Basimglurant (NOE-101) in Children, Adolescents, and Young Adults With TSC

A Phase 2B, Multicenter, 30-week, Prospective, Cross-over, Double-blind, Randomized, Placebo-controlled Study Followed by a 52-Week Open-label Extension Study to Evaluate the Efficacy and Safety of Basimglurant Adjunctive to Ongoing Anticonvulsive Therapy in Children, Adolescents, and Young Adults With Uncontrolled Seizures Associated With Tuberous Sclerosis Complex

The study intends to show that basimglurant (NOE-101) provides effective seizure control in children, adolescents and young adults with Tuberous Sclerosis Complex (TSC).

Study Overview

• Status: Completed
• Conditions: Tuberous Sclerosis Complex
• Intervention / Treatment: Drug: Basimglurant with crossover to Placebo; Drug: Placebo with crossover to Basimglurant

Detailed Description

The study drug (NOE-101, basimglurant) is a potent inhibitor of metabotropic glutamate receptor 5 (mGluR5) which controls a wide range of processes in the brain, spinal cord, retina, and peripheral nervous system. In animal studies, the inhibition of this receptor has shown therapeutic potential for the treatment of Tuberous Sclerosis Complex (TSC). This receptor's inhibition decreases the frequency of seizures. In previous clinical trials, the study drug has shown an advantageous safety profile in children and adolescents.

The objective of this study is to find an optimal dose at which the study drug will lead to a decrease in the duration, frequency and intensity of seizures in children, adolescents and young adults with TSC, while being well tolerated. All patients who positively respond and tolerate the medicine will be offered the possibility to continue in an open label extension.

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 2

Contacts and Locations

Study Locations

• India
  • Andhra Pradesh
    • Hyderabad, Andhra Pradesh, India, 500034
      • Citi Neuro Centre (Site # 806)
    • Hyderabad, Andhra Pradesh, India, 500034
      • Rainbow Childrens Hospital (Site # 803)
  • Delhi
    • New Delhi, Delhi, India, 110029
      • All India Institute of Medical Sciences (Site # 804)
  • Maharashtra
    • Mumbai, Maharashtra, India, 400026
      • Jaslok Hospital and Research Centre (Site # 801)
    • Pune, Maharashtra, India, 411006
      • Deenanath Mangeshkar Hospital and Research Centre (Site # 805)
  • Tamil Nadu
    • Vellore, Tamil Nadu, India, 632004
      • Christian Medical College (Site # 807)
• Israel
  • Jerusalem, Israel, 91120
    • Hadassah Medical Center - PPDS (Site #: 503)
• Italy
  • Lombardia
    • Milano, Lombardia, Italy, 20162
      • ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda (Site # 183)
• Poland
  • Mazowieckie
    • Warsaw, Mazowieckie, Poland, 04-730
      • Instytut Pomnik Centrum Zdrowia Dziecka (Site # 262)
• Spain
  • Málaga, Spain, 29010
    • Hospital Regional Universitario de Malaga - Hospital General (Site # 193)
  • Sevilla, Spain, 41013
    • Centro de Neurología Avanzada (Site # 191)
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitario Germans Trias i Pujol (Site # 194)
    • Esplugues De Llobregat, Barcelona, Spain, 08950
      • Hospital Sant Joan de Deu - PIN (Site # 192)
• Turkey
  • Istanbul
    • Fatih, Istanbul, Turkey, 34093
      • Istanbul Universitesi Istanbul Tip Fakultesi Hastanesi (Site #: 905)
    • Kadıköy, Istanbul, Turkey, 34718
      • Yeditepe University Kosuyolu Hospital (Site #: 904)
    • Sultangazi, Istanbul, Turkey, 34096
      • Istanbul Egitim ve Arastirma Hastanesi (Site #: 901)
• United Kingdom
  • Lancashire
    • Salford, Lancashire, United Kingdom, M6 8HD
      • Salford Royal Hospital - PPDS (Site # 304)
  • South Glamorgan
    • Cardiff, South Glamorgan, United Kingdom, CF14 4XW
      • Noahs Ark Children's Hospital (Site # 306)
• United States
  • California
    • Los Angeles, California, United States, 90095
      • David Geffen School of Medicine at UCLA (Site #: 101)
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Kennedy Krieger Institute (Site #: 110)
  • Massachusetts
    • Boston, Massachusetts, United States, 02115-5724
      • Boston Children's Hospital (Site #: 102)
  • Michigan
    • Royal Oak, Michigan, United States, 48073-6712
      • William Beaumont Hospital - Royal Oak (Site #: 104)
  • Minnesota
    • Roseville, Minnesota, United States, 55113-1306
      • Minnesota Epilepsy Group PA (Site #: 105)
  • New York
    • Hawthorne, New York, United States, 10532
      • Boston Children's Health Physicians (BCHP) (Site #: 111)
  • North Carolina
    • Durham, North Carolina, United States, 27705-4699
      • Duke Children's Hospital and Health Center (Site #: 106)
  • Ohio
    • Cleveland, Ohio, United States, 44106-1716
      • University Hospitals Cleveland Medical Center, Rainbow Babies and Childrens Hospital (Site #: 107)
  • Texas
    • Houston, Texas, United States, 77030-3000
      • The University of Texas Medical School at Houston (Site #: 103)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 30 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria (summary):

• Ability and willingness to provide informed assent or written consent or consent from their legal representative.
• Fluency in the language of the study staff
• Age 5 to 30 years at study entry
• A documented history of TSC
• Refractory seizure history
• Currently receiving one or more anti-epileptic drugs (AEDs)
• Stable medications or interventions for epilepsy
• Willingness to complete Patient Reported Outcome assessments

• For female patients of childbearing potential:

  1. Willingness to undergo serum or urinary pregnancy testing at screening and during the trial period.
  2. Willingness to use contraception.

Exclusion Criteria (summary):

• Neurologic disease other than TSC
• Recent anoxic episode
• Patient weight below 15kg
• Clinically significant unstable medical condition(s)
• Pregnancy or lactation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A (Basimglurant/NOE-101 to Placebo); Basimglurant to Placebo	Drug: Basimglurant with crossover to Placebo; Basimglurant with crossover to Placebo
Placebo Comparator: Arm B (Placebo to Basimglurant/NOE-101); Placebo to Basimglurant	Drug: Placebo with crossover to Basimglurant; Placebo with crossover to Basimglurant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean percentage in monthly seizure frequency during the maintenance dosing in Period 2 (Weeks 13 to 16) and Period 4 (Weeks 27-30).	30 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients considered treatment responders.		30 weeks
Longest seizure free interval (i.e., seizure free days).		30 weeks
Change in the severity of symptoms of TSC as measured by Caregiver Global Impression of Change (CGIC) score during maintenance dosing in Period 2 (Weeks 13 to 16) and Period 4 (Weeks 27-30) compared to Baseline.		30 weeks
Change in the Sheehan Disability Scale during maintenance dosing in Period 2 (Weeks 13 to 16) and Period 4 (Weeks 27-30) compared to baseline.		30 weeks
Safety of the study drug in children, adolescents and young adults with seizures associated with TSC.	Measured in terms of incidence, nature, and severity of adverse events, vital signs, physical examination, clinical chemistry, hematology, electrocardiograms, and urinalysis, as well as treatment delays, dose reductions, and dose discontinuations. In addition, suicidal ideation will be assessed using S-STS.	82 weeks

Other Outcome Measures

Outcome Measure	Time Frame
Change in seriousness of disease as assessed by Most Impactful Symptoms Scale in Periods 2 (weeks 13 to 16) and Period 4 (weeks 27 to 30) compared to baseline.	30 weeks
Frequency of seizures detected by the wearable device evaluated as the change from Baseline compared to study treatment in Period 1 (weeks 13 to 16) and Period 4 (weeks 27 to 30).	30 weeks
Intensity of seizures detected by the wearable device evaluated as the change from Baseline compared to study treatment Periods 1 and 4.	30 weeks

Collaborators and Investigators

• Sponsor: Noema Pharma AG
• Investigators: Study Director: Clinical Director, MD, Noema Pharma AG

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2022
• Primary Completion (Actual): February 6, 2025
• Study Completion (Actual): April 28, 2025

Study Registration Dates

• First Submitted: August 20, 2021
• First Submitted That Met QC Criteria: September 20, 2021
• First Posted (Actual): September 28, 2021

Study Record Updates

• Last Update Posted (Actual): June 4, 2025
• Last Update Submitted That Met QC Criteria: June 3, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Seizures; TSC; Basimglurant; NOE-101
• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Neoplasms; Genetic Diseases, Inborn; Neurodegenerative Diseases; Congenital Abnormalities; Heredodegenerative Disorders, Nervous System; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Hamartoma; Neoplasms, Multiple Primary; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Sclerosis; Tuberous Sclerosis
• Other Study ID Numbers: NOE-TSC-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No