Study to Compare the Efficacy and Safety of NT 201 (Botulinum Toxin) With Placebo for the Treatment of Lower Limb Spasticity Caused by Stroke or Traumatic Brain Injury

Phase 3

Active, not recruiting

• Conditions: Lower Limb or Combined Lower Limb and Upper Limb Spasticity Due to Stroke or Traumatic Brain Injury
• Interventions: Drug: NT 201; Drug: Placebo

• Registration Number: NCT03992404
• Lead Sponsor: Merz Pharmaceuticals GmbH

Brief Summary

The purpose of this study is to determine whether a single treatment with administration of 400 Units NT 201 (botulinum toxin) is superior to placebo (no medicine) for the treatment of lower limb spasticity caused by stroke or traumatic brain injury (Main Period). Participants will be assigned to the treatment groups by chance and neither the participants nor the research staff who interact with them will know the allocation.

The following 4 to 5 treatment cycles will investigate the safety and tolerability of treatment with NT 201 (botulinum toxin) when administered in doses between 400 and 800 Units (Open Label Extension Period). All participants will receive the treatment and the dose will depend on whether only lower limb spasticity or combined upper and lower limb spasticity are treated.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-06-18
• Study First Submitted QC: 2019-06-18
• Study First Posted: 2019-06-20
• Study Start: 2019-09-16
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-24
• Last Update Posted: 2025-06-25
• Primary Completion: 2025-08
• Study Completion: 2027-04-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 603

Inclusion Criteria

• Female or male subject ≥ 18 years and ≤ 85 years at screening
• Diagnosis of lower limb spasticity with or without upper limb spasticity of the same body side caused by stroke or traumatic brain injury
• Disabling ankle flexor spasticity presenting as pes equinus or pes equinovarus
• Modified Ashworth Scale-Bohannon [MAS] score of 2 or 3 points in the ankle plantar flexor of the target lower limb (supine position, knee extended)
• Minimum passive range of motion in ankle of the target lower limb (supine position, knee extended): 10°dorsiflexion and 20°plantarflexion
• At least 4 months since last botulinum neurotoxin [BoNT] injection for treatment of spasticity or any other condition
• For subjects receiving anticoagulation therapy, the investigator confirms and documents that the subject has an:
• Activated partial thromboplastin time [aPTT] ≤ 80 seconds (subjects on dabigatran or other direct thrombin inhibitors) or
• International normalized ratio [INR] value of ≤ 2.5 (subjects on coumarins or other anticoagulants monitored by INR)

Exclusion Criteria

• Generalized disorders of muscle activity (e.g. myasthenia gravis, Lambert Eaton syndrome, amyotrophic lateral sclerosis) or any other significant peripheral neuromuscular dysfunction which might interfere with the study
• Bilateral lower limb paresis/paralysis/spasticity or tetraparesis/paralysis/spasticity
• Body weight < 50 kg
• Severe atrophy of the target limb muscles
• Previous, ongoing or planned treatments of spasticity with intrathecal baclofen
• Previous, ongoing, or planned treatments of spasticity in the target lower limb with any of the following procedures: Surgical Intervention; Alcohol or phenol block; Muscle afferent block
• Physiotherapy or use of orthoses or splints at the target limb initiated less than 4 weeks before screening or expected to change during the double blind phase of the study
• Current or planned treatment with parenterally administered drugs that interfere with neuromuscular transmission (e.g. intrathecal baclofen, tubocurarine type muscle relaxants used in anesthesia), or local anesthetics in the treated region within 2 weeks prior to screening
• Infection or inflammation at the injection sites
• Subjects with presence or history of aspiration pneumonia, recurrent lower respiratory tract infections, or compromised respiratory function as per investigator's clinical judgment
• Pregnancy (as verified by a positive pregnancy test) or breast feeding

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	NT 201	Main Period (1 treatment cycle): subjects to receive intramuscular placebo injection into muscles of the lower limb. Open Label Extension Period (4-5 treatment cycles): subjects to receive intramuscular injection of NT 201 (up to 800 units) into muscles of the lower limb and upper limb, if indicated.
NT 201 (IncobotulinumtoxinA, Xeomin)	NT 201	Main Period (1 treatment cycle): subjects to receive intramuscular injection of NT 201 (400 units) into muscles of the lower limb. Open Label Extension Period (4-5 treatment cycles): subjects to receive intramuscular injection of NT 201 (up to 800 units) into muscles of the lower limb and upper limb, if indicated.
Placebo	Placebo	Main Period (1 treatment cycle): subjects to receive intramuscular placebo injection into muscles of the lower limb. Open Label Extension Period (4-5 treatment cycles): subjects to receive intramuscular injection of NT 201 (up to 800 units) into muscles of the lower limb and upper limb, if indicated.

Primary Outcome Measures

Name	Time	Method
Change from baseline in derived Modified Ashworth Scale-Bohannon (MAS) ankle score (knee extended) at weeks 4 to 6	Baseline to week 4-6	The MAS is a 6-grade scale
Co-Primary: Global Impression of Change Scale (GICS) assessed by physician at Week 4 to 6	Week 4-6	The GICS s a 9-grade scale
Occurrence of treatment emergent adverse events [TEAEs] in the Main Period	Baseline to week 12

Secondary Outcome Measures

Name	Time	Method
Global Impression of Change Scale (GICS) assessed by the caregiver at Week 4 to 6	Week 4-6	The GICS s a 9-grade scale
Change from Study Baseline in Goal Attainment Scale [GAS] at Week 6	Baseline to week 6	The GAS is a 6-grade scale
Global Impression of Change Scale (GICS) assessed by the study subject at Week 4 to 6	Week 4-6	The GICS s a 9-grade scale

Trial Locations

Locations (71)

Physical Medicine and Rehabilitation at University of Alabama at Birmingham; Merz investigational site #0010479; 🇺🇸 Birmingham, Alabama, United States

University of Arkansas for Medical Sciences, Merz investigational site #0010481; 🇺🇸 Little Rock, Arkansas, United States

Rancho Research Institute at Rancho Los Amigos National Rehabilitation Center; Merz investigational site #0010184; 🇺🇸 Downey, California, United States

New England institute for clinical research; Merz Investigational Site #0010441; 🇺🇸 Stamford, Connecticut, United States

Nova Clinical Research, Merz investigational site #0010474; 🇺🇸 Brandenton, Florida, United States

Brooks Rehabilitation Clinical Integration and Research, Merz investigational site #0010483; 🇺🇸 Jacksonville, Florida, United States

Sarasota Memorial Health Care System, Rehabilitation Medicine, Merz investigational site #0010478; 🇺🇸 Sarasota, Florida, United States

Neurology Center of New England P.C., Merz investigative site #0010476; 🇺🇸 Foxborough, Massachusetts, United States

Howard A. Rusk Rehabilitation Center; Merz investigational site #0010283; 🇺🇸 Columbia, Missouri, United States

Icahn School of Medicine at Mount Sinai, Neurology Department, Merz Investigational Site #0010191; 🇺🇸 New York, New York, United States

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