AneurysmPhase 2NCT05845723
Tocilizumab and Tofacitinib in the Treatment of Vascular Behçet's Syndrome
A Phase 2 study testing tocilizumab, tofacitinib and cyclophosphamide in people with Aneurysm and Behcet Syndrome, Vascular Type, run by Peking Union Medical College Hospital at 1 site in China.
Trial summary
This project aims to evaluate the efficacy and safety of the combination of glucocorticoids with tocilizumab or tofacitinib, compared to the traditional combination of glucocorticoids with cyclophosphamide in the treatment of vascular Behçet's syndrome. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Aneurysm, Behcet Syndrome, Vascular Type
- What is being tested?
- tocilizumab, tofacitinib and cyclophosphamide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 81 participants
- Where
- 1 siteChina
- Study dates
- 1 Jun 2023to 1 Jun 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1． Understand and voluntarily sign an informed consent form prior to any study-related assessments/procedures being conducted.
- 2. Male and female subjects aged 18-65 years.
- 3． Fulfill the 2013 International Classification Criteria for Behcet's Disease (ICBD).
- 4． Patients with aneurysmal dilatation/aneurysm of the descending aorta and/or peripheral arteries confirmed by ultrasonography and/or computed tomography angiography (CTA).
- 5. Elevated acute phase reactants ESR and hs-CRP.
Who cannot join
- Cardiovascular manifestations that cannot be distinguished from giant cell arteritis, Burger's disease, or atherosclerotic aneurysm; infectious aneurysm;
- Other active organ involvement related to BS that requires intensified immunosuppressive treatment, including gastrointestinal ulcers, uveitis, and parenchymal neurological involvement;
- Patients with severe aneurysms requiring emergency intervention surgery; patients with elective surgery indications require the consensus between rheumatologists and vascular surgeons to determine inclusion or exclusion.
- Severe organ dysfunction, including ALT, AST, and TBIL exceeding the upper limit of normal by more than 2 times, serum creatinine ≥ 133 mmol/L, white blood cell count < 3×10^9/L, ANC < 2×10^9/L, hemoglobin < 80g/L, platelet count < 100×10^9/L;
- Active infection such as active tuberculosis, hepatitis B or C, syphilis, chronic EBV infection, persistent or severe bacterial or viral infection;
- Primary or secondary immunodeficiency;
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- Malignant tumor;
- Use of immunosuppressants such as Cyclosporin A (CsA), Azathioprine (AZA), Tacrolimus (TAC), Mycophenolate Mofetil (MMF), or Cyclophosphamide (CTX) within 1 month;
- Use of biologics/small molecule drugs within 5 half-lives (baricitinib within 10 days; etanercept within 4 weeks; infliximab within 8 weeks; adalimumab, golimumab, ustekinumab, and abatacept within 10 weeks, secukinumab within 6 months, and previously use of tocilizumab and tofacitinib);
- Pregnant, lactating, or planning a recent pregnancy;
- Subjects who do not agree to or are unable to comply with regular visits.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Peking Union Medical College Hospital
Beijing, Beijing Municipality, 100730
Jinjing Liu
Wenjie Zheng, M.D.
About this study
Official title: Efficacy and Safety of Tocilizumab and Tofacitinib in the Treatment of Patients With Vascular Behçet's Syndrome
This project aims to evaluate the efficacy and safety of the combination of glucocorticoids with tocilizumab or tofacitinib, compared to the traditional combination of glucocorticoids with cyclophosphamide in the treatment of vascular Behçet's syndrome.
Read the detailed description
Behçet's Syndrome (BS) is a recurrent and systemic vasculitis, with an incidence rate of about 14/100,000 in China, higher than that in Europe and America. Vascular Behcet's Syndrome (VBS) is an important subtype of BS characterized by multiple venous and artery lesions. It affects 20-25% of BS patients, predominantly young adult males, and is the leading cause of mortality in BS patients (67%), especially in patients with aneurysms. Therefore, exploring the diagnosis and treatment strategies for VBS is key to improving the prognosis of BS.
This project aims to investigate the efficacy and safety of the combination of glucocorticoids (GCS) with the biologic agent tocilizumab or the targeted small molecule tofacitinib, compared to the combination of GCS with cyclophosphamide in the treatment of VBS aneurysms, as well as to screen for biomarkers related to the response of tocilizumab or tofacitinib, and to improve the assessment and treatment of VBS and establish a precision diagnosis and treatment strategy.
This is a Phase IIb, multi-center, randomized, open-label, GCS plus cyclophosphamide-controlled, parallel design, prospective clinical study. Patients will be randomly assigned to three groups in a 1:1:1 ratio (tocilizumab + GCS vs tofacitinib + GCS vs cyclophosphamide + GCS, 27:27:27) after screening and recruitment. Patients will be followed up every 4 weeks from weeks 0-12, and every 6 weeks from weeks 12-24. The primary endpoint is the complete remission (CR) rate at the 12th-week follow-up. All participants will undergo their final visit at 24 weeks.
- Conditions
- Aneurysm, Behcet Syndrome, Vascular Type
- Being tested
- tocilizumab, tofacitinib, cyclophosphamide
- Keywords
- Tocilizumab, Tofacitinib, Vascular Behçet's Syndrome
- Medical subject headings
- Aneurysm, Behcet Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tocilizumabDrug
Also called ACTEMRA®
Participants will receive intravenous infusion of tocilizumab 8mg/kg every 4 weeks for 24 weeks.
tofacitinibDrug
Also called Xeljanz®
Participants will receive tofacitinib 5mg twice a day for 24 weeks of treatment.
cyclophosphamideDrug
Also called Endoxana
Participants will receive intravenous infusion of cyclophosphamide 0.5g biweekly for 24 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Tocilizumab+GCS for VBS | Experimental | Participants randomized to this arm will receive prednisone 1mg/kg/d, gradually tapered to 10mg/d at week 12, combined with intravenous infusion of tocilizumab 8mg/kg every 4 weeks for 24 weeks. Receives: Drug: tocilizumab |
| Tofacitinib+GCS for VBS | Experimental | Participants randomized to this arm will receive prednisone 1mg/kg/d, gradually tapered to 10mg/d at week 12, combined with oral tofacitinib 5mg twice a day for 24 weeks of treatment. Receives: Drug: tofacitinib |
| Cyclophosphamide+GCS for VBS | Experimental | Participants randomized to this arm will receive prednisone 1mg/kg/d, gradually tapered to 10mg/d at week 12, combined with intravenous infusion of cyclophosphamide 0.5g biweekly for 24 weeks. Receives: Drug: cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint is the complete response (CR) rate at week 12.
CR: the resolution of VBS-related symptoms and abnormal acute phase reactants including erythrocyte sedimentation rate (ESR) and high-sensitivity C reactive protein (hs-CRP), no progression or new occurrence of vascular lesions compared to baseline.
Measured: Baseline to week 12
Secondary outcomes (8)
The secondary endpoints include CR rate at week 24, and partial response (PR) rate at week 12/24.
PR: improvement in clinical symptoms, >50% decrease in inflammatory markers, no progression or new occurrence of vascular lesions.
Measured: Baseline to week 24
Change From Baseline in Disease Activity as Measured by Behçet's Disease Current Activity Form (BDCAF).
The BDCAF consists of 3 component scores: the Behçet's Disease Current Activity Index (BDCAI) score, the Patient's Perception of Disease Activity, and the Clinician's Overall Perception of Disease Activity. The BDCAI consists of 12 questions regarding disease manifestations over the previous 4 weeks, including oral and genital disease activity, as well as other manifestations of BS involving the skin, joints, GI tract, eyes, nervous system, and vascular system. The BDCAI score is the sum score of 12 items and ranges from 0 to 12. The Patient's Perception of Disease Activity and the Clinician's Overall Perception of Disease Activity were assessed on a scale from 1 to 7. A higher score indicates a higher level of disease activity (worsening), and a negative change from baseline indicates improvement.
Measured: BDCAF were assessed at weeks 0, 4, 8, 12, 18, and 24
Change From Baseline in the degree of vasculitis damage as Measured by Behçet's syndrome Overall Damage Index (BODI).
The BODI consists of 4 overarching principles and 34 items with 12 subitems, categorized into 9 organ/system domains: mucocutaneous, musculoskeletal, ocular, vascular, cardiovascular, neuropsychiatric, gastrointestinal, reproductive system, and miscellaneous. Each item and subitem score 1 point. The total score ranges from 0 to 46. The higher the score, the greater the degree of damage.
Measured: BODI were assessed at weeks 0 and 24
4.Change From Baseline in the degree of vasculitis damage as Measured by Vasculitis Damage Index (VDI).
The VDI consists of 64 items, categorized into 11 organ/system domains: musculoskeletal, skin, ear, nose, and throat, pulmonary, cardiovascular, renal, gastrointestinal, peripheral vascular, ocular, neuropsychiatric, and other damage. Each item scores 1 point. The total score ranges from 0 to 64. The higher the score, the greater the degree of damage.
Measured: Time Frame: VDI were assessed at weeks 0, 12, and 24
Change From Baseline in ESR and hs-CRP.
The ESR and hs-CRP are acute phase reactants that are indicative of the patient's degree of disease activity.
Measured: ESR and hs-CRP were assessed at weeks 0, 4, 8, 12, 18, and 24
6.Change From Baseline in imaging changes including vascular ultrasonography, and CTA (including progression, improvement, and stability)
Radiological improvements is defined as the attenuation of radiological abnormalities related to VBS, including a reduction in aneurysm size. Radiological progression is defined as an increase in aneurysm size, aneurysm rupture, or the appearance of new lesions. Radiological stability is defined as the maintenance of aneurysm size and the absence of new lesions.
Measured: Imaging examinations were assessed at weeks 0, 12 and 24
7.Change From Baseline in 36 health survey questionnaire (SF-36).
The SF-36 is primarily used to evaluate eight dimensions of health-related quality of life: physical functioning (PF), role limitations due to physical health problems (RP), bodily pain (BP), general health perceptions (GH), vitality (VT), social functioning (SF), role limitations due to emotional problems (RE), and mental health (MH). In addition, there is a health transition (HT) item that assesses the overall change in health status over the past year. SF-36 also includes another health indicator, Reported Health Transition, which is used to evaluate the overall change in health status over the past year. Higher scores indicate better health status.
Measured: SF-36 were assessed at weeks 0, 12, and 24
Safety assessment: Record the types, frequency, and severity of adverse events, as well as the number of study participants who were discontinued due to any adverse events.
Adverse event: Any medical condition that affects the health of the participant during the study or worsens a pre-existing medical condition, regardless of whether it is causally related to the study, is considered an adverse event. This can be symptoms, signs, or abnormal laboratory tests.
Serious adverse event (SAE): Any significant medical event that causes death, is life-threatening, requires hospitalization, results in permanent or severe disability or loss of function, or the investigator deems it a significant medical event that may seriously harm the participant or require medical intervention to prevent the above outcomes. The causal relationship between the serious adverse event and the study is determined by the investigator's discussion.
Measured: Adverse events were assessed at weeks 0, 4, 8, 12, 18, and 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2023
- Study start1 Jun 2023
- Primary completion1 Jun 2026 (estimated)
- Study completion1 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AneurysmStudies of the same condition, open and under way.
- More trials run by Peking Union Medical College HospitalThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 81 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking Union Medical College Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05845723
- Sponsor's protocol ID
- TCZ/TOF-VBS-PUMCH
- Status last verified
- Jul 2024
- First submitted
- 26 Apr 2023
- Last updated
- 19 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Tocilizumab and Tofacitinib in the Treatment of Patients With Vascular Behçet's Syndrome
- ClinicalTrials.gov ID
- NCT05845723
- Acronym / sponsor ID
- TCZ/TOF-VBS-PUMCH
- Conditions
- Aneurysm, Behcet Syndrome, Vascular Type
- Keywords
- Tocilizumab, Tofacitinib, Vascular Behçet's Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 81 participants (estimated)
- Lead sponsor
- Peking Union Medical College HospitalUniversity, hospital or other
- Study start
- 1 Jun 2023 (actual)
- Primary completion
- 1 Jun 2026 (estimated)
- Study completion
- 1 Jun 2027 (estimated)
- First posted
- 6 May 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.
This project aims to evaluate the efficacy and safety of the combination of glucocorticoids with tocilizumab or tofacitinib, compared to the traditional combination of glucocorticoids with cyclophosphamide in the treatment of vascular Behçet's syndrome.
Detailed description
Behçet's Syndrome (BS) is a recurrent and systemic vasculitis, with an incidence rate of about 14/100,000 in China, higher than that in Europe and America. Vascular Behcet's Syndrome (VBS) is an important subtype of BS characterized by multiple venous and artery lesions. It affects 20-25% of BS patients, predominantly young adult males, and is the leading cause of mortality in BS patients (67%), especially in patients with aneurysms. Therefore, exploring the diagnosis and treatment strategies for VBS is key to improving the prognosis of BS.
This project aims to investigate the efficacy and safety of the combination of glucocorticoids (GCS) with the biologic agent tocilizumab or the targeted small molecule tofacitinib, compared to the combination of GCS with cyclophosphamide in the treatment of VBS aneurysms, as well as to screen for biomarkers related to the response of tocilizumab or tofacitinib, and to improve the assessment and treatment of VBS and establish a precision diagnosis and treatment strategy.
This is a Phase IIb, multi-center, randomized, open-label, GCS plus cyclophosphamide-controlled, parallel design, prospective clinical study. Patients will be randomly assigned to three groups in a 1:1:1 ratio (tocilizumab + GCS vs tofacitinib + GCS vs cyclophosphamide + GCS, 27:27:27) after screening and recruitment. Patients will be followed up every 4 weeks from weeks 0-12, and every 6 weeks from weeks 12-24. The primary endpoint is the complete remission (CR) rate at the 12th-week follow-up. All participants will undergo their final visit at 24 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Tocilizumab+GCS for VBS | Experimental | Drug: tocilizumabParticipants randomized to this arm will receive prednisone 1mg/kg/d, gradually tapered to 10mg/d at week 12, combined with intravenous infusion of tocilizumab 8mg/kg every 4 weeks for 24 weeks. |
| Tofacitinib+GCS for VBS | Experimental | Drug: tofacitinibParticipants randomized to this arm will receive prednisone 1mg/kg/d, gradually tapered to 10mg/d at week 12, combined with oral tofacitinib 5mg twice a day for 24 weeks of treatment. |
| Cyclophosphamide+GCS for VBS | Experimental | Drug: cyclophosphamideParticipants randomized to this arm will receive prednisone 1mg/kg/d, gradually tapered to 10mg/d at week 12, combined with intravenous infusion of cyclophosphamide 0.5g biweekly for 24 weeks. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 1． Understand and voluntarily sign an informed consent form prior to any study-related assessments/procedures being conducted.
- 2. Male and female subjects aged 18-65 years.
- 3． Fulfill the 2013 International Classification Criteria for Behcet's Disease (ICBD).
- 4． Patients with aneurysmal dilatation/aneurysm of the descending aorta and/or peripheral arteries confirmed by ultrasonography and/or computed tomography angiography (CTA).
- 5. Elevated acute phase reactants ESR and hs-CRP.
Key exclusion criteria (11 listed)
- Cardiovascular manifestations that cannot be distinguished from giant cell arteritis, Burger's disease, or atherosclerotic aneurysm; infectious aneurysm;
- Other active organ involvement related to BS that requires intensified immunosuppressive treatment, including gastrointestinal ulcers, uveitis, and parenchymal neurological involvement;
- Patients with severe aneurysms requiring emergency intervention surgery; patients with elective surgery indications require the consensus between rheumatologists and vascular surgeons to determine inclusion or exclusion.
- Severe organ dysfunction, including ALT, AST, and TBIL exceeding the upper limit of normal by more than 2 times, serum creatinine ≥ 133 mmol/L, white blood cell count < 3×10^9/L, ANC < 2×10^9/L, hemoglobin < 80g/L, platelet count < 100×10^9/L;
- Active infection such as active tuberculosis, hepatitis B or C, syphilis, chronic EBV infection, persistent or severe bacterial or viral infection;
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 |
|---|---|---|
| tocilizumabAlso: ACTEMRA®Participants will receive intravenous infusion of tocilizumab 8mg/kg every 4 weeks for 24 weeks. | Drug | Tocilizumab+GCS for VBS |
| tofacitinibAlso: Xeljanz®Participants will receive tofacitinib 5mg twice a day for 24 weeks of treatment. | Drug | Tofacitinib+GCS for VBS |
| cyclophosphamideAlso: EndoxanaParticipants will receive intravenous infusion of cyclophosphamide 0.5g biweekly for 24 weeks. | Drug | Cyclophosphamide+GCS for VBS |
Primary outcome
The primary endpoint is the complete response (CR) rate at week 12.
Time frame: Baseline to week 12
CR: the resolution of VBS-related symptoms and abnormal acute phase reactants including erythrocyte sedimentation rate (ESR) and high-sensitivity C reactive protein (hs-CRP), no progression or new occurrence of vascular lesions compared to baseline.
8 secondary outcomes
The secondary endpoints include CR rate at week 24, and partial response (PR) rate at week 12/24.
Time frame: Baseline to week 24
Change From Baseline in Disease Activity as Measured by Behçet's Disease Current Activity Form (BDCAF).
Time frame: BDCAF were assessed at weeks 0, 4, 8, 12, 18, and 24
Change From Baseline in the degree of vasculitis damage as Measured by Behçet's syndrome Overall Damage Index (BODI).
Time frame: BODI were assessed at weeks 0 and 24
4.Change From Baseline in the degree of vasculitis damage as Measured by Vasculitis Damage Index (VDI).
Time frame: Time Frame: VDI were assessed at weeks 0, 12, and 24
Change From Baseline in ESR and hs-CRP.
Time frame: ESR and hs-CRP were assessed at weeks 0, 4, 8, 12, 18, and 24
6.Change From Baseline in imaging changes including vascular ultrasonography, and CTA (including progression, improvement, and stability)
Time frame: Imaging examinations were assessed at weeks 0, 12 and 24
7.Change From Baseline in 36 health survey questionnaire (SF-36).
Time frame: SF-36 were assessed at weeks 0, 12, and 24
Safety assessment: Record the types, frequency, and severity of adverse events, as well as the number of study participants who were discontinued due to any adverse events.
Time frame: Adverse events were assessed at weeks 0, 4, 8, 12, 18, and 24
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2024.
- Individual participant dataSharing planned: No
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing tocilizumab, tofacitinib and cyclophosphamide in people with Aneurysm and Behcet Syndrome, Vascular Type, run by Peking Union Medical College Hospital at 1 site in China.
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 5 inclusion and 11 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: looking for participants now, as of the sponsor's last update on 19 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jinjing Liu, M.D. (8613581605769, wingsforjane@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary endpoint is the complete response (CR) rate at week 12. (time frame: Baseline to week 12). 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 19 Aug 2024.