None listed
Conditions
Brief summary
This is a Phase 1, open-label study to evaluate the safety, tolerability, and pharmacokinetics of EQ121 following multiple dose administration in adults with RA who are on a stable oral MTX regimen.
Interventions
EQ121 capsule is an oral solid dosage form manufactured at strengths of 1 mg and 12 mg.
Each EQ121 Immediate release (IR) capsule contains EQ121 drug substance; mannitol, pregelatinized starch and microcrystalline cellulose as diluents; croscarmellose sodium as disintegrate; colloidal silicon dioxide as glidant; and magnesium stearate as lubricant.
Approximately 12 adults with RA on a stable oral MTX regimen (15-25 mg/week) will be participating in this study. Eligible participants in New Zealan
EQ121 capsule is an oral solid dosage form manufactured at strengths of 1 mg and 12 mg. Each EQ121 Immediate release (IR) capsule contains EQ121 drug substance; mannitol, pregelatinized starch and microcrystalline cellulose as diluents; croscarmellose sodium as disintegrate; colloidal silicon dioxide as glidant; and magnesium stearate as lubricant. Approximately 12 adults with RA on a stable oral MTX regimen (15-25 mg/week) will be participating in this study. Eligible participants in New Zealand will receive their weekly dose of oral MTX on Days 1 and 8 and 36 mg of EQ121 orally, twice daily (twelve hours apart) on study days 3 to 8. Blood samples for the determination of EQ121 concentrations and corresponding PK analysis will be collected on Day 3, Day 7 and Day 8 at pre-dose (morning dose; within 30 minutes prior to dosing); and after the morning dose at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours. Blood samples for determination of MTX concentration and corresponding PK analysis will be collected on Day 1 at pre-dose (30 minutes prior to dosing), and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose, on Day 2 at 24 and 36 hours post-dose, and Day 3 at 48 hours post-dose; and on Day 8 at pre-dose (30 minutes prior to administering oral MTX and study drug together), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours post-dose, on Day 9 at 24 and 36 hours post-dose and on Day 10 at 48 hours post-dose. Samples may be used to determine concentration of drug metabolites. Safety oversight will be provided by the Principal Investigator and Medical Monitor. A record will be maintained by the investigational site that will account for all dispensing and return of any used and unused study drug. Adherence will be assessed using pill count of the capsules returned.
Sponsors
EQRx, Inc
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used) (Subject, Caregiver)
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
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 for this same period. 11. Considered to be in general good health by the Investigator, based on participant’s reported medical history, full physical examination, clinical laboratory tests, 12-lead ECG, chest x-ray, and vital signs; 12. Willing and able to adhere to study restrictions and to be confined at the clinical research center; 13. Participants must be willing to defer receiving prophylactic immunizations (e.g. influenza or coronavirus or pneumococcal vaccines) during the study.
Exclusion criteria
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
Outcome results
None listed