A Study to Compare the Safety and Efficacy of Dysport® and Botox® in Adults with Upper Limb Spasticity

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ipsen Pharma

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

19 Nov 2021 → 26 Aug 2025

Decision date (initial)

2024-03-21

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Ipsen Pharma

External identifiers

EU CT number

2023-509196-16-00

EudraCT number

2021-000161-32

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To demonstrate non-inferiority as per safety assessment based on the rate of all TEAEs from injection to 12 weeks

Secondary objectives 2

1. To evaluate clinical safety
2. To assess efficacy

Conditions and MedDRA coding

Upper limb spasticity (ULS) of any aetiology (in US and France) or post- stroke ULS (in Canada)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Participant must be 18 to 80 years of age inclusive, at the time of signing the informed consent
2. 2.a. [US/France] Participants with stable ULS for at least 3 months, in whom treatment of only one upper limb is necessary for the duration of the study; 2b. [Canada] Participants with stable post-stroke ULS for at least 3 months, in whom treatment of only one upper limb is necessary for the duration of the study
3. Participants who are either naïve to BoNT-A for ULS or who have been previously treated with BoNT-A for ULS
4. Participants with MAS score of at least 2 in two muscle groups (one of these two muscle groups should be the PTMG) and at least 1 in the remaining muscle group
5. Participants with DAS score of at least 2 on the PTT (one of four functional domains: dressing, hygiene, limb position and pain)
6. Participants who require BoNT-A injection in all of the following muscles: flexor carpi radialis, flexor carpi ulnaris, flexor digitorum profundus, flexor digitorum superficialis and biceps brachii
7. Participants for whom injection of a total dose of 900 Units aboBoNT- A or 360 Units onaBoNT-A is considered by the investigator to be clinically appropriate
8. Participants who have been stable for at least 3 months prior to study entry in terms of oral antispasticity, anticoagulant and/or anticholinergic medication, if treated, and are considered by the investigator likely to remain stable for the duration of the study
9. Male and female participants Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. a. Male participants: Male participants must agree that, if their partner is at risk of becoming pregnant, they will use an effective method of contraception. The participants must agree to use the contraception during the whole period of the study. b. Female participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: • Is a woman of non-childbearing potential, defined as postmenopausal for at least 1 year; surgical sterilisation at least 3 months before entering the study; or hysterectomy. or • Is a woman of childbearing potential (WOCBP) and using an acceptable contraceptive method as described in protocol section 10.4.2. A WOCBP must have a negative highly sensitive pregnancy test at screening (urine or serum) as required by local regulations. •If a urine test cannot be confirmed as negative (e.g. an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive
10. Capable of giving signed informed consent as described in Section 10.1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol

Exclusion criteria 20

1. Major limitations in the passive range of motion in the paretic upper limb
2. Women who are pregnant or lactating
3. In the clinical judgement of the investigator, BoNT treatment is inappropriate
4. BoNT naïve participants with a history of facial neurogenic disorder (facial paralysis, polyradiculoneuropathy) (only for France).
5. Participants treated with BoNT of any type for any indication (e.g. bladder injection, headache or cosmetic) within the previous 12 weeks or planned/likely to be treated during the course of the study
6. Major neurological impairment (other than limb paresis) that could negatively affect functional performance
7. Participants clinically requiring injection into any upper limb muscles other than the five muscles of one arm listed in protocol section 5.1, or requiring injection into both arms or any lower limb within the timeframe of the study
8. Hypersensitivity to any BoNT product or excipients
9. Hypersensitivity to cow's milk protein (casein)
10. Infection at the proposed injection site(s)
11. Known peripheral motor neuropathic diseases, amyotrophic lateral sclerosis or neuromuscular junction disorders (e.g. myasthenia gravis or Lambert-Eaton syndrome)
12. Any medical condition (including dysphagia or breathing difficulties/compromised respiratory function) that, in the opinion of the investigator, might jeopardize the participant's safety
13. Abnormal screening/baseline findings or any other medical condition(s) that, in the opinion of the investigator, might jeopardise the participant's safety
14. Prior history of non-responsiveness to BoNT treatment
15. Previous surgery, or administration of alcohol or phenol in the study limb within the 6 months prior to study enrolment or planned/likely to be treated in the study limb during the course of the study
16. Participants treated with intrathecal baclofen (except if treatment has reached a stable dose for >4 weeks and is likely to remain stable throughout the study), aminoglycosides or other agents interfering with neuromuscular transmission (e.g. curare-like agents) within the previous 4 weeks prior to study enrolment or planned/likely to be treated during the course of the study
17. Participants receiving concomitant treatment with the following PT/OT interventions on the study limb: new splinting/orthotics/casting, serial casting, shockwave therapy, dry needling and needle tenotomies. However, PT/OT interventions not intended to reduce study limb spasticity (e.g. functional training exercises) or with a transient (<1 day) reduction of study limb spasticity (e.g. stretching, weight bearing) are allowed
18. Participants previously randomised for this study
19. Participants unwilling or unable to understand the nature, scope and possible consequences of the study and to comply with study procedures and requirements
20. Participants currently enrolled in any other clinical study or have participated in one within the 12 weeks (or 5 half-lives of investigational product of that study, whichever is longer) prior to enrolment/inclusion visit, or are scheduled to receive a new investigational drug while the study is ongoing

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Rate of TEAEs from injection to 12 weeks

Secondary endpoints 6

1. Rate of ADRs, SAEs and AESIs from injection to 12 weeks
2. Duration of response based on retreatment criteria
3. Muscle tone assessed by the MAS for finger, wrist and elbow flexors at 1, 4, 10, 12 ± 16, 20, 24 weeks based on PTMG and MAS total score
4. Perceived function and pain assessed by the DAS at 1, 4, 10, 12 ± 16, 20, 24 weeks based on PTT and DAS total score
5. PGA of treatment response at 1, 4, 10, 12 ± 16, 20, 24 weeks
6. QoL, using the SF-12 perceived health score and SQoL-6D at 4 weeks, 12 weeks and at end of each cycle

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ipsen Pharma

Sponsor organisation

Ipsen Pharma

Address

70 Rue Balard

City

Paris

Postcode

75015

Country

France

Scientific contact point

Organisation

Ipsen Pharma

Contact name

Ipsen Clinical Study Enquiries

Public contact point

Organisation

Ipsen Pharma

Contact name

Ipsen Clinical Study Enquiries

Third parties 6

Locations

1 EU/EEA country · 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 10 files

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

Application history

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