Prospective, open-label, non-randomized, single-arm, dose titration study to investigate the efficacy and safety of IncobotulinumtoxinA in children deemed to require a total body dose up to 22U/kg (maximum dose 550U) during the study period for the treatment of upper and lower limb spasticity due to cerebral palsy

2024-518447-38-00 Protocol INCIPIT Therapeutic exploratory (Phase II) Ongoing, recruiting

Start 10 Feb 2023 · Status Ongoing, recruiting · 1 EU/EEA countries · 1 sites · Protocol INCIPIT

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)
Status Ongoing, recruiting
Participants planned 30
Countries 1
Sites 1

multifocal spasticity of the upper and lower limb due to cerebral palsy

to investigate the efficacy of IncobotulinumtoxinA in the treatment of both BoNT-A naïve and pretreated children for upper and lower limb spasticity using a dose titration approach over three injection cycles, with a flexible observation period after injection of 12 to 20 weeks and a total duration of exposure up to 60…

Key facts

Sponsor
Azienda Ospedaliera Universitaria Integrata Verona
Participant type
Pediatric, Patients
Age range
0-17 years
Gender
Male and Female
Therapeutic area
Diseases [C] - Nervous System Diseases [C10]
Trial duration
10 Feb 2023 → ongoing
Decision date (initial)
2024-10-29
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
Yes
Funding sources
Merz Pharma Italia

External identifiers

EU CT number
2024-518447-38-00
EudraCT number
2019-003559-12

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

to investigate the efficacy of IncobotulinumtoxinA in the treatment of both BoNT-A naïve and pretreated children for upper and lower limb spasticity using a dose titration approach over three injection cycles, with a flexible observation period after injection of 12 to 20 weeks and a total duration of exposure up to 60 weeks

Secondary objectives 1

  1. to investigate the safety of IncobotulinumtoxinA in the treatment of both BoNT-A naïve and pretreated children for upper and lower limb spasticity using a dose titration approach over three injection cycles, with a flexible observation period after injection of 12 to 20 weeks and a total duration of exposure up to 60 weeks

Conditions and MedDRA coding

multifocal spasticity of the upper and lower limb due to cerebral palsy

VersionLevelCodeTermSystem organ class
20.0 PT 10028335 Muscle spasticity 100000004852

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

  1. Children (female or male) aged 2 to 17 years
  2. Patients with upper and lower limb spasticity due to cerebral palsy
  3. Gross Motor Function Classification System (GMFCS) from Level II to Level V
  4. Selected target clinical pattern diagnosed by a qualified health care professional
  5. Focal spasticity scored at least 2 points on the Ashworth scale (AS) in the joints associate with the selected target clinical pattern
  6. Patient deemed by the investigator to require a total body dose up to 22U/kg (maximum 550U) during the study period
  7. In the case of children pretreated with BoNT-A, time from last injection at least 5 months
  8. Informed consent signed by parents or legal guardian

Exclusion criteria 8

  1. Participation in other trials
  2. BoNT-A treatment contraindicated
  3. Therapy with anticoagulants or other substances that could have an anticoagulant effect
  4. Girls of childbearing potential (defined as females post menarche)
  5. Presence of fixed contractures, or bony deformities of the affected limbs
  6. Previous treatment of spastic muscles with nerve phenolization
  7. Other neurological or orthopedic conditions involving the affected limbs
  8. institutionalized patients

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Changes in Ashworth scale values between the injection cycle baseline visits and the control ones of respective injection cycle (single interventional effect)

Secondary endpoints 10

  1. Efficacy endpoint: Scala di Ashworth
  2. REsistance to PAssive movement Scale (REPAS)
  3. The GMFCS
  4. The visual analog scale (VAS)
  5. The Goal Attainment scale (GAS)
  6. The Global Assessment of Efficacy
  7. Safety endpoints: Values of blood pressure, heart rate, and respiratory rate
  8. Values of Body Weight
  9. adverse events
  10. The Global Assessment of Tolerability

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

XEOMIN, 100 unità, polvere per soluzione iniettabile

PRD1975292 · Product

Active substance
Clostridium Botulinum Neurotoxin Type a (150KD), Free of Complexing Proteins
Substance synonyms
IncobotulinumtoxinA, NT 201, Botulinum toxin type A (150 kD), free from complexing proteins
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INTRAMUSCULAR USE
Max daily dose
550 U unit(s)
Max total dose
550 U unit(s)
Max treatment duration
40 Week(s)
Authorisation status
Authorised
ATC code
M03AX01 — BOTULINUM TOXIN
Marketing authorisation
038232017
MA holder
MERZ PHARMACEUTICALS GMBH
MA country
Italy
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Azienda Ospedaliera Universitaria Integrata Verona

8 Total trials 6 Recruiting
Academic / Non-commercial
Sponsor organisation
Azienda Ospedaliera Universitaria Integrata Verona
Address
Piazzale Ludovico Antonio Scuro 10
City
Verona
Postcode
37134
Country
Italy

Scientific contact point

Organisation
Azienda Ospedaliera Universitaria Integrata Verona
Contact name
Nicola Smania

Public contact point

Organisation
Azienda Ospedaliera Universitaria Integrata Verona
Contact name
Nicola Smania

Locations

1 EU/EEA country · 1 investigational sites

By country

CountryMS statusPlanned subjectsSites
Italy Ongoing, recruiting 30 1
Rest of world 0

Investigational sites

Italy

1 site · Ongoing, recruiting
Azienda Ospedaliera Universitaria Integrata Verona
UOC Neuroriabilitazione, Piazzale Ludovico Antonio Scuro 10, 37134, Verona

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Italy 2023-02-10 2023-02-10

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_Protocollo_2019-003559-12_INCIPIT_v4_p 4
Recruitment arrangements (for publication) BLANK DOCUMENT_new CTR 1
Subject information and informed consent form (for publication) L1_Letter for GP_v2_p 2
Subject information and informed consent form (for publication) L1_SIS and ICF minor_v1_p 1
Subject information and informed consent form (for publication) L1_SIS and ICF parents_v2_p 2
Subject information and informed consent form (for publication) L1_SIS and ICF privacy_v2_p 2
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC Xeomin 1
Synopsis of the protocol (for publication) BLANK DOCUMENT_RA or EC under CTD 1

Application history

1 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-10-02 Italy Acceptable
2024-10-24
2024-10-29