flashes | Nervous system disorders | Systematic Assessment |
|
| Nausea | Nervous system disorders | Systematic Assessment |
|
| Prostate Cancer (study unrelated) | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
|
| Cholesterol lab values out of range | Hepatobiliary disorders | Systematic Assessment |
|
| Muscle Cramps/Aches | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Fever | Infections and infestations | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Hypoglycemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Indigestion | Gastrointestinal disorders | Systematic Assessment |
|
| Dry Mouth | Gastrointestinal disorders | Systematic Assessment |
|
| Cough (related to cold/flu) | Infections and infestations | Systematic Assessment |
|
| Low Hemoglobin | Blood and lymphatic system disorders | Systematic Assessment |
|
| Arm Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
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| D014694 |
| Ventricular Outflow Obstruction |
| D020763 | Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D002128 | Calcium Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |