A Phase IV Study of Safety and Efficacy of Everolimus in Taiwanese Patients With Tuberous Sclerosis Complex Who Have Renal Angiomyolipoma (TSC-AML)

Phase IV, Prospective Single Arm Study of Safety and Efficacy of Votubia (Everolimus) in Taiwanese Adults With Tuberous Sclerosis Complex Who Have Renal Angiomyolipoma

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.

Study Overview

• Status: Recruiting
• Conditions: Renal Angiomyolipoma
• Intervention / Treatment: Drug: Everolimus

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.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: +41613241111; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals

Study Locations

• Taiwan
  • Taipei, Taiwan, 10002
    • Recruiting
    • Novartis Investigative Site
  • Taiwan ROC
    • Taichung, Taiwan ROC, Taiwan, 40201
      • Recruiting
      • Novartis Investigative Site
    • Taoyuan, Taiwan ROC, Taiwan, 33305
      • Recruiting
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female patients from ≥ 20 years of age.
2. Signed informed consent must be obtained prior to participation in the study.
3. Participants with TSC associated with renal AML which is eligible for treatment with everolimus per local reimbursement criteria.

Exclusion Criteria:

1. Patients with severe hepatic impairment (Child-Pugh class C)
2. Prior therapy with systemic mTOR inhibitors (sirolimus, temsirolimus, everolimus).
3. Any severe and/or uncontrolled medical conditions.
4. Pregnant or breast-feeding females.
5. Patients with hypersensitivity to the active substance, to other rapamycin derivatives, or to any of the excipients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Everolimus; Participants with confirmed diagnosis of TSC-AML and who fulfil the local (Taiwan) reimbursement criteria of everolimus for TSC-AML treatment

Drug: Everolimus; 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); Other Names: RAD001

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants with adverse events (AEs), Serious AEs (SAEs) and AEs of special interest (AESI)	Percentage of participants with AEs, SAEs and AESIs.	From first dose of study treatment up to 56 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Up to 52 weeks
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)	Up to 52 weeks
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.	From screening up to 56 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2023
• Primary Completion (Estimated): September 30, 2024
• Study Completion (Estimated): July 19, 2025

Study Registration Dates

• First Submitted: February 16, 2022
• First Submitted That Met QC Criteria: February 16, 2022
• First Posted (Actual): February 23, 2022

Study Record Updates

• Last Update Posted (Estimated): November 20, 2023
• Last Update Submitted That Met QC Criteria: November 17, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Angiomyolipoma; Tuberous Sclerosis Complex; AML; Everolimus; TSC
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Congenital Abnormalities; Genetic Diseases, Inborn; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Neoplastic Syndromes, Hereditary; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Perivascular Epithelioid Cell Neoplasms; Neurocutaneous Syndromes; Neoplasms, Adipose Tissue; Hamartoma; Neoplasms, Multiple Primary; Sclerosis; Tuberous Sclerosis; Angiomyolipoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protein Kinase Inhibitors; MTOR Inhibitors; Everolimus
• Other Study ID Numbers: CRAD001M2402

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No