Prediction of Treatment Response at 6 Months by Combinatorial Analysis of Serum Biomarkers in Biotherapy Naive SpA (PRESHUM)
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| ClinicalTrials.gov Identifier: NCT03561649 |
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Recruitment Status :
Completed
First Posted : June 19, 2018
Last Update Posted : March 17, 2021
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The main objective of this trial is to search for biomarkers associated with the success of adalimumab treatment in order to generate an algorithm to predict the response to this treatment at 6 months in spondyloarthritis and to define its metrological properties on this cohort.
The algorithm will allow to better target patients who will have an important benefit/risk ratio for adalimumab treatment.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Spondylitis, Ankylosing | Drug: Adalimumab | Not Applicable |
The general prevalence of spondyloarthritis (SpA) is 0.5% of the Caucasian population and that of ankylosing spondylitis (AS) is 0.3% in France.
First-line treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) is insufficiently effective in more than half of AS patients in hospitals. These patients are then treated with "anti-tumor necrosis factor alpha" (anti-TNFα). The use of these bio-drugs increasing each year, they become a significant public health and economic challenge. Their development is just beginning, because they are among the largest providers of pharmacy innovations.
The two main cost-drivers appear to be, on the most advanced forms of inflammatory rheumatism, the use of appropriate care structures or services and surgery, especially knee and hip surgery. Among patients treated with biotherapy, clinical practice shows that about one-third (33%) will not respond to selected biopharmaceuticals as these biologics are often prescribed empirically, mainly because of the lack of criteria based on scientific evidence and availability of tools able to predict the response or non-response to these molecules.
Until now, there is no algorithm which can predict the response to biotherapies like adalimumab. The aim of this trial is to search for biomarkers associated with the success of adalimumab treatment in order to generate an algorithm predicting the response to this treatment at 6 months for patients with SpA. This algorithm will be set up from patients' biological and clinical data available after 6 months of adalimumab treatment. A number of 50 patients seems to be statistically sufficient to assess the probability of response or non response to adalimumab in SA with the defined algorithm. A logistic regression model will be used by incorporating the set of available variables.
Then it will be necessary to set up a validation study to determine the metrological properties of the algorithm on an independent cohort.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 50 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Screening |
| Official Title: | Prediction of Adalimumab Treatment Response at 6 Months by Combinatorial Analysis of Serum Biomarkers in Biotherapy Naive Spondyloarthritis: Pilot Study |
| Actual Study Start Date : | June 14, 2018 |
| Actual Primary Completion Date : | December 14, 2019 |
| Actual Study Completion Date : | May 7, 2020 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Adalimumab
Adalimumab is not the experimental study drug. This treatment justifies the inclusion of patients and is used in accordance with its marketing authorization. The patients will be seen as part of their follow-up consultation in Rheumatology. Modality of administration: The baseline visit should take place no more than 4 weeks before the start of adalimumab treatment, 40mg every 2 weeks, subcutaneously, in accordance with Summary of Product Characteristics. At baseline and 6 months follow-up visits, a single blood draw for the biomarker dosage will be added to the standard patient health care follow-up. The clinical examination will also be performed at these two visits, and the clinical response will be assessed after 6 months of adalimumab treatment at M6 follow-up visit. |
Drug: Adalimumab
This trial will be conducted by rheumatologists who can follow patients with SpA and conduct this trial in good conditions and in accordance with regulatory and legal recommendations. |
- Measurement of disease activity: AS-DAS (Ankylosing Spondylitis - Disease Activity Score) [ Time Frame: 6 months after baseline ]The primary endpoint is the clinically important ASAS response corresponding to a variation in ASDAS CRP ≥ 1.1.
- Measurement of BASDAI response (Bath Ankylosing Spondylitis Disease Activity Index) [ Time Frame: 6 months after baseline ]
The major clinical ASAS response corresponds to a variation in ASDAS CRP (C-reactive protein) ≥ 2,0 and the major clinical BASDAI 50 response.
The BASDAI 50 response means an improvement of the BASDAI score by 50% or more. C-Reactive Protein (CRP) in mg/l and Erythrocyte Sedimentation Rate (ESR) in mm at the first hour.
- Biomarkers analysis for personalized medicine [ Time Frame: At baseline and 6 months later ]
Blood draw for selected biomarkers analysis (M0): the dosage data will be used to search for biomarkers associated with successful treatment in order to generate an algorithm predicting the response to adalimumab at 6 months, and to define the metrological properties on this cohort.
Blood draw for selected biomarkers analysis (M6): we know little about the mechanisms underlying the effect of adalimumab treatment at 6 months in spondyloarthritis, particularly on the biomarker profile. In order to identify possible differences in the profile of selected biomarkers between patients treated with adalimumab at 6 months and biotherapy naive patients (at baseline) and to study the individual variations of the response to this treatment, blood samples will also be collected at 6 months. By using proteomic profiles, the analysis and the comparison of predictive factors at M0 and M6 could be very useful.
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| Ages Eligible for Study: | 18 Years to 70 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patients with spondyloarthritis validating ASAS or modified New York criteria for which adalimumab treatment is indicated, and performing the pre-biotherapy assessment;
- Between 18 and 70 years old;
- Biotherapy naive;
- Who can be regularly monitored for 6 months;
- Able to take all the treatment;
- Effective contraception for patients of childbearing age (oral contraceptive, intrauterine device, implant, spermicide, surgical sterilization or abstinence) during the study and at least for 5 months after the last injection;
- Able to read and understand the terms of the protocol;
- Having dated and signed the informed consent form of the trial;
- Affiliated to a social security scheme.
Exclusion Criteria:
- Patients having a contraindication to an anti-TNF;
- Surgical operation scheduled during the trial;
- Having difficulty understanding the French language;
- Having impaired upper functions (dementia of Alzheimer type, etc...);
- Psycho-social instability incompatible with regular follow-up (homeless, addictive behavior, history of psychiatric pathology or any other comorbidity which would make a free and informed consent impossible or limit adherence to the protocol);
- Having previously received a biotherapy. There is no other exclusion criteria taking into account prior therapies and the duration of these therapies;
- Described in articles L.1121-5 to L.1121-8 of the Personal Status Code: pregnant, parturient and nursing women; persons in detention by judicial or administrative decision; adults subject to a legal protection order;
- Already participating in interventional research.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03561649
| France | |
| CH de Belfort | |
| Belfort, France, 90016 | |
| CHU de Besançon | |
| Besançon, France, 25030 | |
| CHRU de Clermont-Ferrand | |
| Clermont-Ferrand, France, 63003 | |
| CHU de Saint-Etienne | |
| Saint-Etienne, France, 42055 | |
| CHU de Grenoble | |
| Échirolles, France, 38434 | |
| Principal Investigator: | Athan BAILLET, MD, PHD | University Hospital, Grenoble |
| Responsible Party: | University Hospital, Grenoble |
| ClinicalTrials.gov Identifier: | NCT03561649 |
| Other Study ID Numbers: |
38RC17.378 |
| First Posted: | June 19, 2018 Key Record Dates |
| Last Update Posted: | March 17, 2021 |
| Last Verified: | March 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
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TNF inhibitor Adalimumab Spondyloarthritis Biomarkers analysis Personalized medicine |
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Spondylitis Spondylitis, Ankylosing Bone Diseases, Infectious Infections Bone Diseases Musculoskeletal Diseases Spinal Diseases Spondylarthropathies |
Spondylarthritis Ankylosis Joint Diseases Arthritis Adalimumab Anti-Inflammatory Agents Antirheumatic Agents |