The BASIC study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Norwegian University Of Science And Technolology

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 Nov 2019 → ongoing

Decision date (initial)

2024-11-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-515166-14-00

EudraCT number

2018-003148-21

ClinicalTrials.gov

NCT03944876

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

This project aims to determine the efficacy of botulinum toxin towards the sphenopalatine ganglion (SPG) in treatment of refractory chronic cluster headache using an image-guided surgical device (MultiGuide®).

Secondary objectives 8

1. Safety
2. Cluster attack frequency
3. Responder frequencies
4. Cluster headache attack features
5. Frequency of headache days
6. Quality of life measures
7. Use of medication
8. Patient global impression

Conditions and MedDRA coding

Chronic cluster headache

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Informed and written consent.
2. Male or female, 18-85 years of age
3. Headache attacks fulfilling the International Classification of Headache Disorders (ICHD) III criteria for chronic cluster headache (CCH) 3.1.2.
4. Dominant headache laterality with ≥ 80% of cluster headache attacks on one side.
5. Subject reports an average of ≥ 4 cluster attacks/week on the side of their dominant headache laterality in the 3 months prior to inclusion and in the baseline period.
6. The condition is pharmacologically refractory defined as suboptimal effect or intolerable side effects or contraindication for verapamil or lithium or suboccipital steroid injection.
7. Subject agrees to maintain current preventive headache medication regimens (no change in type, frequency, or dose) during the whole study period.
8. Subject is able to differentiate concomitant headaches from cluster headache.
9. In case of women of childbearing potential (WOCBP) they have to be using highly effective contraception in a period of 4 weeks after injection.
10. Ability to understand study procedures and to comply with them for the entire length of the study

Exclusion criteria 32

1. Subject has had a change in type, dosage or dose frequency of preventive headache medications ≥ two weeks prior to baseline/screening or 5 half-lives, whichever is longer.
2. Subject currently treated with occipital nerve stimulation, deep brain stimulation or other implantable device, that have changed parameters in the last month, or are unable to keep parameters stable throughout the study.
3. Current or previous treatment with implanted medical devices targeting the SPG
4. Subject has had a change in type, dosage or dose frequency of preventive headache medications during the baseline period, eg. prior to IMP administration.
5. Non-responder to both oxygen and triptan.
6. Participation in a clinical study of a new chemical entity or a prescription medicine within 2 months before study drug administration or 5 half-lives, whichever is longer
7. 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- Basic Study Protocol, Version 3.0, 18.06.2023 17 investigational drug or device.
8. Allergy or hypersensitivity reactions to marcaine, lidocaine, xylocaine, adrenaline, any botulinum toxin or similar substance
9. Abuse of drugs or alcohol.
10. Use of opioids for ≥10 days per month.
11. Treatment with pharmacological substances that may interact with BTA (aminoglycosids, spectinomycin, neuromuscular blockers, both depolarizing agents (such as succinylcholine) or non-depolarizing (tubocurarine derivates), lincosamides, polymyxins, quinidine, magnesium sulfate or anticholinestases.).
12. WOCBP that do not adhere to the requirements for HEC, as noted in inclusion criteria 9 and outlined in section 3.3.
13. Pregnancy or breastfeeding in the study period
14. ubject has undergone facial surgery in the area of the pterygopalatine fossa or zygomaticomaxillary buttress ipsilateral to the planned injection site that, in the opinion of the Investigator, may lead to an inability to properly conduct the procedure.
15. Facial anomaly or trauma which renders the procedure difficult.2
16. Subject currently has an active oral or dental abscess or a local infection at the site of injection based on present symptoms.
17. 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.
18. 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.
19. Patients with comorbid psychiatric disorders with psychotic or other symptoms making compliance with the study protocol difficult, at the discretion of the investigator.
20. Patient with active infectious disease or infections that warrants special infection control measures, such as human immunodeficiency virus, tuberculosis, or chronic hepatitis B or C infection.
21. Patient with disorders that are known contraindication for Botox® treatment, especially neuromuscular disorders such as motorneuron disorders and myasthenic syndromes
22. Subject has had previous radiofrequency ablation, balloon compression, gamma knife, or chemical denervation (e.g. glycerol treatments) of the ipsilateral trigeminal ganglion or any branch of the trigeminal nerve.
23. Subject has had previous radiofrequency ablation (including non-lesional pulsed radiofrequency), balloon compression, gamma knife, or chemical denervation (e.g. glycerol treatments) of the ipsilateral SPG.
24. Subject has had blocks of short-acting anaesthetics of the ipsilateral SPG in the last 3 months.
25. Subject has undergone onabotulinumtoxinA injections of the head and/or neck in the last 3 months.
26. Subject is anticipated to require any excluded medication, device, or procedure during the study.
27. Subject has a history of bleeding disorders and in the opinion of the Investigator, may lead to an inability to properly conduct the procedure.
28. Subject has a history of coagulopathy
29. Subject is unable to stop antithrombotic medication, eg. anticoagulants and/or antiplatelet therapy, before procedure.
30. The subject has been diagnosed with another trigeminal autonomic cephalalgia or trigeminal neuralgia.
31. 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.
32. 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 the last 28 day period of the baseline in mean number of cluster headache attacks per week at weeks 5 – 8 post-intervention in the treatment group versus the placebo group.

Secondary endpoints 7

1. Difference in occurrence of AEs and SAEs in the active group versus the placebo group
2. Difference in change from baseline week 5-8 in mean number of cluster headache attacks per week during weeks 9-12 post-intervention in the active group versus the placebo group
3. Difference in change from baseline week 5-8 in mean number of cluster headache attacks per week at weeks 5-8 post-intervention in the active group versus the placebo group, in the prespecified subgroups (cf 8.4.1.2) 3.1. In the high and the low frequency subgroups 3.2. In the high and the low frequency variation subgroups
4. Difference in change from baseline week 5-8 in mean number of cluster headache attacks per week during weeks 9-12 post-intervention in the active group versus the placebo group, in the prespecified subgroups (cf 8.4.1.2) 4.1. In the high and the low frequency subgroups 4.2. In the high and the low frequency variation subgroups
5. Difference in the number of therapeutic responders (≥ 30% reduction in attack frequency, intensity or both during weeks 5 – 8 post-intervention compared to baseline) in the active group versus the placebo group. 5.1. In the entire randomized population 5.2. In the high and the low frequency subgroups 5.3. In the high and the low frequency variation subgroups
6. Difference in the number of attack frequency responders (≥ 30% reduction in attack frequency during weeks 5 – 8 post-intervention compared to baseline). 6.1. In the entire randomized population 6.2. In the high and the low frequency subgroups 6.3. In the high and the low frequency variation subgroups
7. Difference in change from baseline week 5-8 in mean attack intensity week 5 – 8 post-intervention in the active group versus the placebo group. 7.1. In the entire randomized population 7.2. In the high and the low frequency subgroups 7.3. In the high and the low frequency variation subgroups

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Norwegian University Of Science And Technolology

Sponsor organisation

Norwegian University Of Science And Technolology

Address

Hoegskoleringen 1

City

Trondheim

Postcode

7034

Country

Norway

Scientific contact point

Organisation

Norwegian University Of Science And Technolology

Contact name

Coordinating investigator

Public contact point

Organisation

Norwegian University Of Science And Technolology

Contact name

Study nurse

Locations

2 EU/EEA countries · 3 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 7 files

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

Application history

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