Back to resultsA Phase IV Study of Safety and Efficacy of Everolimus in Taiwanese Patients With Tuberous Sclerosis Complex Who Have Renal Angiomyolipoma (TSC-AML)
Primary Purpose
Renal Angiomyolipoma
Status
Recruiting
Phase
Phase 4
Locations
Taiwan
Study Type
Interventional
Intervention
Everolimus
Sponsored by
About this trial
This is an interventional treatment trial for Renal Angiomyolipoma focused on measuring Tuberous Sclerosis Complex, TSC, Angiomyolipoma, AML, Everolimus
Eligibility Criteria
Inclusion Criteria:
- Signed informed consent must be obtained prior to participation in the study.
With TSC associated with renal AML which is eligible for treatment with everolimus per locally approved label (at least one of below):
- Tumor size of ≥ 4 cm with history of clinically meaningful hemorrhage.
- Aneurysm lesion ≥ 5 mm, ineligible for trans-arterioemolization or surgery.
- More than one lesion.
- Recurrence after/refractory to trans-arterioemolization or surgery.
- Presence of at least one AML lesion ≥ 1 cm in its longest diameter via CT or MRI imaging.
Exclusion Criteria:
- Patients with severe hepatic impairment (Child-Pugh class C)
- Prior therapy with systemic mTOR inhibitors (sirolimus, temsirolimus, everolimus).
- Any severe and/or uncontrolled medical conditions.
- Pregnant or breast-feeding females.
- Patients with hypersensitivity to the active substance, to other rapamycin derivatives, or to any of the excipients.
Sites / Locations
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Everolimus
Arm Description
Participants with confirmed diagnosis of TSC-AML and who fulfil the local (Taiwan) reimbursement criteria of everolimus for TSC-AML treatment
Outcomes
Primary Outcome Measures
Percentage of participants with adverse events (AEs), Serious AEs (SAEs) and AEs of special interest (AESI)
Percentage of participants with AEs, SAEs and AESIs.
Secondary Outcome Measures
Angiomyolipoma (AML) response rate
AML response rate is defined as the percentage of patients with an AML response. AML response will be defined as: A reduction in AML volume of at least 50% relative to screening, where AML volume is the sum of the volumes of all target AML identified at screening. In addition, AML response have to satisfy: no new AML ≥ 1 cm in longest diameter are identified, neither kidney increases in volume by more than 20% from nadir (where nadir is the lowest kidney volume at the screening), the participant does not have any angiomyolipoma-related bleeding of grade equal or over 2 (as defined by NCI CTCAE, version 5).
AML progression rate
AML progression rate is defined as the percentage of patients with an AML progression. AML progression status is defined as one or more of the following: an increase from nadir of 25% or more in AML volume to a value greater than screening AML (where nadir is the lowest AML volume obtained for the participant previously in the trial), the appearance of a new AML ≥ 1.0 cm in longest diameter, an increase from nadir of 20% or more in the volume of either kidney to a value greater than screening (where nadir is the lowest kidney volume obtained for the participant previously in the trial), angiomyolipoma-related bleeding grade ≥2 (as defined by NCI CTCAE, version 5)
Percentage of participants with laboratory abnormalities
The laboratory assessment (including hematology, coagulation, biochemistry, and urinalysis) will be recorded at baseline and during the study based on changes in grade of laboratory abnormality.
Full Information
NCT ID
NCT05252585
First Posted
February 16, 2022
Last Updated
May 10, 2023
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT05252585
Brief Title
A Phase IV Study of Safety and Efficacy of Everolimus in Taiwanese Patients With Tuberous Sclerosis Complex Who Have Renal Angiomyolipoma (TSC-AML)
Official Title
Phase IV, Prospective Single Arm Study of Safety and Efficacy of Votubia (Everolimus) in Taiwanese Adults With Tuberous Sclerosis Complex Who Have Renal Angiomyolipoma
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 1, 2023 (Actual)
Primary Completion Date
September 30, 2024 (Anticipated)
Study Completion Date
July 19, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this prospective study is to assess the safety and efficacy of everolimus in Taiwanese patients with renal angiomyolipoma (AML) associated with tuberous sclerosis complex (TSC) . Only patients who fulfil the local reimbursement criteria of everolimus for TSC-AML will be included in this study.
Detailed Description
This open-label, prospective, single-arm, multicenter Phase IV post approval commitment (PAC) study is planned to be conducted in approximately 10 patients with confirmed diagnosis of TSC-AML and who fulfil the local reimbursement criteria of everolimus for TSC-AML treatment.
The study will have a 30-day screening phase, and each patient will be on treatment up to 52 weeks. Enrollment will end at the latest within 52 weeks from Day 1 of the study, regardless of the number of patients actually recruited. After completion of the treatment phase/end of treatment (EOT), eligible patients will enter a 4-week safety follow up (FU) phase. Patients who continue to be on treatment beyond 52 weeks, based on the investigator's judgment will not be included in the 4-week safety FU phase.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Angiomyolipoma
Keywords
Tuberous Sclerosis Complex, TSC, Angiomyolipoma, AML, Everolimus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Everolimus
Arm Type
Experimental
Arm Description
Participants with confirmed diagnosis of TSC-AML and who fulfil the local (Taiwan) reimbursement criteria of everolimus for TSC-AML treatment
Intervention Type
Drug
Intervention Name(s)
Everolimus
Other Intervention Name(s)
RAD001
Intervention Description
Everolimus tablets for oral use. The recommended everolimus starting dose will be 10 mg orally taken once daily for all patients, except for those with impaired liver function, for whom the everolimus dose will be:
Child-Pugh grade A: 7.5 mg once daily (for patients with mild hepatic impairment)
Child-Pugh grade B: 5.0 mg once daily (for patients with moderate hepatic impairment)
Primary Outcome Measure Information:
Title
Percentage of participants with adverse events (AEs), Serious AEs (SAEs) and AEs of special interest (AESI)
Description
Percentage of participants with AEs, SAEs and AESIs.
Time Frame
From first dose of study treatment up to 56 weeks
Secondary Outcome Measure Information:
Title
Angiomyolipoma (AML) response rate
Description
AML response rate is defined as the percentage of patients with an AML response. AML response will be defined as: A reduction in AML volume of at least 50% relative to screening, where AML volume is the sum of the volumes of all target AML identified at screening. In addition, AML response have to satisfy: no new AML ≥ 1 cm in longest diameter are identified, neither kidney increases in volume by more than 20% from nadir (where nadir is the lowest kidney volume at the screening), the participant does not have any angiomyolipoma-related bleeding of grade equal or over 2 (as defined by NCI CTCAE, version 5).
Time Frame
Up to 52 weeks
Title
AML progression rate
Description
AML progression rate is defined as the percentage of patients with an AML progression. AML progression status is defined as one or more of the following: an increase from nadir of 25% or more in AML volume to a value greater than screening AML (where nadir is the lowest AML volume obtained for the participant previously in the trial), the appearance of a new AML ≥ 1.0 cm in longest diameter, an increase from nadir of 20% or more in the volume of either kidney to a value greater than screening (where nadir is the lowest kidney volume obtained for the participant previously in the trial), angiomyolipoma-related bleeding grade ≥2 (as defined by NCI CTCAE, version 5)
Time Frame
Up to 52 weeks
Title
Percentage of participants with laboratory abnormalities
Description
The laboratory assessment (including hematology, coagulation, biochemistry, and urinalysis) will be recorded at baseline and during the study based on changes in grade of laboratory abnormality.
Time Frame
From screening up to 56 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed informed consent must be obtained prior to participation in the study.
With TSC associated with renal AML which is eligible for treatment with everolimus per locally approved label (at least one of below):
Tumor size of ≥ 4 cm with history of clinically meaningful hemorrhage.
Aneurysm lesion ≥ 5 mm, ineligible for trans-arterioemolization or surgery.
More than one lesion.
Recurrence after/refractory to trans-arterioemolization or surgery.
Presence of at least one AML lesion ≥ 1 cm in its longest diameter via CT or MRI imaging.
Exclusion Criteria:
Patients with severe hepatic impairment (Child-Pugh class C)
Prior therapy with systemic mTOR inhibitors (sirolimus, temsirolimus, everolimus).
Any severe and/or uncontrolled medical conditions.
Pregnant or breast-feeding females.
Patients with hypersensitivity to the active substance, to other rapamycin derivatives, or to any of the excipients.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Phone
+41613241111
Email
novartis.email@novartis.com
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Taichung
State/Province
Taiwan ROC
ZIP/Postal Code
40201
Country
Taiwan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Kuei Shan Chiang
State/Province
Taoyuan Taiwan ROC
ZIP/Postal Code
33305
Country
Taiwan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
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
Learn more about this trial
A Phase IV Study of Safety and Efficacy of Everolimus in Taiwanese Patients With Tuberous Sclerosis Complex Who Have Renal Angiomyolipoma (TSC-AML)
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