Long-term Open-label Study of Botulinumtoxin Type A to Treat Spasticity of Leg(s) or Leg(s) and Arm in Cerebral Palsy

NCT ID: NCT01905683

Last Updated: 2017-10-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 370 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31
• Study Completion Date: 2017-01-31

Brief Summary

The purpose of this study is to determine whether injections of Botulinum toxin type A into muscles of the leg(s) or of leg(s) and one arm are safe in treating children/adolescents (age 2-17 years) long-term with increased muscle tension/uncontrollable muscle stiffness (spasticity) due to cerebral palsy.

Conditions

Lower Limb and Combined Lower Limb and Upper Limb Spasticity Due to Cerebral Palsy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

16-20 Units per kg body weight incobotulinumtoxinA

Group Type: EXPERIMENTAL

IncobotulinumtoxinA (16-20 Units per kg body weight)

Intervention Type: DRUG

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); Total dose per injection cycle: up to 500 units; Mode of administration: intramuscular injection into spastic muscles.

Interventions

IncobotulinumtoxinA (16-20 Units per kg body weight)

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); Total dose per injection cycle: up to 500 units; Mode of administration: intramuscular injection into spastic muscles.

Intervention Type: DRUG

Other Intervention Names

Xeomin; NT 201; Botulinum toxin type A (150 kiloDalton), free from complexing proteins

Eligibility Criteria

Inclusion Criteria

• Subject with lower limb [LL] spasticity who completed lead-in study MRZ60201_3070_1 in any of the three dose groups with duration of both injection cycles between 12 and 16 weeks.
• Ashworth scale [AS] score ≥2 in plantar flexors (at least unilaterally). For subjects with an AS score of 1, the investigator has to decide on the clinical need for reinjection.
• Clinical need for spasticity treatment with NT 201 according to the clinical judgment of the investigator for:

Unilateral treatment of LL spasticity with 8 U/kg BW NT 201 (maximum of 200 U) into pes equinus and need for additional 8 U/kg BW NT 201 (maximum of 200 U) for treatment of clinical pattern flexed knee or adducted thigh (ipsilateral) or bilateral treatment of LL spasticity with 8 U/kg BW NT 201 (maximum of 200 U) into pes equinus on each side.

No treatment of other clinical patterns is allowed.

• Female or male subject of 2 to 17 years age (inclusive).
• Uni- or bilateral CP with clinical need for BoNT injection to treat limb spasticity.
• AS score ≥ 2 in plantar flexors (at least unilaterally).
• Clinical need according to the clinical judgment of the investigator in one out of four treatment combinations:

1. For LL(s) treatment only (Gross Motor Function Classification System [GMFCS] levels IV): Unilateral treatment of LL spasticity with 8 U/kg BW NT 201 (maximum of 200 U) into pes equinus, and 8 U/kg BW NT 201 (maximum of 200 U) into flexed knee or adducted thigh or bilateral treatment of LL spasticity with 8 U/kg BW NT 201 (maximum of 200 U) into each pes equinus (AS score ≥ 2 on both sides).

2. For combined unilateral UL and unilateral LL, (GMFCS levels I-III): Unilateral treatment of LL spasticity with 8 U/kg BW NT 201 (maximum of 200 U) into pes equinus, and 8 U/kg BW NT 201 (maximum of 200 U) into flexed knee or adducted thigh plus Unilateral treatment of UL spasticity with 4 U/kg BW NT 201 (maximum of 100 U) into flexed elbow, flexed wrist, clenched fist, thumb in palm and/or pronated forearm.

3. For combined unilateral UL and unilateral LL (GMFCS level IV-V): Unilateral treatment of LL spasticity with 8 U/kg BW NT 201 (maximum 200 U) into pes equinus, and 4 U/kg BW NT201 (maximum 100 U) into flexed knee or adducted thigh plus unilateral treatment of UL spasticity with 4 U/kg BW NT 201 (maximum of 100 U) into flexed elbow, flexed wrist, clenched fist, thumb in palm and/or pronated forearm.

4. For combined unilateral UL and bilateral LL (GMFCS levels I-III): Bilateral treatment of LL spasticity with 8 U/kg BW NT 201 (maximum of 200 U) into each pes equinus (AS score ≥ 2 on both sides) plus unilateral treatment of UL spasticity with 4 U/kg BW NT 201 (maximum of 100 U) into flexed elbow, flexed wrist, clenched fist, thumb in palm and/or pronated forearm.

Exclusion Criteria

• Infection and/or inflammation in the area of the planned injection points.
• Pregnancy for female with history of menarche.
• Clinically relevant pathological findings indicating active disease of vital organs.

• Fixed contracture defined as severe restriction of the range of joint movement on passive stretch in the target clinical pattern(s) or predominant forms of muscle hypertonia other than spasticity (e.g., dystonia) in the target limb(s).
• Surgery in the pes equinus on side(s) intended to treat with BoNT injections within 12 months prior to Screening Visit (V1), within the screening period or planned for the time of participation in this study.
• Hip flexion requiring BoNT injection.
• Limitation of hip abduction to less than 40° or pre-diagnosed migrational percentage greater than 30.
• Vaccination within 2 weeks prior to Screening Visit (V1) and/or within the screening period.
• Non-resolved fractures of the treated limb.
• Ventilator dependency.
• Severe neurological diagnosis and comorbidity outside the spectrum of cerebral palsy.
• Pure dyskinetic CP or mixed CP with predominantly dyskinetic movements.
• Treatment with BoNT (other than study drug in this study) for any body region within 14 weeks prior to Screening Visit (V1), within the screening period and/or intended to be administered during the study period.
• Treatment with phenol or alcohol of any muscle within 6 months prior to Screening Visit (V1), within the screening period, and/or intended to be administered during the study period.
• Treatment with

• drugs acting as peripheral muscle relaxants
• intrathecal baclofen, or
• oral anticoagulants administered within 2 weeks prior to Screening Visit (V1), within the screening period, and/or intended to be administered during the study period.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merz Pharmaceuticals GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Merz Medical Expert

Role: STUDY_DIRECTOR

Merz Pharmaceuticals GmbH

Locations

Merz Investigational Site #043036

Vienna, , Austria

Merz Investigational Site #420029

Brno, , Czechia

Merz Investigational Site #420028

Olomouc, , Czechia

Merz Investigational Site #372001

Tallinn, , Estonia

Merz Investigational Site #372002

Tartu, , Estonia

Merz Investigational Site #049328

Bochum, , Germany

Merz Investigational Site #049327

Munich, , Germany

Merz Investigational Site #049329

Münster, , Germany

Merz Investigational Site #049326

Vogtareuth, , Germany

Merz Investigational Site #972003

Jerusalem, , Israel

Merz Investigational Site #972001

Tel Aviv, , Israel

Merz Investigational Site #972002

Tel Aviv, , Israel

Merz Investigational Site #048089

Bialystok, , Poland

Merz Investigational Site #048063

Gdansk, , Poland

Merz Investigational Site #048059

Krakow, , Poland

Merz Investigational Site #048084

Lublin, , Poland

Merz Investigational Site #048072

Luboń, , Poland

Merz Investigational Site #048075

Sandomierz, , Poland

Merz Investigational Site #048061

Warsaw, , Poland

Merz Investigational Site #040003

Bucharest, , Romania

Merz Investigational Site #040001

Bucharest, , Romania

Merz Investigational Site #040002

Iași, , Romania

Merz Investigational Site #007014

Kazan', , Russia

Merz Investigational Site #007015

Khabarovsk, , Russia

Merz Investigational Site #007018

Novosibirsk, , Russia

Merz Investigational Site #007017

Saint Petersburg, , Russia

Merz Investigational Site #007013

Smolensk, , Russia

Merz Investigational Site #007019

Stavropol, , Russia

Merz Investigational Site #421003

Banská Bystrica, , Slovakia

Merz Investigational Site #421008

Bratislava, , Slovakia

Merz Investigational Site #421006

Krompachy, , Slovakia

Merz Investigational Site #421004

Levoča, , Slovakia

Merz Investigational Site #082019

Goyang, , South Korea

Merz Investigational Site #082021

Incheon, , South Korea

Merz Investigational Site #082018

Seongnam-si, , South Korea

Merz Investigational Site #082020

Seoul, , South Korea

Merz Investigational Site #090005

Elâzığ, , Turkey (Türkiye)

Merz Investigational Site #090003

Izmir, , Turkey (Türkiye)

Merz Investigational Site #090002

İzmit, , Turkey (Türkiye)

Merz Investigational Site #380001

Dnipropetrovsk, , Ukraine

Merz Investigational Site #380005

Kharkiv, , Ukraine

Merz Investigational Site #380002

Kiev, , Ukraine

Merz Investigational Site #380003

Odesa, , Ukraine

Countries

Austria; Czechia; Estonia; Germany; Israel; Poland; Romania; Russia; Slovakia; South Korea; Turkey (Türkiye); Ukraine

References

Berweck S, Banach M, Gaebler-Spira D, Chambers HG, Schroeder AS, Geister TL, Althaus M, Hanschmann A, Vacchelli M, Bonfert MV, Heinen F, Dabrowski E. Safety Profile and Lack of Immunogenicity of IncobotulinumtoxinA in Pediatric Spasticity and Sialorrhea: A Pooled Analysis. Toxins (Basel). 2022 Aug 25;14(9):585. doi: 10.3390/toxins14090585.

Reference Type: DERIVED

PMID: 36136523 (View on PubMed)

Other Identifiers

2012-005055-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MRZ60201_3071_1

Identifier Type: -

Identifier Source: org_study_id