A Randomized, Controlled, Open-label, Multicenter Clinical Trial Comparing the Efficacy and Safety of a Precision Treatment Regimen Based on Clinical-molecular Phenotypes with a Conventional Treatment Regimen in the Treatment of Patients with Active Takayasu's Arteritis

NCT06498089 | Recruiting Phase 4 DMC

• 1 other identifier: B2024-200R
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 1

Brief Summary

This study aimed to compare the efficacy and safety of a precision treatment regimen based on clinical-molecular phenotypes with a conventional treatment regimen in the treatment of patients with active Takayasu's arteritis based on a randomized, controlled, open-label, multicenter study.

Conditions

Takayasu Arteritis

Keywords

Precise treatment; Clinical-molecular phenotype

Outcome Measures

Primary Outcomes (1)

• Effectiveness rate

  Effectiveness is defined if patients meet the following three in criteria ①-④ and criteria ⑤. * No systemic symptoms such as fever, malaise, or wasting; * No new onset of vascular symptoms and signs; * Normal blood sedimentation (in case of abnormality, it is necessary to exclude non-disease active factors and to review and evaluate with the review value); ④ Imaging: no progression of primary vascular lesions or new vascular lesions; ⑤ Glucocorticoids are reduced to 7.5mg/day and maintained for at least 4 weeks.

  6 months

Secondary Outcomes (9)

• Effectiveness rate

  12 months

• Relapse rate

  12 months

• Time to the first relapse

  12 months

• Adverse events

  12 months

• Vascular imaging changes

  12 months

Study Arms (2)

The precise therapy arm

EXPERIMENTAL

Patients will be given treatment based on their clinical-molecular phenotype according to a predesigned scheme: 1. Patients in constitutional type will be given treatments with GCs combined with TCZ and MTX. 2. Patients in vascular inflammation type without IL-6 and TNF-α elevation will be given treatments with GCs combined with TOF. 3. Patients in vascular inflammation type with IL-6 elevation will be given treatments with GCs combined with TCZ and MTX. 4. Patients in vascular inflammation type with TNF-α elevation will be given treatments with GCs combined with ADA and MTX.

Drug: Prednisone; Drug: Methotrexate; Drug: Tocilizumab; Drug: Tofacitinib; Drug: Adalimumab

The traditional therapy arm

ACTIVE COMPARATOR

Patients will be given traditional treatment based on their clinical-molecular phenotype according to a predesigned scheme.

Drug: Prednisone; Drug: Methotrexate

Interventions

Prednisone DRUG

This drug will be used in both arms. Patients' initial daily prednisone dose will be calculated according to their weights (0.6mg \* weight(kg), maximum 50mg/day), and then tapered gradually during the study course.

Also known as: Glucocorticoids

The precise therapy arm; The traditional therapy arm

Methotrexate DRUG

This drug will be used in the traditional arm. A dose of 15mg per week will be used.

Also known as: MTX

The precise therapy arm; The traditional therapy arm

Tocilizumab DRUG

This drug will be used in the precise treatment arm. For patients in constitutional type a dose (8mg/kg weight) will be used every 2 weeks (iv drip) for 12 weeks, then a dose (8mg/kg weight) will be used every 4 weeks (iv drip). For patients in vascular inflammation type, a dose (8mg/kg weight) will be used every 4 weeks (iv drip).

Also known as: TCZ

The precise therapy arm

Tofacitinib DRUG

This drug will be used in the precise treatment arm. A sustained release tablet will be used (11mg per day).

Also known as: TOF

The precise therapy arm

Adalimumab DRUG

This drug will be used in the precise treatment arm. A dose of 40mg (ih) will used every 2 weeks.

Also known as: ADA

The precise therapy arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \) Meet the 2022 ACR/EULAR classification criteria for aortitis; 2) Women or men aged 18-65 years; 4) Be in active disease: a National Institutes of Health (NIH) score of ≥2; 5) Females with negative serum or urine pregnancy test results and no plans to have children during the clinical trial; (6) If the patient is taking prednisone or its equivalent, the pre-enrolment dose does not exceed 0.6 mg/kg/day and the dose has been stable for at least 4 weeks; 7) If the patient is receiving other medications for aortitis that are inconsistent with the assigned regimen, discontinuation is required for ≥4 weeks for methotrexate, azathioprine, mycophenolate mofetil, cyclosporine, and tacrolimus; for leflunomide, discontinuation is required for 11 days if elimination methods are used (kolexanil or activated charcoal), or ≥8 weeks if elimination is not used; for cyclophosphamide, discontinuation is required for ≥6 months; for biologics, stopping for ≥ 3 weeks is required for etanercept, ≥ 4 weeks for IL-6 receptor antagonists and tumour necrosis factor inhibitors, and ≥ 6 months for rituximab.
• )For patients with no obvious active tuberculosis lesions but elevated T-spot, it is recommended that infectious specialists evaluate them, and preventive anti-tuberculosis therapy should be performed first if necessary. After T-spot declines, researchers will assess the relevant risks before deciding whether they are suitable to participate in this study, and continue preventive anti-tuberculosis therapy for a total of 9 months.
• )For patients with HBV, if the viral replication was detected, it is recommended to take anti-viral treatment for 2-4 weeks, and researchers will evaluate whether they are suitable to participate in this study when no DNA replication is detected.

You may not qualify if:

• Presence of organ failure;
• undergoing haemodialysis or major surgery (grade III and above) within 3 months;
• the presence of other autoimmune diseases;
• severe, progressive organ damage;
• Subjects with other comorbidities that may result in the need for additional moderate to high doses of glucocorticoids (prednisone ≥ 10 mg/day or equivalent doses of prednisone equivalents) during the study period;
• Have a history of malignancy;
• Have any serious acute or chronic infection, including hepatitis B surface antigen positive, active tuberculosis.

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead

Study Sites (1)

Zhongshan Hospital, Fudan University

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Conditions

Takayasu Arteritis

Interventions

Prednisone; Glucocorticoids; Methotrexate; tocilizumab; tofacitinib; Adalimumab

Condition Hierarchy (Ancestors)

Aortic Arch Syndromes; Aortic Diseases; Vascular Diseases; Cardiovascular Diseases; Arteritis; Vasculitis; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Lindi Jiang, PhD

  Fudan University

  STUDY CHAIR

Central Study Contacts

Xiufang Kong, PhD

CONTACT

+8618317070593; kongxiufang2007@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The outcome assessor is blinded to the intervention.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study was a randomized, controlled study, including two arms.

Study Record Dates

• First Submitted: June 29, 2024
• First Posted: July 12, 2024
• Study Start: June 28, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: October 17, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)