A study investigating single injection of new botulinum toxin to determine safety and efficacy for treating spasticity in the upper limb

Phase 1

• Conditions: pper limb spasticity after stroke or traumatic brain injury.; MedDRA version: 20.0Level: LLTClassification code 10041416Term: SpasticitySystem Organ Class: 100000004852; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2020-003623-42-CZ
• Lead Sponsor: Ipsen Innovation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-12-01
• Last Update Posted: 3 June 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 244

Inclusion Criteria

Age
1. Participant must be 18 to 70 years of age inclusive (except for dose-escalation must be 18 to 65 years of age) at the time of signing the informed consent.
Type of Participant and Disease Characteristics
2. Has spastic hemiparesis following stroke or TBI
3. Is at least 6 months post-stroke or TBI
4. Has never received BoNT or if previously treated, should have received their last injection of any commercialised BoNT-A or B at least 4 months prior to study Baseline
5. Has a MAS score =2 in the PTMG to be injected
6. Is eligible to receive a total recommended dose 1000 U Dysport in the upper limb when applicable.
7. Has angle of spasticity =5° in the PTMG to be injected.
8. Does not have any fixed contractures as defined by:
• Complete fingers extension with XV1 =160°
• Complete wrist extension with XV1 =90°
• Complete elbow extension with XV1 =160°
9. Physiotherapy, occupational therapy, splinting, use of benzodiazepine, and muscle relaxants had to be stable from at least 30 days preceding the study Baseline up to the
Month 3 visit, and whenever possible until the end of the study.
10. In good health (i.e. absence of any uncontrolled systemic disease or other significant
medical condition) as determined by medical history, physical and neurological examinations, clinical laboratory studies, electrocardiograms (ECGs), vital signs, and Investigator's judgement prior to randomisation
Sex
11. 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.
• 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.
• Female participants:
o 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 (WONCBP) as defined in Section 10.4 Appendix 4:
Contraceptive and Barrier Guidance.
OR
Is a WOCBP and using an acceptable contraceptive method as described in Section 10.4 Appendix 4: Contraceptive and Barrier
Guidance during the study intervention period (at a minimum until after
the last dose of study intervention). The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance,
recently initiated) in relationship to the first dose of study intervention.
o A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations), see Section 8.2.5.
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.
o Additional requirements for pregnancy testing during and after study
intervention are located in Section 8.2.5.
o The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
Informed Consent
12. Capable of giving signed informed consent as described in Appendix 10.1 which includes
compliance with the requirements and restrictions listed in the informed consent form
(ICF) and in this protocol.
Are the trial

Exclusion Criteria

Medical Conditions
1. Any medical condition (including severe dysphagia or airway disease) that may increase, in the opinion of the investigator, the likelihood of adverse events (AEs) related to BoNT treatment.
Known disease of the neuromuscular junction (e.g. Lambert-Eaton myasthenic syndrome, myasthenia gravis or amyotrophic lateral sclerosis etc.).
3. Has a history of hypersensitivity to the investigational medicinal products (or other
BoNTs) or any excipient used in their formulation.
4. Clinically diagnosed significant anxiety disorder, or any other significant psychiatric disorder (e.g. depression) that might interfere with the participant’s participation in the study. Prior/concomitant Therapy
5. Likely treatment with any serotype of BoNT for any condition during the study.
6. Undergone previous surgery to treat spasticity in the affected upper limb.
7. Has initiated physiotherapy within 30 days prior to Baseline (if physiotherapy initiated
more than 30 days prior to Baseline and ongoing, the therapy regimen should be
maintained at the same frequency and intensity throughout the study if possible or at least
up to 3-months post-injection).
8. Has received previous treatment with phenol and or alcohol in the targeted upper limb any time before the study.
9. Has been treated or is likely to be treated with intrathecal baclofen during the 30 days prior to study Baseline or during the course of the study.
10. Current or planned treatment with any medications that interfere either directly or indirectly with neuromuscular transmission, such as curare-like non depolarising agents,
lincosamides, polymyxins, anticholinesterases and aminoglycoside antibiotics, within 30 days prior to Baseline.
11. Use of concomitant therapy which, in the investigator’s opinion, would interfere with the
evaluation of the safety or efficacy of the study intervention, including medications affecting bleeding disorders. For patients taking vitamin K
antagonists, the INR values should be controlled (between 2 and 3).
12. Currently planned or a history of tendon lengthening surgery, significant contracture or
muscle atrophy at target joint or muscle in the past 6 months prior to Screening.
Prior/concurrent Clinical Study Experience
13. Use of any experimental device within 30 days or use of any treatment with an
experimental drug within five times the documented terminal half-life of the respective drug or its metabolites or if the half-life is unknown within 30 days prior to the start of
the study (prior to Baseline) and during the conduct of the study.
Diagnostic Assessments
14. Presence of any other condition (e.g. neuromuscular disorder, muscular dystrophies,
cancer cachexia, sarcopenia or other disorder that could interfere with neuromuscular
function), laboratory finding or circumstance that, in the judgement of the investigator, might increase the risk to the participant or decrease the chance of obtaining satisfactory data to achieve the objectives of the study.
15. Pregnant or lactating women, or women of childbearing potential not willing to practice a highly effective form of contraception method at the beginning of the study, for the duration of the study and for a minimum of 12 weeks following last administration of
study treatment. Highly effective methods of contraception are defined as methods of birth control which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly suc

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified