Renal AngiomyolipomaPhase 4NCT03525834
Safety and Efficacy of Everolimus (Afinitor®) in Chinese Adult Patients With Angiomyolipoma Associated With Tuberous Sclerosis Complex.
A Phase 4 study testing Everolimus in people with Renal Angiomyolipoma, run by Novartis Pharmaceuticals at 5 sites in China.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Angiomyolipoma
- What is being tested?
- Everolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 5 sitesChina
- Study dates
- 9 Nov 2018to 25 Sep 2020
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
China5 sites
Novartis Investigative Site
Beijing, 100028
Novartis Investigative Site
Beijing, 100730
Novartis Investigative Site
Chengdu, Sichuan, 610041
Novartis Investigative Site
Shanghai, Shanghai Municipality, 200032
Novartis Investigative Site
Wuhan, Hubei, 430030
About this study
Official title: 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).
Read the 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.
- Conditions
- Renal Angiomyolipoma
- Being tested
- Everolimus
- Keywords
- TSC, tuberous sclerosis complex, AML, afinitor, everolimus, RAD001, mTOR, kidney, lymphangioleiomyomatosis, renal angiomyolipoma
- Medical subject headings
- Angiomyolipoma, Tuberous Sclerosis, Lymphangioleiomyomatosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
Also called RAD001, Afinitor®
Everolimus 2.5 mg and 5 mg tablets with dosage regimen of 10 mg orally once daily.
| Study group | Role | What they receive |
|---|---|---|
| Everolimus | Experimental | Participants targeted to receive Everolimus tablets 10 mg orally once daily for 48 weeks. Receives: Drug: Everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.
Measured: From the start of treatment to 30 days after end of treatment, assessed up to maximum duration of 52 weeks
Secondary outcomes (4)
Percentage of Participants With Best Overall Response (BOR) Status of Angiomyolipoma (AML) Response During Maximum Treatment Duration of 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.
Measured: Baseline, 48 weeks
Percentage of Participants With Best Overall Response Status of Angiomyolipoma (AML) Progression During Maximum Treatment Duration of 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.
Measured: Baseline, 48 weeks
Percentage of Participants With Severe Renal Impairment
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
Measured: Baseline, 48 weeks
Percentage of Participants With NCI CTCA Grade 3/4 Serum Creatinine
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).
Measured: Baseline, 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2018
- Study start9 Nov 2018
- Primary completion25 Sep 2020
- Study completion25 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Renal AngiomyolipomaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single arm, open label
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03525834
- Sponsor's protocol ID
- CRAD001M2401
- Status last verified
- Sep 2021
- First submitted
- 3 May 2018
- Last updated
- 9 Sep 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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/.
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03525834
- Acronym / sponsor ID
- CRAD001M2401
- Conditions
- Renal Angiomyolipoma
- Keywords
- TSC, tuberous sclerosis complex, AML, afinitor, everolimus, RAD001, mTOR, kidney
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 9 Nov 2018 (actual)
- Primary completion
- 25 Sep 2020 (actual)
- Study completion
- 25 Sep 2020 (actual)
- First posted
- 16 May 2018 (actual)
- Results
- Posted 9 Sep 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single arm, open label
| Arm | Type | Receives |
|---|---|---|
| Everolimus | Experimental | Drug: EverolimusParticipants targeted to receive Everolimus tablets 10 mg orally once daily for 48 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EverolimusAlso: RAD001, Afinitor®Everolimus 2.5 mg and 5 mg tablets with dosage regimen of 10 mg orally once daily. | Drug | Everolimus |
Primary outcome
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.
4 secondary outcomes
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
Percentage of Participants With Best Overall Response Status of Angiomyolipoma (AML) Progression During Maximum Treatment Duration of 48 Weeks
Time frame: Baseline, 48 weeks
Percentage of Participants With Severe Renal Impairment
Time frame: Baseline, 48 weeks
Percentage of Participants With NCI CTCA Grade 3/4 Serum Creatinine
Time frame: Baseline, 48 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. 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/.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Everolimus in people with Renal Angiomyolipoma, run by Novartis Pharmaceuticals at 5 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2021.