Adult upper limb spasticity
Conditions
Interventions
- Stage 3:
1. IPN10200 Cohort 1: IPN10200 Lower Reference Dose confirmed in Stage 2 administered as a single injection locally into several muscle groups of the upper limb.
2. IPN10200 Cohort 2: IPN10
Sponsors
Makino Maako
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Participant must be 18 to 70 years of age inclusive, at the time of signing the informed consent. 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.Has angle of spasticity >= 5 deg in the PTMG to be injected. 7.Has the angle of arrest as measured by the Tardieu scale (XV1) in the muscle groups to be injected as follows: - XV1 >=160 deg for finger flexors - XV1 >=90 deg for wrist flexors - XV1 >=160 deg for elbow flexors 8.Stage 3: Physiotherapy, occupational therapy, splinting, use of benzodiazepine, and muscle relaxants had to be stable from at least 3 months preceding the study Baseline up to the Month 3 visit, and whenever possible until the end of the study. 9.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 judgement prior to randomisation. 10.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. 11.Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Exclusion criteria
Exclusion criteria: 1.Any medical condition that may increase, in the opinion of the investigator, the likelihood of adverse events (AEs) related to BoNT treatment. 2.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 participation in the study. 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 received previous treatment with phenol and or alcohol in the targeted upper limb any time before the study. 8.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. 9.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. 10.Use of concomitant therapy which, in the investigator opinion, would interfere with the evaluation of the safety or efficacy of the study intervention, including medications affecting bleeding disorders. 11.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. 12.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. 13.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. 14.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 and for the duration of the study. 15.Inability to understand protocol procedures and requirements which, in the opinion of the investigator, could negatively impact on protocol compliance or inability or unwillingness to comply with the protocol. 16.Infection at the injection site(s). 17.Male participants who are not vasectomised and who have female partners of childbearing potential and are not willing to use condoms with spermicide throughout study participation. 18.Any prior administration with the study intervention (IPN10200) either in previous stages of the study or in other studies regardless of the indication.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - Incidence, severity, and nature of treatment emergent adverse events (TEAEs). - Incidence, severity, and nature of adverse events of special interest (AESI). - Abnormal and clinically significant vital sign findings. - Abnormal and clinically significant ECG findings. - Abnormal and clinically significant clinical laboratory evaluations. - Presence of BoNT-A and IPN10200 antibodies (binding and neutralising). - Abnormal and clinically significant physical examination findings. | — |
Secondary
| Measure | Time frame |
|---|---|
| For the duration of All Stages - Change from Baseline to all post-treatment visits in MAS score in the PTMG - Change from Baseline to post-treatment Day 29 in MAS score in the PTMG). - Change from Baseline to all post-treatment visits in MAS score in all injected muscle groups. - PD characteristics of IPN10200 in the PTMG - Response to treatment as measured by at least one grade reduction in MAS score in the PTMG from Baseline to all post treatment visits. - Response to treatment as measured by at least one grade reduction in MAS score in all injected muscle groups from Baseline to all post-treatment visits. - PGA score of overall treatment response at all post-treatment visits. - PGI-C at all post-treatment visits. - Change from Baseline to all post-treatment visits in the Disability Assessment Scale (Stage 3). - Reduction of pain in the shoulder using the Numeric Rating Scale (Stage 3). For the duration of Stage 3: - Change from Baseline to all post-treatment visits in the Tardieu Scale in the PTMG - Change from Baseline in the AROM in all injected muscle groups including the PTMG - Incidence, severity, and nature of TEAEs. - Incidence, severity, and nature of AESIs. - Abnormal and clinically significant vital sign findings. - Abnormal and clinically significant ECG findings. - Abnormal and clinically significant clinical laboratory evaluations. - Presence of IPN10200 antibodies (binding and neutralising). - Abnormal and clinically significant physical examination findings. For the duration of Open-label Extension Period - Change from Baseline to all post-treatment visits in MAS score in the PTMG. - Change from Baseline to all post-treatment visits in MAS score in all injected muscle groups. - Response to treatment as measured by at least one grade reduction in MAS score in the PTMG from Baseline to all post-treatment visits. - Response to treatment as measured by at least one grade reduction in MAS score in all injected muscle groups from Baseline to all post | — |
Countries
Austria, Bulgaria, Czech Republic, France, Germany, Hungary, Italy, Japan, Poland, Portugal, South Korea, Spain, USA
Contacts
Public ContactMaako Makino
CMIC Co., Ltd.
Outcome results
None listed