Clinical trial NCT04638426: Phase 2a Clinical Trial of HL237 for Rheumatoid Arthritis
Official title: For 12 Weeks, the Multi Center, Randomized, Double Blinded, Placebo Controlled, Parallel, Dose-finding Clinical Study for the Therapeutic Exploration of Safety and Efficacy Assessment of HL237 Tablet in Patients With Rheumatoid Arthritis (Phase IIa)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Lead sponsor: Hanlim Pharm. Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-11-20
Enrollment: 196
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this clinical trial is to determine the optimal dose of HL237 tablets in rheumatoid arthritis patients by comparing the efficacy and safety of the three dose groups of HL237 tablets and the control group.


Eligibility criteria: Inclusion Criteria:

* Male or Female, 19 years ≤ age ≤ 80 years
* In the case of women of childbearing age, those who have a negative pregnancy test before randomization
* Patients who agree to use a medically accepted method of contraception during the clinical trial
* Patients corresponding to ACR functional class Ⅰ,Ⅱ,Ⅲ
* Patients with active rheumatoid arthritis with DAS28-ESR \> 3.2 in the evaluation of DAS28-ESR identified at the screening
* Patients who were diagnosed with rheumatoid arthritis according to the 2010 ACR/EULAR classification criteria at least 3 months prior to the screening, and showed insufficient response or refractory to treatment with one or more DMARDs.
* Among the subjects who have previously been continuously administering the following rheumatoid arthritis drugs without stopping, those who have used them according to the conditions before randomization and can maintain the current administration regimen and dose during the clinical trial.

  * cDMARDs : Patients who received the same cDMARDs for 12 weeks or more continuously and did not change the dosage and administration of the cDMARDs for 4 weeks or more until the 2nd visit(ex. methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, bucillamine etc.)
  * Prednisolone : Patients who received corticosteroids with a daily dose of 10mg or less of oral prednisolone equivalent continuously, and did not change the dosage and administration for more than 2 weeks until the 2nd visit.
  * Tramadol or NSAIDs : Patients who did not change the dosage and administration for more than 2 weeks consecutively until the 2nd visit
* Patients who have completed the wash-out period as follows until the 2nd visit including the screening period (each period refers to the case where it continues consecutively, and these drugs are contraindicated from the screening).

  * bDMARDs abatacept, adalimumab, certolizumab pegol, golimumab : 10 weeks or more anakinra : 10 days or more etanercept : 3 weeks or more infliximab : 8 weeks or more tocilizumab : 5 weeks or more rituximab : 6 months or more
  * JAK inhibitors tofacitinib, baricitinib : 2 weeks or more
  * immunosuppressants tacrolimus, cyclosporin, azathioprine, cyclophosphamide mizoribine etc : 4 weeks or more
  * tramadol, analgesics and anti-inflammatory analgesic other than NSAIDs : 4 days or more
* Volunteer, be willing and able to provide written informed consent for the trial
* Patients who can read and understand written instructions

Exclusion Criteria:

* Patients corresponding to ACR functional class Ⅳ
* Patients with acquired immune deficiency syndrome or autoimmune diseases other than rheumatoid arthritis
* Severe heart failure, congestive heart failure (NYHA II～IV), ischemic heart disease, peripheral artery disease and/or cerebrovascular disease
* Patients with a history of gastrointestinal bleeding or perforation due to treatment of nonsteroidal anti-inflammatory drugs
* Patients with bleeding or a current history of blood coagulation disorder
* Patients suffering from infectious disease (including tuberculosis, shingles, etc.) at the time of screening or undergoing treatment with the medical history
* Patients with a history of malignant tumors within 5 years prior to screening
* Patients with peptic ulcer confirmed by endoscopy or radiographic examination within 6 months prior to screening
* Patients with a history of gastric or duodenal perforation or obstruction, patients with a history of gastrointestinal surgery (except appendicitis), and patients with a history of upper or lower gastrointestinal bleeding (excluding simple hemorrhoids) within the past year
* Patients with symptoms or signs of pyloric obstruction
* Patients diagnosed with malabsorption within 12 weeks prior to the screening
* Patients with hypersensitive reaction or history of clinically significant hypersensitive reaction to investigational product or its excipients
* Patients with aspirin asthma (asthma attacks caused by nonsteroidal anti-inflammatory drugs) or a history of the same
* Patients with inflammatory bowel disease such as crohn's disease or ulcerative colitis
* Pregnant or breast-feeding
* Patients administered intraarticular, intramuscular, intravenous corticosteroids within 4 weeks priro to the screening.
* Patients with significant psychiatric disorders or taking antidepressants, anticonvulsants, or sedatives
* Patients with substance or alcohol abuse or dependence
* Patients who participate in other clinical trials within 12 weeks prior to the screening and administer investigational drugs or apply clinical trial medical devices
* Patients expected to inevitably administer contraindicated drugs during the clinical trial
* Patients with severe renal dysfuntion(seurum creatinine is 2.0 times higher than the upper limit of normal (based on the institution))
* Patients with severe liver dysfuntion(ALT, AST or total bilirubin is 2.0 times higher than the upper limit of normal (based on the institution))
* Patients that the investigator deems unsuitable for participation in the clinical trial

Primary outcomes:
measure: ACR20(american college of rheumatology 20) response rate
timeFrame: at 12 weeks after administering investigational products
Secondary outcomes:
measure: ACR20(american college of rheumatology 20) response rate
timeFrame: at 4, 8 weeks after administering investigational products
measure: DAS28-ESR(Disease Activity Score 28- erythrocyte sedimentation rate) score
timeFrame: at 4, 8, 12 weeks after administering investigational products
measure: DAS28-CRP(Disease Activity Score 28-C-reactive protein) score
timeFrame: at 4, 8, 12 weeks after administering investigational products
measure: Tender joint count
timeFrame: at 4, 8, 12 weeks after administering investigational products
measure: Swollen joint count
timeFrame: at 4, 8, 12 weeks after administering investigational products
measure: Investigator's composite assessment of disease activity
timeFrame: at 4, 8, 12 weeks after administering investigational products
measure: Subject's composite assessment of disease activity
timeFrame: at 4, 8, 12 weeks after administering investigational products
measure: Subject's assessment of pain (visual analog scale)
timeFrame: at 4, 8, 12 weeks after administering investigational products
measure: Subject's assessment of physical function (Korean health assessment questionnaire)
timeFrame: at 4, 8, 12 weeks after administering investigational products
measure: Erythrocyte Sedimentation Rate (ESR)
timeFrame: at 4, 8, 12 weeks after administering investigational products
measure: C-Reactive Protein (CRP)
timeFrame: at 4, 8, 12 weeks after administering investigational products
measure: morning stiffness duration
timeFrame: at 4, 8, 12 weeks after administering investigational products
measure: The average number of times of use the remedy per day
timeFrame: at 4, 8, 12 weeks after administering investigational products
measure: The percentage of subjects who use the remedy
timeFrame: at 4, 8, 12 weeks after administering investigational products
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Seoul ST.MARY'S Hospital
Study officials:
References: