New Biomarkers for Diagnosis and Follow-up of Patients With LRBA or CTLA4 Deficiencies

NCT04377867 | Unknown

• 1 other identifier: 09.2018.624
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Primary immune deficiencies (PID) are a group of chronic diseases characterized by recurrent infections. Apart from recurrent infections, in some of PIDs autoimmunity, allergy or malignancy could be accompanied to the diseases. Recently, the advanced sequencing technologies have led to the identification of a growing number of novel PIDs including the immune dysregulation syndromes caused by loss of function mutations in the LRBA (encoding lipopolysaccharide-responsive beige like anchor protein) and CTLA4 (encoding cytotoxic T lymphocyte antigen 4) genes, which are in common associated with autoimmunity in addition to a predisposition to recurrent infections. PIDs with autoimmune components usually tend to have a more protracted clinical course and poorer prognosis rendering early diagnosis and treatment more crucial. The accurate diagnosis largely relies on the molecular diagnosis due to the significant overlaps between the phenotypic expression of these various genetic defects. The project aims to provide better and early diagnosis for LRBA, CTLA4 deficiencies by using basic and advanced immunological, genetic and molecular assays and rendering an early targeting therapy for patients, discover disease related new pathways and biomarkers that can be helpful during diagnosis and monitoring abatacept targeted therapy responses.

Conditions

LRBA Deficiency; CTLA4 Haploinsufficiency

Outcome Measures

Primary Outcomes (2)

• Clinical Efficacy of abatacept in normalizing symptoms of disease

  The symptoms including lymphoproliferation, autoimmunity and chronic diarrhea should be controlled.

  3-9 months

• Clinical tolerability of abatacept in patients

  Drug related side effects should not be observed (Severe viral or bacterial infections)

  1-24 months

Secondary Outcomes (1)

• Discontinuation of other immunosuppressants

  3-12 months

Study Arms (3)

LRBA deficient patients on abatacept

These patients will prospectively followed and biological samples collected at baseline as well as periodically every 3 months under therapy. Abatacept will be provided on an off-label basis upon approval of the physician's request of the drug by Turkish Medicines and Medical Devices Agency (TMMDA) of Turkish Ministry of Health. The dosage and interval of the drug is determined according to drug instructions provided by the drug company based on the weight of the patients.

Drug: Abatacept Injection [Orencia]

CTLA4 haploinsufficient patients on abatacept

These patients will prospectively followed and biological samples collected at baseline as well as periodically every 3 months under therapy. Abatacept will be provided on an off-label basis upon approval of the physician's request of the drug by Turkish Medicines and Medical Devices Agency (TMMDA) of Turkish Ministry of Health. The dosage and interval of the drug is determined according to drug instructions provided by the drug company based on the weight of the patients.

Drug: Abatacept Injection [Orencia]

Control group

Age matched healthy control group will be used during the study to determine the reference values of the immunological assays.

Interventions

Abatacept Injection [Orencia] DRUG

Patients on abatacept to control disease symptoms

CTLA4 haploinsufficient patients on abatacept; LRBA deficient patients on abatacept

Eligibility Criteria

• Age: 1 Year - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Primary immune deficiencies characterized by immunodyregulatory diseases (LRBA and CTLA4 deficiencies). Age matched healthy individuals.

You may qualify if:

• Patients diagnosed with LRBA and CTLA4 deficiencies and eligible for the study
• Patients accept consent to participate in this study and followed prospectively on abatacept treatment.

You may not qualify if:

• History of hypersensitivity to abatacept
• History of acquired immunodeficiency diseases like HIV
• EBV viremia during the study screening
• Documented malignancy
• Current active infectious disease (bacterial or fungal) like tuberculosis
• Chronic hepatitis B or hepatitis C infections

Sponsors & Collaborators

• Marmara University: lead
• The Scientific and Technological Research Council of Turkey: collaborator

Study Sites (1)

Marmara University

Istanbul, Pendik, 34903, Turkey (Türkiye)

RECRUITING

Related Publications (4)

• Kiykim A, Ogulur I, Dursun E, Charbonnier LM, Nain E, Cekic S, Dogruel D, Karaca NE, Cogurlu MT, Bilir OA, Cansever M, Kapakli H, Baser D, Kasap N, Kutlug S, Altintas DU, Al-Shaibi A, Agrebi N, Kara M, Guven A, Somer A, Aydogmus C, Ayaz NA, Metin A, Aydogan M, Uncuoglu A, Patiroglu T, Yildiran A, Guner SN, Keles S, Reisli I, Aksu G, Kutukculer N, Kilic SS, Yilmaz M, Karakoc-Aydiner E, Lo B, Ozen A, Chatila TA, Baris S. Abatacept as a Long-Term Targeted Therapy for LRBA Deficiency. J Allergy Clin Immunol Pract. 2019 Nov-Dec;7(8):2790-2800.e15. doi: 10.1016/j.jaip.2019.06.011. Epub 2019 Jun 22.

  PMID: 31238161 BACKGROUND

• Alroqi FJ, Charbonnier LM, Baris S, Kiykim A, Chou J, Platt CD, Algassim A, Keles S, Al Saud BK, Alkuraya FS, Jordan M, Geha RS, Chatila TA. Exaggerated follicular helper T-cell responses in patients with LRBA deficiency caused by failure of CTLA4-mediated regulation. J Allergy Clin Immunol. 2018 Mar;141(3):1050-1059.e10. doi: 10.1016/j.jaci.2017.05.022. Epub 2017 Jun 7.

  PMID: 28601686 BACKGROUND

• Tesch VK, Abolhassani H, Shadur B, Zobel J, Mareika Y, Sharapova S, Karakoc-Aydiner E, Riviere JG, Garcia-Prat M, Moes N, Haerynck F, Gonzales-Granado LI, Santos Perez JL, Mukhina A, Shcherbina A, Aghamohammadi A, Hammarstrom L, Dogu F, Haskologlu S, Ikinciogullari AI, Kostel Bal S, Baris S, Kilic SS, Karaca NE, Kutukculer N, Girschick H, Kolios A, Keles S, Uygun V, Stepensky P, Worth A, van Montfrans JM, Peters AMJ, Meyts I, Adeli M, Marzollo A, Padem N, Khojah AM, Chavoshzadeh Z, Avbelj Stefanija M, Bakhtiar S, Florkin B, Meeths M, Gamez L, Grimbacher B, Seppanen MRJ, Lankester A, Gennery AR, Seidel MG; Inborn Errors, Clinical, and Registry Working Parties of the European Society for Blood and Marrow Transplantation and the European Society for Immunodeficiencies. Long-term outcome of LRBA deficiency in 76 patients after various treatment modalities as evaluated by the immune deficiency and dysregulation activity (IDDA) score. J Allergy Clin Immunol. 2020 May;145(5):1452-1463. doi: 10.1016/j.jaci.2019.12.896. Epub 2019 Dec 27.

  PMID: 31887391 BACKGROUND

• Baris S, Alroqi F, Kiykim A, Karakoc-Aydiner E, Ogulur I, Ozen A, Charbonnier LM, Bakir M, Boztug K, Chatila TA, Barlan IB. Severe Early-Onset Combined Immunodeficiency due to Heterozygous Gain-of-Function Mutations in STAT1. J Clin Immunol. 2016 Oct;36(7):641-8. doi: 10.1007/s10875-016-0312-3. Epub 2016 Jul 5.

  PMID: 27379765 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral blood mononuclear cells, Serum, Plasma, Stool

MeSH Terms

Conditions

Diabetes Mellitus, Insulin-Dependent, 12

Interventions

Abatacept

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Study Officials

• Safa Baris, M.D.

  Marmara University

  STUDY DIRECTOR

Central Study Contacts

Safa Baris, M.D.

CONTACT

+905052614986; safabaris@hotmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2020
• First Posted: May 6, 2020
• Study Start: January 15, 2020
• Primary Completion: July 15, 2022
• Study Completion: January 15, 2023
• Last Updated: May 8, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)