NCT05437419已完成1 期
A Phase 1, Randomized, Placebo-controlled, Double-blind, Multiple Ascending Dose Study to Investigate Safety, Tolerability, and Pharmacokinetics of Oral Doses of TCK-276 in Patients With Rheumatoid Arthritis
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 8
- 主要终点
- Number ot Participants With Treatment Emergent Adverse Events
研究概览
简要总结
The study is to evaluate the safety, tolerability, and pharmacokinetic (PK) of multiple orally administered TCK-276 in both males and females with Rheumatoid Arthritis (RA).
详细描述
This is a Phase 1, multi-center, double-blind, randomized, placebo-controlled, multiple ascending dose (MAD) study.
The study will consist of a Screening Visit (Days -1 to Day 10), Treatment duration (up to 11 days) and a Follow-up/end of treatment (EOT) visit.
This MAD study will consist of 4 cohorts of 8 patients (6 active treatment and 2 matching placebo, or a 3:1 ratio), each receiving an oral dose of TCK-276 or matching placebo for 7 days (once daily (QD) under fed condition). The first cohort will be divided into 2 subgroups to implement the sentinel dosing approach.
The study duration is approximately 42 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of RA and meeting the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for RA.
- •Patients between the ages of 18 and 64 years, inclusive, at the Screening Visit.
- •Female patient must be not pregnant, not breast feeding and one of the following conditions need to apply:
- •Of non-childbearing potential based on documented surgical treatment or post-menopausal, meaning patient had spontaneous amenorrhea for at least 12 months without alternate medical cause prior to Screening Visit and follicle stimulating hormone (FSH) > 40 U/mL at the Screening Visit.
- •Of childbearing potential and using a highly effective method of contraception and agrees to remain on a highly effective method from the time of signing the informed consent form (ICF) until 21 days after the last dose.
- •Male patient must agree to stay abstinent or must use together with his female partner(s) a form of highly effective contraceptive (failure rate of < 1% per year) from the time of signing the ICF until up to 3 months after the last dose of the study drug.
- •Nonsmokers (or other nicotine use) as determined by history and by negative urine cotinine concentration at the Screening Visit and at Admission.
- •Body mass index (BMI) between 18.5 and 32.0 kg/m2, inclusive, at the Screening Visit.
- •Patient is required to have completed a COVID-19 vaccine regimen within no more than 5 months prior to screening to be eligible for the study.
- •Permitted concomitant medications for any reason, must be on a stable dose.
- •Permitted medications include: anti-malarials; nonsteroidal anti-inflammatory drugs including selective cyclooxygenase-2 inhibitors at approved dosage, and low dose oral corticosteroids; methotrexate concomitantly with folic acid or folinic acid.
排除标准
- •Female patients who are breastfeeding or have a positive urine pregnancy test.
- •Patients who are unable to eat the prescribed meals during the stay at the site; vegetarian or vegan.
- •Patient has a history of significant drug allergy.
- •Patient has used a study drug, any prohibited medication(s), over-the-counter (OTC) medications, vitamins, dietary and herbal supplements.
- •Patient has a history of active suicidal ideation, or any psychiatric disorders that will affect the patient's ability to participate in the study.
- •Patient has a current or recent history of uncontrolled, clinically significant infectious, hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease.
- •Patient with any of the laboratory abnormalities as per reference.
- •Patient has a history of alcohol and/or drug abuse within 24 weeks.
- •Patient has positive results for drug testing and breath alcohol test.
- •Regular consumption of alcohol within 6 months prior to the Screening Visit.
- •Patient has positive test for hepatitis B surface antigen (HBsAg), anti-hepatitis B core (HBc) antibodies, hepatitis C virus (HCV) antibody, and/or human immunodeficiency virus (HIV) antibody at Screening Visit.
- •Patient has QT interval corrected for heart rate (QTc) using Fridericia's correction (QTcF) > 450 ms for males or QTcF > 470 ms for females either at the Screening Visit or Admission, based on safety 12-lead electrocardiogram (ECG). Patient has Screening or Admission ECG with second- or third-degree atrioventricular block, bundle branch block, arrhythmia (but not sinus arrhythmia or supraventricular premature beats), or illegible QT interval.
- •Patient has history or evidence of cardiopathy, acute coronary syndrome, hypertrophic cardiomyopathy, myocarditis or QT prolongation syndrome.
- •Patient is unwilling to abstain from drinks and foods containing alcohol, grapefruit, or caffeine
- •Patient has donated blood or experienced acute blood loss (including plasmapheresis) of greater than 500 mL within 90 days prior to the first dose of study drug.
- •Patients with a known immunodeficiency disorder. Have a history of a major organ transplant or hematopoietic stem cell/marrow transplant.
- •Patients with infections requiring treatment or hospitalization within 14 days prior to the Screening Visit, parenteral antimicrobial therapy within 60 days prior to the Screening Visit, infected joint prosthesis; history of herpes zoster, active herpes simplex, or herpes simplex on suppressive therapy.
- •Patient has a chronic hepatic disease or hepatic impairment.
- •Patient has a history of Mycobacterium tuberculosis or positive interferon gamma release assay for tuberculosis (IGRA-TB) or abnormal chest X-ray (for positive IGRA-TB patients).
- •Patient has a history of any lymphoproliferative disorder.
- •Patient has a history of COVID-19 unless fully recovered with no sequelae for 14 days.
- •Patient who had a severe course of COVID-19 (extracorporeal membrane oxygenation, mechanically ventilated).
- •Patient who has recent exposure to someone who has COVID-19 symptoms or positive test result.
- •Patient who has a positive reverse transcription polymerase chain reaction (RT-PCR) test for Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2).
- •Patient who has clinical signs and symptoms consistent with SARS-CoV-2 infection.
- •Patients may not receive any live/attenuated vaccine from 30 days prior to the Screening Visit until Day 14 Follow-up Visit.
- •COVID-19 vaccine should not be given 1 week prior to the Screening Visit.
- •Patients with malignancy or history of malignancy except adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ. Previous treatment with total lymphoid irradiation.
- •History of recurrent inflammatory joint disease other than RA or history of any other autoimmune rheumatic diseases other than Sjogren's syndrome.
- •Major surgery within 30 days prior to the Screening Visit or patients with planned surgery.
- •Patients who have an abnormal chest X-ray for interstitial lung disease (ILD) and/or patients with history of ILD.
- •History of fainting or family history of sudden death.
- •Patient has any disorder that would interfere with the absorption, distribution, metabolism or excretion of study drug.
- •Patient has a history of deep vein thrombosis and/or pulmonary embolism.
- •Patient has poor venous access.
研究组 & 干预措施
Cohort 1
Experimental
The patient will receive Dose A of TCK-276 or matching placebo orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
干预措施: TCK-276 (Drug)
Cohort 1
Experimental
The patient will receive Dose A of TCK-276 or matching placebo orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
干预措施: TCK-276 Placebo (Drug)
Cohort 2
Experimental
The patient will receive Dose B of TCK-276 or matching placebo orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
干预措施: TCK-276 (Drug)
Cohort 2
Experimental
The patient will receive Dose B of TCK-276 or matching placebo orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
干预措施: TCK-276 Placebo (Drug)
Cohort 3
Experimental
The patient will receive Dose C of TCK-276 or matching placebo orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
干预措施: TCK-276 (Drug)
Cohort 3
Experimental
The patient will receive Dose C of TCK-276 or matching placebo orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
干预措施: TCK-276 Placebo (Drug)
Cohort 4
Experimental
The patient will receive Dose D of TCK-276 or matching placebo orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
干预措施: TCK-276 (Drug)
Cohort 4
Experimental
The patient will receive Dose D of TCK-276 or matching placebo orally from Day 1 to Day 7 (once daily (QD) under fed conditions).
干预措施: TCK-276 Placebo (Drug)
结局指标
主要结局
Number ot Participants With Treatment Emergent Adverse Events
时间窗: 42 days (duration of study)
To evaluate the safety and tolerability of multiple oral doses of TCK-276 or placebo in patients with rheumatoid arthritis (RA)
次要结局
- Metabolic Ratio (MR) for Cmax(Day 1 and Day 7)
- Fe 0-72: Percentage of Study Drug Excreted Unchanged in the Urine(Day 7 0-72 hours)
- Cmax: Plasma Concentrations of TCK-276 and TEI-W00595 (Metabolite)(Day 1 and Day 7)
- Tmax: Time of Maximum Plasma Concentration Determined Directly From the Concentration-time Profile(Day 1 and Day 7)
- t½: Terminal Elimination Half-life(Day 1 and Day 7)
- AUCtau: Area Under the Plasma Concentration-time Curve Over a Dosing Interval, Tau = 24 Hours(Day 1 and Day 7)
- AUC0-inf: Area Under the Plasma Concentration Time Curve From Pre-dose (Time 0) Extrapolated to Infinite Time(Day 1 and Day 7)
- Clearance (CL)/F: Apparent Total Body Clearance (Parent Only)(Day 1 and Day 7)
- Vz/F: Apparent Volume of Distribution Based on Terminal Phase (Parent Only)(Day 1 and Day 7)
- MRT0-inf: Mean Residence Time Extrapolated to Infinity(Day 1 and Day 7)
- Racc (Cmax): Accumulation Ratio Based on Cmax(Day 1 and Day 7)
- Racc (AUCtau): Accumulation Ratio Based on AUCtau(Day 1 and Day 7)
- MR for Area Under the Plasma Concentration-time Curve (AUC)Tau(Day 1 and Day 7)
- MR for Area Under the Plasma Concentration-time Curve (AUC)0-inf(Day 1 and Day 7)
- Ae 0-24: Amount of Study Drug Excreted Unchanged in the Urine (Days 1 and 7)(Day 1 and Day 7)
- Fe 0-24: Percentage of Study Drug Excreted Unchanged in the Urine (Days 1 and 7)(Day 1 and Day 7)
- Clearance Renal (CLr): Renal Clearance (Days 1 and 7)(Day 1 and Day 7)
- Ae 0-72: Amount of Study Drug Excreted Unchanged in the Urine (Day 7)(Day 7 0-72 hours)
研究者
研究点 (8)
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