Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruiting
Participants planned
80
Countries
1
Sites
1
Trigeminal neuralgia
To investigate if botulinum toxin A is more effective than placebo in the treatment of trigeminal neuralgia.
Key facts
- Sponsor
- Rigshospitalet
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Nervous System Diseases [C10]
- Trial duration
- 15 Nov 2023 → ongoing
- Decision date (initial)
- 2023-08-10
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- No
- Funding sources
- Rigshospitalet, 145681, Henrik Schytz
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy, Therapy
To investigate if botulinum toxin A is more effective than placebo in the treatment of trigeminal neuralgia.
Secondary objectives 1
- To investigate if neuroinflammatory biomarkers are predictive of botulinum toxin A treatment response in trigeminal neuralgia
Conditions and MedDRA coding
Trigeminal neuralgia
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | PT | 10044652 | Trigeminal neuralgia | 100000004852 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Randomization Participants receive a total of 1.7 ml saline with 85 units BTX-A in 17 predefined injection sites in the face (see protocol, Section 6.2).
|
Randomised Controlled | Double | [{"id":168619,"code":5,"name":"Carer"},{"id":168616,"code":2,"name":"Investigator"},{"id":168615,"code":4,"name":"Analyst"},{"id":168617,"code":1,"name":"Subject"},{"id":168618,"code":3,"name":"Monitor"}] | Placebo: Participants receive a total of 1.7 ml saline in 17 predefined injection sites in the face (see protocol, Section 6.2). Botulinum toxin A (BTX-A): Participants receive a total of 1.7 ml saline with 85 units BTX-A in 17 predefined injection sites in the face (see protocol, Section 6.2). |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 5
- A diagnosis of classical trigeminal neuralgia or idiopathic trigeminal neuralgia according to criteria of The International Classification of Headache Disorders 3rd edition.
- Age between 18 and 85 years
- Subjects must experience pain defined as minimum one TN related pain paroxysm per day of an average intensity of 3 to 10, inclusive, on the 11-point NRS (0 = no pain; 10 = maximum pain imaginable) during the last 4 weeks to enter the baseline phase.
- During baseline phase subjects must experience pain defined as minimum one TN related pain paroxysm per day of an average intensity of 3 to 10, inclusive, on the 11-point NRS (0= no pain; 10= maximum pain imaginable) to be randomized.
- Fluency in Danish
Exclusion criteria 9
- Severe cardiovascular and cerebrovascular disease such as ischemic heart disease, myocardial infarction or previous stroke or transient ischemic attack, major CVD interventions during the last three months.
- Expected poor compliance, i.e., considered unlikely to be able to complete all protocol required study visits or procedures, and/or to comply with all required study procedures to the best of the subject’s and investigator’s knowledge
- Ongoing and unstable severe psychiatric disease.
- Anamnestic or clinical symptoms of any kind that are deemed relevant for study participation by the physician who examines the patient.
- Change of trigeminal neuralgia treatment or treatment dose within two weeks prior to the baseline visit.
- Previous treatment with botulinum toxin A for facial pain.
- Loading treatment within 4 weeks with phenytoin or sodium valproate.
- Female subjects either pregnant, breastfeeding or with planned conception within the study period.
- Female subject of childbearing potential who is unwilling to use an acceptable method of effective contraception during the study (see protocol for acceptable methods).
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The proportion of responders in botulinum toxin A (BTX-A) and placebo group during the evaluation period (week 2 to 5) compared with baseline (week -4 to -1) (see protocol for definition of responders).
Secondary endpoints 11
- The degree of change in inflammatory biomarkers in responders versus non-responders in BTX-A and placebo group.
- The difference in inflammatory biomarkers between the symptomatic side and the asymptomatic side.
- The proportion of subjects reaching ≥50% reduction in mean ADP during the evaluation period (week 2 to 5) compared with baseline (week -4 to -1).
- The proportion of subjects reaching ≥75% reduction in mean ADP during the evaluation period (week 2 to 5) compared with baseline (week -4 to -1).
- The proportion of subjects reaching ≥30% reduction in mean ADP during week 9 to 12 compared with baseline (week -4 to -1).
- Change in mean number of daily pain paroxysms during the evaluation period (week 2 to 5) and week 9 to 12 compared with baseline (week -4 to -1) in BTX-A and placebo group.
- Proportion of subjects with a PGI-C scale response of “much improved” or “very much improved” at week 5 in BTX-A group and placebo group.
- Change from baseline to week 5 in the PENN-FPS-R score in BTX-A and placebo group.
- Proportion of subjects correctly guessing whether they received BTX-A or placebo.
- Proportion of dropouts caused by increased intake of trigeminal neuralgia medication or use of prohibited rescue medication in botulinum toxin A group compared to the placebo group.
- Proportion of subjects with side-effects registered in weeks 2 to 5 during treatment with botulinum toxin A compared with placebo
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
BOTOX, pulver til injektionsvæske, opløsning 100 Allergan-enheder
PRD9474853 · Product
- Active substance
- Botulinum Toxin Type A
- Substance synonyms
- Onaclostox, Botulinum toxin, type A, purified neurotoxin component, OnabotulinumtoxinA, BOTULINUM TOXIN A, BOTULIN TOXIN A
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 85 U unit(s)
- Max total dose
- 85 U unit(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- M03AX01 — BOTULINUM TOXIN
- Marketing authorisation
- 31350
- MA holder
- ABBVIE A/S
- MA country
- Denmark
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 1
Natriumklorid Fresenius Kabi 9 mg/ml, spädningsvätska för parenteral användning
PRD2503459 · Product
- Active substance
- Sodium Chloride
- Substance synonyms
- SODIUM CHLORID, SODIUM CHLORIDE (FOR PH ADJUSTMENT)
- Pharmaceutical form
- SOLVENT FOR PARENTERAL USE
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 1.7 ml millilitre(s)
- Max total dose
- 1.7 ml millilitre(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- V07AB — SOLVENTS AND DILUTING AGENTS, INCL. IRRIGATING SOLUTIONS
- Marketing authorisation
- 8703
- MA holder
- FRESENIUS KABI AB
- MA country
- Sweden
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Rigshospitalet
- Sponsor organisation
- Rigshospitalet
- Address
- Nordre Ringvej 57
- City
- Glostrup
- Postcode
- 2600
- Country
- Denmark
Scientific contact point
- Organisation
- Rigshospitalet
- Contact name
- Henrik Schytz
Public contact point
- Organisation
- Rigshospitalet
- Contact name
- Henrik Schytz
Third parties 1
| Organisation | City, country | Duties |
|---|---|---|
| GCP-enheden ved Københavns Universitetshospital ORL-000001661
|
Frederiksberg, Denmark | On site monitoring |
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Denmark | Ongoing, recruiting | 80 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Denmark | 2023-11-15 | 2023-11-15 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 19 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | TN_BTX-A_Appendix_1_Penn_ FPS-R | 1 |
| Protocol (for publication) | TN_BTX-A_Appendix_2_PGIC_scale | 1 |
| Protocol (for publication) | TN_BTX-A_Pain_dairy | 1 |
| Protocol (for publication) | TN_BTX-A_Protocol | 03 |
| Protocol (for publication) | TN_BTX-A_Protocol_TC | 03 |
| Recruitment arrangements (for publication) | TN_BTX-A_Recruitment | 1 |
| Recruitment arrangements (for publication) | TN_BTX-A_Recruitment_Advertisement_Lynet_Trigeminus_Foreningen | 03 |
| Recruitment arrangements (for publication) | TN_BTX-A_Recruitment_Advertisement_Lynet_Trigeminus_Foreningen_TC | 03 |
| Recruitment arrangements (for publication) | TN_BTX-A_Recruitment_Advertisement_Print_Lynet_Trigeminus_Foreningen | 02 |
| Recruitment arrangements (for publication) | TN_BTX-A_Recruitment_Dr_to_Dr_letter | 03 |
| Recruitment arrangements (for publication) | TN_BTX-A_Recruitment_Dr_to_Dr_letter_TC | 03 |
| Recruitment arrangements (for publication) | TN_BTX-A_Recruitment_Post_RH_website | 02 |
| Recruitment arrangements (for publication) | TN_BTX-A_Recruitment_Poster | 02 |
| Recruitment arrangements (for publication) | TN_BTX-A_Recruitment_SoMe_Trigeminus_Foreningen | 1 |
| Subject information and informed consent form (for publication) | TN_BTX-A_Deltagerinformation | 02 |
| Subject information and informed consent form (for publication) | TN_BTX-A_ICF_Danish | 02 |
| Subject information and informed consent form (for publication) | TN_BTX-A_Information_ICF | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | TN_BTX-A_Appendix_A_BOTOX_SmPC | 1 |
| Synopsis of the protocol (for publication) | TN_BTX-A_Protocol_synopsis_Danish | 02 |
Application history
4 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-05-25 | Denmark | Acceptable 2023-08-09
|
2023-08-10 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-03-22 | Denmark | Acceptable 2024-04-15
|
2024-04-16 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-4 | 2025-08-14 | Denmark | Acceptable 2024-04-15
|
2025-08-14 |
| 4 | NON SUBSTANTIAL MODIFICATION | NSM-5 | 2026-01-29 | Denmark | Acceptable 2024-04-15
|
2026-01-29 |