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

• NT 201 (Drug), also known as IncobotulinumtoxinA, Incobotulinumtoxin A, Xeomin, Botulinum toxin type A (150 kiloDalton), free from complexing proteins: 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).
• Placebo (Drug): Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).

Primary outcomes

• 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 outcomes

• 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
• 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

Sex: All, ages: 18 Years to 85 Years

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

• Merz Medical Expert, Study director, Merz Pharmaceuticals GmbH

NIH grants: 2018