Knee Osteoarthritis
Conditions
Brief summary
This is a Phase III, double-blinded, placebo-controlled, multicenter study to investigate the efficacy and safety of a new study intervention, ELIXCYTE, compared to placebo (normal saline) in subjects with knee osteoarthritis. The primary hypothesis of the study is to demonstrate that ELIXCYTE is superior to placebo (saline) in improving knee pain on the target knee from baseline. During the study, each participant will receive either ELIXCYTE (study intervention) or placebo (normal saline) intra-articular injection once on the target knee after eligibility criteria check. The target knee will be assessed by X-ray, MRI and subject self-evaluation knee questionnaires (WOMAC, KSS and KOOS) in the following visits. Other safety assessments, including lab test, physical examination, vital sign, medical/medication history and adverse events will also be collected throughout the study.
Detailed description
This Phase III study is a prospective, double-blind, parallel, multicenter, 2-arm study to evaluate the efficacy and safety of intra-articular ELIXCYTE injection compared to placebo in subjects with knee OA. All the subjects will be enrolled in Taiwan. Subjects aged 40 to 80 years with knee OA will be enrolled in the study. Approximately 165 eligible subjects will be randomized to receive either ELIXCYTE, or placebo in a 2:1 ratio. The target population will be composed of subjects with unilateral or bilateral knee OA. For subjects with bilateral OA knees, only the knee with more severe symptoms will be selected as the target knee, while the non-target knee can continue the regular local treatment for ethical consideration. If the severities of the OA symptoms will be the same for both knees, the knee with more pain should be selected based on the WOMAC pain score. Eligible subjects will be randomized into one of the study groups (ELIXCYTE, or placebo in a 2:1 ratio). The study consists of 9 visits and the duration per subject will be approximately 50 weeks (14 days of screening period, a treatment visit on Day 1, and 48 weeks of evaluation period). Unscheduled visit(s) may be arranged when deem necessary by the investigator. In addition, if ELIXCYTE provided medical benefits with no safety issues to ELIXCYTE group at the end of week 48, subjects assigned to placebo group will be offered a treatment with ELIXCYTE under an extension study after study unblinding.
Interventions
BIOLOGICALELIXCYTE
ELIXCYTE, a new investigational product developed by UnicoCell Biomed, contains allogenic Adipose-derived stem cells (ADSCs). The ADSCs of ELIXCYTE for subjects were obtained from donors, and the Sponsor followed the manufacturing and testing procedures described in chemistry, manufacturing and control (CMC) information in order to assure the quality of final products.
DRUGSaline
Placebo control used in the study.
Sponsors
UnicoCell Biomed CO. LTD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double-blinded
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
A subject is eligible for the study if all of the following apply: 1. Either gender, aged 40 to 80 2. With unilateral/bilateral knee OA of Kellgren-Lawrence grading II-III (determined by American College of Rheumatology criteria of knee OA). 3. WOMAC pain score of 7 - 17 in the target knee even if treated with chronic doses of NSAID. 4. Has received 1 - 3 types of pharmacological therapies for knee OA for more than 3 months but the symptoms have not relieved. 5. Unwilling or not suitable to undergo knee surgery (including total knee replacement and knee arthroplasty). 6. Understands and has signed the informed consent form. 7. With adequate hematological indices: * White blood cell (WBC) ≥ 3,000/mm3 * Platelet count ≥ 80,000/μL 8. With adequate coagulation indices: Prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (APTT) ≤ 1.5 times the upper limit of the normal range (ULN). 9. With adequate liver function where serum total bilirubin ≤ 1.5 times ULN, aspartate aminotransferase (AST) ≤ 3 times ULN, and alanine aminotransferase (ALT) ≤ 3 times ULN. 10. Has an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m2, calculated by the Modification of Diet in Renal Disease (MDRD) equation.
Exclusion criteria
Any subject meeting any of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of WOMAC pain score on the target knee | Baseline, Week 24 | WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) is a questionnaire to evaluate the condition of subjects with knee OA. The pain score ranges from 0 to 20. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total scores of WOMAC | Screening visit, Day 1, Week 2, 4, 12, 24, 36 and 48 | Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) is a standardized questionnaire to evaluate the condition of subjects with knee OA in terms of pain, stiffness, and physical functioning of the joints. It contains 5 items for pain (score range 0 \ 20), 2 for stiffness (score range 0 \ 8), and 17 for functional limitation (score range 0 \ 68). The total score of the question ranges from 0 to 96 |
| Pain subscale of WOMAC | Screening visit, Day 1, Week 2, 4, 12, 24, 36 and 48 | Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) is a standardized questionnaire to evaluate the condition of subjects with knee OA in terms of pain, stiffness, and physical functioning of the joints. It contains 5 items for pain, and the total pain score ranges from 0 to 20. |
| Stiffness subscale of WOMAC | Screening visit, Day 1, Week 2, 4, 12, 24, 36 and 48 | Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) is a standardized questionnaire to evaluate the condition of subjects with knee OA in terms of pain, stiffness, and physical functioning of the joints. It contains 2 items for stiffness, and the total stiffness score ranges from 0 to 8. |
| Functional subscale of WOMAC | Screening visit, Day 1, Week 2, 4, 12, 24, 36 and 48 | Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) is a standardized questionnaires to evaluate the condition of subjects with knee OA in terms of pain, stiffness, and physical functioning of the joints. It contains 17 items for functional limitation, and the total functional score is ranging from 0 to 68. |
| Visual Analogue Scale (VAS) for pain | Screening visit, Day 1, Week 2, 4, 12, 24, 36 and 48 | Visual analog scale (VAS) is a scale of 100 mm in length to measure subject's pain intensity. |
| Objective knee score of Knee Society Knee Scoring System (KSS) | Screening visit, Day 1, Week 2, 4, 12, 24, 36 and 48 | The Knee Society Knee Scoring System (KSS) is a system that combines both objective physician-derived and subjective patient-derived component to evaluates OA knee. Five components are included: (1) patient demographics, (2) objective knee score, (3) patient expectation, (4) patient satisfaction, and (5) functional knee score. The objective knee score of KSS includes surgeon part with maximum 75 points and patient self-evaluation part with maximum 25 points. |
| Functional knee score of Knee Society Knee Scoring System (KSS) | Screening visit, Day 1, Week 2, 4, 12, 24, 36 and 48 | The Knee Society Knee Scoring System (KSS) is a system that combines both objective physician-derived and subjective patient-derived component to evaluates OA knee. Five components are included: (1) patient demographics, (2) objective knee score, (3) patient expectation, (4) patient satisfaction, and (5) functional knee score. The total score of functional knee score ranging from 0 to 100. |
| Total score of Knee Injury and Osteoarthritis Outcome Score (KOOS) | Screening visit, Day 1, Week 2, 4, 12, 24, 36 and 48 | Knee injury and osteoarthritis outcome score (KOOS) is a questionnaire to assess the patient's opinion about their knee and associated problems. It contains 42 questions and each question is assigned with five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems). The total score of the question ranging from 0 to 168. |
| Total score of Whole-Organ Magnetic Resonance Imaging Score (WORMS) | Screening, Week 24 and Week 48 | The Whole-Organ-MRI Scores (WORMS) evaluates articular cartilage lesions in 14 anatomic compartments from magnetic resonance imaging (MRI) of the knee by an independent radiologist. Each compartment is scored by 8-point scale (0, 1, 2, 2,5, 3, 4, 5 and 6) and the total score is ranging from 0 to 84. |
| Cartilage thickness in the total femorotibial joint | Screening, Week 24 and Week 48 | The cartilage thickness will be evaluated by knee MRI |
| Percentage of pain responders (WOMAC pain score) | Week 24 and Week 48 | The responders are defined as subjects who had at least a 20% reduction in WOMAC pain score from baseline. |
| Total used amount of rescue medications used | Screening, through Day 1 to Week 24, through Day 1 to Week 48 | Rescue medication(s) is defined as acetaminophen, and/or tramadol used during the study. |
| Number of days of rescue medications consumption | Screening, through Day 1 to Week 24, through Day 1 to Week 48 | Rescue medication(s) is defined as acetaminophen, and/or tramadol used during the study. |
| Time to the first consumption of rescue medications after treatment | through study completion, an average of 1 year | Rescue medication(s) is defined as acetaminophen, and/or tramadol used during the study. |
| Incidence of Adverse event (AE) and serious adverse event (SAE) | through study completion, an average of 1 year | AE means any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product or intervention and which does not necessarily have a causal relationship with this treatment. A SAE is an AE in the view of either the investigator or Sponsor results in any of the following outcomes: death, life-threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect or the event may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed above by medical judgement. |
| Incidence of AE of special interest (AESI) | through study completion, an average of 1 year | AEs of special interest (AESI) includes arthralgia, injection site joint pain, injection site joint swelling, and joint swelling. |
| Incidence of immediate AE | Day 1 | Any adverse event that happens within 30 minutes post-administration of ELIXCYTE or placebo will be considered as an immediate adverse event. |
| Number of subjects with abnormal vital signs | Screening Visit, Day 1, Week 2, 4, 12, 24, 36 and 48 | Vital signs measurement will consist of respiratory rate, pulse rate, systolic/diastolic blood pressure, and body temperature. |
| Number of subjects with abnormal findings in laboratory tests | Screening Visit, Day 1, Week 2, 4, 12, 24, 36 and 48 | The laboratory examination includes hematology, biochemistry, immunogenicity and pregnancy tests. |
| Number of subjects with abnormal findings in physical examination | Screening Visit, Day 1, Week 2, 4, 12, 24, 36 and 48 | The physical examination items include general appearance, skin, eyes, ears, nose, throat, head and neck, heart, chest and lungs, abdomen, extremities, lymph nodes, musculoskeletal, neurological, other body systems if applicable for describing the status of the subject's health. |
| Percentage of subjects using the rescue medication(s) | Screening, through Day 1 to Week 24, through Day 1 to Week 48 | Rescue medication(s) is defined as acetaminophen, and/or tramadol used during the study. |
Countries
Taiwan
Outcome results
None listed