Primary objective:- To identify the immunological signature specific of patients who are treated with BP and develop ADA compared to those who do not develop ADA, patients who are BP naive and healthy donors. Secondary objective:- To identify…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint: activation, maturation and differentiation of biological
specific lymphocytes.ten
Secondary outcome
Secondary parameters/outcomes:
- Ex-vivo evaluation of early biomarkers as potential predictors of
immunogenicity
- Evaluation of AD T cell response
- T- and B-cell AD responses: clonality analysis and epitope mapping
- Evaluation of B cell AD cellular response
- Genetic susceptibility of ADA
Different variables will be evaluated; these techniques are still partly under
construction. It involves serological, cellular, immunological and genetic
markers.
Background summary
The number of biological/biotechnology-derived proteins used as therapeutic
agents (called Biopharmaceuticals) is steadily increasing. Biopharmaceuticals
(BP) may induce an unwanted immune response in treated patients. Immunogenicity
related to Biopharmaceuticals (BP) therapy refers to a specific anti-drug
antibody (ADA) response. Such immunogenicity may represent a major factor
impairing the efficacy of BP due to BP neutralization and also to
hypersensitivity reactions that are IgE or non-IgE-mediated. Production of ADA
represents the final stage of a complex immune process involving antigen
presentation followed by activation of both adaptive and regulatory cellular
immune responses. The prediction, prevention and cure of anti-drug (AD)
immunization are major goals in BP development. Therefore, in order to minimize
the risk of ADA induction and improve sustainable BP efficacy, ABIRISK project
is focusing its efforts on understanding mechanisms by which BP drive immune
cell activation and ADA production.
Many factors (patient-, disease- or product-related) may influence the
potential risk of BP immunogenicity. Therefore, the immunogenic potential of
BPs can only be definitively assessed in human studies.
Study objective
Primary objective:
- To identify the immunological signature specific of patients who are treated
with BP and develop ADA compared to those who do not develop ADA, patients who
are BP naive and healthy donors.
Secondary objective:
- To identify molecular, cellular and genetic biomarkers associated with the
presence of ADA after three months treatment with BP.
- To identify the specific functional features of immune cells (including T and
B lymphocytes, monocyte and dendritic cells) associated with the development of
ADA compared to patients that do not develop ADA, BP naive patients and healthy
volunteers.
- To identify the genetic signature associated with the development of ADA
compared to patients that do not develop ADA, BP naive patients and healthy
volunteers.
Study design
Cross-sectional cohort in patients with immune-mediated inflammatory diseases
(IMID).
The total duration of study is 1 year, it includes 9 months for inclusion
period and 3 months for duration of patient participation
Study duration for each patient:
1. minimum 3 months and maximum 2 years after BP therapy
If ADA+:
2. when ADA status is known (approximately 3 months after the first visit)
Study burden and risks
Since the BP therapy will be prescribed by the Treating Physician this study is
not an intervention trail. Therefore, the pre-screening of patients for
administration of BP therapy and safety follow-up will be done according to
national guidelines for BP*s. This will be the responsibility of the Treating
Physician.
The procedures of this study are;
1. gathering clinical data
2. drawing of blood for further analysis
Blood drawing has a relatively low risk of adverse reactions. Due to the fact
that this study is accompanied with a small risk of adverse reactions we do not
expect serious adverse reactions to occur.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
- Male and female patients of more than 18 years old diagnosed with an IMID
- Patients being treated in the usual manner in accordance with the terms of the marketing authorization and independently from entry into this study:
* Patients treated with Anti TNF therapy for over three months i.e. adalimumab, etanercept or infliximab in first line independently from inclusion into study or,
* Patients treated with Rituximab after failure with anti-TNF therapy or other biotherapy or given in first line or
* Patients treated with Tocilmumab after failure with anti-TNF therapy or other biotherapy or given in first line
- Having given written informed consent prior to undertaking any study-related procedures.
- Covered by a health insurance system where applicable, and/or in compliance with the recommendations of the national laws in force relating to biomedical research.
Exclusion criteria
- Under any administrative or legal supervision.
- Conditions/situations such as:
* Patients with conditions/concomitant diseases making them non evaluable for the primary endpoint
* Impossibility to meet specific protocol requirements (e.g. blood sampling)
* Patient is the Investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol
* Uncooperative or any condition that could make the patient potentially non-compliant to the study procedures
- Pregnant or breast-feeding women, currently or in the last three months prior to inclusion.
- Patients who have been vaccinated in the last three months prior to inclusion.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL56053.018.15 |