Safety and Efficacy of TollB-001 Tablets in Moderate to Severe Rheumatoid Arthritis

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase IIa Clinical Study to Evaluate the Efficacy and Safety of TollB-001 Tablets in Patients With Moderate to Severe Active Rheumatoid Arthritis

The goal of this study is to evaluate the safety, pharmacokinetic (PK) characteristics, and preliminary efficacy of a new oral chemical drug in : adults aged 18-70 years (male or female) with moderate to severe active rheumatoid arthritis (RA), who have had inadequate response to or intolerance of at least one conventional synthetic disease-modifying antirheumatic drug (csDMARDs) .

Participants will take the assigned study drug (either tollB-001 Tablets or placebo) once daily orally for 4 weeks, follow up for 1 week.

Study Overview

• Status: Recruiting
• Conditions: Rheumatoid Arthritis (RA)
• Intervention / Treatment: Drug: Group 1: TollB-001 100mg qd po; Group 2: TollB-001 200mg qd po; Group 3: TollB-001400mg qd po; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Weili Wang; Phone Number: +86 10 80710966; Email: wangweili@toll-biotech.com

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China
      • Recruiting
      • The First Affiliated Hospital Of Bengbu Medical College
      • Contact: Changhao Xie; Phone Number: not provide
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 102206
      • Recruiting
      • Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
      • Principal Investigator: Xinping Tian
      • Principal Investigator: Xiaofeng Zeng
      • Contact: Xiaofeng Zeng; Phone Number: not provide; Email: zengxfpumc@163.com
  • Henan
    • Puyang, Henan, China
      • Recruiting
      • Puyang Oilfield General Hospital
      • Contact: Fengju Li; Phone Number: not provide
  • Inner Mongolia
    • Hohhot, Inner Mongolia, China
      • Recruiting
      • Affiliated Hospital of Inner Mongolia Medical University
      • Contact: Hongbin Li; Phone Number: not provide
  • Jiangxi
    • Pingxiang, Jiangxi, China
      • Recruiting
      • Pingxiang People's Hospital
      • Contact: Dai Senhua; Phone Number: not provide
  • Shanxi
    • Linfen, Shanxi, China
      • Recruiting
      • Linfen Central Hospital
      • Contact: Shuhua Qiang; Phone Number: not provide

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged 18 to 70 years (inclusive) at the time of signing the informed consent form, regardless of gender.
2. Diagnosis of RA according to the 1987 American College of Rheumatology (ACR) criteria or the 2010 ACR/European League Against Rheumatism (EULAR) classification criteria.
3. DAS28-CRP > 3.2 at screening (joints that have undergone major surgical treatment or intra-articular injection of glucocorticoids or hyaluronic acid within 6 weeks before randomization are not counted in the TJC and SJC counts).
4. C-reactive protein (CRP)/high-sensitivity C-reactive protein (hsCRP) ≥ upper limit of normal (ULN) at screening.
5. Prior to the first administration of the study drug, has received continuous treatment with at least one conventional synthetic disease-modifying antirheumatic drug (csDMARDs, including methotrexate, chloroquine, hydroxychloroquine, sulfasalazine, leflunomide, iguratimod) with inadequate response or intolerance, and agrees to discontinue use during the study.
6. Female and male subjects of childbearing potential must use effective contraceptive measures during the study and for 3 months after the last study drug administration. Male subjects whose spouses or partners are females of childbearing potential must also agree to use effective contraceptive measures during the study and for 3 months after the last administration, and shall not donate sperm during this period. Female subjects of childbearing potential must have a negative pregnancy test.
7. Must provide written informed consent and be willing and able to comply with the study protocol (e.g., understand and complete questionnaires, follow the visit schedule, take medications as prescribed).

Exclusion Criteria:

1. Hypersensitivity to the study drug or any of its components.
2. ACR functional class IV or being bedridden/wheelchair-bound for a long time.

3. Use of any of the following drugs or treatments:

   Prior use of Janus kinase (JAK) inhibitors (including but not limited to tofacitinib, baricitinib, upadacitinib), biologic disease-modifying antirheumatic drugs (bDMARDs), or participation in clinical trials of the aforementioned drugs.

   Use of csDMARDs within 28 days before randomization (leflunomide within 56 days before administration, or subjects who have received standard cholestyramine treatment or activated charcoal washout within 28 days are not eligible for enrollment).

   Use of other known drugs with strong immunosuppressive or immunomodulatory effects (such as puerarin, tripterygium wilfordii, mycophenolate mofetil, cyclosporine, tacrolimus, azathioprine, 6-mercaptopurine, etc.) other than the above within 4 weeks before randomization.

   Receipt of any parenteral (intramuscular or intravenous) or intra-articular glucocorticoids within 4 weeks before randomization.

   Receipt of interferon treatment within 4 weeks before randomization. Oral traditional Chinese medicine for the treatment of RA and other inflammatory diseases within 4 weeks before randomization.

   Use of opioid drugs within 1 week or 5 drug half-lives (whichever is longer) before the first administration of the study drug.

   Receipt of integrin αV antibodies or cell depletion therapy within 3 months or 5 half-lives (whichever is longer) before the screening visit.

4. History or evidence of any of the following diseases:

   Other systemic inflammatory diseases except RA (excluding secondary Sjögren's syndrome), including but not limited to juvenile chronic arthritis, Crohn's disease, ulcerative colitis, psoriatic arthritis, systemic lupus erythematosus, ankylosing spondylitis, reactive arthritis, systemic vasculitis, gout, or other joint diseases that may affect efficacy evaluation (e.g., osteoarthritis with significant joint pain).

   Felty's syndrome. Any active malignant tumor or history of malignant tumor. Chronic pain history that may affect study evaluation. Active tuberculosis, latent untreated tuberculosis, or incompletely cured tuberculosis as judged by the investigator and/or specialist.

   History of any persistent or chronic infection (e.g., chronic pyelonephritis, bronchiectasis, osteomyelitis) deemed inappropriate for study participation by the investigator, or oral anti-infective drugs (excluding onychomycosis) within 14 days before the first administration of the study drug; history of deep space/tissue infection (e.g., fasciitis, abscess, osteomyelitis) within 52 weeks before the screening visit.

   Poorly controlled severe diseases such as diabetes mellitus, hypertension, kidney disease, neurological disease, liver disease, severe heart disease (e.g., decompensated heart failure [New York Heart Association Class III or IV], unstable angina pectoris, myocardial infarction, etc.), respiratory disease, severe chronic gastrointestinal disease (e.g., active or recurrent peptic ulcer), or prior treatment that may affect drug absorption (e.g., gastrointestinal surgery) and deemed by the investigator to potentially hinder the subject's participation in the study.

   Major surgery within 8 weeks before randomization or expected to undergo major surgery after enrollment.

5. Any laboratory abnormalities meeting the following criteria at screening:

   Hemoglobin < 90.0 g/L. Total white blood cell count < 2.5 × 10⁹/L. Neutrophil count < 1.5 × 10⁹/L. Lymphopenia (lymphocyte count < 750 cells/μL). Platelet count < 100 × 10⁹/L.

6. Positive hepatitis B surface antigen (HBsAg); or positive hepatitis B core antibody (HBcAb) with HBV DNA above the lower limit of detection; positive hepatitis C virus (HCV) antibody with positive HCV-RNA; positive human immunodeficiency virus (HIV) antibody or positive syphilis antibody.
7. Drug or alcohol abuse or dependence at screening, or history of drug or alcohol abuse or dependence within 6 months before randomization.
8. Participation in any clinical trial of drugs or medical devices within 4 weeks or 5 half-lives (whichever is longer) before randomization.
9. Blood donation ≥ 400 mL or receipt of blood transfusion within 3 months before randomization.
10. Any other factors deemed by the investigator to potentially affect the conduct or result evaluation of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; matching placebo qd po for 4 weeks
Experimental: TollB-001	Drug: Group 1: TollB-001 100mg qd po; Group 2: TollB-001 200mg qd po; Group 3: TollB-001400mg qd po; for 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety-AE/lab tests/PE/VS/ECG	Safety parameters including the incidence of adverse events (AEs), abnormalities in laboratory tests, physical examinations, vital signs, and routine 12-lead electrocardiograms	up to week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy-ACR20	Proportion of patients achieving 20% improvement in the ACR RA disease activity core criteria (ACR20) at each post-baseline visit;	Day8, Day15, Day29, Day56
EfficacyACR50/70	Proportion of patients achieving 50% (ACR50) and 70% (ACR70) improvement at each post-baseline visit;	Day8, Day15, Day29, Day56
Efficacy-DAS28	Proportion of patients achieving DAS28-CRP < 2.6, DAS28-CRP ≤ 3.2, DAS28-ESR < 2.6, and DAS28-ESR ≤ 3.2 at each post-baseline visit	Day8, Day15, Day29, Day56
Efficacy-CDAI	Changes in Clinical Disease Activity Index (CDAI) from baseline at each post-baseline visit	Day8, Day15, Day29, Day56
Efficacy-morning stiffness	Changes in morning stiffness duration from baseline at each post-baseline visit; Assessment Time: Each post-baseline visit	Day8, Day15, Day29, Day56
Efficay-patient assessment of arthritis pain	Changes in Patient's Assessment of Arthritis Pain (PtAAP) from baseline at each post-baseline visit	Day8, Day15, Day29, Day56
Efficacy-patient global assessment	Changes in Patient's Global Assessment of Disease Activity (PtGA) from baseline at each post-baseline visit;	Day8, Day15, Day29, Day56
Efficacy-physician's global assessemnt	Changes in Physician's Global Assessment of Disease Activity (PhGA) from baseline at each post-baseline visit	Day8, Day15, Day29, Day56
Efficacy-DAQ-DI	Changes in Health Assessment Questionnaire-Disability Index (HAQ-DI) scores from baseline at each post-baseline visit	Day8, Day15, Day29, Day56
Efficay-ESR	Changes in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) from change in ESR from baseline at each post-baseline visit	Day8, Day15, Day29, Day56
Efficay-CRP	Changes in C-reactive protein (CRP) from baseline at each post-baseline visit	Day8, Day15, Day29, Day56
Secondary	Serum concentration of TollB-001	Up to week 4

Collaborators and Investigators

• Sponsor: Toll Biotech Co. Ltd. (Beijing)

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: January 29, 2026
• First Submitted That Met QC Criteria: February 5, 2026
• First Posted (Actual): February 12, 2026

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 12, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin and Connective Tissue Diseases; Arthritis, Rheumatoid
• Other Study ID Numbers: TLBT-TOLLB-001-IIa; CTR20253314 (Other Identifier: CDE)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No