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

Ipsen

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Spasticity

Treatments: Biological: Dysport; Biological: IPN10200; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04752774

D-FR-10200-001

2020-003623-42 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 240 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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240 participants in 3 patient groups

Dose escalation

Experimental group

Description:

One single administration of study medication (IPN10200, Dysport or placebo) will be injected in a dose-escalation manner. Dose-escalation will include several cohorts.

Treatment:

Drug: Placebo

Biological: IPN10200

Biological: Dysport

Dose ranging

Experimental group

Description:

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)

Treatment:

Biological: IPN10200

Biological: Dysport

Total dose

Experimental group

Description:

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).

Treatment:

Drug: Placebo

Biological: IPN10200