Clinical trial NCT05059327: Basimglurant (NOE-101) in Children, Adolescents, and Young Adults With TSC
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Tuberous Sclerosis Complex
Keywords: Basimglurant
TSC
Seizures
NOE-101
Lead sponsor: Noema Pharma AG
Sponsor class: INDUSTRY
First posted: 2021-09-28
Enrollment: 61
Sex: ALL
Minimum age (years): 5
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This is a multi-center, randomized, double-blind, placebo-controlled, 30-week, cross-over (Part A) followed by a 52-week open-label extension (OLE) (Part B) study.
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Mean percentage in monthly seizure frequency during the maintenance dosing in Period 2 (Weeks 13 to 16) and Period 4 (Weeks 27-30).
timeFrame: 30 weeks
Secondary outcomes:
measure: Number of patients considered treatment responders.
timeFrame: 30 weeks
measure: Longest seizure free interval (i.e., seizure free days).
timeFrame: 30 weeks
measure: 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.
timeFrame: 30 weeks
measure: 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.
timeFrame: 30 weeks
measure: Safety of the study drug in children, adolescents and young adults with seizures associated with TSC.
timeFrame: 82 weeks
Other outcomes:
measure: 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.
timeFrame: 30 weeks
measure: 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).
timeFrame: 30 weeks
measure: Intensity of seizures detected by the wearable device evaluated as the change from Baseline compared to study treatment Periods 1 and 4.
timeFrame: 30 weeks
Locations:
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA (Site #: 101)
state: California
city: Baltimore
country: United States
facility: Kennedy Krieger Institute (Site #: 110)
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital (Site #: 102)
state: Massachusetts
city: Royal Oak
country: United States
facility: William Beaumont Hospital - Royal Oak (Site #: 104)
state: Michigan
city: Roseville
country: United States
facility: Minnesota Epilepsy Group PA (Site #: 105)
state: Minnesota
city: Hawthorne
country: United States
facility: Boston Children's Health Physicians (BCHP) (Site #: 111)
state: New York
city: Durham
country: United States
facility: Duke Children's Hospital and Health Center (Site #: 106)
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center, Rainbow Babies and Childrens Hospital (Site #: 107)
state: Ohio
city: Houston
country: United States
facility: The University of Texas Medical School at Houston (Site #: 103)
state: Texas
city: Hyderabad
country: India
facility: Citi Neuro Centre (Site # 806)
state: Andhra Pradesh
city: Hyderabad
country: India
facility: Rainbow Childrens Hospital (Site # 803)
state: Andhra Pradesh
city: New Delhi
country: India
facility: All India Institute of Medical Sciences (Site # 804)
state: Delhi
city: Mumbai
country: India
facility: Jaslok Hospital and Research Centre (Site # 801)
state: Maharashtra
city: Pune
country: India
facility: Deenanath Mangeshkar Hospital and Research Centre (Site # 805)
state: Maharashtra
city: Vellore
country: India
facility: Christian Medical College (Site # 807)
state: Tamil Nadu
city: Jerusalem
country: Israel
facility: Hadassah Medical Center - PPDS (Site #: 503)
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda (Site # 183)
state: Lombardia
city: Warsaw
country: Poland
facility: Instytut Pomnik Centrum Zdrowia Dziecka (Site # 262)
state: Mazowieckie
city: Badalona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol (Site # 194)
state: Barcelona
city: Esplugues De Llobregat
country: Spain
facility: Hospital Sant Joan de Deu - PIN (Site # 192)
state: Barcelona
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Malaga - Hospital General (Site # 193)
city: Sevilla
country: Spain
facility: Centro de Neurología Avanzada (Site # 191)
city: Fatih
country: Turkey
facility: Istanbul Universitesi Istanbul Tip Fakultesi Hastanesi (Site #: 905)
state: Istanbul
city: Kadıköy
country: Turkey
facility: Yeditepe University Kosuyolu Hospital (Site #: 904)
state: Istanbul
city: Sultangazi
country: Turkey
facility: Istanbul Egitim ve Arastirma Hastanesi (Site #: 901)
state: Istanbul
city: Salford
country: United Kingdom
facility: Salford Royal Hospital - PPDS (Site # 304)
state: Lancashire
city: Cardiff
country: United Kingdom
facility: Noahs Ark Children's Hospital (Site # 306)
state: South Glamorgan
Study officials:
affiliation: Noema Pharma AG
name: Clinical Director, MD
role: STUDY_DIRECTOR
References: