A Study to Assess the Safety and Efficacy of IPN10200 in Adult Participants With Upper Limb Spasticity.

Официальное название

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.

Обзор

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

Вмешательства

• Биопрепарат Corabotase
  Powder and solvent for solution for injection
• Препарат Placebo
  Powder and solvent for solution for injection
• Биопрепарат Dysport
  Powder for solution for injection

Первичные конечные точки

• Percentage of participants with treatment emergent adverse events (TEAEs). [Срок оценки: From baseline until the end of study (9 months)]
• Percentage of participants with adverse events of special interest (AESI). [Срок оценки: From baseline until the end of study (9 months)]
• Change from baseline in vital sign parameter (blood pressure) [Срок оценки: 9 months]
• Change from baseline in vital sign parameter (Heart rate) [Срок оценки: 9 months]
• Change from baseline in clinical laboratory test results. [Срок оценки: 9 months]
• Presence of IPN10200 and BoNT-A antibodies (binding and neutralising) [Срок оценки: From baseline until the end of study (9 months)]
• Change from baseline in physical examination findings. [Срок оценки: 9 months]

Вторичные конечные точки (12)

• Change from Baseline to all post-treatment visits in Modified Ashworth scale (MAS) score in the Primary target muscle group (PTMG) [Срок оценки: from baseline until the end of study (9 months)]
• Change from Baseline to post-treatment Day 29 in MAS score in the PTMG. [Срок оценки: From baseline until post-treatment Day 29]
• Change from Baseline in MAS score in all injected muscle Groups [Срок оценки: From baseline until the end of study (9 months)]
• Time to onset - time to the response to treatment (a reduction of at least one grade in the MAS score). [Срок оценки: From baseline until the end of study (9 months)]
• Peak of effect - maximal decrease in the MAS score from Baseline. [Срок оценки: From baseline until the end of study (9 months)]
• Time to peak - time to reach the peak of effect (maximal decrease in the MAS score from Baseline). [Срок оценки: From baseline until the end of study (9 months)]
• Duration of effect - duration between time to onset and last timepoint with a response to Treatment. [Срок оценки: From baseline until the end of study (9 months)]
• Response to treatment as measured by at least one grade reduction in MAS score in the PTMG from Baseline [Срок оценки: From baseline until the end of study (9 months)]
• Response to treatment as measured by at least one grade reduction in MAS score in all injected muscles from Baseline [Срок оценки: From baseline until the end of study (9 months)]
• Physician's Global Assessment (PGA) score of overall treatment response [Срок оценки: From baseline until the end of study (9 months)]
• Patient Global Impression of Change in the Spastic Clinical Pattern using specific scale (PGI-c) [Срок оценки: from baseline until the end of study (9 months)]
• Change from Baseline in the Disability Assessment Scale (DAS) [Срок оценки: From baseline until the end of study (9 months)]

Критерии участия

Критерии включения

• 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 Traumatic brain injury (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 commercialized 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.
• 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°
• 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.
• 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
• 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.

Критерии исключения

• 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.).
• 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. For patients taking vitamin K antagonists, the INR values should be controlled (between 2 and 3)
• 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 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.
• 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
• Inability to understand protocol procedures and requirements
• Infection at the injection site(s)
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Польша · 15 центров

• St Wojciech - Adalbertus Hospital, Neurology Department — Gdansk
• Specialist Doctor Practice — Katowice
• Ma-Lek MS Therapy Centre — Katowice
• Neuro-Medic — Katowice
• Specialist Practises LLC — Krakow
• Linden Medical Center — Krakow
• Clinical Center for Neurology Sp. z o .o. (LLC) — Krakow
• NeuroKlinika - Private Practice Prof. Andrzej Bogucki — Lodz
• … и ещё 7 центров

Германия · 8 центров

• University Hospital Bonn, Clinic and Policlinic for Neurology — Bonn
• Heinrich Heine University Medical Center, Department of Neurology — Düsseldorf
• University Medicine Goettingen, Department of Neurology — Goettigen
• University Hospital Hamburg-Eppendorf, Clinic and Polyclinic of Neurology — Hamburg
• University Hospital Johannes Gutenberg - University of Mainz, Clinic and Polyclinic of Neu — Mainz
• Ludwig Maximilians University Hospital, Campus Grosshadern, Department of Neurology — Munich
• GFO Clinics Troisdorf, St. Johannes Sieglar — Troisdorf
• University Hospital Tuebingen, Department of Neurology — Tübingen

Испания · 7 центров

• Hospital Maritimo de Oza — A Coruña
• University Hospital Vall d'Hebron — Barcelona
• Juan Ramon Jimenez Hospital — Huelva
• University Hospital de La Princesa, Physical Medicine and Rehabilitation — Madrid
• Santiago de Compostela Clinical Hospital, Physical Medicine and Rehabilitation — Santiago de Compostela
• University Hospital Virgen Macarena, Physical Medicine and Rehabilitation — Seville
• … и ещё 1 центр

Чехия · 6 центров

• University Hospital Hradec Kralove, Clinic of Neurology — Hradec Králové
• Hospital Jihlava, Department of Neurology — Jihlava
• University Hospital Ostrava, Clinic of Neurology, Center for Demyelinating diseases — Ostrava
• Regional Hospital Pardubice, Clinic of Neurology — Pardubice
• University Hospital Kralovske Vinohrady, Clinic of Neurology — Prague
• General University Hospital in Prague, Clinic of Neurology — Prague

Россия · 6 центров

• Federal Siberian Research and Clinical Center, Department of Nervous Diseases, Traditional — Krasnoyarsk
• National Medical Research Center Treatment and Rehabilitation Center, Department of Neurol — Moscow
• "Praximed" - Diagnostic and Rehabilitation Center, Rehalibitation Department — Saint Petersburg
• N.P. Bekhtereva Research Institute of Human Brain — Saint Petersburg
• Astarta, LLC, Department of Neurology — Saint Petersburg
• Medical and Sanitary Unit #70 of "Passazhiravtotrans" — Saint Petersburg

США · 5 центров

• Rancho Los Amigos National Rehab — Downey
• Kansas Institute of Research — Overland Park
• Quest Research Institute — Farmington Hills
• Einstein Physical Medicine and Rehabilitation at Elkins Park — Elkins Park
• The University of Texas Southwestern Medical Center — Dallas

Болгария · 5 центров

• Multiprofile Hospital for Active Treatment "Heart and Brain" — Pleven
• Medical Center "Rusemed" EOOD — Rousse
• Multiprofile Hospital for Active Treatment of Neurology and Psychiatry "Sveti Naum", Sofia — Sofia
• Diagnostic Consulting Center - Convex EOOD — Sofia
• Medical Center Medica Plus Ltd — Veliko Tarnovo

Венгрия · 5 центров

• Semmelweis University, Rehabilitation Clinic, Rehabilitation Department of Brain Injuries — Budapest
• University of Debrecen Clinical Center, Department of Medical Rehabilitation and Physical — Debrecen
• Petz Aladar University Teaching Hospital, Department of Neurology — Győr
• Szent Damjan Greek Catholic Hospital, Department of Neurology and Stroke — Kisvárda
• Borsod-Abauj-Zemplen County Central Hospital and University Educational Hospital, Departme — Miskolc

Австрия · 4 центра

• Medical University Innsbruck, Department of Neurology — Innsbruck
• Kepler University Hospital GmbH, Department of Neurology and Psychiatry — Linz
• Brothers of Charity Hospital Linz, Department of Neurology I — Linz
• Medical University Vienna, Department of Neurology — Vienna

Франция · 4 центра

• Bastia Hospital Center — Bastia
• Bordeaux University Hospital Center - Pellegrin Hospital Group — Bordeaux
• Brest University Hospital Center - Morvan Hospital — Brest
• Raymond-Poincare Hospital - APHP — Garches

Италия · 4 центра

• ASST Spedali Civili Brescia — Brescia
• University Hospital "Federico II" — Naples
• University Polyclinic Foundation "Agostino Gemelli" - IRCCS — Rome
• Clinical Research Center of Verona S.r.l. - CRC — Verona

Япония · 4 центра

• Fukuoka Rehabilitation Hospital — Fukuoka
• Chutoen General Medical Center, Department of Rehabilitation — Shizuoka
• Tokushima University Hospital — Tokushima
• NHO Murayama Medical Center, Department of Rehabilitation — Tokyo

Португалия · 4 центра

• Alto Ave Central Hospital — Guimarães
• Local Health Unit Loures-Odivelas E.P.E. — Loures
• Local Health Unit of Matosinhos (ULSM), EPE - Pedro Hispano Hospital — Matosinhos Municipality
• Local Unit of Health in Alto Minho, EPE — Viana do Castelo

South Korea · 4 центра

• Dongguk University Ilsan Hospital — Goyang-si
• The Catholic University of Korea - Incheon St. Mary's Hospital — Incheon
• Seoul National University Bundang Hospital — Seongnam-si
• Severance Hospital, Yonsei University Health System — Seoul

Идентификаторы

NCT: NCT04752774 · D-FR-10200-001 · 2020-003623-42

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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