An international randomized clinical study, measuring safety and effectiveness of basimglurant for the treatment of pain in patients with Trigeminal Neuralgia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Noema Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

24 Mar 2022 → ongoing

Decision date (initial)

2024-10-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Neoma Pharma, AG

External identifiers

EU CT number

2024-514497-41-00

EudraCT number

2021-001866-39

ClinicalTrials.gov

NCT05217628

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Efficacy, Pharmacokinetic, Safety

Period 1: Run-in: To evaluate the safety, tolerability, and efficacy of basimglurant daily dosing 1.5 - 3.5 mg in pain associated with TN.
Period 2: Double Blind: To assess the maintenance of effect on pain of doubleblind 12-week once daily dosing of basimglurant
1.5 – 3.5 mg compared with placebo in patients with TN.
Open-Label Extension: To evaluate the long-term safety of basimglurant daily dosing 1.5-3.5 mg.

Secondary objectives 3

1. Period 1: Run-in: To evaluate the efficacy of 8-week once daily treatment with basimglurant on pain associated with trigeminal neuralgia on the following disease aspects: • Impact on facial pain • Patient perceived change of the pain • Quantitative and qualitative pain assessments • Pain freedom • Patient medication satisfaction • Assess functional impairment
2. Period 2: Double Blind: To evaluate the effect of double-blind treatment of once daily dose of basimglurant versus placebo on the following disease aspects: • Impact on facial pain • Pain frequency and severity • Patient perceived perception of change in pain • Patient medication satisfaction • Safety of basimglurant once daily dosing 1.5-3.5 mg compared with placebo
3. Open-Label Extension: To evaluate the continued efficacy of basimglurant with once daily dosing 1.5-3.5 mg on the following disease aspects: • Impact on facial pain • Pain frequency and severity • Patient perceived severity of pain

Conditions and MedDRA coding

Trigeminal neuralgia

Study design 4 periods

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Inclusion Criteria (Summary): 1. Ability and willingness to provide written informed consent and to comply with the study procedures.
2. 2. Fluency in the language of the investigator, study staff and the informed consent.
3. 3. Age 18-75 years.
4. 4. Diagnosis of primary trigeminal neuralgia (TN) as per the ICHD3 criteria confirmed by the study neurologist.
5. 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. 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 15

1. Exclusion Criteria (Summary): 1. Current or prior history of any major psychiatric diagnoses unrelated to TN. Patients with TN-related depressive symptoms are permitted.
2. 2. Current or prior history of mania, or psychotic episodes.
3. 3. History of DSM-5-defined substance dependence and/or substance abuse in the last six months [180 days], except for nicotine.
4. 4. Patient not willing to discontinue their current TN analgesic medication.
5. 5. Use of opioids, except for pain control on a prn basis as long as it does not exceed 2 days per week.
6. 6. Known allergic reaction to the investigational drug or one of its components.
7. 7. Patients with secondary TN as per the ICHD3 criteria.
8. Medication history: 8. Previous treatment with basimglurant, except with the prior agreement of the medical monitor.
9. 9. Treatment with antipsychotics within six months (180 days) of screening.
10. 10. Any investigational drug within 90 days prior to initiation of study drug.
11. 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. 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. 13. Body mass index > 39 kg/m2.
14. 14. Patients with severely impaired hepatic function, ie, Child-Pugh score C.
15. 15. Patients with severe renal impairment, ie, eGFR or creatinine clearance lower than 30 mL/min.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Period 1: Run-in: Change in pain as measured by the pain diary (TnED). Incidence and severity of AEs. Laboratory, vital signs and cardiovascular safety will also be evaluated. Changes in psychiatric status as measured by the BPRS. Treatment emergent suicidal ideation and behavior as measured by the S-STS.
2. Period 2: Double Blind: Time to Loss of Efficacy for each participant as determined by the IAC.
3. Open-Label Extension: Incidence and severity of AEs. Laboratory, vital signs and cardiovascular safety will also be evaluated. Changes in psychiatric status as measured by the BPRS. Treatment emergent suicidal ideation and behavior as measured by the S-STS.

Secondary endpoints 6

1. Period 1: Run-in: • Proportion of pain free days as measured by TnED. • Number and severity of attacks (paroxysms) as well as duration and severity of continuous pain compared with BL1, as measured by TnED • Changes in pain interference with daily activities compared to BL1, as measured by TnED • Mean change from BL1 to Week 8 in the total patient-rated PENN-FPS-R • PGI-C from BL1 to Week 8 • Patient reported rating of the MSQ. • Changes from BL1 to Week 8 in SDS
2. Period 2: Double Blind: • Proportion of pain free days as measured by TnED in the double-blind randomized withdrawal period until end of double-blind randomized treatment or start of pain rescue medication intake. • Number and severity of attacks (paroxysms) as well as severity and duration of continuous pain, as measured by TnED
3. • Changes in pain interference with daily activities compared to BL2, as measured by TnED
4. '• Change at the end of double-blind randomized treatment or start of rescue medication intake during the double-blind randomized withdrawal period in the total patient-rated PENN-FPS-R compared with BL2 • PGI-C at the end of double-blind randomized treatment or start of rescue medication intake during the double-blind randomized withdrawal period • Patient reported rating of the MSQ
5. '• Incidence and severity of AEs. Laboratory and cardiovascular safety will also be evaluated. Changes in psychiatric status as measured by the BPRS. Treatment emergent suicidal ideation and behavior as measured by the S-STS.
6. 'Open-Label Extension: • Proportion of pain free days as measured by TnED. • Number and severity of attacks (paroxysms) as well as severity and duration of continuous pain, as measured by TnED. • Pain interference with daily activities, as measured by TnED. • Mean scores in the total patient-rated PENN-FPSR. • Overall patient global impression measured by the PGI-S.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Noema Pharma AG

Sponsor organisation

Noema Pharma AG

Address

Barfusserplatz 3

City

Basel

Postcode

4051

Country

Switzerland

Scientific contact point

Organisation

Noema Pharma AG

Contact name

Global Regulatory Affairs

Public contact point

Organisation

Noema Pharma AG

Contact name

Global Regulatory Affairs

Third parties 6

Locations

5 EU/EEA countries · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 39 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications