E1K Intra Articular(IA) Treatment for Knee Osteoarthritis

A Multicenter, Randomized, Double-blinded, Placebo-controlled, Phase 2 Clinical Trial to Evaluate the Efficacy and Safety of E1K After Single Dose in Patients With Knee Osteoarthritis

The objective of this study is to evaluate the efficacy and safety of pain relief treatment on knee osteoarthritis when administered E1K or placebo in patients with knee osteoarthritis aged 40 to 70 to determine the optimal dose.

Study Overview

• Status: Completed
• Conditions: Osteoarthrosis
• Intervention / Treatment: Drug: E1K 1,200 ㎍/joint; Drug: E1K 2,400 ㎍/joint; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female adult, who is 40 years~70 years of age(inclusive of both age) at the date of consent

2. Subject who diagnosed knee osteoarthritis according to ACR criteria at screening visit, 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. Prior to administration of IP, Subject with 50mm~70mm of 100mm Pain Visual Analog Scale (VAS) during activity of the knee of osteoarthritis(target lesion).
4. Subject with Grade 2 or Grade 3 on the knee osteoarthritis(target lesion) by Kellgren & Lawrence radiographic grading system
5. Subject who has pain on the knee osteoarthritis at least for 6 months before screening visit.
6. Subject who agrees not to use rescue medication within 48-hour of regular visit date.
7. Subject who agrees not to have ancillary physiotherapy

8. One-sided knee osteoarthritis subject or both-sided knee osteoarthritis subject who can designate the Target Lesion to one side, according to the follow criteria.

   • Designate the one with a higher 100 mm Pain Visual Analog Scale (VAS) than another, as the target lesion.
   • If 100 mm Pain Visual Analog Scale (VAS) is the same, designate the one with a higher Kellgren & Lawrence Grade than another, as the target lesion.
   • If both 100 mm Pain Visual Analog Scale (VAS) and Kellgren & Lawrence Grade are the same, designate the one that causes more clinical symptoms other than pain.
   • If above criteria are all the same, designate the right knee as the target lesion.
9. Subject who has voluntarily written informed consent for study participation.

Exclusion Criteria:

1. Subject who has secondary knee osteoarthritis such as inflammatory or infectious joint disease or rheumatoid arthritis.
2. Subject who has surgical history(ex. knee replacement surgery) on the knee osteoarthritis lesion(target lesion).
3. 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.
4. Subject whose BMI greater than or equal to 30kg/m2 at screening.

5. Subject who is applicable to the followings prior to first day of IP administration.

   • Intra-articular injected hyaluronic acid, cell therapy and gene therapy within 6 months prior to IP administration
   • Intra-articular injected steroids into the knee osteoarthritis lesion(target lesion) within 3 months prior to IP administration
   • Administered NSAIDs or glucosamine, chondroitin sulfate, oral steroid within 14 days prior to IP administration.
   • Administered analgesics within 1 days prior to IP administration
6. Subject who has a psychological disorder(alcohol or drug addiction) and is judged by the investigator to have problems with the safety of the subject or to cause confusion in the interpretation of clinical trial results
7. Subject who has osteoarthritis on the other sites not knee(ex. Hip joint) or has pain due to other disorder so that the investigator determined not suitable for participation of the clinical trial.
8. Subject who has uncontrolled type 1 or type 2 diabete mellitus at screening visit(Glycated Hemoglobin (HbA1c) > 8%)
9. Subject has a positive test result for HIV antibody or hepatitis B antigen, hepatitis C antibody.
10. Subject who has malignant tumor history within 5 year prior to screening visit.
11. Subject who is participated in other clinical trials within 30 days prior to screening.
12. 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.
13. Subject who is pregnant or breastfeeding
14. Subject who does not agree to use a medically acceptable method of contraception during clinical trial.
15. Besides, in case investigator determine that subject is unsuitable for study participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: E1K 1,200 ㎍/joint; Injected 1,200 ㎍/joint/3 mL on target lesion	Drug: E1K 1,200 ㎍/joint; Injection of E1K 1,200 ㎍/joint/ml on target lesion
Experimental: E1K 2,400 ㎍/joint; Injected 2,400 ㎍/joint/3 mL on target lesion	Drug: E1K 2,400 ㎍/joint; Injection of E1K 2,400 ㎍/joint/ml on target lesion
Placebo Comparator: Placebo; Injected 3ml of saline on target lesion	Drug: placebo; Injection of 3ml saline on target lesion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
WOMAC(Western Ontario and McMaster Universities Osteoarthritis Index)	Changes in the Sub-Scale(Pain) score of the WOMAC questionnaire	12 weeks after administration of IP versus baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain VAS 100mm	Changes in 100 mm Pain VAS (Pain during activity and at rest during the last 24 hours) scores	at 4, 8, and 12 weeks after administration of IP versus baseline
WOMAC(Western Ontario and McMaster Universities Osteoarthritis Index)	Changes in scores by WOMAC questionnaire total score and Sub-Scale (physical function, stiffness)	at 4, 8, and 12 weeks after IP administration compared to baseline
WOMAC(Western Ontario and McMaster Universities Osteoarthritis Index)	Changes in the Sub-Scale(Pain) score of the WOMAC questionnaire	at 4 to 8 weeks after administration of IP compared to the baseline
KOOS	Changes in KOOS questionnaire scores	at 4, 8, and 12 weeks after administration of IP compared to baseline
Quality of life(EQ-5D-5L)	Changes in EQ-5D-5L questionnaire scores	at 4, 8, and 12 weeks after administration of IP compared to baseline
Frequency of Rescue drug	Percentage and number of subjects who took the rescue medication during the clinical trial period	Day 0 to Day 84

Collaborators and Investigators

• Sponsor: Ensol Bioscience
• Investigators: Principal Investigator: Young-Wan Moon, M.D., Ph.D., Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2022
• Primary Completion (Actual): November 29, 2023
• Study Completion (Actual): November 29, 2023

Study Registration Dates

• First Submitted: January 15, 2023
• First Submitted That Met QC Criteria: January 15, 2023
• First Posted (Actual): January 26, 2023

Study Record Updates

• Last Update Posted (Actual): April 4, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: E1K-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No