Crohn DiseasePhase 4NCT05813860
HLADQA1*05 Genotype and the Efficacy of Treatment With Infliximab in Chinese Population Crohn's Disease
A Phase 4 study testing Azathioprine and Infliximab in people with Crohn Disease and Infliximab, run by Sixth Affiliated Hospital, Sun Yat-sen University.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Crohn Disease, Infliximab
- What is being tested?
- Azathioprine and Infliximab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 976 participants
- Where
- No sites listed yet
- Study dates
- 30 Apr 2023to 31 Oct 2026
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
About this study
Official title: Preemptive HLADQA1*05 Genotyping for the Use of Infliximab in Chinese Crohn's Disease：A Multicenter, Prospective, Controlled, Randomized Study
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.
- Conditions
- Crohn Disease, Infliximab
- Being tested
- Azathioprine, Infliximab
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzathioprineDrug
azathioprine in combination with Infliximab, with a dose of 1-2 mg/kg/d.
InfliximabDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Infliximab | Experimental | Infliximab monotherapy, the first dose of 5 mg/kg of this product is provided, followed by the same dose at weeks 2 and 6 after the first dose and every 8 weeks thereafter. Receives: Drug: Infliximab |
| Infliximab+azathioprine | Active comparator | Infliximab was given in combination with azathioprine, and Infliximab dosing was the same as in the experimental group, with azathioprine at 1-2 mg/kg/d. Receives: Drug: Azathioprine; Drug: Infliximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical remission without corticosteroid use at 102 weeks
CDAI score below 150 and no systemic corticosteroids at any dose or Budesonide ≥ 3 weeks.
Measured: 102 weeks
Secondary outcomes (6)
Clinical response at 14 weeks
Decrease in CDAI score ≥70 or CDAI score <150
Measured: 14 weeks
Positive for ADA
Transient or persistent serum ADA concentration ≥ 10 AU/mL
Measured: 102 weeks
IFX Intensive Therapy
Includes increased doses and shorter cycles due to the recurrence of disease
Measured: 102 weeks
IFX Failure to Respond
Recurrence of disease during treatment with IFX with increased in CDAI score ≥ 70 or CDAI score ≥150
Measured: 102 weeks
Adverse drug events
Allergies, infusion reactions, infections, tumors, liver damage, bone marrow suppression, hair loss, etc.
Measured: 102 weeks
IFX discontinuation
Includes discontinuation due to IFX non-response or adverse events
Measured: 102 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2023
- Study start30 Apr 2023 (estimated)
- Primary completion31 May 2026 (estimated)
- Study completion31 Oct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Crohn DiseaseStudies of the same condition, open and under way.
- More trials run by Sixth Affiliated Hospital, Sun Yat-sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 976 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05813860
- Sponsor's protocol ID
- 2023ZSLYEC-123
- Status last verified
- May 2023
- First submitted
- 3 Apr 2023
- Last updated
- 9 May 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preemptive HLADQA1*05 Genotyping for the Use of Infliximab in Chinese Crohn's Disease：A Multicenter, Prospective, Controlled, Randomized Study
- ClinicalTrials.gov ID
- NCT05813860
- Acronym / sponsor ID
- 2023ZSLYEC-123
- Conditions
- Crohn Disease, Infliximab
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 976 participants (estimated)
- Lead sponsor
- Sixth Affiliated Hospital, Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 30 Apr 2023 (estimated)
- Primary completion
- 31 May 2026 (estimated)
- Study completion
- 31 Oct 2026 (estimated)
- First posted
- 14 Apr 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Infliximab | Experimental | Drug: InfliximabInfliximab monotherapy, the first dose of 5 mg/kg of this product is provided, followed by the same dose at weeks 2 and 6 after the first dose and every 8 weeks thereafter. |
| Infliximab+azathioprine | Active comparator | Drug: Azathioprine, Drug: InfliximabInfliximab was given in combination with azathioprine, and Infliximab dosing was the same as in the experimental group, with azathioprine at 1-2 mg/kg/d. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (8 listed)
- 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.)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Azathioprineazathioprine in combination with Infliximab, with a dose of 1-2 mg/kg/d. | Drug | Infliximab+azathioprine |
| Infliximab5mg/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. | Drug | Infliximab, Infliximab+azathioprine |
Primary outcome
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.
6 secondary outcomes
Clinical response at 14 weeks
Time frame: 14 weeks
Positive for ADA
Time frame: 102 weeks
IFX Intensive Therapy
Time frame: 102 weeks
IFX Failure to Respond
Time frame: 102 weeks
Adverse drug events
Time frame: 102 weeks
IFX discontinuation
Time frame: 102 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Azathioprine and Infliximab in people with Crohn Disease and Infliximab, run by Sixth Affiliated Hospital, Sun Yat-sen University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 May 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical remission without corticosteroid use at 102 weeks (time frame: 102 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2023.