Clinical trial NCT05217628: An Efficacy and Safety Study of Basimglurant (NOE-101) in Patients With Trigeminal Neuralgia.
Official title: A Phase II/III, Multicentre, 8-week run-in Phase Followed by a 12-week, Prospective, Parallel-group, Double-blind, Randomized Withdrawal, Placebo-controlled Study, With a 52 Week Open Label Extension, to Evaluate the Efficacy and Safety of Daily 1.5 to 3.5 mg Basimglurant in Patients With Pain Associated With Trigeminal Neuralgia With Suboptimal Response to Their Current Anti-pain Therapy.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Trigeminal Neuralgia
Lead sponsor: Noema Pharma AG
Sponsor class: INDUSTRY
First posted: 2022-02-01
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Trigeminal neuralgia (TN), also called "tic douloureux", is the most common form of craniofacial neuropathic pain and is considered the cause of one of the most painful afflictions known in medical practice.

This study is designed to evaluate the efficacy and safety of 1.5mg - 3.5mg basimglurant in adults with TN.

Detailed description: This study is designed to evaluate the efficacy and safety of basimglurant (NOE-101) in patients with TN. Basimglurant is a potent inhibitor of metabotropic glutamate receptor 5 (mGluR5) which controls a wide range of processes in both central and peripheral nervous system. Inhibition of the mGluR5 receptor has shown therapeutic potential for pain associated with conditions such as TN. The drug has been shown to have a favorable safety profile in adults, children and adolescents. The aim of the study is to determine whether Basimglurant decreases both duration and intensity of facial pain associated with TN by use of a patient pain diary and the Patient-reported Global Impression of Change (PGI-C) compared to baseline.

Eligibility criteria: Inclusion Criteria (Summary):

1. Ability and willingness to provide written informed consent and to comply with the study procedures.
2. Fluency in the language of the investigator, study staff and the informed consent.
3. Age 18-75 years.
4. Diagnosis of primary trigeminal neuralgia (TN) as per the ICHD3 criteria confirmed by the study neurologist.
5. Experience pain due to TN and at baseline, experience at least 3 paroxysms per day of at least intensity of 4 or more on a pain intensity numerical rating scale (PI-NRS) during the last 7 days.
6. Female patients who are either sterile or menopausal. For female patients with childbearing potential, must be neither pregnant nor lactating (with appropriate contraceptive precautions and prior negative pregnancy tests).

Exclusion Criteria (Summary):

Patients who meet any of the following criteria will be excluded from participation in this study:

1. Current or prior history of any major psychiatric diagnoses unrelated to TN. Patients with TN-related depressive symptoms are permitted.
2. Current or prior history of mania, or psychotic episodes.
3. History of DSM-5-defined substance dependence (Diagnostic and Statistical Manual for Mental Disorders, 5th edition) and/or substance abuse in the last six months \[180 days\], except for nicotine.
4. Patient not willing to discontinue their current TN analgesic medication.
5. Use of opioids, except for pain control on a prn basis as long as it does not exceed 2 days per week.
6. Known allergic reaction to the investigational drug or one of its components.
7. Patients with secondary TN as per the ICHD3 criteria.

   Medication history:
8. Previous treatment with basimglurant, except with the prior agreement of the medical monitor.
9. Treatment with antipsychotics within six months (180 days) of screening.
10. Any investigational drug within 90 days prior to initiation of study drug.

    Medical status:
11. Evidence of clinically significant, uncontrolled, unstable medical conditions or recently diagnosed cardiovascular disease, such as ischemic heart disease, coronary artery vasospasm, and cerebral ischemia. Subjects with myocardial infarction, acute coronary syndrome, percutaneous coronary intervention, cardiac surgery, stroke or transient ischemic attack during the 6 months prior to screening.
12. Subject has a history of gastric, or small intestinal surgery (including gastric bypass, gastric banding, gastric sleeve, gastric balloon, etc.) that may, in the opinion of the investigator, may cause malabsorption, or has a disease of the GI tract that causes malabsorption.
13. Body mass index \> 39kg/m²
14. Patients with moderate or severely impaired hepatic function, ie, Pugh-Child score C.
15. Patients with severe renal impairment, ie, eGFR or creatinine clearance lower than 30mL/min.

Primary outcomes:
measure: Period 1: Incidence and severity of adverse events, laboratory, vital signs and cardiovascular events.
timeFrame: 8 weeks
measure: Period 2: Time to Loss of Efficacy or pain recurrence defined as the confirmed increase in the number of weekly paroxysms or re-emergence of continuous pain and/or the need for rescue medication.
timeFrame: 12 weeks
measure: Open Label Extension: Incidence and severity of adverse events, laboratory, vital signs and cardiovascular events.
timeFrame: 52 weeks
Secondary outcomes:
measure: Period 2: Mean change in the total patient-rated Penn-Facial Pain Scale-Revised (Penn-FPS-R) scale compared with Period 2 baseline (BL2).
timeFrame: 12 weeks
measure: Period 2: Frequency of attacks (paroxysms).
timeFrame: 12 weeks
measure: Period 2: Severity of attacks (paroxysms).
timeFrame: 12 weeks
measure: Period 2: Severity of continuous pain.
timeFrame: 12 weeks
measure: Period 2: Duration of continuous pain.
timeFrame: 12 weeks
measure: Period 2: Change in Patient Global Impression of Change (P-GIC).
timeFrame: 12 weeks
measure: Period 2: Change in Medication Satisfaction Questionnaire (MSQ).
timeFrame: 12 weeks
measure: Open Label Extension: Frequency of attacks (paroxysms).
timeFrame: 52 weeks
measure: Open Label Extension: Severity of attacks (paroxysms).
timeFrame: 52 weeks
measure: Open Label Extension: Severity and duration of continuous pain reported in patient pain diary.
timeFrame: 52 weeks
measure: Open Label Extension: Measure Global Impression of Severity as captured by PGI-S.
timeFrame: 52 weeks
Other outcomes:
measure: Period 1: Mean change from Period 1 baseline (BL1) to Week 8 in the total patient-rated Penn-Facial Pain Scale-Revised (Penn-FPS-R) scale.
timeFrame: 8 weeks
measure: Period 1: Measure Global Impression of change from Period 1 baseline (BL1) to Week 8.
timeFrame: 8 weeks
measure: Period 1: Number and severity of attacks (paroxysms).
timeFrame: 8 weeks
measure: Period 1: Duration of continuous pain compared with BL1.
timeFrame: 8 weeks
measure: Period 1: Severity of continuous pain compared with BL1.
timeFrame: 8 weeks
measure: Period 1: Number of pain free days.
timeFrame: 8 weeks
measure: Period 1: Patient reported rating of the Medication Satisfaction Questionnaire (MSQ).
timeFrame: 8 weeks
measure: Period 2: The impact of pain on general activities of daily living captured in patient diary cards.
timeFrame: 12 weeks
Locations:
city: La Jolla
country: United States
facility: Kaizen Brain Center (Site #: 1001)
state: California
city: Miami
country: United States
facility: L & A Morales Healthcare INC (Site#: 1011)
state: Florida
city: Tampa
country: United States
facility: University of South Florida (Site #: 1002)
state: Florida
city: Newnan
country: United States
facility: Vista Clinical Research,LLC (Site#: 1010)
state: Georgia
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center (Site #: 1004)
state: Massachusetts
city: Las Vegas
country: United States
facility: Altea Research - Nevada - ClinEdge - PPDS (Site #1006)
state: Nevada
city: New York
country: United States
facility: Columbia University - Irving Medical Center (Site #: 1008)
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati (Site #: 1007)
state: Ohio
city: Glostrup
country: Denmark
facility: Danish Headache Center (Site #: 1201)
city: Frankfurt am Main
country: Germany
facility: Kopfschmerzzentrum Frankfurt (Site #: 1706)
state: Hessen
city: Essen
country: Germany
facility: Universitätsklinikum Essen (Site #: 1702)
state: Nordrhein-Westfalen
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn (Site #: 1707)
city: Höxter
country: Germany
facility: St. Ansgar Krankenhaus Höxter -Klinikum Weser Egge (Site #: 1701)
city: Roma
country: Italy
facility: Università Campus Bio Medico Di Roma (Site #: 1805)
state: Lazio
city: Roma
country: Italy
facility: IRCCS San Raffaele Pisana (Site #: 1801)
state: Lazio
city: Roma
country: Italy
facility: La Sapienza-Università di Roma-Policlinico Umberto I (Site #: 1802)
state: Lazio
city: Florence
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi (Site #: 1806)
city: Milano
country: Italy
facility: Fondazione IRCCS Di Rilievo Nazionale Istituto Nazionale Neurologico Carlo Besta (Site #: 1804)
city: Dąbrowa Górnicza
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej (NZOZ) Zespo (Site #: 2602)
city: Kraków
country: Poland
facility: Centrum Medyczne Linden (Site #: 2605)
city: Lublin
country: Poland
facility: Prywatny Gabinet Lekarski U. Chyrchel-Paszkiewicz (Site #: 2604)
city: Wrocław
country: Poland
facility: MIGRE Polskie Centrum Leczenia Migreny Anna Gryglas-Dworak (Site #: 2601)
city: Łódź
country: Poland
facility: FutureMeds - Lodzi - PPDS (Site #: 2606)
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz (Site #: 1903)
city: Madrid
country: Spain
facility: Hospital Universitario La Paz - PPDS (Site #: 1907)
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio - PPDS (Site #: 1904)
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia (Site #: 1906)
city: Selçuklu
country: Turkey
facility: Selcuk University Medical Faculty (Site #: 9006)
state: Konya
city: Afyonkarahisar
country: Turkey
facility: Afyon Kocatepe University Faculty of Medicine (Site #: 9005)
city: Bursa
country: Turkey
facility: Uludag University Faculty of Medicine Hospital (Site #: 9001)
city: Düzce
country: Turkey
facility: Duzce University Health Application and Research Center (9008)
city: Istanbul
country: Turkey
facility: Istanbul University Istanbul Medical Faculty Hospital (Site #: 9003)
city: Istanbul
country: Turkey
facility: Bagcilar Medipol Mega University Hospital (Site #: 9002)
city: Kocaeli
country: Turkey
facility: Kocaeli University Faculty of Medicine Hospital (Site #: 9004)
city: Mersin
country: Turkey
facility: Mersin University Faculty of Medicine Hospital (Site #: 9007)
city: London
country: United Kingdom
facility: St Pancras Clinical Research (Site #: 2503)
state: Middlesex
city: London
country: United Kingdom
facility: St. Thomas' Hospital (Site #: 2504)
Study officials:
References: