The MiBlock study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

St. Olavs Hospital HF

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

1 Oct 2019 → 13 Jun 2025

Decision date (initial)

2024-07-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Nasjonalt program for klinisk behandlingsforskning i spesialisthelsetjenesten (KlinBeForsk))

External identifiers

EU CT number

2024-515165-34-00

EudraCT number

2018-004053-24

ClinicalTrials.gov

NCT04069897

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The primary objective is to determine the efficacy of treatment with botulinum toxin towards the sphenopalatine ganglion (SPG) in treatment refractory chronic migraine using an image-guided surgical device (MultiGuide®).

Secondary objectives 1

1. Secondary objectives are the assessment of safety, feasibility, number of responders, number of migraine days and crystal clear headache free days, acceptability of treatment, migraine headache attack features (intensity, autonomic symptoms, duration), use of acute medication and quality of life measures.

Conditions and MedDRA coding

Chronic migraine

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Informed and written consent
2. Male or female, between 18 and 70 years of age
3. Masters a Scandinavian language at level sufficient to fully understand the written and verbal study information
4. Migraine, with or without aura, fulfilling the International Classification of Headache Disorders (ICHD) III criteria 1.3. for chronic migraine at time of inclusion
5. Chronic migraine at least for a period of 1 year prior to inclusion
6. Debut of episodic migraine before the age of 50, and chronic migraine before the age of 65.
7. The condition is pharmacologically refractory as defined in this study as insufficient treatment effect, contraindication(s) or intolerable side effect(s) of at least 3 medications from at least 2 of the following medication (drug) classes a. Beta-blockers b. RA(A)S-inhibitors c. Calcium-antagonists d. Antiepileptic drugs e. Tricyclic antidepressants f. Botulinum toxin A g. CGRP antagonists
8. Subject has had no change in type, dosage or dose frequency of preventive headache medications < 3 months prior to baseline/screening, or a minimum of 5 half-lives, whichever is longer.
9. Subject agrees to maintain current preventive headache medication regimens (no change in type, frequency, or dose) during the whole study period.
10. In the case of women of childbearing potential (WOCBP) they have to commit to highly effective contraception in a period of 4 weeks after injection (for details, confer section 4.3)
11. Ability to understand study procedures and to comply with them for the entire length of the study

Exclusion criteria 31

1. Allergy or hypersensitivity reactions to marcaine, lidocaine, xylocaine, adrenaline, any botulinum toxin or similar substances.
2. Subject is unable to differentiate migraine from other concomitant headaches.
3. Subject with secondary headache conditions, with the exception of medication overuse headache.
4. Non-responder in regular clinical practice to preventive medications from ≥6 of the following 7 drug classes: a. Beta-blockers b. RA(A)S-inhibitors c. Calcium-antagonists d. Antiepileptic drugs e. Tricyclic antidepressants f. Botulinum toxin A g. CGRP antagonists
5. Subject has had a change in type, dosage or dose frequency of preventive headache medications < 3 months prior to baseline/screening, or a minimum of 5 half-lives, whichever is longer.
6. Subject has had a change in type, dosage or dose frequency of preventive headache medications during the baseline period, eg. prior to IMP administration
7. Botulinum toxin injections in the head and neck region, as part of migraine treatment or otherwise indicated on medical or cosmetic grounds, in the last 4 months before inclusion.
8. The discontinuation of CGRP-antagonists within 3 months before study inclusion or 5 half-lives, whichever is longer.
9. Participation in a clinical study of a new chemical entity or a prescription medicine within 2 months before study inclusion or 5 half-lives, whichever is longer.
10. Subject is currently participating or has participated in the last 3 months in another clinical study in which the subject has, is, or will be exposed to an investigational or non-investigational drug or device.
11. Subject has had previous radiofrequency ablation, balloon compression, gamma knife, or chemical denervation (e.g. glycerol treatments) of the trigeminal ganglion or any branch of the trigeminal nerve.
12. Subject has had previous radiofrequency ablation (including non-lesional pulsed radiofrequency), balloon compression, gamma knife, or chemical denervation (e.g. glycerol treatments) of the SPG.
13. Subject has had blocks of short-acting anaesthetics of the SPG in the last 3 months.
14. Subject is or has been treated with occipital nerve stimulation or deep brain stimulation.
15. Ongoing abuse of drugs (including narcotics) or alcohol.
16. More than 4 days of opioid use per month (including codeine and tramadol), and any use of barbiturates
17. Treatment with pharmacological substances prior to SPG-injection that may interact with BTA (aminoglycosides, spectinomycin, neuromuscular blockers, both depolarizing agents (such as succinylcholine) or non-depolarizing (tubocurarine derivates), and anticholinesterases).
18. Inadequate contraceptive use. Women of childbearing potential (WOCBP) who do not use highly effective contraception (HEC) or use other medication that may interact and/or otherwise reduce the efficacy of the contraceptiva in use.
19. Subject has undergone facial surgery in the area of the pterygopalatine fossa or zygomaticomaxillary at the planned injection site that, in the opinion of the Investigator, may lead to an inability to properly conduct the procedure.
20. Facial anomaly or trauma which renders the procedure difficult.
21. Subject currently has an active oral or dental abscess or a local infection at the site of injection based on present symptoms.
22. Subject has been diagnosed with any major infectious processes such as osteomyelitis, or primary or secondary malignancies involving the face that have been active or required treatment in the past 6 months.
23. Patients with comorbid psychiatric disorders with psychotic or other symptoms making compliance with the study protocol difficult, at the discretion of the investigator
24. Patients exhibiting a high degree of comorbidity and/or frailty associated with reduced life expectancy or high likelihood of hospitalization, at the discretion of the investigator
25. Patients with disorders that severely inhibits lacrimation, at the discretion of the investigator
26. Patients with previous ischemic cardiovascular and cerebrovascular disorder with, in the opinion of the investigator, a moderate to high risk of new ischemic episodes.
27. Known infection or history of human immunodeficiency virus, tuberculosis, or chronic hepatitis B or C infection.
28. Subject has a history of bleeding disorders or coagulopathy, that, in the opinion of the Investigator, may lead to an inability to properly conduct the procedure.
29. Unable to stop antithrombotic medication e.g. platelet aggregation inhibitors and/or anticoagulation therapy, prior to procedure.
30. The patient cannot participate or successfully complete the study, in the opinion of their healthcare provider or the investigator, for any of the following reasons: • mentally or legally incapacitated or unable to give consent for any reason • in custody due to an administrative or a legal decision, under tutelage, or being admitted to a sanatorium or social institution • has any other condition, which, in the opinion of the investigator, makes the patient inappropriate for inclusion in the study
31. The patient is a study centre employee who is directly involved in the study or the relative of such an employee.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Difference in change from baseline in the mean monthly headache days at weeks 5 – 8 post intervention in the treatment versus the placebo group

Secondary endpoints 7

1. Difference in occurrence of adverse events and serious adverse events in the treatment versus the placebo group
2. Difference in change from baseline in the mean monthly migraine days* in the treatment versus the placebo group
3. Difference in number of treatment responders (≥ 30% reduction in mean monthly headache days at weeks 5 – 8 post-intervention compared to baseline) in the treatment versus the placebo group.
4. Difference in change from baseline in the mean monthly headache intensity in the treatment versus the placebo group.
5. Difference in change from baseline in the mean monthly occurrence of cumulative hours per 28 days of moderate/severe pain in the treatment versus the placebo group.
6. Difference in change from baseline in the mean monthly number of days with rescue medication in the treatment versus the placebo group.
7. Migraine specific quality of life questionnaire

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

St. Olavs Hospital HF

Sponsor organisation

St. Olavs Hospital HF

Address

Prinsesse Kristinas G. 3

City

Trondheim

Postcode

7030

Country

Norway

Scientific contact point

Organisation

St. Olavs Hospital HF

Contact name

National coordinating investigator

Public contact point

Organisation

St. Olavs Hospital HF

Contact name

Study nurse

Locations

1 EU/EEA country · 4 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 8 files

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

Application history

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