A study to evaluate the effectiveness and safety of Dysport® for the prevention of chronic migraine in adults

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ipsen Innovation

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

18 Mar 2024 → ongoing

Decision date (initial)

2023-11-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Ipsen Innovation, 5 Avenue du Canada 91940 Les Ulis Cedex, France

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To evaluate the efficacy of Dysport compared with placebo in reducing monthly migraine days (MMD) in adult participants

Secondary objectives 9

1. To evaluate the efficacy of Dysport compared with placebo in reducing MMD in adult participants
2. To evaluate the efficacy of Dysport compared with placebo in reducing monthly headache days (MHD) of moderate or severe intensity in adult participants
3. To evaluate the efficacy of Dysport compared with placebo in reducing acute migraine specific/headache medication use in adult participants with migraine
4. To evaluate the efficacy of Dysport compared with placebo for participant’s assessment of overall change in migraine
5. To evaluate the efficacy of Dysport compared with placebo in improving function/QoL in adult participants with migraine
6. To evaluate the effect of Dysport compared with placebo on transition from chronic migraine in adult participants
7. To evaluate the efficacy profile of Dysport compared with placebo with secondary efficacy measures
8. To evaluate the time to onset of MMD response in adult participants
9. To demonstrate the safety profile of Dysport compared with placebo in adult participants with migraine

Conditions and MedDRA coding

Chronic migraine

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of study participants. Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Participant must be ≥18 years of age inclusive, at the time of signing the informed consent and privacy/data protection documentation.
2. Participant has a diagnosis for more than 12 months, prior to screening visit, of chronic migraine according to the International Classification of Headache Disorders definition and diagnostic criteria
3. Migraine onset occurred when participant was <50 years of age.
4. Has baseline number of monthly headache days (MHD) ≥15 and baseline number of monthly migraine days (MMD) of ≥8, using eDiary data collected during the 4 weeks nearest to randomisation on Day 1 (but prior to randomisation).
5. Has baseline number of valid diary days ≥22 days collected during the 4 weeks nearest to randomisation on Day 1.
6. Participant must have previously used, or is currently using, preventive treatment (pharmacological) for migraine (i.e. non-naïve) prior to start of screening eDiary.

Exclusion criteria 4

1. History or current diagnosis of migraine with brainstem aura, retinal migraine, complications of migraine, tension-type headache, trigeminal autonomic cephalalgias, hypnic headache, hemicrania continua, or new daily persistent headache.
2. Headache attributed to another disorder (e.g. secondary headaches), except medication overuse headache, which is permitted.
3. Use of any of the following medications in the specified timeframe prior to start of the screening daily headache eDiary.: a. Within 24 weeks i. Botulinum toxin for migraine (or for any other medical/aesthetic reason within 16 weeks) b. Within 12 weeks i. CGRP antagonists (monoclonal antibody or gepant) for preventive treatment of migraine (acute treatment of headache/migraine with a gepant is permitted, but limited to no more than six days per month (i.e. 6 days per each 4-week period with gepant intake)). ii. Cannabidiol or other types of cannabinoids c. Within 4 weeks i. Anaesthetic or steroid injection in any region targeted for injection with study intervention ii. Use of medical device to treat migraine (e.g. non-invasive neuromodulation therapies such as nerve stimulation (gammaCore), transcranial magnetic stimulation (cephaly), external trigeminal nerve stimulation, transcutaneous electrical nerve stimulation, and peripheral neuroelectrical stimulation) iii. Other interventions for migraine assessed to interfere with study evaluations (e.g. acupuncture in head and neck region, cranial traction, nociceptive trigeminal inhibition, occipital nerve block treatments, and dental splints for headache) iv. Use of opioids or barbiturates for more than 2 days/month. Note: participants are permitted to take one concomitant migraine preventative treatment (not listed above); however, the dose of this medication should be stable for ≥3 months before start of the screening eDiary.
4. Known history of treatment failure to more than four medications prescribed for the prevention of migraine (two of which have different mechanisms of action) or known history of treatment failure to botulinum toxin prescribed for the prevention of migraine.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline at Week 24 in MMD (Weeks 21-24)

Secondary endpoints 30

1. Change from baseline in monthly migraine days (MMD) of ≥50%. Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24).
2. Change from baseline in MMD of ≥75% Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24).
3. Cumulative number of MMD from Day 1 to Week 24
4. Change from baseline in MMD of moderate or severe intensity Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24)
5. Change from baseline in MHD of moderate or severe intensity Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24)
6. Change from baseline in MHD of moderate or severe intensity of ≥50% Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24)
7. Change from baseline in MHD of moderate or severe intensity of ≥75% Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24)
8. Cumulative number of MHD of moderate or severe intensity from Day 1 to Week 24
9. Change from baseline in the number of days per month of acute migraine specific medication intake Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24)
10. Headache medication over user (yes, no) Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24) • Defined as a participant with ≥10 days/month if ergotamine, triptan, gepant, ditan, opioid or combination analgesic, or ≥15 days/month if non-opioid analgesic (such as paracetamol, aspirin, NSAID)
11. Use of acute migraine specific medication (yes or no) Every 4 weeks from Week 4 (Weeks 1-4) to Week 24 (Weeks 21-24)
12. PGIC score at Week 12 and Week 24
13. PGIC score of grade ≥1 and ≥2 at Week 12 and Week 24.
14. Change from baseline in role function restrictive domain of Migraine Specific Quality of Life Questionnaire (MSQ) at Week 12 and Week 24
15. Change from baseline in total MSQ score at Week 12 and Week 24
16. Change in MSQ score to MIC threshold at Week 12 and Week 24
17. Change from baseline in total HIT-6 score at Week 12 and Week 24
18. Change from baseline in HIT-6 score to MIC threshold at Week 12 and Week 24
19. Change from baseline in SF-12 score at Week 12 and Week 24
20. Change from baseline on chronic migraine status at Week 24 (Weeks 21-24).
21. Time to onset of effect (first time point post randomisation where MMD is reduced from baseline ≥50%), evaluated for MMD responders and all participants, From first time point post randomisation to Week 24
22. Incidence of Treatment Emergent Adverse Events (TEAEs) during the DBPC Phase, i.e. up to Week 24
23. Percentage of Participants with clinically significant changes in vital signs from baseline up to Week 24
24. Change from baseline in clinically significant laboratory parameters (blood chemistry, haematology) From baseline up to Week 24
25. Treatment-emergence of suicidal ideation/suicidal behaviour from baseline at Week 24
26. Percentage of participants with Binding antibodies to Dysport® at Week 24. Presence of binding antibodies will be assessed using a validated method of electrochemiluminescence assay (ECLA).
27. Percentage of participants with neutralising antibodies to Dysport® at Week 24. It will be performed only for confirmed positive samples with ECLA (confirmation of the presence of binding antibodies). Presence of neutralizing antibodies will be assessed using a validated cell-based assay (CBA).
28. Change from baseline in the number of MMD over the last 12 weeks prior to Week 24 (Weeks 13-24).
29. Change from baseline in role function-preventive (RFP) domain of MSQ Questionnaire at Week 12 and Week 24]
30. Change from baseline in emotional function (EF) domain of MSQ Questionnaire at Week 12 and Week 24]

Investigational products

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

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ipsen Innovation

Sponsor organisation

Ipsen Innovation

Address

70 Rue Balard

City

Paris

Postcode

75015

Country

France

Scientific contact point

Organisation

Ipsen Innovation

Contact name

Ipsen Clinical Study Enquiries

Public contact point

Organisation

Ipsen Innovation

Contact name

Ipsen Clinical Study Enquiries

Third parties 6

Locations

5 EU/EEA countries · 38 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 100 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