To evaluate the safety, tolerability and pharmacokinetics of EQ121 following multiple dose administration in adults with Rheumatoid Arthritis who are on a stable oral methotrexate (MTX) regimen.
- Conditions
- Rheumatoid arthritisInflammatory and Immune System - Rheumatoid arthritis
- Registration Number
- ACTRN12621001047886
- Lead Sponsor
- EQRx, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Stopped early
- Sex
- All
- Target Recruitment
- 1
1. Are capable of giving informed consent and complying with study procedures;
2. Male or female between the ages of 18 and 75 years, inclusive;
3. BMI of 18.0 to 32.0 kg per m2, inclusive, at Screening;
4. Diagnosis of RA based on the 2010 American College of Rheumatology (ACR) per European League Against Rheumatism (EULAR) criteria greater than or equal to 6 months;
5. Patients must have less than or equal to 5 swollen joints (based on 28 joint counts) and less than and equal to 5 tender joints (based on 28 joint counts) at Screening and Baseline Visits;
6. Patients must have been on oral MTX therapy greater than or equal to 3 months and on folic acid for greater than and equal to 4 weeks prior to the first dose of study drug. Subjects must be on a stable dose of oral MTX (15-25 mg per week, given once weekly) with or without sulfasalazine (less than and equal to 3000 mg per day), hydroxychloroquine (less than and equal to 400 mg per day), or chloroquine (less than and equal to 250 mg per day), or leflunomide (10-20 mg/day) for more than or equal to 4 weeks prior to the first dose of study drug and must be able to continue on this stable dose for the duration of the study;
7. If on disease-modifying antirheumatic drugs (DMARDs) other than MTX plus or minus sulfasalazine or hydroxychloroquine or chloroquine or leflunomide, participants must have discontinued these medications for at least 3 months or 5 half-lives, whichever is longer, before the first dose of study drug.
8. If on a current therapy with Janus Kinase (JAK) Inhibitor, participants must have discontinued the JAK inhibitor at least 4 weeks prior to Screening. Participants who have prior exposure to any JAK inhibitor are eligible, unless the JAK inhibitor was discontinued due to safety reasons.
9. Female participants must not be currently breast-feeding, and must meet one of the following criteria:
a. Surgically sterile for at least 3 months prior to Screening by one of the following means:
- Bilateral tubal ligation
- Bilateral salpingectomy (with or without oophorectomy)
- Surgical hysterectomy
- Bilateral oophorectomy (with or without hysterectomy)
b. Postmenopausal, defined as the following:
- Last menstrual period greater than 12 months prior to Screening without an alternative medical cause, AND
- Postmenopausal status confirmed by serum FSH concentration at Screening greater than 40 mIU per mL
c. Female subjects of childbearing potential:
• must not have a positive serum pregnancy test at Screening and must have a negative urine pregnancy test on admission
• must use at least one of the following protocol specified highly effective methods of birth control, AND must agree to use barrier contraception (male condom) during heterosexual intercourse, from the time of Screening until at least 30 days after the last dose of study drug.
- Partner vasectomy (at least 6 months prior to Screening; vasectomized partner should be the sole partner of the female subject)
- Combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal, injectable)
- Progestogen-only hormonal contraception (oral, injectable, implantable)
- Implantable device (implantable rod or intrauterine device)
10. Male participants must agree to utilize a highly effective method of contraception (condom) during heterosexual intercoursefrom clinic admission until at least 90 days following the end of study visit and must refrain from donating sperm
1. Inability to attend all the study visits or comply with study procedures;
2. Hospital admission or major surgery within 3 months prior to Screening;
3. History of prescription drug abuse, or illicit drug use within 6 months prior to Screening;
4. History of alcohol abuse according to medical history within 6 months prior to Screening; (drinking 14 units of alcohol per week: 1 unit equals to 360 mL of beer, or 37 mL of spirits, or 120 mL of wine) at Screening or upon admission to the clinical site;
5. History of inflammatory joint disease other than RA (e.g., mixed connective tissue disease, seronegative spondyloarthropathy, psoriatic arthritides, Reiter’s syndrome, fibromyalgia, systemic lupus erythematosus, or any arthritides with onset prior to age 17);
6. History of RA disease flares in the preceding 90 days before Screening;
7. Current or expected need for oral corticosteroids (greater than 10 mg prednisone/day or equivalent);
8. Positive blood screen for HIV, hepatitis B core (IgG and IgM) and surface antigen (HBsAg), hepatitis C antibody at Screening;
9. History of any infection requiring treatment with IV anti-infectives within 30 days prior to Admission, or oral anti-infectives within 14 days prior to Admission;
10. History or evidence of active or latent tuberculosis (TB). Participants will be evaluated for latent TB infection. Subjects must demonstrate absence of TB infection or exposure by a negative chest x-ray and a negative QuantiFERON-TB Gold Test at Screening;
11. History of malignancy or evidence of dysplasia, other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma, or localized carcinoma in situ of the cervix;
12. History of myocardial infarction, coronary stenting, greater than Class I angina, or cerebrovascular accident within 6 months prior to the first dose of study drug, or history of cardiac arrest, significant cardiac arrhythmia, pacemaker, or clinically significant cardiovascular disease;
13. History of clinically significant psychiatric, neurologic, respiratory, endocrine, hepatic, or renal disease;
14. Laboratory values meeting the following criteria within the Screening period prior to the first dose of study drug: serum aspartate transaminase greater than 1.5 into ULN; serum alanine transaminase greater than 1.5 into ULN; estimated glomerular filtration rate by simplified 4-variable Modification of Diet in Renal Disease formula less than 40 mL per min per 1.73m2; total WBC count less than 2,500 per µL; absolute neutrophil count less than 1,500 per µL; platelet count less than 100,000 per µL; absolute lymphocyte count less than 1,000 per µL; and hemoglobin less than 10 g per dL.
15. Any condition or finding that in the opinion of the Principal Investigator or designee would put the participant or study conduct at risk if the participant were to participate in the study.
16. Receipt of inducers of CYP2C9 (e.g. rifampin) moderate or strong inhibitors of CYP2C9 (e.g. fluconazole), strong inducers of CYP3A4 (e.g. carbamazepine, phenytoin, rifampin, St. John's Wort) or strong inhibitors of CYP3A4 (e.g. itraconazole, ketoconazole, clarithromycin, telithromycin, nefazodone) from screening through the end of sub study.
17. History of organ transplant, including history of bone marrow transplant
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method