A Study to Investigate Safety, Tolerability, and PK of Oral Doses of TCK-276 in Patients With Rheumatoid Arthritis

NCT ID: NCT05437419

Last Updated: 2024-10-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-10
• Study Completion Date: 2023-07-27

Brief Summary

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).

Detailed Description

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.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Cohort 1

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).

Group Type: EXPERIMENTAL

TCK-276

Intervention Type: DRUG

Patients will receive an oral dose of TCK-276 QD under fed conditions from Day 1 to Day 7.

TCK-276 Placebo

Intervention Type: DRUG

Patients will receive an oral dose of TCK-276 matching placebo QD under fed conditions from Day 1 to Day 7.

Cohort 2

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).

Group Type: EXPERIMENTAL

TCK-276

Intervention Type: DRUG

Patients will receive an oral dose of TCK-276 QD under fed conditions from Day 1 to Day 7.

TCK-276 Placebo

Intervention Type: DRUG

Patients will receive an oral dose of TCK-276 matching placebo QD under fed conditions from Day 1 to Day 7.

Cohort 3

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).

Group Type: EXPERIMENTAL

TCK-276

Intervention Type: DRUG

Patients will receive an oral dose of TCK-276 QD under fed conditions from Day 1 to Day 7.

TCK-276 Placebo

Intervention Type: DRUG

Patients will receive an oral dose of TCK-276 matching placebo QD under fed conditions from Day 1 to Day 7.

Cohort 4

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).

Group Type: EXPERIMENTAL

TCK-276

Intervention Type: DRUG

Patients will receive an oral dose of TCK-276 QD under fed conditions from Day 1 to Day 7.

TCK-276 Placebo

Intervention Type: DRUG

Patients will receive an oral dose of TCK-276 matching placebo QD under fed conditions from Day 1 to Day 7.

Interventions

TCK-276

Patients will receive an oral dose of TCK-276 QD under fed conditions from Day 1 to Day 7.

Intervention Type: DRUG

TCK-276 Placebo

Patients will receive an oral dose of TCK-276 matching placebo QD under fed conditions from Day 1 to Day 7.

Intervention Type: DRUG

Other Intervention Names

Cyclin Dependent Kinase 4/6 (CDK 4/6) Inhibitor; TEI-T01276; Placebo

Eligibility Criteria

Inclusion Criteria

• 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:

1. 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.

2. 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Parexel

INDUSTRY

Sponsor Role: collaborator

Teijin America, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tatyana Zubkovskaya

Role: STUDY_DIRECTOR

Medical Director

Locations

Orange County Research Center

Tustin, California, United States

St. Jude Clinical Research, LLC

Doral, Florida, United States

SouthCoast Research Center, Inc

Miami, Florida, United States

Allied Biomedical Research Institute

Miami, Florida, United States

San Marcus Research Clinic, Inc.

Miami Lakes, Florida, United States

Floridian Clinical Research, LLC

Miami Lakes, Florida, United States

Clinical Site Partners, LLC dba CSP Orlando

Winter Park, Florida, United States

SMS Clinical Research, LLC

Mesquite, Texas, United States

Countries

United States

References

Tasaki D, Tsuruda K, Sun S, Tsumura Y, Asano S, Suzuki Y, Tsujimoto S, Miura D, Sato H. A double-blind, placebo-controlled, randomized multiple dose phase 1b trial of a CDK4/6 inhibitor, TCK-276, in patients with active rheumatoid arthritis. Rheumatology (Oxford). 2025 Mar 1;64(3):1036-1044. doi: 10.1093/rheumatology/keae357.

Reference Type: DERIVED

PMID: 39002122 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

TCK-276-102

Identifier Type: -

Identifier Source: org_study_id