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NCT04752774PHASE1, PHASE2Recruiting

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

Ipsen

Start Date

4/29/2021

Completion Date

3/30/2029

Summary

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.

Eligibility Criteria

Age Range: 18 years to 70 years

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.

Interventions

BIOLOGICAL

Corabotase

DRUG

Placebo

BIOLOGICAL

Dysport

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Conditions

Spasticity

Locations

Rancho Los Amigos National Rehab

Downey, California 90242

United States

Kansas Institute of Research

Overland Park, Kansas 66211

United States

Quest Research Institute

Farmington Hills, Michigan 48334

United States

Einstein Physical Medicine and Rehabilitation at Elkins Park

Elkins Park, Pennsylvania 19027

United States

The University of Texas Southwestern Medical Center

Dallas, Texas 75390

United States

Medical University Innsbruck, Department of Neurology

Innsbruck, 6020

Austria

Kepler University Hospital GmbH, Department of Neurology and Psychiatry

Linz, 4021

Austria

Brothers of Charity Hospital Linz, Department of Neurology I

Linz, A-4021

Austria

Medical University Vienna, Department of Neurology

Vienna, 1090

Austria

Multiprofile Hospital for Active Treatment "Heart and Brain"

Pleven, 5800

Bulgaria

Medical Center "Rusemed" EOOD

Rousse, 7005

Bulgaria

Multiprofile Hospital for Active Treatment of Neurology and Psychiatry "Sveti Naum", Sofia, Neurological Diseases Clinic for Neurodegenerative and Peripheral Neurological Diseases

Sofia, 1113

Bulgaria

Diagnostic Consulting Center - Convex EOOD

Sofia, 1680

Bulgaria

Medical Center Medica Plus Ltd

Veliko Tarnovo, 5006

Bulgaria

University Hospital Hradec Kralove, Clinic of Neurology

Hradec Králové, 500 05

Czechia

Hospital Jihlava, Department of Neurology

Jihlava, 586 33

Czechia

University Hospital Ostrava, Clinic of Neurology, Center for Demyelinating diseases

Ostrava, 708 52

Czechia

Regional Hospital Pardubice, Clinic of Neurology

Pardubice, 532 03

Czechia

University Hospital Kralovske Vinohrady, Clinic of Neurology

Prague, 100 34

Czechia

General University Hospital in Prague, Clinic of Neurology

Prague, 120 00

Czechia

Bastia Hospital Center

Bastia, 20600

France

Bordeaux University Hospital Center - Pellegrin Hospital Group

Bordeaux, 33076

France

Brest University Hospital Center - Morvan Hospital

Brest, 29200

France

Raymond-Poincare Hospital - APHP

Garches, 92380

France

University Hospital Bonn, Clinic and Policlinic for Neurology

Bonn, 53127

Germany

Heinrich Heine University Medical Center, Department of Neurology

Düsseldorf, 40225

Germany

University Medicine Goettingen, Department of Neurology

Goettigen, 37075

Germany

University Hospital Hamburg-Eppendorf, Clinic and Polyclinic of Neurology

Hamburg, 20246

Germany

University Hospital Johannes Gutenberg - University of Mainz, Clinic and Polyclinic of Neurology

Mainz, 55131

Germany

Ludwig Maximilians University Hospital, Campus Grosshadern, Department of Neurology

Munich, 81377

Germany

GFO Clinics Troisdorf, St. Johannes Sieglar

Troisdorf, 53844

Germany

University Hospital Tuebingen, Department of Neurology

Tübingen, 72076

Germany

Semmelweis University, Rehabilitation Clinic, Rehabilitation Department of Brain Injuries

Budapest,

Hungary

University of Debrecen Clinical Center, Department of Medical Rehabilitation and Physical Medicine

Debrecen, H-4031

Hungary

Petz Aladar University Teaching Hospital, Department of Neurology

Győr,

Hungary

Szent Damjan Greek Catholic Hospital, Department of Neurology and Stroke

Kisvárda, H-4600

Hungary

Borsod-Abauj-Zemplen County Central Hospital and University Educational Hospital, Department of Neurology

Miskolc,

Hungary

ASST Spedali Civili Brescia

Brescia, 25123

Italy

University Hospital "Federico II"

Naples, 80131

Italy

University Polyclinic Foundation "Agostino Gemelli" - IRCCS

Rome, 00168

Italy

Clinical Research Center of Verona S.r.l. - CRC

Verona, 37134

Italy

Fukuoka Rehabilitation Hospital

Fukuoka,

Japan

Chutoen General Medical Center, Department of Rehabilitation

Shizuoka,

Japan

Tokushima University Hospital

Tokushima, 770-8503

Japan

NHO Murayama Medical Center, Department of Rehabilitation

Tokyo,

Japan

St Wojciech - Adalbertus Hospital, Neurology Department

Gdansk, 80-462

Poland

Specialist Doctor Practice

Katowice, 40-097

Poland

Ma-Lek MS Therapy Centre

Katowice, 40-571

Poland

Neuro-Medic

Katowice, 40-686

Poland

Specialist Practises LLC

Krakow, 30-539

Poland

Linden Medical Center

Krakow, 30-721

Poland

Clinical Center for Neurology Sp. z o .o. (LLC)

Krakow, 31-505

Poland

NeuroKlinika - Private Practice Prof. Andrzej Bogucki

Lodz, 90-640

Poland

Health Institute Dr n. med. Magdalena Boczarska-Jedynak

Oświęcim, 32-600

Poland

Clinical Research Center SP. ZOO MEDIC-R

Poznan, 61-731

Poland

Neuro-Kard Ilkowski and Partners

Poznan, 61-853

Poland

Holy Spirit Specialist Hospital in Sandomierz - Neurology Teaching Hospital, Neurology Department

Sandomierz, 27-600

Poland

Wolski Hospital, Neurological Department

Warsaw, 01-211

Poland

NeuroProtect Medical Center

Warsaw, 01-684

Poland

EuroMediCare Specialist Outpatient Clinics in Wroclaw

Wroclaw, 50-220

Poland

Alto Ave Central Hospital

Guimarães, 4835-044

Portugal

Local Health Unit Loures-Odivelas E.P.E.

Loures, 2674-514

Portugal

Local Health Unit of Matosinhos (ULSM), EPE - Pedro Hispano Hospital

Matosinhos Municipality, 4464-513

Portugal

Local Unit of Health in Alto Minho, EPE

Viana do Castelo, 4904-858

Portugal

Federal Siberian Research and Clinical Center, Department of Nervous Diseases, Traditional Medicine with Course in Postgraduate Education

Krasnoyarsk, 660049

Russia

National Medical Research Center Treatment and Rehabilitation Center, Department of Neurology

Moscow, 125367

Russia

"Praximed" - Diagnostic and Rehabilitation Center, Rehalibitation Department

Saint Petersburg, 194223

Russia

N.P. Bekhtereva Research Institute of Human Brain

Saint Petersburg, 197376

Russia

Astarta, LLC, Department of Neurology

Saint Petersburg, 199226

Russia

Medical and Sanitary Unit #70 of "Passazhiravtotrans"

Saint Petersburg,

Russia

Dongguk University Ilsan Hospital

Goyang-si, 10326

South Korea

The Catholic University of Korea - Incheon St. Mary's Hospital

Incheon, 21431

South Korea

Seoul National University Bundang Hospital

Seongnam-si, 13620

South Korea

Severance Hospital, Yonsei University Health System

Seoul, 03722

South Korea

Hospital Maritimo de Oza

A Coruña, 15006

Spain

University Hospital Vall d'Hebron

Barcelona, 08035

Spain

Juan Ramon Jimenez Hospital

Huelva, 21005

Spain

University Hospital de La Princesa, Physical Medicine and Rehabilitation

Madrid, 28006

Spain

Santiago de Compostela Clinical Hospital, Physical Medicine and Rehabilitation

Santiago de Compostela, 15706

Spain

University Hospital Virgen Macarena, Physical Medicine and Rehabilitation

Seville, 41009

Spain

Meixoeiro Hospital at Vigo University Hospital Complex

Vigo, 36200

Spain