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NCT Number: NCT05813860

HLADQA1*05 Genotype and the Efficacy of Treatment With Infliximab in Chinese Population Crohn's Disease

Crohn's disease (CD) is a chronic non-specific inflammatory disease of the intestine. Infliximab (IFX) is a kind of one of the anti-tumor necrosis factor agents (anti-TNF) and is the main clinical treatment drug for Crohn's disease, but approximately 30-50% of patients develop a secondary non-response to respond within one year. The main cause of secondary non-response failure is the formation of anti-IFX anti-drug antibodies (ADA). The human leukocyte antigen (HLA) gene is a complex allele that has been associated with susceptibility to a variety of diseases. Studies have shown that HLADQA1*05 allele carriage significantly increases the immunogenicity of anti-tumor necrosis factor agents (anti-TNF) and the risk of ADA formation, resulting in a significant reduction in the efficacy of IFX. Our previous retrospective study found an increased risk of ADA, IFX failure to respond and discontinuation in patients with HLADQA1*05 variants, and that IFX in combination with immunosuppression improved clinical outcomes in wild-type genotype patients, whereas combination therapy in patients with variant genotype did not optimize clinical outcomes significantly. Therefore, we believe that the impact of HLADQA1*05 on the efficacy of IFX in the Chinese population is unclear, and the combination of immunosuppressants in patients with variant HLADQA1*05 genotype remains to be validated due to insufficient sample size. We hypothesized that HLADQA1*05 wild-type CD patients would have better clinical remission when treated with IFX than HLADQA1*05 variant patients and that the combination of immunosuppressants would improve the outcome in wild-type patients but not in variant patients. By advancing this project, we hope to provide high quality evidence on the clinical use of IFX in Crohn's disease in the Chinese population and help physicians to be more selective in the use of IFX alone or in combination with azathioprine, or to switch treatment in a timely manner.

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Key information

Conditions

Crohn Disease Digestive System Diseases Gastroenteritis Gastrointestinal Diseases Inflammatory Bowel Diseases Infliximab Intestinal Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Participants with Crohn's disease who meet the diagnostic criteria of the Consensus Opinion on the Diagnosis and Treatment of Inflammatory Bowel Disease (Beijing, 2018)
  • Meet the indications for IFX use
  • CDAI score of 220-450; age≥18 years, regardless of gender
  • Participants or family members able to understand the study protocol and willing to participate in this study by providing written informed consent

Exclusion criteria

  • NUDT 15 CT and TT genotypes; previous treatment with IFX and/or other anti-TNF biologics
  • Participants who are proposed to have given birth and/or breastfeeding in the 12 months
  • those with immunosuppressive intolerance or contraindications
  • concurrent chronic diseases or factors of other systems (including severe cardiopulmonary, hepatic and renal, neurological, psychiatric, rheumatic and immune diseases, alcoholism, drug dependence, other chronic active diseases and long-term hormonal or immunosuppressive drugs)
  • Excluding infectious diseases (tuberculosis, etc.)
  • Excluding tumor-related diseases (lymphoma, gastrointestinal tract tumors, etc.)
  • any medical condition/combined surgery/medication/other clinically significant abnormal laboratory tests which, in the judgment of the investigator, may affect the results of the test
  • Known refusal or inability to follow protocol requirements for any reason (including planned clinical visits and examinations)

Treatment and study plan

azathioprine

Drug

azathioprine in combination with Infliximab, with a dose of 1-2 mg/kg/d.

Infliximab

Drug

5mg/kg for the first dose, and the same dose at weeks 2 and 6 after the first dose and every 8 weeks thereafter. Treatment with single Infliximab or combined azathioprine, respectively.

Primary outcomes

  1. Clinical remission without corticosteroid use at 102 weeks

    Time frame: 102 weeks

    CDAI score below 150 and no systemic corticosteroids at any dose or Budesonide ≥ 3 weeks.

Secondary outcomes

  1. Clinical response at 14 weeks

    Time frame: 14 weeks

    Decrease in CDAI score ≥70 or CDAI score <150

  2. Positive for ADA

    Time frame: 102 weeks

    Transient or persistent serum ADA concentration ≥ 10 AU/mL

  3. IFX Intensive Therapy

    Time frame: 102 weeks

    Includes increased doses and shorter cycles due to the recurrence of disease

  4. IFX Failure to Respond

    Time frame: 102 weeks

    Recurrence of disease during treatment with IFX with increased in CDAI score ≥ 70 or CDAI score ≥150

  5. Adverse drug events

    Time frame: 102 weeks

    Allergies, infusion reactions, infections, tumors, liver damage, bone marrow suppression, hair loss, etc.

  6. IFX discontinuation

    Time frame: 102 weeks

    Includes discontinuation due to IFX non-response or adverse events

Sponsors and collaborators

Lead sponsor

Sixth Affiliated Hospital, Sun Yat-sen University

Other

Registry information

Official study title

Preemptive HLADQA1*05 Genotyping for the Use of Infliximab in Chinese Crohn's Disease：A Multicenter, Prospective, Controlled, Randomized Study

Important dates

Study start
2023
Primary completion
2026
Study completion
2026
First posted
Apr 14, 2023
Registry last updated
May 9, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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