A Single-center, Dose Block-Randomized, Double-blinded, Placebo-controlled, Dose-escalation, Phase 1b Clinical Trial to Evaluate the Safety and Tolerability of E1K after Multiple Dose in patients with Osteoarthritis
- Conditions
- Diseases of the musculoskeletal system and connective tissue
- Registration Number
- KCT0006030
- Lead Sponsor
- Ensol Biosciences
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 18
1.Male or female subjects, who older than 40 years of age at the date of consent
2.Subjects with osteoarthritis according to ACR criteria, having pain in the knee and osteophyte formation in the X-ray, and one or more criteria as follows:
-Aged >50
-Morning stiffness < 30 minutes
-Crepitus on knee motion
3.Subjects with visit 1(screening) and Visit 2 VAS score = 40mm on a 100mm scale during activity of the knee of degenerative osteoarthritis(target lesion) .
4.Subjects with Grade 2 or Grade 3 on the knee of osteoarthritis(target lesion) by Kellgren & Lawrence radiographic grading system
5.Subjects who have single-sided osteoarthritis or target lesion to be designated according to the following criteria in case of both-sided osteoarthritis:
If both knees meet inclusion/exclusion criteria, the target lesion shall be designated according to the following criteria.
1)Designate higher Kellgren & Lawrence Grade side as target lesion
2)If the Kellgren & Lawrence grade is the same, designate higher 100mm pain VAS score side as target lesion.
3)If the Kellgren & Lawrence grade and the 100mm pain VAS score are the same, designate as the side which induces clinical symptoms other than pain.
6.Subjects who has voluntarily written informed consent for study participation.
1.Subject who has inflammatory joint disease, such as rheumatoid arthritis, and septic arthritis.
2.Subject who has conditions that can affect the joints(gout, recurrent caustic gout, joint fracture, primary osteochondrosis, Paget's disease, ochronosis, acromegaly, hematochromatosis, Wilson's disease, genetic disease(ex: hyperkinesia) and collagen gene related disorders.
3.Subject whose BMI greater than or equal to 30kg/m2 at screening.
4.Subject who has surgical history on the knee osteoarthritis lesion(target lesion).
5.Subject who is applicable to the followings.
-Administered NSAIDs or glucosamine, chondroitin sulfate within 14 days prior to IP administration.
-Administered Narcotic or non-narcotic analgesics within 1 days prior to IP administration
-Intra-articular injected steroids into the knee osteoarthritis lesion(target lesion) within 3 months prior to IP administration
-Intra-articular injected hyaluronic acid, cell therapy and gene therapy within 6 months prior to IP administration
-Administered E1K
6.As a result of screening examination(laboratory or ECG, vital sign), subject who has clinically significant findings that are not suitable for participation in the clinical trials.
7.Subject who has clinically significant disorders on cardiovascular system, digestive system, endocrine system, immune system, CNS, mental system.
8.The subject has a positive test result for HIV antibody or hepatitis B antigen, hepatitis C antibody.
9.The subject is unable to collect blood through vein during the clinical trial period.
10.The subject has donated 400 ml or more of blood volume within 12 weeks based on screening visit or 200ml or more within 4 weeks based on screening visit or donated blood between screening visit and IP administration day.
11.Subject who has drug or alcohol dependence within 1 year.
12.Person who do not agree to use a medically acceptable method of contraception* among those who are likely to become pregnant by themselves or whose partner during the clinical trials, or are pregnant, nursing, or planning to become pregnant.
*Medically acceptable method of contraception
1) Single contraception: Intra-Uterine Device (IUD), subject’s or subject’s male partner’s vasectomy, tubal ligation
2) combined contraception: condom or combination usage of septum and spermicide
13.In case of male subject, those who do not agree to ban sperm donation up to 12 weeks after IP administration.
14.Subject who is participated in other clinical trials within 3 months prior to screening.
15.Besides, in case investigator determine that subject is unsuitable for study participation.
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 1. Evaluation of Safety and Maximum Tolerated Dose 1) Evaluate the safety after IP administration. - DLT, Adverse Event, Laboratory, Vital Sign, ECG, Physical examination 2) Evaluate the MTD
- Secondary Outcome Measures
Name Time Method Evaluation of Exploratory efficacy 1)Changes in 100 mm pain VAS(Pain during activity and rest in the last 24 hrs) at each evaluation point compared to the baseline 2)Changes in WOMAC total score and sub-scale(Pain, physical function, stiffness) at 8 Week, 16 Week, 24 Week compared to the baseline 3)Changes in joint space width evaluated by x-ray at 24 week compared to the baseline 4)Changes in Biomarkers at every evaluation point - Anabolic biomarkers: PIINP, PIICP, CS846 - Catabolic biomarkers: MMP-13, CTX-II, COMP, NTX-I, MMP-3, DPD, PYD 5 5)Ratio of subject who took rescue medication and number of times it was taken during the entire clinical trial period