Effectiveness of ambroxol in children and adults with Gaucher disease 3: n-of-1 series

2024-514012-28-00 Protocol NL76160.018.21 Therapeutic confirmatory (Phase III) Ongoing, recruiting

Start 25 Nov 2024 · Status Ongoing, recruiting · 1 EU/EEA countries · 1 sites · Protocol NL76160.018.21

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Ongoing, recruiting
Participants planned 4
Countries 1
Sites 1

Gaucher disease type 3

Effect of ambroxol on cerebrospinal fluid (CSF) Lyso-GL1 in GD3 patients receiving ambroxol.

Key facts

Sponsor
Amsterdam UMC Stichting
Participant type
Pediatric, Patients
Age range
0-17 years, 18-64 years
Gender
Male and Female
Therapeutic area
Diseases [C] - Nutritional and Metabolic Diseases [C18]
Trial duration
25 Nov 2024 → ongoing
Decision date (initial)
2024-11-25
Transition trial
Yes
Low-intervention
No
Rare-disease indication
Yes
Vulnerable population
Yes
Funding sources
MetaKids · Vriendenloterij

External identifiers

EU CT number
2024-514012-28-00
EudraCT number
2021-002550-82

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

Effect of ambroxol on cerebrospinal fluid (CSF) Lyso-GL1 in GD3 patients receiving ambroxol.

Secondary objectives 9

  1. Effect of ambroxol on plasma Lyso-GL1, GL-1, chitotriosidase and Lyso-GM3 in GD3 patients receiving ambroxol
  2. Effect of ambroxol on CSF GL-1 and Lyso-GM3 in GD3 patients receiving ambroxol
  3. Effect of ambroxol on GCase activity in leukocytes from GD3 patients receiving ambroxol
  4. Effect of ambroxol on functional/developmental outcomes using the Goal Attainment Scaling (GAS) in GD3 patients
  5. Effect of ambroxol on quality of life using the Pediatric Quality of Life Inventory (PedsQL) in GD3 patients
  6. Effect of ambroxol on ataxia using the Scale for the Assessment and Rating of Ataxia (SARA) in GD3 patients
  7. Effect of ambroxol on neuropsychological outcomes using the Attention Network Task (ANT) and/or Wechsler scale in GD3 patients
  8. Effect of ambroxol on behaviour using the Strengths and Difficulties Questionnaire (SDQ) and Strengths and Weaknesses of ADHD symptoms and Normal behaviour scale (SWAN) in GD3 patients
  9. If epilepsy: effect of ambroxol on seizure control using the Unified Myoclonus Rating Scale (UMRS) and a seizure log book in GD3 patients

Conditions and MedDRA coding

Gaucher disease type 3

VersionLevelCodeTermSystem organ class
20.0 HLGT 10027424 Metabolic and nutritional disorders congenital 10010331

Study design 1 period

#TitleAllocationBlindingRoles blindedArms
1 Treatment phase
Ambroxol HCL vs Placebo
 Randomised Controlled Double [{"id":93763,"code":5,"name":"Carer"},{"id":93764,"code":2,"name":"Investigator"},{"id":93762,"code":1,"name":"Subject"}] Arm 1: Ambroxol HCl
Arm 2: Placebo

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

  1. The patient or the parent(s) / legal guardian(s) must provide written informed consent before start of the study
  2. Male and female patients with documented deficiency of GCase activity and GBA genotype fitting GD3
  3. Male and female patients of all ages
  4. Able to travel to the study site
  5. Patients receive ERT with treatment ongoing at the time of enrollment

Exclusion criteria 8

  1. The patient is transfusion dependent
  2. The patient has received an investigational product within 30 days prior to enrollment
  3. Known hypersensitivity reactions, intolerance or adverse reactions to ambroxol or to the inactive ingredients
  4. Pregnancy, because there are no sufficient data for the use of ambroxol in pregnant women (see Summary of Product Characteristics (SPC))
  5. The patient is lactating. Ambroxol crosses into the breast milk. As there is no adequate experience in humans to date, ambroxol should not be used in lactation in a study setting (see SPC)
  6. The patient is unwilling or, in the investigator's opinion, unable to adhere to the requirements of the study
  7. The patient is unable to swallow powder and has no other enteral access (e.g. gastrostomy)
  8. Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patients

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Change in cerebrospinal fluid (CSF) Lyso-GL1, from GD3 patients receiving ambroxol

Secondary endpoints 8

  1. Change in plasma Lyso-GL1, GL-1, chitotriosidase and Lyso-GM3, from GD3 patients receiving ambroxol
  2. Change in CSF GL-1 and Lyso-GM3, from GD3 patients receiving ambroxol
  3. Change in GCase activity in leukocytes, from GD3 patients receiving ambroxol
  4. Effect of ambroxol on functional/developmental outcomes using the Goal Attainment Scaling (GAS) in GD3 patients
  5. Effect of ambroxol on quality of life using the Pediatric Quality of Life Inventory (PedsQL) in GD3 patients
  6. Effect of ambroxol on ataxia using the Scale for the Assessment and Rating of Ataxia (SARA) in GD3 patients
  7. Effect of ambroxol on neuropsychological outcomes using the Attention Network Task (ANT) and/or Wechsler scale in GD3 patients
  8. If epilepsy: effect of ambroxol on seizure control using the Unified Myoclonus Rating Scale (UMRS) and a seizure log book in GD3 patients

Investigational products

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

Test 1

Ambroxol Hydrochloride

SCP101864681 · ATC

Active substance
Ambroxol Hydrochloride
Substance synonyms
TRANS-4-[(2-AMINO-3,5-DIBROMOBENZYL) AMINO] CYCLOHEXANOL HYDROCHLORIDE
Route of administration
ORAL
Max daily dose
1300 mg milligram(s)
Max total dose
949 Kg kilogram(s)
Max treatment duration
24 Month(s)
Authorisation status
Authorised
ATC code
R05CB06 — AMBROXOL
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
Yes
Modification description
Ambroxol HCL drug substance had strong cohesive and poor flow properties, making the compounding of capsules from the drug substance less easy. By adding ca. 1% silica colloidal anhydrous as lubricant these properties improved slightly. An additional approximate 1:1 ratio of lactose monohydrate to ambroxol HCl made the powder mixture suitable for compounding into capsules.

Placebo 1

lactose monohydrate

N/A · Product

Other product name
N/A
Pharmaceutical form
N/A
ATC code
N/A — N/A
Marketing authorisation
N/A
MA holder
N/A
MA country
Iceland
Paediatric formulation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amsterdam UMC Stichting

75 Total trials 44 Recruiting 14 Ended
Academic / Non-commercial
Sponsor organisation
Amsterdam UMC Stichting
Address
De Boelelaan 1117
City
Amsterdam
Postcode
1081 HV
Country
Netherlands

Scientific contact point

Organisation
Amsterdam UMC Stichting
Contact name
Marion Brands

Public contact point

Organisation
Amsterdam UMC Stichting
Contact name
Marion Brands

Locations

1 EU/EEA country · 1 investigational sites

By country

CountryMS statusPlanned subjectsSites
Netherlands Ongoing, recruiting 4 1
Rest of world — 0 —

Investigational sites

Netherlands

1 site · Ongoing, recruiting
Amsterdam UMC Stichting
Kindergeneeskunde, De Boelelaan 1117, 1081 HV, Amsterdam

Country notifications

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

Country Trial startTrial end Recruitment startRecruitment end Early termination
Netherlands 2024-11-25 2024-11-25

Results and documents

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

Documents 16 files

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

TypeTitleVersion
Protocol (for publication) D1_Protocol 2024-514012-28-00 5
Protocol (for publication) D4_Patient facing documents epilepsy dairy adult 1
Protocol (for publication) D4_Patient facing documents epilepsy dairy children 1
Protocol (for publication) D4_Patient facing documents epilepsy dairy parents 1
Protocol (for publication) D4_Patient facing documents medication dairy 1
Protocol (for publication) D4_Patient facing documents patient card 1
Protocol (for publication) D4_Patient facing documents questionnaire GAS 1
Protocol (for publication) D4_Patient facing documents questionnaire PedsQL 1
Protocol (for publication) D4_Patient facing documents questionnaire SDQ 17+ jaar 2
Protocol (for publication) D4_Patient facing documents questionnaire SDQ 2-4 jaar 2
Protocol (for publication) D4_Patient facing documents questionnaire SDQ 4-17 jaar 2
Protocol (for publication) D4_Patient facing documents questionnaire SWAN 1
Recruitment arrangements (for publication) K1_Recruitment arrangements 1
Subject information and informed consent form (for publication) L1_SIS and ICF 12-16 yrs 4
Subject information and informed consent form (for publication) L1_SIS and ICF adults 4
Subject information and informed consent form (for publication) L1_SIS and ICF parents 4

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-10-15 Netherlands Acceptable
2024-11-25
 2024-11-25

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