A Study of Single and Multiple Oral Doses of TollB-001

NCT06103773 | Unknown Phase 1

• 1 other identifier: TLBT-TOLLB-001-I
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective is to evaluate the safety and tolerability of TollB-001 following the administration of single or multiple oral doses in healthy adult subjects

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (38)

• Red blood cell count(physiological parameter) by investigator

  Red blood cell count

  Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days)

• hematocrit(physiological parameter) by investigator

  hematocrit

  Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days)

• hemoglobin(physiological parameter) by investigator

  hemoglobin

  Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days)

• white blood cell count(physiological parameter) by investigator

  white blood cell count

  Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days)

• whiteblood cell differential count(physiological parameter) by investigator

  whiteblood cell differential count

  Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days)

• plateletcount(physiological parameter) by investigator

  plateletcount

  Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days)

• Alanine aminotransferase(physiological parameter) by investigator

  Alanine aminotransferase

  Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days)

• aspartateaminotransferase(physiological parameter) by investigator

  aspartateaminotransferase

  Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days)

• alkaline phosphatase(physiological parameter) by investigator

  alkaline phosphatase

  Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days)

• gamma-glutamyl transpeptidase(physiological parameter) by investigator

  gamma-glutamyl transpeptidase

  Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days)

• total bilirubin(physiological parameter) by investigator

  total bilirubin

  Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days)

• direct bilirubin(physiological parameter) by investigator

  direct bilirubin

  Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days)

• blood ureanitrogen (or blood urea)(physiological parameter) by investigator

  blood ureanitrogen (or blood urea)

  Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days)

• creatinine(physiological parameter) by investigator

  creatinine

  Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days)

• glucose(physiological parameter) by investigator

  glucose

  Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days)

• total protein(physiological parameter) by investigator

  total protein

  Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days)

• creatine kinase(physiological parameter) by investigator

  creatine kinase

  Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days)

• Activated partial thromboplastin time(physiological parameter) by investigator

  Activated partial thromboplastin time

  Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days)

• prothrombin time(physiological parameter) by investigator

  prothrombin time

  Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days)

• internationalnormalized ratio(physiological parameter) by investigator

  internationalnormalized ratio

  Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days)

• fibrinogen(physiological parameter) by investigator

  fibrinogen

  Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days)

• urine pH(physiological parameter) by investigator

  urine pH

  Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days)

• urine specific gravity(physiological parameter) by investigator

  urine specific gravity

  Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days)

• urine glucose(physiological parameter) by investigator

  urine glucose

  Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days)

• urine protein(physiological parameter) by investigator

  urine protein

  Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days)

• urobilinogen(physiological parameter) by investigator

  urobilinogen

  Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days)

• urine bilirubin(physiological parameter) by investigator

  urine bilirubin

  Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days)

• urine leukocyte(physiological parameter) by investigator

  urine leukocyte

  Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days)

• urine ketone body(physiological parameter) by investigator

  urine ketone body

  Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days)

• urine red blood cells(physiological parameter) by investigator

  urine red blood cells

  Baseline（Screening）up to last follow-up visit(SAD:Screening up to Week 1;MAD:Screening up to Week 2;FE:Screening up to Week 2 plus 10 days)

• AE/SAE monitoring by ToxicityGrading Scale for Healthy Adults and Volunteers Enrolled in Preventative Vaccine Trials,2007 (70 FR 22664)

  AE/SAE monitoring

  First dose up to last follow-up visit（for a maximum of 20 days）

• physical examination(physiological parameter) by investigator

  The assessments of general appearance, head(including ears, eyes, nose, throat), neck, skin, cardiovascular system, respiratory system,abdominal system, nervous system, musculoskeletal system, and lymphatic system

  First dose up to last follow-up visit（for a maximum of 20 days）;SAD:Screening,Day2,Day5 or ET Visit;MAD:Screening,Day3,Day6,Day9 or ET Visit;FE:Screening,Period 1 Day2,Period 1 Day5;Period 2 Day-1,Period 2 Day2,Period 2 Day5 or ET Visit.

• blood pressure(systolic pressure and diastolic pressure)(physiological parameter) by investigator

  blood pressure(systolic pressure and diastolic pressure)

  For a maximum of 20 days;SAD:Screening,Day1 to Day5 or ET Visit;MAD:Screening,Day1 to Day9 or ET Visit;FE:Screening,Period 1 Day1 to Day5;Period 2 Day-1 to Day5 or ET Visit.

• pulse(physiological parameter) by investigator

  pulse

  For a maximum of 20 days;SAD:Screening,Day1 to Day5 or ET Visit;MAD:Screening,Day1 toDay9 or ET Visit;FE:Screening,Period 1 Day1 to Day5;Period 2 Day-1 to Day5 or ET Visit.

• respiratory rate(physiological parameter) by investigator

  respiratory rate

  For a maximum of 20 days;SAD:Screening,Day1 to Day5 or ET Visit;MAD:Screening,Day1 toDay9 or ET Visit;FE:Screening,Period 1 Day1 to Day5;Period 2 Day-1 to Day5 or ET Visit.

• body temperature(physiological parameter) by investigator

  body temperature

  For a maximum of 20 days;SAD:Screening,Day1 to Day5 or ET Visit;MAD:Screening,Day1 toDay9 or ET Visit;FE:Screening,Period 1 Day1 to Day5;Period 2 Day-1 to Day5 or ET Visit.

• 12-lead ECGs

  ECGs done in triplicate; heart rate, PR interval, QT and QTc interval and QRS duration

  For a maximum of 20 days;SAD:Screening,Day1 to Day5 or ET Visit;MAD:Screening,Day1 to Day9 or ET Visit;FE:Screening,Period 1 Day1,Period 1 Day3,Period 1 Day5;Period 2 Day-1,Period 2 Day1,Period 2 Day3,Period 2 Day5 or ET Visit.

• B-ultrasound(physiological parameter) by investigator

  liver, gallbladder, spleen, pancreas, kidney and bladder

  For a maximum of 20 days;SAD:Screening,Day5 or ET Visit;MAD:Screening,Day9 or ET Visit;FE:Screening,Period 1 Day5;Period 2 Day5 or ET Visit.

Study Arms (12)

SAD-TollB-001 50mg Dosage groups

EXPERIMENTAL

drug：TollB-001 tablets（50mg，single-dose, on the first day）

Drug: TollB-001 tablets; Drug: TollB-001 placebo

SAD-TollB-001 100mg Dosage groups

EXPERIMENTAL

drug：TollB-001 tablets （100mg，single-dose, on the first day）

Drug: TollB-001 tablets; Drug: TollB-001 placebo

SAD-TollB-001 200mg Dosage groups

EXPERIMENTAL

drug：TollB-001 tablets （200mg，single-dose, on the first day）

Drug: TollB-001 tablets; Drug: TollB-001 placebo

SAD-TollB-001 400mg Dosage groups

EXPERIMENTAL

drug：TollB-001 tablets （400mg，single-dose, on the first day）

Drug: TollB-001 tablets; Drug: TollB-001 placebo

SAD-TollB-001 800mg Dosage groups

EXPERIMENTAL

drug：TollB-001 tablets （800mg，single-dose, on the first day）

Drug: TollB-001 tablets; Drug: TollB-001 placebo

SAD-TollB-001 1000mg Dosage groups

EXPERIMENTAL

drug：TollB-001 tablets （1000mg，single-dose, on the first day）

Drug: TollB-001 tablets; Drug: TollB-001 placebo

MAD- TollB-001 100mg Dosage groups

EXPERIMENTAL

drug：TollB-001 tablets （100mg，Multiple-dose, once per day for 5 days）

Drug: TollB-001 tablets; Drug: TollB-001 placebo

MAD- TollB-001 200mg Dosage groups

EXPERIMENTAL

drug：TollB-001 tablets （200mg，Multiple-dose, once per day for 5 days）

Drug: TollB-001 tablets; Drug: TollB-001 placebo

MAD-TollB-001 400mg Dosage groups

EXPERIMENTAL

drug：TollB-001 tablets （400mg，Multiple-dose, once per day for 5 days）

Drug: TollB-001 tablets; Drug: TollB-001 placebo

MAD-TollB-001 800mg Dosage groups

EXPERIMENTAL

drug：TollB-001 tablets （800mg，Multiple-dose, once per day for 5 days）

Drug: TollB-001 tablets; Drug: TollB-001 placebo

FE-Low Dosage groups

EXPERIMENTAL

drug：TollB-001 tablets（Subjects in the fasting-fed sequence group will be administered with TollB-001 under fasting condition in the first period and under fed condition in the second period; subject in the fed-fasting sequence group will be administered with TollB-001 under fed condition in the first period and under fasting condition in the second period. The two periods of cross-administration will have a washout period of 5-10 days）

Drug: TollB-001 tablets

FE-High Dosage groups

EXPERIMENTAL

drug：TollB-001 tablets Subjects in the fasting-fed sequence group will be administered with TollB-001 under fasting condition in the first period and under fed condition in the second period; subject in the fed-fasting sequence group will be administered with TollB-001 under fed condition in thefirst period and under fasting condition in the second period. The two periods of cross-administration will have a washout period of 5-10 days）

Drug: TollB-001 tablets

Interventions

TollB-001 tablets DRUG

TollB-001 treatment

Also known as: TollB-001

FE-High Dosage groups; FE-Low Dosage groups; MAD- TollB-001 100mg Dosage groups; MAD- TollB-001 200mg Dosage groups; MAD-TollB-001 400mg Dosage groups; MAD-TollB-001 800mg Dosage groups; SAD-TollB-001 1000mg Dosage groups; SAD-TollB-001 100mg Dosage groups; SAD-TollB-001 200mg Dosage groups; SAD-TollB-001 400mg Dosage groups; SAD-TollB-001 50mg Dosage groups; SAD-TollB-001 800mg Dosage groups

TollB-001 placebo DRUG

TollB-001 Placebo

MAD- TollB-001 100mg Dosage groups; MAD- TollB-001 200mg Dosage groups; MAD-TollB-001 400mg Dosage groups; MAD-TollB-001 800mg Dosage groups; SAD-TollB-001 1000mg Dosage groups; SAD-TollB-001 100mg Dosage groups; SAD-TollB-001 200mg Dosage groups; SAD-TollB-001 400mg Dosage groups; SAD-TollB-001 50mg Dosage groups; SAD-TollB-001 800mg Dosage groups

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male and female subjects between the age of 18 and 45 (both inclusive) when signing the informed consent form (ICF)
• Able to give a signed written ICF (the consent form must be signed by the subject prior to any study-specific procedures); have a full understanding of the study content, procedures, and possible AEs; and be willing and able to comply with study procedures and follow-up examinations
• Body mass index (BMI, weight \[kg\]/height2 \[m2\]) within 19.0-26.0 kg/m2 (both inclusive), with total body weight \> 50 kg for male subjects and \> 45 kg for female subjects.
• The subjects must be willing to use efficient physical contraception methods with a contraceptive failure rate of\<1% with their reproductive age partners within 90 days from signing the ICF to the last administration of the investigational drug (such as condoms , intrauterine devices)
• Male subjects must also be willing to refrain from donating sperm for 90 days from the first administration of the investigational drug to the last administration of the investigational drug
• Results of vital signs, physical examination, laboratory examinations, abdominal and urinary B-ultrasound, 12-lead ECG, and other examination are normal or abnormal but not clinically significant. QT interval corrected for heart rate according to Fridericia's formula (QTcF) must be within the following ranges: QTcF ≤ 450 msec for male subjects, and QTcF ≤ 470 msec for female subjects. Assessment may be repeated if deemed appropriate by the investigator.
• Ability to swallow all IMPs.

You may not qualify if:

• Known or suspected allergy or hypersensitivity to any component of TollB-001, known allergic constitution or allergy to two or more foods or drugs.
• Severe gastrointestinal diseases, such as patients who have undergone major gastrointestinal surgery that would potentially alter absorption and/or excretion of orally administered drugs (except for cholecystectomy, appendectomy, hernia repair), or medical history of ulcer, gastrointestinal bleeding, gastritis, etc.
• History or clinical manifestations of any clinically significant gastrointestinal, gallbladder or biliary tract, renal, urologic, pulmonary, neurological, cardiovascular, endocrinological, hematological, immunologic, dermatologic, metabolic disorder, or psychiatric disease (as determined by the investigator).
• Current or chronic history of liver disease or known hepatic ,or clinically significant of biliary abnormalities , or clinically significant abnormal results of liver function test at screening, including alanine amino transferase (ALT) or/and aspartate aminotransferase (AST) \> 1.5 × upper limit of normal (ULN)or/and total bilirubin \> ULN.
• eGFR \< 90 mL/min/1.73 m2 calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation at screening or on Day-1.
• Current or history of clinically significant cardiac arrhythmias (symptomatic or asymptomatic).
• Serious infection within 3 months prior to dosing or symptoms of infection within 7 days before dosing, including acute and chronic infections and local infections (bacterial, viral, parasitic, fungal, or other opportunistic pathogens), which is inappropriate to participant as deemed by the investigator.
• Major illness or surgery within 3 months before dosing ,or planned surgery during the study period.
• Intolerance to venipuncture.
• Participation in any clinical study or received any other investigational product or device within 4 weeks prior to the first dose or 5 times the half-life of the specific drug/biologics(whichever is longer), or plan to take an investigational agent during the study.
• Donated blood \> 400 mL or significant blood loss (equivalent to 400 mL), or received blood transfusion within 3 months of prior to screening, or have plans to donate blood during the study.
• History of malignancy within 5 years prior to screening (excluding non-melanoma skin cancer that has been resected).
• Positive results of any of the following tests at screening: serum hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV RNA or HCV antibodies \[Ab\]), human immunodeficiency virus 1 and 2 (HIV)Ab, or Treponema pallidum (TP) Ab.
• Active tuberculosis (TB) infection indicated by chest radiography orγ-interferon at screening or within 3 months prior to screening. TB test positive, or active or latent TB infection as discretion of the investigator according to clinical practice, or history of TB, or currently receiving treatment for this disease.
• Plans to receive administration of any live vaccine within 4 weeks before dosing or up to 30 days after the last dose of IMP.

Sponsors & Collaborators

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

Study Sites (1)

Chengdu Fifth People's Hospital

Chengdu, Sichuan, 611130, China

RECRUITING

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• wen he

  Chengdu Fifth People's Hospital

  STUDY DIRECTOR

Central Study Contacts

min xv, Master

CONTACT

15198081852; Xm15198081852@163.com

xuehong deng, Doctor

CONTACT

183 8218 4974; dxuehong7y@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2023
• First Posted: October 27, 2023
• Study Start: September 28, 2023
• Primary Completion: June 9, 2024
• Study Completion: June 9, 2024
• Last Updated: October 27, 2023

Record last verified: 2023-10

Locations

CN (1)