Safety and Efficacy of Everolimus (Afinitor®) in Chinese Adult Patients With Angiomyolipoma Associated With Tuberous Sclerosis Complex.

September 3, 2021 updated by: Novartis Pharmaceuticals

Phase IV, Single Arm Study of Safety and Efficacy of Everolimus in Chinese Adults With Tuberous Sclerosis Complex Who Have Renal Angiomyolipoma Not Requiring Immediate Surgery

The purpose of this study was to assess the safety and efficacy of everolimus (Afinitor®) in Chinese patients with renal angiomyolipoma (AML) associated with tuberous sclerosis complex (TSC).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This was an open label, single arm, multi-center, Phase IV Post-Approval Commitment (PAC) study with once daily oral dose of 10 mg everolimus in participants with renal AML associated with TSC. There were three separate phases in this study: a Screening phase, an Open-label treatment phase where participants received everolimus for 48 weeks or until disease progression, and a Treatment discontinuation follow-up phase for patients who discontinue study drug for reasons other than disease progression. Every participant had an End of Treatment visit within 28 days after last dose and a safety follow-up visit 30 days after last dose.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Beijing, China, 100730
        • Novartis Investigative Site
      • Beijing, China, 100028
        • Novartis Investigative Site
    • Hubei
      • Wuhan, Hubei, China, 430030
        • Novartis Investigative Site
    • Shanghai
      • Shanghai, Shanghai, China, 200032
        • Novartis Investigative Site
    • Sichuan
      • Chengdu, Sichuan, China, 610041
        • Novartis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Eligible for treatment with everolimus as per the locally approved label.
  • Presence of at least one AML ≥ 3 cm in its longest diameter using CT or MRI.

Exclusion Criteria:

  • AML related bleeding or embolization during the 6 months prior to enrollment.
  • History of myocardial infarction, angina or stroke related to atherosclerosis.
  • Impaired lung function.
  • Significant hematological or hepatic abnormality.
  • Any severe and/or uncontrolled medical conditions.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Everolimus
Participants targeted to receive Everolimus tablets 10 mg orally once daily for 48 weeks.
Drug: Everolimus
Everolimus 2.5 mg and 5 mg tablets with dosage regimen of 10 mg orally once daily.
Other Names:
  • RAD001, Afinitor®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: From the start of treatment to 30 days after end of treatment, assessed up to maximum duration of 52 weeks
Percentage of participants with AEs and SAEs including significant changes from baseline in vital signs, electrocardiograms and laboratory parameters (laboratory assessments included hematology, biochemistry, coagulation and urinalysis) qualifying and reported as AEs. The percentage of participants in each category is reported in the table.
From the start of treatment to 30 days after end of treatment, assessed up to maximum duration of 52 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Best Overall Response (BOR) Status of Angiomyolipoma (AML) Response During Maximum Treatment Duration of 48 Weeks
Time Frame: Baseline, 48 weeks

BOR status is the best status recorded from start of treatment until disease progression. AML response status: reduction in AML volume of at least 50% relative to screening AML. 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 4.03).

Up to five of the largest measurable lesions (≥ 1 cm in longest diameter) in each kidney were measured at screening via Magnetic Resonance Imaging/Computed tomography (MRI/CT) and were defined as screening AML. The sum of the volumes of these individual lesions was defined as AML volume and it was measured at each assessment during the trial. Increases in the AML volume were evidence of worsening AML, decreases were evidence of clinical response.
Baseline, 48 weeks
Percentage of Participants With Best Overall Response Status of Angiomyolipoma (AML) Progression During Maximum Treatment Duration of 48 Weeks
Time Frame: Baseline, 48 weeks

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 4.03).

Up to five of the largest measurable lesions (≥ 1 cm in longest diameter) in each kidney were measured at screening via Magnetic Resonance Imaging/Computed tomography (MRI/CT) and were defined as screening AML. The sum of the volumes of these individual lesions was defined as AML volume and it was measured at each assessment during the trial. Increases in the AML volume were evidence of worsening AML.
Baseline, 48 weeks
Percentage of Participants With Severe Renal Impairment
Time Frame: Baseline, 48 weeks

Renal impairment is defined as calculated Creatinine Clearance (CrCl) < 30 mL/min. CrCl was measured at baseline and at four other time points; only the baseline and the worst post-baseline value for every participant were counted (lowest value for CrCl).

Creatinine clearance was estimated using the Cockcroft-Gault formula:

creatinine clearance (mL/minute) = urine creatinine concentration (mL/dL) x volume of urine (mL/24 hour) / plasma creatinine concentration (mg/dL) x 1440 minute/24 hour
Baseline, 48 weeks
Percentage of Participants With NCI CTCA Grade 3/4 Serum Creatinine
Time Frame: Baseline, 48 weeks
NCI CTCAE grade 3/4 serum creatinine is defined as > 3.0 x upper limits of normal (ULN). Serum creatinine was measured at baseline and at four other time points; only the worst post-baseline value for every participant was counted (highest value for serum creatinine).
Baseline, 48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 9, 2018

Primary Completion (Actual)

September 25, 2020

Study Completion (Actual)

September 25, 2020

Study Registration Dates

First Submitted

May 3, 2018

First Submitted That Met QC Criteria

May 3, 2018

First Posted (Actual)

May 16, 2018

Study Record Updates

Last Update Posted (Actual)

September 9, 2021

Last Update Submitted That Met QC Criteria

September 3, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CRAD001M2401

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 https://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

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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