A single patient trial with Ataluren in one case of severe common variable immunodeficiency with autoimmunity due to homozygous stop codon mutations of LRBA

2024-518919-19-00 Protocol LRBA01 Therapeutic exploratory (Phase II) Ended

Start 9 Jul 2021 · End 31 Jul 2025 · Status Ended · 1 EU/EEA countries · 1 sites · Protocol LRBA01

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)
Status Ended
Participants planned 1
Countries 1
Sites 1

LRBA deficiency due homozygous nonsense mutations. It is a rare genetic disorder of the immune system caused by mutation in LRBA gene. This disease results in excessive number of immune cells calls lymphocytes ,autoimmunity, low levels of antibodies and recurrent infections. Excess of lymphocytes caused a variety of symptoms, the infiltration is most commun in the gut, lungs, and brain. LRBA deficiency (called LATAIE disease) may increase a person's risk of lymphoma, a type of cancer.

a. Clinical efficacy of Ataluren in normalizing lymphoproliferative symptom of LRBA deficiency (including lymphoproliferation, chronic diarrhea and ascites) b. Clinical tolerability of Ataluren in the single LRBA deficient patient.

Key facts

Sponsor
Centre Hospitalier Universitaire De Liege
Participant type
Patients
Age range
18-64 years
Gender
Male
Therapeutic area
Diseases [C] - Immune System Diseases [C20]
Trial duration
9 Jul 2021 → 31 Jul 2025
Decision date (initial)
2024-11-04
Transition trial
Yes
Low-intervention
No
Rare-disease indication
Yes
Vulnerable population
No

External identifiers

EU CT number
2024-518919-19-00
EudraCT number
2021-003004-41

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

a. Clinical efficacy of Ataluren in normalizing lymphoproliferative symptom of LRBA deficiency (including lymphoproliferation, chronic diarrhea and ascites)
b. Clinical tolerability of Ataluren in the single LRBA deficient patient.

Secondary objectives 1

  1. Efficacy of Ataluren in vivo expression of LRBA and membrane expression of CTLA4. Efficacy of Ataluren on classical biomarkers of LRBA deficiency such percentage of follicular T helper cells and soluble CD25

Conditions and MedDRA coding

LRBA deficiency due homozygous nonsense mutations. It is a rare genetic disorder of the immune system caused by mutation in LRBA gene. This disease results in excessive number of immune cells calls lymphocytes ,autoimmunity, low levels of antibodies and recurrent infections. Excess of lymphocytes caused a variety of symptoms, the infiltration is most commun in the gut, lungs, and brain. LRBA deficiency (called LATAIE disease) may increase a person's risk of lymphoma, a type of cancer.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

  1. Single patient protocol: LRBA deficiency to homzygous nonsense mutations

Exclusion criteria 1

  1. Not applicable

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. In comparison with a pre treatment period of five years improvement of quality of life, weight, diarrhea episode and number of hospitalisations

Secondary endpoints 1

  1. Expression of LRBA by PBMC, normalisation of CTLA4 expression of CD4 T cells. Normalisation of soluble CD25 and follicular T helper cells

Investigational products

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

Test 2

Translarna 250 mg granules for oral suspension

PRD1622983 · Product

Active substance
Ataluren
Substance synonyms
PTC-124, 3-(5-(2-FLUOROPHENYL)-1,2,4-OXADIAZOL-3-YL)BENZOIC ACID
Pharmaceutical form
ORAL SUSPENSION
Route of administration
ORAL
Max daily dose
2 g gram(s)
Max total dose
2 g gram(s)
Max treatment duration
60 Month(s)
Authorisation status
Authorised
ATC code
M09AX03 — -
Marketing authorisation
EU/1/13/902/002
MA holder
PTC THERAPEUTICS INTERNATIONAL LIMITED
MA country
EU
Paediatric formulation
No
Orphan designation
Yes
Orphan designation number
EU/3/05/278
Modified vs. Marketing Authorisation
No

Translarna 1000 mg granules for oral suspension

PRD1622984 · Product

Active substance
Ataluren
Substance synonyms
PTC-124, 3-(5-(2-FLUOROPHENYL)-1,2,4-OXADIAZOL-3-YL)BENZOIC ACID
Pharmaceutical form
ORAL SUSPENSION
Route of administration
ORAL
Max daily dose
2 g gram(s)
Max total dose
2 g gram(s)
Max treatment duration
60 Month(s)
Authorisation status
Authorised
ATC code
M09AX03 — -
Marketing authorisation
EU/1/13/902/003
MA holder
PTC THERAPEUTICS INTERNATIONAL LIMITED
MA country
EU
Paediatric formulation
No
Orphan designation
Yes
Orphan designation number
EU/3/05/278
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Liege

Sponsor organisation
Centre Hospitalier Universitaire De Liege
Address
Avenue De L'hopital 1
City
Liege
Postcode
4000
Country
Belgium

Scientific contact point

Organisation
Centre Hospitalier Universitaire De Liege
Contact name
Michel Moutschen

Public contact point

Organisation
Centre Hospitalier Universitaire De Liege
Contact name
Michel Moutschen

Locations

1 EU/EEA country · 1 investigational sites

By country

CountryMS statusPlanned subjectsSites
Belgium Ended 1 1
Rest of world 0

Investigational sites

Belgium

1 site · Ended
Centre Hospitalier Universitaire De Liege
Infectious diseases, Avenue De L'hopital 1, 4000, Liege

Country notifications

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

Country Trial startTrial end Recruitment startRecruitment end Early termination
Belgium 2021-07-09 2021-07-28

Results and documents

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

Documents 5 files

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

TypeTitleVersion
Protocol (for publication) D1_Protocol_2024-518919-19-00 2
Recruitment arrangements (for publication) K1_recruitment arrangement 1
Subject information and informed consent form (for publication) L1_ICF 2
Summary of Product Characteristics (SmPC) (for publication) Blank document 1
Summary of Product Characteristics (SmPC) (for publication) Blank document 1

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-10-15 Belgium Acceptable
2024-11-04
2024-11-04