Clinical trial NCT04752774: A Study to Assess the Safety and Efficacy of IPN10200 in Adult Participants With Upper Limb Spasticity.
Official title: An Integrated Phase I/II, Multicentre, Double-blind, Randomised, Dysport and Placebo-controlled, Dose Escalation and Dose-finding Study to Evaluate the Safety and Efficacy of IPN10200 in the Treatment of Adult Upper Limb Spasticity.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Spasticity
Keywords: Upper limb spasticity after stroke or traumatic brain injury
Lead sponsor: Ipsen
Sponsor class: INDUSTRY
First posted: 2021-02-12
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to assess the safety and efficacy of increasing doses of IPN10200 with the aim to evaluate the Pharmacodynamics (PD) profile of IPN10200 and to establish the total IPN10200 doses(s) that offer the best efficacy/safety profile when used for the treatment of Adult upper limb (AUL) spasticity.


Eligibility criteria: Inclusion Criteria:

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.
2. Has spastic hemiparesis following stroke or Traumatic brain injury (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 commercialized 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 Angle of arrest at slow speed (Tardieu Scale) (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 judgment prior to randomization
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 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.

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 woman of childbearing potential (WOCBP) and using an acceptable contraceptive method (until the end of the study). The investigator should evaluate the potential for contraceptive method failure in relationship to the first dose of study intervention. A WOCBP must have a negative highly sensitive pregnancy test.

Exclusion Criteria:

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.
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's 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 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.
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.
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 judgment 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 the duration of the study
16. Inability to understand protocol procedures and requirements
17. Infection at the injection site(s)
18. A history of drug or alcohol abuse
19. 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.

Primary outcomes:
measure: Percentage of participants with treatment emergent adverse events (TEAEs).
timeFrame: From baseline until the end of study (9 months)
measure: Percentage of participants with adverse events of special interest (AESI).
timeFrame: From baseline until the end of study (9 months)
measure: Change from baseline in vital sign parameter (blood pressure)
timeFrame: 9 months
measure: Change from baseline in vital sign parameter (Heart rate)
timeFrame: 9 months
measure: Change from baseline in clinical laboratory test results.
timeFrame: 9 months
measure: Presence of IPN10200 and BoNT-A antibodies (binding and neutralising)
timeFrame: From baseline until the end of study (9 months)
measure: Change from baseline in physical examination findings.
timeFrame: 9 months
Secondary outcomes:
measure: Change from Baseline to all post-treatment visits in Modified Ashworth scale (MAS) score in the Primary target muscle group (PTMG)
timeFrame: from baseline until the end of study (9 months)
measure: Change from Baseline to post-treatment Day 29 in MAS score in the PTMG.
timeFrame: From baseline until post-treatment Day 29
measure: Change from Baseline in MAS score in all injected muscle Groups
timeFrame: From baseline until the end of study (9 months)
measure: Time to onset - time to the response to treatment (a reduction of at least one grade in the MAS score).
timeFrame: From baseline until the end of study (9 months)
measure: Peak of effect - maximal decrease in the MAS score from Baseline.
timeFrame: From baseline until the end of study (9 months)
measure: Time to peak - time to reach the peak of effect (maximal decrease in the MAS score from Baseline).
timeFrame: From baseline until the end of study (9 months)
measure: Duration of effect - duration between time to onset and last timepoint with a response to Treatment.
timeFrame: From baseline until the end of study (9 months)
measure: Response to treatment as measured by at least one grade reduction in MAS score in the PTMG from Baseline
timeFrame: From baseline until the end of study (9 months)
measure: Response to treatment as measured by at least one grade reduction in MAS score in all injected muscles from Baseline
timeFrame: From baseline until the end of study (9 months)
measure: Physician's Global Assessment (PGA) score of overall treatment response
timeFrame: From baseline until the end of study (9 months)
measure: Patient Global Impression of Change in the Spastic Clinical Pattern using specific scale (PGI-c)
timeFrame: from baseline until the end of study (9 months)
measure: Change from Baseline in the Disability Assessment Scale (DAS)
timeFrame: From baseline until the end of study (9 months)
measure: Reduction of pain in the shoulder (adducted/rotated pattern) using the Numeric Rating Scale
timeFrame: From baseline until the end of study (9 months)
measure: The number and percentage of participants with presence of IPN10200 and BoNT-A antibodies and titres (binding and neutralising)
timeFrame: At baseline
Other outcomes:
Locations:
city: Downey
country: United States
facility: Rancho Los Amigos National Rehab
state: California
city: Overland Park
country: United States
facility: Kansas Institute of Research
state: Kansas
city: Farmington Hills
country: United States
facility: Quest Research Institute
state: Michigan
city: Elkins Park
country: United States
facility: Einstein Physical Medicine and Rehabilitation at Elkins Park
state: Pennsylvania
city: Linz
country: Austria
facility: Kepler University Hospital GmbH, Department of Neurology and Psychiatry
city: Linz
country: Austria
facility: Brothers of Charity Hospital Linz, Department of Neurology I
city: Pleven
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment "Heart and Brain"
city: Ruse
country: Bulgaria
facility: Medical Center "Rusemed" EOOD
city: Sofia
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment of Neurology and Psychiatry "Sveti Naum", Sofia, Neurological Diseases Clinic for Neurodegenerative and Peripheral Neurological Diseases
city: Sofia
country: Bulgaria
facility: "Diagnostic Consulting Center - Convex" EOOD
city: Veliko Tarnovo
country: Bulgaria
facility: Medical Center Medica Plus Ltd
city: Pardubice
country: Czechia
facility: Regional Hospital Pardubice, Clinic of Neurology
city: Prague
country: Czechia
facility: General University Hospital in Prague, Clinic of Neurology
city: Bonn
country: Germany
facility: University Hospital Bonn, Clinic and Policlinic for Neurology
city: Duesseldorf
country: Germany
facility: Heinrich Heine University Medical Center, Department of Neurology
city: Hamburg
country: Germany
facility: University Hospital Hamburg-Eppendorf, Clinic and Polyclinic of Neurology
city: Mainz
country: Germany
facility: University Hospital Johannes Gutenberg - University of Mainz, Clinic and Polyclinic of Neurology
city: Troisdorf
country: Germany
facility: GFO Clinics Troisdorf, St. Johannes Sieglar
city: Tuebingen
country: Germany
facility: University Hospital Tuebingen, Department of Neurology
city: Debrecen
country: Hungary
facility: University of Debrecen Clinical Center, Department of Medical Rehabilitation and Physical Medicine
city: Győr
country: Hungary
facility: Petz Aladar University Teaching Hospital, Department of Neurology
city: Kisvárda
country: Hungary
facility: Szent Damjan Greek Catholic Hospital, Department of Neurology and Stroke
city: Miskolc
country: Hungary
facility: Borsod-Abauj-Zemplen County Central Hospital and University Educational Hospital, Department of Neurology
city: Gdańsk
country: Poland
facility: St Wojciech - Adalbertus Hospital, Neurology Department
city: Katowice
country: Poland
facility: Specialist Doctor Practice
city: Katowice
country: Poland
facility: Neuro-Medic
city: Kraków
country: Poland
facility: Specialist Practises LLC
city: Kraków
country: Poland
facility: Linden Medical Center
city: Kraków
country: Poland
facility: Clinical Center for Neurology Sp. z o .o. (LLC)
city: Oświęcim
country: Poland
facility: Health Institute Dr n. med. Magdalena Boczarska-Jedynak
city: Poznan
country: Poland
facility: Clinical Research Center SP. ZOO MEDIC-R
city: Poznań
country: Poland
facility: Neuro-Kard Ilkowski and Partners
city: Sandomierz
country: Poland
facility: Holy Spirit Specialist Hospital in Sandomierz - Neurology Teaching Hospital, Neurology Department
city: Wrocław
country: Poland
facility: EuroMediCare Specialist Outpatient Clinics in Wroclaw
city: A Coruña
country: Spain
facility: Hospital Maritimo de Oza
city: Barcelona
country: Spain
facility: University Hospital Vall d'Hebron
city: Madrid
country: Spain
facility: University Hospital de La Princesa, Physical Medicine and Rehabilitation
city: Santiago De Compostela
country: Spain
facility: Santiago de Compostela Clinical Hospital, Physical Medicine and Rehabilitation
city: Vigo
country: Spain
facility: Meixoeiro Hospital at Vigo University Hospital Complex
Study officials:
affiliation: Ipsen
name: Ipsen Medical Director
role: STUDY_DIRECTOR
References: