Phase I/II Multicentre, Double-Blind, Randomised Study of IPN10200 vs. Dysport and Placebo in Adult Upper Limb Spasticity Post-Stroke or Traumatic Brain Injury
- Trial ID
- 2023-507202-14-00
- Protocol
- D-FR-10200-001
- Sponsor
- Ipsen Innovation
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to assess the **safety** and tolerability of increasing doses of a single treatment of IPN10200 in participants with upper limb spasticity, specifically in the primary target muscle group (PTMG), compared with Dysport and placebo. This evaluation is crucial for determining the appropriate dose levels for further investigation, ensuring both efficacy and safety in managing spasticity, a common and debilitating condition following stroke or traumatic brain injury.
Secondary objectives include:
- Assessing the efficacy of IPN10200 over time compared with Dysport and/or placebo in reducing upper limb muscle tone in hemiparetic participants.
- Evaluating the pharmacodynamic (PD) characteristics of IPN10200, including time to onset, peak of effect, time to peak, and duration of effect.
- Comparing the PD profile of IPN10200 to Dysport, including the duration of treatment response.
- Evaluating the overall treatment response and benefit of IPN10200 as assessed by both the investigator and the participant.
- Assessing the safety and tolerability of IPN10200 for the treatment of upper limb spasticity.
- Evaluating the functional treatment response by measuring active range of motion (AROM) in all injected muscles.
- In the open-label extension period, evaluating the efficacy and PD characteristics of IPN10200 over multiple treatment cycles, as well as the overall treatment response and benefit as assessed by both the investigator and the participant.
Participants
The clinical trial involves a total of **85 participants** who are being studied for **upper limb spasticity** following a stroke or traumatic brain injury. The study population includes both male and female participants, aged between **18 to 70 years**, with a specific age range of 18 to 65 years for dose escalation. Participants are required to be in good health, as determined by comprehensive medical evaluations, and must have spastic hemiparesis at least six months post-stroke or traumatic brain injury. The selection criteria ensure that participants have not received botulinum toxin (BoNT) treatment within four months prior to the study baseline. Lifestyle considerations include the stability of physiotherapy, occupational therapy, splinting, and the use of benzodiazepines and muscle relaxants, which must be maintained from at least 30 days to three months before the study baseline, depending on the study stage. The trial includes a vulnerable population, and participants must be capable of providing informed consent. The study does not specify any dietary or physical activity requirements beyond the mentioned therapies.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, and **controlled** study to evaluate the safety and efficacy of IPN10200 in treating **upper limb spasticity** following stroke or traumatic brain injury. The trial is structured in multiple stages, including a dose-escalation and dose-finding phase, followed by an open-label extension period. The study is expected to run from February 2021 to March 2029, with participant involvement varying based on the stage of the trial they are enrolled in.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, health status, and previous treatment history. The trial includes several follow-up visits to monitor safety and efficacy outcomes, with assessments such as the Modified Ashworth Scale (MAS) score and the presence of treatment-emergent adverse events (TEAEs). The end-of-study visit will conclude the participant's involvement, ensuring all necessary data is collected and any post-treatment evaluations are completed.
The expected length of participant involvement will depend on the specific stage of the trial, with some participants potentially continuing into the open-label extension period. Conditions that may lead to early termination from the study include the development of significant adverse events, non-compliance with study protocols, or withdrawal of consent. The trial aims to provide comprehensive data on the safety and efficacy of IPN10200, contributing to the understanding and management of upper limb spasticity in affected individuals.
Treatment
The clinical trial involves the administration of **IPN10200**, a solution for injection containing **Clostridium botulinum, neurotoxin serotype A/B**. This experimental medication is provided in a pharmaceutical form suitable for **intramuscular use**. The dosing regimen involves a single treatment with escalating doses to evaluate safety and efficacy in the treatment of adult upper limb spasticity. The trial aims to identify two dose levels for further investigation, with the ultimate goal of determining the lowest effective dose that provides the required duration of response. Participant compliance will be monitored throughout the study to ensure adherence to the dosing schedule.
In addition to the experimental treatment, the study includes a **placebo** group. The placebo is formulated as a powder for solution for injection, mimicking the administration route and form of the active treatment to maintain the double-blind nature of the trial. The placebo is administered intramuscularly, following the same dosing schedule as the experimental medication, to serve as a control for evaluating the efficacy and safety of IPN10200.
The trial also utilizes **Dysport 500 Unités Speywood**, a comparator treatment containing **botulinum toxin type A - haemagglutinin complex**. This comparator is provided as a solution for injection and is administered intramuscularly. Dysport serves as a standard-of-care therapy to benchmark the safety and efficacy of IPN10200. The dosing schedule for Dysport aligns with the trial's protocol to ensure consistent comparison across treatment groups. Monitoring of participant compliance with Dysport administration is conducted to maintain the integrity of the trial data.
Efficacy
The efficacy of the investigational product IPN10200 in the treatment of adult upper limb spasticity will be assessed through a series of primary and secondary endpoints. The primary efficacy endpoint involves the response to treatment, specifically measured by at least one grade reduction in the **Modified Ashworth Scale (MAS)** score in the primary targeted muscle group (PTMG). This scale is a widely recognized tool for evaluating spasticity, providing a quantifiable measure of muscle tone.
Secondary efficacy endpoints include changes from baseline to all post-treatment visits in the MAS score in the PTMG, as well as in all injected muscle groups. Additional parameters include the time to onset of response, peak of effect, time to peak, and duration of effect, all defined by changes in the MAS score. The Physician’s Global Assessment (PGA) score and the Patient Global Impression of Change (PGI-c) will also be utilized to evaluate overall treatment response and patient-perceived changes in the spastic clinical pattern, respectively.
Other secondary endpoints involve changes from baseline in the Disability Assessment Scale (DAS), reduction of pain in the shoulder using the Numeric Rating Scale, and changes in the Tardieu Scale and active range of motion (AROM) in all injected muscle groups. These assessments will be conducted at various timepoints throughout the study, including baseline, post-treatment Day 29, and all subsequent visits, to comprehensively evaluate the efficacy of IPN10200 in improving spasticity symptoms.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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.
- Has spastic hemiparesis following stroke or TBI
- Is at least 6 months post-stroke or TBI
- 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
- Has a MAS score ≥2 in the PTMG to be injected
- Is eligible to receive a total recommended dose 1000 U Dysport in the upper limb when applicable
- Has angle of spasticity ≥5° in the PTMG to be injected
- Has the angle of arrest as measured by the Tardieu scale (XV1) in the muscle groups to be injected as follows: • XV1 ≥160° for finger flexors • XV1 ≥90° for wrist flexors • XV1 ≥160° for elbow flexors
- Stage 1 and 2: 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. 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.
- 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
- 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) OR Is a WOCBP and using an acceptable contraceptive method 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) 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.
- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and protocol.
Exclusion Criteria
- Any medical condition (including, but not limited to: severe dysphagia or airway disease, severe impairment of ability to walk (e.g. wheelchair-bound) and/or living in long-term care facilities due to loss of autonomy) that may increase, in the opinion of the investigator, the likelihood of adverse events related to BoNT treatment.
- A history of drug or alcohol abuse
- 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.
- Known disease of the neuromuscular junction (e.g. Lambert-Eaton myasthenic syndrome, myasthenia gravis or amyotrophic lateral sclerosis etc.).
- Has a history of hypersensitivity to the investigational medicinal products (or other BoNTs) or any excipient used in their formulation.
- 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.
- Likely treatment with any serotype of BoNT for any condition during the study.
- Undergone previous surgery to treat spasticity in the affected upper limb.
- 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)
- Has received previous treatment with phenol and or alcohol in the targeted upper limb any time before the study.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Inability to understand protocol procedures and requirements
- Infection at the injection site(s)
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Austria | Recruiting | 19 Feb 2021 | 7 |
 Bulgaria | Recruiting | 19 Feb 2021 | 33 |
 Czechia | Recruiting | 19 Feb 2021 | 19 |
 France | Not Recruiting | 19 Feb 2021 | 4 |
 Germany | Recruiting | 19 Feb 2021 | 43 |
 Hungary | Recruiting | 19 Feb 2021 | 30 |
 Italy | Recruiting | 19 Feb 2021 | 10 |
 Poland | Recruiting | 19 Feb 2021 | 104 |
 Portugal | Recruiting | 19 Feb 2021 | 17 |
 Spain | Recruiting | 19 Feb 2021 | 29 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
IPN10200 placebo, Powder for solution for injection | Placebo | N/A | — | — | — | N/A |
DYSPORT 500 UNITES SPEYWOOD, poudre pour solution injectable | Comparator | POUDRE POUR SOLUTION INJECTABLE | INTRAMUSCULAR USE | — | — | PRD522041 |