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

• Sponsor: Ipsen (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04752774
• Collaborator: (none)
• Enrollment: 209
• Locations: 37
• Arms: 3
• Anticipated Duration (Months): 35
• Patients Per Site: 5.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Spasticity	Biological: IPN10200; Drug: Placebo; Biological: Dysport	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 209 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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.
• Actual Study Start Date: Apr 29, 2021
• Anticipated Primary Completion Date: Mar 29, 2024
• Anticipated Study Completion Date: Mar 29, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose escalation One single administration of study medication (IPN10200, Dysport or placebo) will be injected in a dose-escalation manner. Dose-escalation will include several cohorts.	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
Experimental: Dose ranging Two fixed doses of IPN10200 will be administrated as a single injection into several muscle groups of the upper limb. Participants will be randomised in the ratio of 3:3:2 (total IPN10200 dose 1: 30 participants; total IPN10200 dose 2: 30 participants; Dysport: 20 participants)	Biological: IPN10200; Powder and solvent for solution for injection; Biological: Dysport; Powder for solution for injection
Experimental: Total dose One single injection of study medication will be administered locally into several muscle groups of the upper limb. Participants will be randomized in the ratio of 2:1 (Total IPN10200 dose: 30 participants; placebo: 15 participants, resulting in a total of 45 participants in Stage 3). Or Participants will be randomized in the ratio of 3:1 (IPN10200 lower dose: 30 participants; placebo: 10 participants, then IPN10200 higher dose: 30 participants; placebo: 10 participants, resulting in a total of 80 participants in Stage 3).	Biological: IPN10200; Powder and solvent for solution for injection; Drug: Placebo; Powder and solvent for solution for injection

Outcome Measures

Primary Outcome Measures

1. Incidence, severity and nature of treatment emergent adverse events (TEAEs). [from baseline until the end of study (9 months)]

2. Incidence, severity and nature of adverse events of special interest (AESI). [from baseline until the end of study (9 months)]

3. Change from baseline in vital sign parameter (blood pressure) [9 months]

4. Change from baseline in vital sign parameter (Heart rate) [9 months]

5. Change from baseline in clinical laboratory test results. [9 months]

   Number and percentage of participants with low, normal or high values and normal or abnormal examinations will be presented.

6. Presence of IPN10200 and BoNT-A antibodies (binding and neutralising) [from baseline until the end of study (9 months)]

7. Change from baseline in physical examination findings. [9 months]

   Number of Participants with change in physical examination findings

Secondary Outcome Measures

1. Change from Baseline to all post-treatment visits in Modified Ashworth scale (MAS) score in the Primary target muscle group (PTMG) [from baseline until the end of study (9 months)]

   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.

2. Change from Baseline to post-treatment Day 29 in MAS score in the PTMG [from baseline until port-treatment Day 29]

   if PD profile of IPN10200 in dose escalation indicates a peak of effect different than Day 29, the endpoint will be modified accordingly)

3. Change from Baseline in MAS score in all injected muscle Groups [from baseline until the end of study (9 months)]

4. 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)]

5. Peak of effect - maximal decrease in the MAS score from Baseline. [from baseline until the end of study (9 months)]

6. 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)]

7. 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)]

8. 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)]

9. 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)]

10. Physician's Global Assessment (PGA) score of overall treatment response [from baseline until the end of study (9 months)]

    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.

11. Patient Global Impression of Change in the Spastic Clinical Pattern using specific scale (PGI-c) [from baseline until the end of study (9 months)]

    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

12. Change from Baseline in the Disability Assessment Scale (DAS) [from baseline until the end of study (9 months)]

    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.

13. Reduction of pain in the shoulder (adducted/rotated pattern) using the Numeric Rating Scale [from baseline until the end of study (9 months)]

14. The number and percentage of participants with presence of IPN10200 and BoNT-A antibodies and titres (binding and neutralising) [At baseline]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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°

1. 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.

2. 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

3. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kepler University Hospital GmbH, Department of Neurology and Psychiatry	Linz		Austria	4021
2	Brothers of Charity Hospital Linz, Department of Neurology I	Linz		Austria	A-4021
3	Medical University Vienna, Department of Neurology	Vienna		Austria	1090
4	University Hospital Hradec Kralove, Clinic of Neurology	Hradec Králové		Czechia	500 05
5	Regional Hospital Pardubice, Clinic of Neurology	Pardubice		Czechia	532 03
6	University Hospital Kralovske Vinohrady, Clinic of Neurology	Prague		Czechia	100 34
7	General University Hospital in Prague, Clinic of Neurology	Prague		Czechia	120 00
8	Heinrich Heine University Medical Center, Department of Neurology	Duesseldorf		Germany	40225
9	University Hospital Johannes Gutenberg - University of Mainz, Clinic and Polyclinic of Neurology	Mainz		Germany	55131
10	Ludwig Maximilians University Hospital, Campus Grosshadern, Department of Neurology	Munich		Germany	81377
11	GFO Clinics Troisdorf, St. Johannes Sieglar	Troisdorf		Germany	53844
12	University Hospital Tuebingen, Department of Neurology	Tuebingen		Germany	72076
13	St Wojciech - Adalbertus Hospital, Neurology Department	Gdańsk		Poland	80-462
14	Specialist Doctor Practice	Katowice		Poland	40-097
15	Ma-Lek MS Therapy Centre	Katowice		Poland	40-571
16	Neuro-Medic	Katowice		Poland	40-686
17	Specialist Practises LLC	Kraków		Poland	30-539
18	Linden Medical Center	Kraków		Poland	30-721
19	Clinical Center for Neurology Sp. z o .o. (LLC)	Kraków		Poland	31-505
20	Health Institute Dr n. med. Magdalena Boczarska-Jedynak	Oświęcim		Poland	32-600
21	Clinical Research Center SP. ZOO MEDIC-R	Poznan		Poland	61-731
22	Neuro-Kard Ilkowski and Partners	Poznań		Poland	61-853
23	Holy Spirit Specialist Hospital in Sandomierz - Neurology Teaching Hospital, Neurology Department	Sandomierz		Poland	27-600
24	Wolski Hospital, Neurological Department	Warsaw		Poland	01-211
25	EuroMediCare Specialist Outpatient Clinics in Wroclaw	Wrocław		Poland	50-220
26	NeuroKlinika - Private Practice Prof. Andrzej Bogucki	Łódź		Poland	90-640
27	Federal Siberian Research and Clinical Center, Department of Nervous Diseases, Traditional Medicine with Course in Postgraduate Education	Krasnoyarsk		Russian Federation	660049
28	National Medical Research Center Treatment and Rehabilitation Center, Department of Neurology	Moscow		Russian Federation	125367
29	"Praximed" - Diagnostic and Rehabilitation Center, Rehalibitation Department	Saint Petersburg		Russian Federation	194223
30	N.P. Bekhtereva Research Institute of Human Brain	Saint Petersburg		Russian Federation	197376
31	Astarta, LLC, Department of Neurology	Saint Petersburg		Russian Federation	199226
32	Medical and Sanitary Unit #70 of "Passazhiravtotrans"	Saint Petersburg		Russian Federation
33	Hospital Maritimo de Oza	A Coruña		Spain	15006
34	University Hospital Vall d'Hebron	Barcelona		Spain	08035
35	University Hospital de La Princesa, Physical Medicine and Rehabilitation	Madrid		Spain	28006
36	Santiago de Compostela Clinical Hospital, Physical Medicine and Rehabilitation	Santiago De Compostela		Spain	15706
37	Meixoeiro Hospital at Vigo University Hospital Complex	Vigo		Spain	36200

Sponsors and Collaborators

• Ipsen

Investigators

• Study Director: Ipsen Medical Director, Ipsen

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ipsen
• ClinicalTrials.gov Identifier: NCT04752774
• Other Study ID Numbers: D-FR-10200-001; 2020-003623-42
• First Posted: Feb 12, 2021
• Last Update Posted: Aug 24, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Ipsen: Upper limb spasticity after stroke or traumatic brain injury
• Additional relevant MeSH terms: Muscle Spasticity; abobotulinumtoxinA

Study Results

No Results Posted as of Aug 24, 2022