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

Spasticity Clinical Trial

— LANTIMA  

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04752774
• Other study ID #: D-FR-10200-001
• Secondary ID: 2020-003623-42
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 29, 2021
• Est. completion date: June 30, 2026

Study information

• Verified date: March 2024
• Source: Ipsen
• Contact: Ipsen Recruitment Enquiries
• Phone: see email
• Email: clinical.trials[@]ipsen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 209
• Est. completion date: June 30, 2026
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Muscle Spasticity
• Spasticity

Intervention

Biological:
• IPN10200
Powder and solvent for solution for injection

Drug:
• Placebo
Powder and solvent for solution for injection

Biological:
• Dysport
Powder for solution for injection

Locations

Country	Name	City	State
Austria	Brothers of Charity Hospital Linz, Department of Neurology I	Linz
Austria	Kepler University Hospital GmbH, Department of Neurology and Psychiatry	Linz
Austria	Medical University Vienna, Department of Neurology	Vienna
Bulgaria	Multiprofile Hospital for Active Treatment "Heart and Brain"	Pleven
Bulgaria	Medical Center "Rusemed" EOOD	Ruse
Bulgaria	"Diagnostic Consulting Center - Convex" EOOD	Sofia
Bulgaria	Multiprofile Hospital for Active Treatment of Neurology and Psychiatry "Sveti Naum", Sofia, Neurological Diseases Clinic for Neurodegenerative and Peripheral Neurological Diseases	Sofia
Bulgaria	Medical Center Medica Plus Ltd	Veliko Tarnovo
Czechia	University Hospital Hradec Kralove, Clinic of Neurology	Hradec Králové
Czechia	Regional Hospital Pardubice, Clinic of Neurology	Pardubice
Czechia	General University Hospital in Prague, Clinic of Neurology	Prague
Czechia	University Hospital Kralovske Vinohrady, Clinic of Neurology	Prague
Germany	University Hospital Bonn, Clinic and Policlinic for Neurology	Bonn
Germany	Heinrich Heine University Medical Center, Department of Neurology	Duesseldorf
Germany	University Medicine Goettingen, Department of Neurology	Goettigen
Germany	University Hospital Hamburg-Eppendorf, Clinic and Polyclinic of Neurology	Hamburg
Germany	University Hospital Johannes Gutenberg - University of Mainz, Clinic and Polyclinic of Neurology	Mainz
Germany	Ludwig Maximilians University Hospital, Campus Grosshadern, Department of Neurology	Munich
Germany	GFO Clinics Troisdorf, St. Johannes Sieglar	Troisdorf
Germany	University Hospital Tuebingen, Department of Neurology	Tuebingen
Hungary	University of Debrecen Clinical Center, Department of Medical Rehabilitation and Physical Medicine	Debrecen
Hungary	Petz Aladar University Teaching Hospital, Department of Neurology	Gyor
Hungary	Szent Damjan Greek Catholic Hospital, Department of Neurology and Stroke	Kisvárda
Hungary	Borsod-Abauj-Zemplen County Central Hospital and University Educational Hospital, Department of Neurology	Miskolc
Poland	St Wojciech - Adalbertus Hospital, Neurology Department	Gdansk
Poland	Ma-Lek MS Therapy Centre	Katowice
Poland	Neuro-Medic	Katowice
Poland	Specialist Doctor Practice	Katowice
Poland	Clinical Center for Neurology Sp. z o .o. (LLC)	Kraków
Poland	Linden Medical Center	Kraków
Poland	Specialist Practises LLC	Kraków
Poland	NeuroKlinika - Private Practice Prof. Andrzej Bogucki	Lódz
Poland	Health Institute Dr n. med. Magdalena Boczarska-Jedynak	Oswiecim
Poland	Clinical Research Center SP. ZOO MEDIC-R	Poznan
Poland	Neuro-Kard Ilkowski and Partners	Poznan
Poland	Holy Spirit Specialist Hospital in Sandomierz - Neurology Teaching Hospital, Neurology Department	Sandomierz
Poland	NeuroProtect Medical Center	Warsaw
Poland	Wolski Hospital, Neurological Department	Warsaw
Poland	EuroMediCare Specialist Outpatient Clinics in Wroclaw	Wroclaw
Russian Federation	Federal Siberian Research and Clinical Center, Department of Nervous Diseases, Traditional Medicine with Course in Postgraduate Education	Krasnoyarsk
Russian Federation	National Medical Research Center Treatment and Rehabilitation Center, Department of Neurology	Moscow
Russian Federation	"Praximed" - Diagnostic and Rehabilitation Center, Rehalibitation Department	Saint Petersburg
Russian Federation	Astarta, LLC, Department of Neurology	Saint Petersburg
Russian Federation	Medical and Sanitary Unit #70 of "Passazhiravtotrans"	Saint Petersburg
Russian Federation	N.P. Bekhtereva Research Institute of Human Brain	Saint Petersburg
Spain	Hospital Maritimo de Oza	A Coruña
Spain	University Hospital Vall d'Hebron	Barcelona
Spain	University Hospital de La Princesa, Physical Medicine and Rehabilitation	Madrid
Spain	Santiago de Compostela Clinical Hospital, Physical Medicine and Rehabilitation	Santiago De Compostela
Spain	Meixoeiro Hospital at Vigo University Hospital Complex	Vigo
United States	Rancho Los Amigos National Rehab	Downey	California
United States	Einstein Physical Medicine and Rehabilitation at Elkins Park	Elkins Park	Pennsylvania
United States	Quest Research Institute	Farmington Hills	Michigan
United States	Kansas Institute of Research	Overland Park	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Ipsen

Countries where clinical trial is conducted

United States,  Austria,  Bulgaria,  Czechia,  Germany,  Hungary,  Poland,  Russian Federation,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence, severity and nature of treatment emergent adverse events (TEAEs).		from baseline until the end of study (9 months)
Primary	Incidence, severity and nature of adverse events of special interest (AESI).		from baseline until the end of study (9 months)
Primary	Change from baseline in vital sign parameter (blood pressure)		9 months
Primary	Change from baseline in vital sign parameter (Heart rate)		9 months
Primary	Change from baseline in clinical laboratory test results.	Number and percentage of participants with low, normal or high values and normal or abnormal examinations will be presented.	9 months
Primary	Presence of IPN10200 and BoNT-A antibodies (binding and neutralising)		from baseline until the end of study (9 months)
Primary	Change from baseline in physical examination findings.	Number of Participants with change in physical examination findings	9 months
Secondary	Change from Baseline to all post-treatment visits in Modified Ashworth scale (MAS) score in the Primary target muscle group (PTMG)	MAS is a scale to assess muscle tone in the injected muscles. The muscle tone will be rated as per grading from 0 to 4, there 0 =No increase in muscle tone and 4 =Affected part(s) rigid in flexion or extension.	from baseline until the end of study (9 months)
Secondary	Change from Baseline to post-treatment Day 29 in MAS score in the PTMG	if PD profile of IPN10200 in dose escalation indicates a peak of effect different than Day 29, the endpoint will be modified accordingly)	from baseline until port-treatment Day 29
Secondary	Change from Baseline in MAS score in all injected muscle Groups		from baseline until the end of study (9 months)
Secondary	Time to onset - time to the response to treatment (a reduction of at least one grade in the MAS score).		from baseline until the end of study (9 months)
Secondary	Peak of effect - maximal decrease in the MAS score from Baseline.		from baseline until the end of study (9 months)
Secondary	Time to peak - time to reach the peak of effect (maximal decrease in the MAS score from Baseline).		from baseline until the end of study (9 months)
Secondary	Duration of effect - duration between time to onset and last timepoint with a response to Treatment.		from baseline until the end of study (9 months)
Secondary	Response to treatment as measured by at least one grade reduction in MAS score in the PTMG from Baseline		from baseline until the end of study (9 months)
Secondary	Response to treatment as measured by at least one grade reduction in MAS score in all injected muscles from Baseline		from baseline until the end of study (9 months)
Secondary	Physician's Global Assessment (PGA) score of overall treatment response	The PGA is a 9-point scale (from -4= markedly worse to +4=markedly improved) used to assess global overall treatment response by the investigator.	from baseline until the end of study (9 months)
Secondary	Patient Global Impression of Change in the Spastic Clinical Pattern using specific scale (PGI-c)	PGI-C is a scale to assess global impression of change in the spastic clinical pattern using a 7-point Likert scale (from -3: very much worse to +3: very much improved) by answering a specific question	from baseline until the end of study (9 months)
Secondary	Change from Baseline in the Disability Assessment Scale (DAS)	The DAS will be used to assess the effect of upper limb spasticity on hygiene, dressing, limb position and pain. Participants will be assessed in an interview format.	from baseline until the end of study (9 months)
Secondary	Reduction of pain in the shoulder (adducted/rotated pattern) using the Numeric Rating Scale		from baseline until the end of study (9 months)
Secondary	The number and percentage of participants with presence of IPN10200 and BoNT-A antibodies and titres (binding and neutralising)		At baseline