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TNF and IL23 Blocking Agents Gene Expression Ratios in the Psoriatic Arthritis Synovium_(TIGERS) Study (TIGERS)

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ClinicalTrials.gov Identifier: NCT04261010
Recruitment Status : Recruiting
First Posted : February 7, 2020
Last Update Posted : February 7, 2020
Sponsor:
Collaborators:
Janssen-Cilag International NV
University Hospital, Ghent
Information provided by (Responsible Party):
Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Brief Summary:
This study compare the genomics profiles in synovial biopsies obtained prior to, and 24 weeks after a biologic disease modifying anti-rheumatic drugs (DMARDs)(Adalimumab, Ustekinumab, Guselkumab) in patients with active psoriatic arthritis despite a treatment with a conventional synthetic DMARDs (such as methotrexate).

Condition or disease Intervention/treatment Phase
Psoriatic Arthritis Procedure: Global/single cell gene expression profiles obtained from Synovial biopsies Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomization 1:1:1
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: TNF and IL23 Blocking Agents Gene Expression Ratios in the Psoriatic Arthritis Synovium
Actual Study Start Date : January 14, 2020
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : April 2022


Arm Intervention/treatment
Experimental: Ustekinumab
Group 1 (n=12): ustekinumab 45 mg (or 90 mg for patients > 100 kg) subcutaneously at baseline (W0), 4 weeks later (W4), and every 12 weeks until week 24 (i.e. W0, W4, and W16).
Procedure: Global/single cell gene expression profiles obtained from Synovial biopsies
Global/single cell gene expression profiles obtained from synovial biopsies before and after 24 weeks of treatment with the drug.

Experimental: Guselkumab
Group 2 (n=12): guselkumab 100 mg subcutaneously (regardless of the weight of the patient) at weeks 0 and 4, followed by a maintenance dose every 8 weeks through week 24 (i.e. W0, W4, W12 and W20).
Procedure: Global/single cell gene expression profiles obtained from Synovial biopsies
Global/single cell gene expression profiles obtained from synovial biopsies before and after 24 weeks of treatment with the drug.

Active Comparator: ADALIMUMAB
Group 3 (n=12): adalimumab 40 mg (regardless of the weight of the patient), subcutaneously every other week, starting from the baseline until week 24 (i.e.W0, W2, W4, W6, W8, W10, W12, W14, W16, W18, W20 and W22).
Procedure: Global/single cell gene expression profiles obtained from Synovial biopsies
Global/single cell gene expression profiles obtained from synovial biopsies before and after 24 weeks of treatment with the drug.




Primary Outcome Measures :
  1. Quantitative measurement of the molecular changes in relation to the up-regulated or down-regulated genes in the synovium. [ Time Frame: 24 weeks ]

    The primary endpoint of the study is not the comparative efficacy of the 3 drugs, but the comparative molecular changes they induce in the synovium.

    In a first set of analyses, the magnitude of fold-changes in (global and single cell) gene expression profiles between baseline and W24 will be analysed in each group. The higher values correspond to the high intensity in the up-regulation or down-regulation of the gene expression.



Secondary Outcome Measures :
  1. Comparison between the magnitude of molecular changes (up-regulation or down-regulation of the genes) and clinical changes (improvement or worsening of the swollen joints count). [ Time Frame: 24 weeks ]
    The swollen joints count (0 to 66) will be assessed. Lowered scores correspond to an improvement (remission or low disease activity), and increased value to a worsening of the clinical conditions (high disease activity). The value of the joints count will be compared to the magnitude of the up-regulation or down-regulation in the gene expression profiles.

  2. Comparison between the magnitude of molecular changes (up-regulation or down-regulation of the genes) and imaging changes on ultrasound (US). [ Time Frame: 24 weeks ]
    Synovitis (inflammation in the synovium) is scored by US in Grey-Scale (GS) (0 to 3) and Power Doppler (PD) (0 to 3). 0 correspond to lack of inflammation, and 3 to high amount of inflammation. The US changes in GS and PD will be compared to the magnitude of up-regulation or down-regulation in the gene expression profiles.

  3. Comparison between the magnitude of molecular changes (up-regulation or down-regulation of the genes) and imaging changes on Magnetic Resonance Imaging (MRI). [ Time Frame: 24 weeks ]
    MRI assessments for synovitis or bone marrow edema (water in the bone's head related to inflammation) will be binary (0 for absence of inflammation, and 1 for presence). MRI changes will be compared to the magnitude of up-regulation or down-regulation in the gene expression profiles.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients eligible for inclusion in this study have to fulfil all of the following criteria:

  1. Patient must be able to understand and communicate with the investigator and comply with the requirements of the study and must give a written, signed and dated informed consent before any study assessment is performed.
  2. Male or non-pregnant, non-nursing female patients at least 18 years of age. Before randomization, a woman of childbearing potential must be on a highly effective method of birth control consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies: eg, established use of oral, injected or implanted hormonal methods of contraception associated with inhibition of ovulation; placement of an intrauterine device (IUD) or intrauterine system (IUS); male partner sterilization (the vasectomized partner should be the sole partner for that subject); true abstinence (when this is in line with the preferred and usual lifestyle of the subject).

    A woman of childbearing potential must have a negative serum (β-human chorionic gonadotropin [β-hCG]) at baseline before randomization. A woman must agree not to donate ovocytes for the purposes of assisted reproduction during the study and for 3 months after receiving the last dose of study agent.

    Note: If the childbearing potential changes after start of the study (eg, woman who is not heterosexually active becomes active, premenarchal woman experiences menarche) that woman must begin a highly effective method of birth control, as described above.

    A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control eg, either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men must also not donate sperm during the study and for 3 months after receiving the last dose of study agent

    The method of birth control will be clearly documented in patient file.

  3. Patients with active PsA according to CASPAR criteria for ≥6 months, despite ≥3 months of csDMARD therapy, and ≥4 weeks of non-steroidal anti- inflammatory drugs (NSAIDs) therapy.
  4. At least 1 swollen joint at screening or baseline (despite csDMARD therapy) with ability to perform a synovial biopsy at W0.
  5. Patients with newly documented latent TB are eligible provided initiation of appropriate treatment.
  6. Concomitant MTX or SSZ is permitted if started ≥3 months prior to study start and at a stable dose (≤25 mg/week for MTX and ≤ 3 g/day for SSZ) for ≥4 weeks.
  7. Patients on MTX must be on stable folic acid supplementation before randomization.
  8. Concomitant NSAIDs and oral corticosteroids (≤10 mg prednisone/day) are permitted if stable for at least 2 weeks.
  9. Allowed concomitant medications are to remain stable through week 24.
  10. Patients cannot have previously received any biologic agent
  11. DMARDs other than MTX or sulfasalazine (SSZ) must be interrupted. DMARDs other than MTX are not allowed within 4 weeks prior to or during trial participation. A washout period needs to be considered. (8 weeks for leflunomide).
  12. At least one joint (small or large) to biopsy in order to get synovial tissue. Small joints must have an US grey-scale score > 2 on Doppler

Exclusion Criteria:

Patients fulfilling any of the following criteria are not eligible for inclusion in this study.

  1. Contraindications for needle-arthroscopy such as joint replacement (in the affected knee or ankle joint) or anticoagulation.
  2. Use of any investigational drug and/or devices within 4 weeks of baseline, or a period of 5 half-lives of the investigational drug, whichever is longer.
  3. Conditions/situations such as:

    1. Patients with conditions/concomitant diseases making them non evaluable for the primary endpoint
    2. Impossibility to meet specific protocol requirements (e.g. blood sampling)
    3. 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
    4. Uncooperative or any condition that could make the patient potentially noncompliant to the study procedures
  4. Any therapy by intra-articular injections (e.g. corticosteroid) within 4 weeks before baseline.
  5. Any intramuscular corticosteroid injection within 2 weeks before baseline.
  6. Prior treatment with a biologic agent.
  7. A history of active tuberculosis (TB).

Information from the National Library of Medicine

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): NCT04261010


Contacts
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Contact: Adrien NZEUSSEU TOUKAP, MD +32.2.764.11.11 ext 49389 Adrien.Nzeusseu@uclouvain.be
Contact: Charlene MOUAFO TOUKAM, MS +32.2.764.53.96 ext 45396 Charlene.Mouafo@uclouvain.be

Locations
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Belgium
Dirk ELEWAUT Active, not recruiting
Gent, East Flanders, Belgium
Adrien NZEUSSEU TOUKAP Recruiting
Brussels, Belgium, 1200
Contact: Adrien NZEUSSEU TOUKAP, MD    +32.2.764.11.11 ext 4.9389    Adrien.Nzeusseu@uclouvain.be   
Contact: Charlene MOUAFO TOUKAM, MS    +32.2.764.53.96 ext 4.5396    Charlene.Mouafo@uclouvain.be   
Principal Investigator: Adrien NZEUSSEU TOUKAP, MD         
Sub-Investigator: Bernard LAUWERYS, MD, PhD         
Sub-Investigator: Maria STOENOIU, MD, PhD         
Sub-Investigator: Laurent MERIC de BELLEFON, MD         
Sub-Investigator: Patrick DUREZ, MD         
Sponsors and Collaborators
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Janssen-Cilag International NV
University Hospital, Ghent
Investigators
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Principal Investigator: Adrien NZEUSSEU TOUKAP, MD Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Principal Investigator: Dirk ELEWAUT, MD, PhD University Hospital, Ghent

Publications:

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Responsible Party: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
ClinicalTrials.gov Identifier: NCT04261010    
Other Study ID Numbers: P1200_32 (TIGERS)
2017-003249-18 ( EudraCT Number )
FAGG/R&D/SEJ/sej ( Other Identifier: FAMHP )
First Posted: February 7, 2020    Key Record Dates
Last Update Posted: February 7, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Cliniques universitaires Saint-Luc- Université Catholique de Louvain:
Synovium, Biologics, Genomics
Additional relevant MeSH terms:
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Arthritis
Arthritis, Psoriatic
Joint Diseases
Musculoskeletal Diseases
Spondylarthropathies
Spondylarthritis
Spondylitis
Spinal Diseases
Bone Diseases
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
Ustekinumab
Dermatologic Agents