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

Purpose

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.

Condition

  • Lower Limb or Combined Lower Limb and Upper Limb Spasticity Due to Stroke or Traumatic Brain Injury

Eligibility

Eligible Ages
Between 18 Years and 85 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
NT 201 (IncobotulinumtoxinA, Xeomin) 		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.
  • Drug: NT 201
    Active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).
    Other names:
    • IncobotulinumtoxinA
    • Incobotulinumtoxin A
    • Xeomin
    • Botulinum toxin type A (150 kiloDalton), free from complexing proteins
Placebo Comparator
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.
  • Drug: NT 201
    Active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).
    Other names:
    • IncobotulinumtoxinA
    • Incobotulinumtoxin A
    • Xeomin
    • Botulinum toxin type A (150 kiloDalton), free from complexing proteins
  • Drug: Placebo
    Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).

Recruiting Locations

Physical Medicine and Rehabilitation at University of Alabama at Birmingham; Merz investigational site #0010479
Birmingham, Alabama 35233

University of Arkansas for Medical Sciences, Merz investigational site #0010481
Little Rock, Arkansas 72205

Rancho Research Institute at Rancho Los Amigos National Rehabilitation Center; Merz investigational site #0010184
Downey, California 90242

New England institute for clinical research; Merz Investigational Site #0010441
Stamford, Connecticut 06905

Nova Clinical Research, Merz investigational site #0010474
Brandenton, Florida 34209

Sarasota Memorial Health Care System, Rehabilitation Medicine, Merz investigational site #0010478
Sarasota, Florida 34239

Neurology Center of New England P.C., Merz investigative site #0010476
Foxborough, Massachusetts 02035

Howard A. Rusk Rehabilitation Center; Merz investigational site #0010283
Columbia, Missouri 65203

Weill Cornell Medical Center, Department of Rehabilitation Medicine; Merz Investigational Site #0010440
New York, New York 10065

University of Pittsburgh Medical Center, Physical Medicine & Rehabiliation, Merz Investigational Site #0010211
Pittsburgh, Pennsylvania 15213

UT Southwestern Medical Center, Department of Physical Medicine & Rehabilitation, Merz investigational site #0010082
Dallas, Texas 75390-9055

University of Texas Health Science Center McGovern, Medical School Department of PM&R; merz investigational site #0010183
Houston, Texas 77030

Medical College of Wisconsin,Department of PM&R, Merz Investigational Site #0010237
Milwaukee, Wisconsin 53226

More Details

NCT ID
NCT03992404
Status
Recruiting
Sponsor
Merz Pharmaceuticals GmbH

Study Contact

Public Disclosure Manager
+49 69 1503 0
clinicaltrials@merz.de