CTRI/2023/05/052172 [Registered on: 01/05/2023] Trial Registered Prospectively
Last Modified On:
05/05/2025
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Crossover Trial
Public Title of Study
Clinical trial to assess both the safety and effectiveness of a drug called Basimglurant, which will be given in addition to ongoing anticonvulsive therapy in children, adolescents, and young adults with seizures related to Tuberous Sclerosis Complex.
Scientific Title of Study
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 Seizures Associated with Tuberous Sclerosis Complex
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
NOE-TSC-201, Version 4.0, dated 28/April/2022
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Shiv Issar
Designation
Head, Clinical and RA
Affiliation
CliniRx Research Pvt Ltd
Address
Patriot House, 4th Floor, 3 BSZ Marg
New Delhi New Delhi Central DELHI 110002 India
Phone
09868167119
Fax
Email
shiv.issar@clinirx.com
Details of Contact Person Scientific Query
Name
Shiv Issar
Designation
Head, Clinical and RA
Affiliation
CliniRx Research Pvt Ltd
Address
Patriot House, 4th Floor, 3 BSZ Marg
New Delhi New Delhi
DELHI 110002 India
Phone
09868167119
Fax
Email
shiv.issar@clinirx.com
Details of Contact Person Public Query
Name
Shiv Issar
Designation
Head, Clinical and RA
Affiliation
CliniRx Research Pvt Ltd
Address
Patriot House, 4th Floor, 3 BSZ Marg
New Delhi New Delhi
DELHI 110002 India
Phone
09868167119
Fax
Email
shiv.issar@clinirx.com
Source of Monetary or Material Support
Noema Pharma AG
Primary Sponsor
Name
Noema Pharma AG
Address
Barfüsserplatz 3, 4051 Basel, Switzerland
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
CliniRx Research Pvt Ltd
Patriot House, 4th Floor, 3 BSZ Marg, New Delhi-110002
Countries of Recruitment
Australia India Israel United States of America Italy Poland Spain Turkey United Kingdom
Sites of Study
No of Sites = 7
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Sheffali Gulati
AIIMS
Room no 805, A wing, 8th floor, Mother & child Block, Child neurology division, Department of Pediatrics, AIIMS, New Delhi -110029, India Central DELHI
09810386847
sheffaligulati@gmail.com
Dr Maya Mary Thomas
Christian Medical College
Room no 910, West Block, First floor, Pediatric Neurology Unit, Department of Neurological Sciences, Christian Medical College, IDA Scudder Rd, Vellore, Tamil Nadu 632004 India Vellore TAMIL NADU
8300207060
maya@cmcvellore.ac.in
Dr Rukmini Mridula
Citi Neuro Center
B3, Parkinsons Disorder and Movement Disorder Research Centre (PDMDRC), Road No. 12, near Shri Jagannath Temple, Venkateswara colony, Banjara Hills, Hyderabad, Telangana 500034, India Hyderabad TELANGANA
9966446950
rukminimridula@gmail.com
Dr Sujit Abajirao Jagtap
Deenanath Mangeshkar Hospital and Research Centre
7th floor, old building, Department of Neurology,
Near Mhatre Bridge, Erandwane, Pune-411004, Maharashtra Pune MAHARASHTRA
9822290200
sujitjagtap@gmail.com
Dr Lakshminarayanan Kannan
Gleneagles Global Health City
Room No.18, Ground floor, Institute of Neuro Science, OP block,
439, Embassy Residency Rd, Cheran Nagar, Perumbakkam, Chennai, Tamil Nadu 600100, India Chennai TAMIL NADU
09791191618
dr_kln@yahoo.co.in
Dr Anaita Hegde
Jaslok Hospital And Research Centre
9th floor, pediatric Research Department, South side
15, Dr. G, Deshmukh Marg, pedder Road, Mumbai- 400026, Maharashtra, lndia Mumbai MAHARASHTRA
09820186155
anaitahegde@gmail.com
Dr Lokesh Lingappa
Rainbow Children’s Hospital
Room no 19& 20, Lower ground floor, Department of Pediatrics, Road No - 2, Banjara Hills, Near L V Prasad Eye Hospital, Next to Hotel Park Hyatt, Hyderabad – 500034. Telangana, India Hyderabad TELANGANA
Institutional Ethics Committee Deenanath Mangeshkar Hospital and Research Center
Submittted/Under Review
Institutional Ethics Committee, Gleneagles Global Health City
Approved
Institutional Review Board, Christian Medical College
Approved
Rainbow Children’s Medicare Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: Q851||Tuberous sclerosis,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Basimglurant (NOE-101)
Fixed oral doses of 0.5mg, 1 mg OD orally for 82 weeks therapy of NOE-101 adjunctive to ongoing Anticonvulsive therapy.
Comparator Agent
Matching Placebo
Fixed oral dose as an Adjunctive to ongoing anticonvulsant therapy
Inclusion Criteria
Age From
12.00 Year(s)
Age To
30.00 Year(s)
Gender
Both
Details
1. Ability and willingness to provide informed assent or written consent, or consent from their legal representative and willingness to comply with the study procedures.
2. Fluency in the language of the investigator, study staff and the informed assent or consent form when applicable.
3. Age 5 to 30 years.
4. A documented history of TSC, diagnosed according to the International Tuberous Sclerosis Complex diagnostic criteria of 2021 and including a record of either genetic test or MRI/CT scan documenting tumours.
5. Continued seizures associated with TSC (including absences, atonic, tonic, tonic-clonic or myoclonic) despite adequate dosage of at least 2 or more appropriate antiseizure drugs (AEDs) at adequate doses, within approximately the previous 3 years.
6. Refractory seizure treatment status, defined as between 3 and 20 per month over the last year and at least 5 or more seizures within the past 30 days.
7. Currently receiving one or more anti-epileptic drugs (AEDs) with no change in doses in the 30 days prior to enrolment in the study and no planned dose change during the study and through the primary endpoint.
8. All medications or interventions for epilepsy (including ketogenic diet and any neurostimulation devices for epilepsy) must have been stable for 30 days prior to screening and the patient must be willing to maintain a stable regimen throughout the study. The ketogenic diet and neurostimulation treatments are not considered AEDs for the purpose of this study.
9. Patients or their caregiver must be willing to complete daily PRO assessments.
10. For female patients of childbearing potential: a. willingness to undergo serum or urinary pregnancy testing at screening and during the trial period. b. willingness to use contraception.
ExclusionCriteria
Details
1. Etiology of a patient’s seizures is a progressive neurologic disease other than TSC.
2. Anoxic episode requiring resuscitation within 6 months of screening.
3. Patient weight below 15kg.
4. Clinically significant unstable medical conditions other than epilepsy including, but not limited to, cardiovascular, gastrointestinal, renal, hepatic, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or other major physical impairment that is not stable in the opinion of the investigator and could affect the safety of the patient throughout the study, influence the findings of the study or their interpretation, or might impede the patient’s ability to complete the entire duration of the study.
5. Any clinically significant abnormal findings in physical examination, vital signs, haematology, clinical chemistry, or urinalysis during screening which, in the opinion of the investigator, may put the patient at risk because of his/her participation in the study, or might influence the results of the study, or the patient’s ability to complete the entire duration of the study.
6. Clinically relevant symptoms or a clinically significant illness in the 4 weeks prior to screening or randomization, other than epilepsy.
7. Current or past use of recreational or medicinal cannabis within the three months prior to study entry and unwillingness to abstain for the duration of the study or a positive result on a urine tetrahydrocannabinol (THC) panel test. Epidiolex is an AED and is therefore allowed for the treatment of TSC with no change in doses in the 30 days prior to enrolment in the study and no planned dose change during the study and through the primary endpoint).
8. Participation in a clinical trial involving another investigational product (IP) in the previous 6 months or at any time in a gene therapy clinical trial.
9. Patient has previously had brain surgery for the treatment of epilepsy. (Surgery for removal of tumours ≥6 months prior to entry into the study is acceptable.).
10. Patient has bipolar disorder.
11. Subject is currently taking long-term systemic steroids (excluding inhaled medication for asthma treatment) or any other daily medication known exacerbate epilepsy. An exception will be made for prophylactic medication such as medications for idiopathic nephrotic syndrome or asthma.
12. Pregnancy or lactation.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
Primary Outcome
Outcome
TimePoints
To evaluate the efficacy of a double-blind, daily basimglurant administration, adjunctive to ongoing anticonvulsive therapy compared with placebo adjunctive to ongoing anticonvulsive therapy in patients with Tuberous Sclerosis Complex (TSC).
86 weeks including 4 week of placebo then 30 weeks of DB study, and 52 weeks of OL study
Secondary Outcome
Outcome
TimePoints
Change from baseline in Sheehan Disability Scale (SDS score at Week 16 in Period 2 and at Week 30 in Period 4.
Adverse events,
Absolute values and changes from baseline in vital signs, physical examination, electrocardiogram, and clinical laboratory test parameters
Treatment delays, dose reductions, and dose discontinuations
S-STS score for suicidal ideation
Seizure types
86 weeks
Target Sample Size
Total Sample Size="54" Sample Size from India="30" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
Tuberous
Sclerosis Complex (TSC) is an orphan condition with limited treatment options
and high medical need, impacting over one million individuals worldwide. It is
a genetic disorder characterized by the uncontrolled growth of numerous benign tumours
in many parts of the body including the brain, where it might lead to treatment
resistant seizures causing serious or life-threatening complications and often
resulting in developmental and behavioural problems. TSC is one of the leading
genetic causes of epilepsy, with about 85% of TSC patients suffering from
associated seizures, frequently refractory to treatment. With onset in early
childhood and life-long duration, TSC is a disease impacting whole families.
This condition has a profound impact on health, quality of life, and both
direct and indirect financial costs representing a long-term burden to society.
Current
treatment of epilepsy associated with TSC is almost identical to those with
epilepsy not related to TSC, focusing on a variety of anti-convulsant for both
generalized and focal epilepsy. However, even adjunctive standard of care
therapies often provides limited efficacy and intolerable side effects. There
is a need for safe and well-tolerated treatments that provide seizure control,
to prevent any deleterious effect on psychomotor development of children
affected by this condition.
Basimglurant
(NOE-101) is an investigational negative allosteric modulator of metabotropic
glutamate receptor 5 (mGluR5). It decreases neuronal excitability caused by
overactive glutamatergic signalling and normalizes overactive neuronal activity
in key brain areas. Demonstrating robust CNS engagement, basimglurant has the
potential to provide safe and effective seizure control in children,
adolescents, and young adults with TSC.
This
study is designed to validate the efficacy observed in a transgenic animal
model. In this model,
2-chloro-4-((2,5-dimethyl-1-(4-(trifluoromethoxy)phenyl)-1H-imidazol-4-yl)ethynyl)pyridine
(CTEP), an analogue of basimglurant reduced the frequency and duration of
seizures in a TSC2 knock down mouse model. Further effect was observed on the
increased protein synthesis a landmark feature of TSC. The mGluR5 CTEP was
found to normalize protein synthesis in two independent experiments.
The goal of the study is to show that basimglurant provides
effective seizure control in children, adolescents, and young adults with TSC.