- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03481972
A Study of Doxycycline and Tauroursodeoxycholic Acid (Doxy/TUDCA) Plus Standard Supportive Therapy Versus Standard Supportive Therapy Alone in Cardiac Amyloidosis Caused by Transthyretin
A Phase III Randomized Study of Doxycycline and Tauroursodeoxycholic Acid (Doxy/TUDCA) Plus Standard Supportive Therapy Versus Standard Supportive Therapy Alone in Cardiac Amyloidosis Caused by Transthyretin
Cardiac amyloidosis caused by transthyretin either mutated (in ATTRm amyloidosis) or wildtype (in ATTRwt, formerly senile, amyloidosis) is a rare disease but is diagnosed with increasing frequency thanks to the availability of non-invasive scintigraphy-based means. Cardiac ATTR amyloidosis is characterized by progressive heart failure with a median survival of less than 4 years, and there is no standard treatment for this disease. It was proved that the marketed antibiotic doxycycline (Doxy) disrupts amyloid fibrils in vitro and in animal models synergistically with tauroursodeoxycholic acid (TUDCA). Based on these pre-clinical data, a clinical trial of Doxy/TUDCA in ATTR Amyloidosis (NCT01171859) was conducted.
Treatment was well tolerated and was able to prevent progression of cardiac dysfunction.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
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Pavia, Italy, 27100
- Fondazione IRCCS Policlinico San Matteo
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
Subjects must meet all of the following criteria:
- Diagnosis of ATTRwt amyloidosis, or ATTRm p.Ile68Leu and p.Val122Ile;
- the diagnosis of amyloidosis needs to be biopsy-proven, and amyloid deposits need to be characterized as ATTR-type by immuno-electron microscopy or mass spectrometry. Biopsy can be omitted in patients with a positive (score 3) cardiac 99mTc-DPD scintigraphy, provided serum and urine immunofixation does not show monoclonal components. Wild-type and mutated ATTR amyloidosis will be differentiated by DNA analysis;
- 18 years or older;
- cardiac involvement (mean left ventricular wall thickness >12 mm in the absence of other causes);
- history of occurrence of at least 1 event of symptomatic heart failure;
- stable diuretic dosage for at least 2 weeks before treatment initiation;
- female patients who are postmenopausal for at least 1 year before the screening visit, or are surgically sterile, or if they are of childbearing potential, agree to practice effective methods of contraception from the time of signing the informed consent through 30 days after the last dose of study drug, or agree to completely abstain from intercourse;
- voluntary written consent must be given before performance of any study-related procedure not part of standard medical care with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
Exclusion Criteria:
Subjects must meet none of the following criteria:
- Non-ATTR amyloidosis;
- NYHA class IV;
- enzyme-documented myocardial infarction within 6 months before enrollment;
- pregnant or nursing women;
- uncontrolled bacterial, viral, fungal, HIV, HBV, or HCV infection;
- presence of other active malignancy with the exception of non-melanoma skin cancer, cervical cancer, treated early-stage prostate cancer provided that prostate specific antigen is within normal limit, or any completely resected carcinoma in situ;
- known allergy to any of the study medications, their analogues, or excipients in the various formulations;
- treatment with drugs potentially affecting doxycycline absorption;
- significant acute gastrointestinal symptoms;
- active peptic ulceration and/or esophageal reflux disease;
- treatment with any investigational products within 28 days before the first dose of study drug;
- requirement for other concomitant chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered to be investigational;
- any other serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Doxy/TUDCA
doxycicline (100 mg / BID) tauroursodeoxycholic acid (250 mg / TID) |
doxycicline and tauroursodeoxycholic acid
Other Names:
|
Active Comparator: Standard of care
Standard of care therapies.
|
Standard of care
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
evaluate the efficacy of Doxy/TUDCA in patients with cardiac ATTR amyloidosis, comparing survival free at 18 months of patients receiving Doxy/TUDCA + standard supportive therapy with that of patients in standard supportive therapy alone.
Time Frame: 18 MONTHS
|
Doxy/TUDCA efficacy
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18 MONTHS
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Compare overall survival at 18 and 30 months of patients receiving Doxy/TUDCA in addition to standard supportive therapy with that of patients receiving standard supportive therapy alone.
Time Frame: 18 and 30 months
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Survival
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18 and 30 months
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- AC 011 IT
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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