Everolimus (RAD001) Therapy for Epilepsy in Patients With Tuberous Sclerosis Complex (TSC)

NCT01070316 | Completed Phase 1 Results DMC

• 1 other identifier: 2009-0998
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this study is to learn if the study drug RAD001 can reduced the number of epileptic seizures, and can be taken safety by people who have epilepsy associated with Tuberous Sclerosis Complex.

Conditions

Epilepsy; Tuberous Sclerosis Complex

Keywords

Epilepsy; Tuberous Sclerosis Complex; Everolimus; RAD001; Mammalian Target of Rapamycin (MTOR)

Outcome Measures

Primary Outcomes (2)

• Reduction in Seizure Frequency

  The primary efficacy endpoint was the percentage of participants demonstrating a 50% or greater reduction in seizure frequency at the end of the maintenance phase (weeks 13-16) compared to baseline (weeks 1-4)

  Baseline (Weeks 1-4), Week 16

• Number of Participants Continuing Study Medication Over Time

  Individual subjects will be assessed every 6 months for up to 48 months; aggregate analysis will take place at end of study

Study Arms (1)

Everolimus

EXPERIMENTAL

Subjects will be administered study drug if they meet study criteria after 4 weeks of baseline phase. The starting dose will be 5 mg/m2/day, rounded to the nearest 2.5 mg/dose, to be taken daily.

Drug: Everolimus

Interventions

Everolimus DRUG

Everolimus is available in tablet form. The starting dose will be 5 mg/m2/day, rounded to the nearest 2.5 mg/dose, to be taken daily. After two weeks, serum trough level will be measured and dose adjusted according to the following algorithm If Blood trough level is less than 2.5 ng/ml than increase dose by 5 mg/m2/day; If Blood trough level is 2.5-5.0 ng/ml than increase dose by 2.5 mg/m2/day; If Blood trough level is 5.1-10.0 ng/ml than increase dose by 0 mg/m2/day (no change); If Blood trough level is 10.1-15.0 ng/ml than decrease dose by 2.5 mg/m2/day

Also known as: RAD001, Certican, Afinitor

Everolimus

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female individuals aged two years and older.
• History of epilepsy and at least eight reported seizures in previous 30 days prior to informed consent
• Failure of two or more approved antiepileptic drug therapies
• Clinically definite diagnosis of tuberous sclerosis (modified Gomez criteria or positive genetic test)
• Parents/Caregivers are English-speaking (primary or secondary language acceptable)
• If female and of child bearing potential, documentation of negative pregnancy test at time of informed consent. Sexually active pre-menopausal female or male patients must use adequate contraceptive measures, excluding use of estrogen-containing birth control contraceptive regimen while on study medication. Prior hysterectomy, tubal ligation, complete abstinence, barrier methods which include both a cervical diaphragm and spermicidal jelly, intrauterine devices (IUD), progesterone based contraceptives, or vasectomy in partner are all acceptable forms of contraception
• Adequate bone marrow function as shown by ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, and Hb \>9 g/dL
• Adequate liver function as shown by serum bilirubin ≤ 1.5 x upper limit of normal (ULN), ALT and AST ≤ 2.5x ULN, INR and PTT ≤1.5. (Anticoagulation is allowed if target INR ≤ 1.5 on a stable dose of warfarin or on a stable dose of LMW heparin for \>2 weeks at time of randomization.)
• Adequate renal function as shown by a serum creatinine ≤ 1.5 x ULN
• Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication

You may not qualify if:

• Significant hematological or hepatic abnormality (i.e., transaminase levels \> 2.5 x ULN or serum bilirubin \>1.5 x ULN, Hemoglobin \< 9 g/dL, platelets \< \< 100 X 109/L , absolute neutrophil count \< 1.5 x 109/L)
• Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, etc.)
• Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study
• Prior treatment with any investigational drug within the preceding 4 weeks prior to informed consent
• Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed
• Patients should not receive immunization with attenuated live vaccines within one week of informed consent or during study period
• Patients with coexisting malignancies within past 3 years, except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin
• Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
• Symptomatic congestive heart failure of New York heart Association Class III or IV, unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
• Severely impaired lung function defined as spirometry and DLCO that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air and/or requirement for continuous supplemental O2
• Uncontrolled diabetes as defined by fasting serum glucose \>1.5 x ULN
• Active (acute or chronic) or uncontrolled severe infections
• Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
• A known history of HIV seropositivity

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• Novartis: collaborator

Study Sites (2)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Krueger DA, Wilfong AA, Holland-Bouley K, Anderson AE, Agricola K, Tudor C, Mays M, Lopez CM, Kim MO, Franz DN. Everolimus treatment of refractory epilepsy in tuberous sclerosis complex. Ann Neurol. 2013 Nov;74(5):679-87. doi: 10.1002/ana.23960. Epub 2013 Sep 10.

  PMID: 23798472 RESULT

MeSH Terms

Conditions

Epilepsy; Tuberous Sclerosis; Hereditary Sensory and Autonomic Neuropathies

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hamartoma; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Elizabeth Hoskins
• Organization: Cincinnati Children's Hospital Medical Center

elizabeth.hoskins@cchmc.org

(513) 803-7263

Study Officials

• Darcy Krueger, M.D. Ph.D

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2010
• First Posted: February 18, 2010
• Study Start: January 1, 2010
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: March 13, 2017
• Results First Posted: September 23, 2016

Record last verified: 2017-02

Locations

US (2)