Clinical trial NCT03850587: Clinical Trial of YYC301 for Treatment of Osteoarthritis of the Knee
Official title: A Multi-center, Double-blinded, Randomized, Active-controlled, Parallel Design, phaseII Study to Investigate the Efficacy and Safety of YYC301 in Subject With Knee Osteoarthritis.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Osteoarthritis, Knee
Lead sponsor: Yooyoung Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: CliPS Co., Ltd
First posted: 2019-02-22
Enrollment: 261
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The purpose of this study is to investigate the efficacy and safety after administration of YYC301(Experimental) or Celecoxib(Comparator) in subjects with knee osteoarthritis in a state of uncontrolled pain who took Celecoxib(Cox-2 inhibitor).
Primary purpose: TREATMENT

Brief summary: A Multi-center, Double-blinded, Randomized, Active-controlled, Parallel Design, phaseII Study to Investigate the Efficacy and Safety of YYC301 in Subject With Knee Osteoarthritis


Eligibility criteria: Inclusion Criteria:

* Men/Women aged over 20
* Subjects who are diagnosed with one- or both-sided knee osteoarthritis according to the standards of clinical diagnosis from American College of Rheumatology(ACR)have knee osteoarthritis pain and meet over three of the following conditions.

  1. Older than 50
  2. Morning stiffness for less than 30 minutes
  3. Crepitus on active motion
  4. Bony tenderness
  5. Bony enlargement
  6. Not have heat-generating site
* Subjects who are diagnosed with degenerative osteoarthritis and have its pain at least for over 3 months before the screening visit.
* Subjects who are uncontrolled with pain after administration of Celecoxib at least for over 2 weeks before the randomization and have more than 40mm out of 100mm VAS at randomization.
* Subjects who voluntarily agree to participate in this clinical trial in writing.

Exclusion Criteria:

* Subjects with rheumatoid arthritis or inflammatory, infectiousand metabolic arthritis.
* Subjects with ochronosis, hemochromatosis, secondary knee osteoarthritis by systemic disease.
* Subjects who have severe pain such as Sudek's atrophy, Paget's disease and spinal disc herniation.
* Subjects with poly-articular affected by severe pain of knee osteoarthritis.
* Subjects who take psychtrophic medicine and narcotic analgesics for over 3 months that might affect on pain sensory system.
* Subjects who had Tramadol but there was no improvement in pain.
* Subjects who got the follwing treatment and medicine before the screening;

  1. Subjects who had surgery on knee ligaments within a year, cartilage transplant and scarf osteotomy.
  2. Subjects who had arthroscopy within 6 months.
  3. Subjects with intra-articular knee joint steroid injection within 3 months.
  4. Subjects with HA injection in knee joint within 2 months.
  5. Subjects with systemic steroid injection within a month(but inhaled steroids)
  6. Subjects with knee replacement surgery.
* Subjects who hot the following treatment and medicine before the randomization;

  1. Subjects who had Celecoxib, acetaminophen or steroidal/non-steroidal anti-inflammatory drugs except low dose aspirin(before 300mg/day) But, acetaminophen and low dose aspirin (before 300mg/day) are prohibited within 24 hours)
  2. Nutritional supplements, physical therapy and Korean herbal medicine for knee osteoarthritis and it pain within 2 weeks.
* Subjects who have to take anticoagulant drugs such as warfarin and coumarin during this clinical trial.
* Subjects who took MAO inhibitors within 14 days before the screening or needed to take these drugs during this clinical trials.
* Subjects with drug and opioid hypersensitivity and who have history.
* Subjects with sulfanilamide allergy and who have history.
* Subjects with asthmma, acute rhinitis, nasal polyp, angioedema, urticaria, allergic reaction to aspirin or any oher NSAIDs(incluing COX-2 inhibitors)
* Subjects with significant investigations - Hyperkalemia(Exceeded 5.5mmol/L)
* Subjects with severe liver dysfunction (ALT or AST of more than 3.0 times the upper limit of ULN and 1.5 tmines the upper limit of ULN)
* Subjects with severe renal impairment (Serum Creatine \> 3x ULN).
* Subjects with active peptic ulcer and gastrointestinal bleeding.
* Severe blood disease (Agranulocytosis, aplastic anemia, hemolytic anemia, Thrombocytopenia, etc.).
* Subjects with Crohn's disease or inflammatory bowel disease such as ulcerative clitis.
* Subjects with congestive heart failure(NYHA 2-4)
* Subjects with severe ischaemic heart disease, peripheral artery disease and/or cerebrovascular disease.
* Subjects with genetic problesa such as galactose intolerance), lapp lactase deficiency or glucose-galactose malabsorption).
* Subjects with acute alcohol intoxification.
* Subjects who are addicted with took central nervous system drugs such as painkillers, sleeping pills, anti-anxiety medications, etc.
* Subjects with severe bronchopulmonary dysplasia.
* Subjects with head injury history of brain structure lesions which may be in danger of mental confusion.
* Subjects with epilepsy who are treated properly.
* Subjects who use Tramadol to cure for narcotic withdrawal.
* Subjects who took other clinical drugs more than once within 30 days before the clinical trial.
* Subjects suspected to be pregnant who don't agree with the clinical method which is permitted medically during clinical trial(Method of hormone contraception, IUD(Intrauterine device) or IUS(Intrauterine system)), tubal ligation, bilateral tubal ligation(condom, Diaphragm, etc).
* Pregnant woman and breastfeeding woman.
* Subjects who can increase risk due to clinical test and administraion of drugs or have severe grade / chronic medical, mental condition or abnormal laboratory result that may interfere with the analysis of thest results.
* Any other ineligible condition at the direction of investigator that would be ineligible to participate the study.

Primary outcomes:
measure: 100mm Pain VAS
timeFrame: at 1,4,8,12 weeks after randomization after administration of YYC301(Experimental drug).
measure: KOOS(Knee Injury and Osteoarthritis Outcome Score)
timeFrame: at 4,8,12 weeks after randomization after administration of YYC301(Experimental drug).
measure: Patient Global Assessment(PGA)
timeFrame: at 4,8,12 weeks after randomization after administration of YYC301(Experimental drug).
measure: Total dosage and dosage rate of rescue treatment.
timeFrame: at screening time(visit 1; 2 weeks before next visit 2), randomization(visit 2), 4, 8 weeks after randomization.
Secondary outcomes:
Other outcomes:
Locations:
city: Busan
country: Korea, Republic of
facility: Dong-A University Hospital.
city: Seoul
country: Korea, Republic of
facility: Bundang Seoul University Hospital
city: Seoul
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital at Gangdong
city: Seoul
country: Korea, Republic of
facility: KyungHee University Medical Center
city: Seoul
country: Korea, Republic of
facility: Soonchungyand University Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul ST. Mary's Hospital.
Study officials:
References: