A Phase III, Randomized, Parallel, Double-blinding, 2-Arm Study to Investigate the Efficacy and Safety of Intra-articular ELIXCYTE (Adipose-Derived Stem Cells) Injection Compared With Placebo in Subjects With Knee Osteoarthritis
Overview
- Phase
- Phase 3
- Intervention
- ELIXCYTE
- Conditions
- Knee Osteoarthritis
- Sponsor
- UnicoCell Biomed CO. LTD
- Enrollment
- 165
- Locations
- 4
- Primary Endpoint
- Change of WOMAC pain score on the target knee
- Status
- Active, not recruiting
- Last Updated
- 5 months ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •A subject is eligible for the study if all of the following apply:
- •Either gender, aged 40 to 80
- •With unilateral/bilateral knee OA of Kellgren-Lawrence grading II-III (determined by American College of Rheumatology criteria of knee OA).
- •WOMAC pain score of 7 - 17 in the target knee even if treated with chronic doses of NSAID.
- •Has received 1 - 3 types of pharmacological therapies for knee OA for more than 3 months but the symptoms have not relieved.
- •Unwilling or not suitable to undergo knee surgery (including total knee replacement and knee arthroplasty).
- •Understands and has signed the informed consent form.
- •With adequate hematological indices:
- •White blood cell (WBC) ≥ 3,000/mm3
- •Platelet count ≥ 80,000/μL
Exclusion Criteria
- •Any subject meeting any of the exclusion criteria will be excluded from study participation.
- •With previous surgery of articular fracture, ligament reconstruction, meniscal reconstruction (with the exception of meniscal debridement), and knee arthroplasty on the target knee joint.
- •With any IA intervention of the target knee within 3 months prior to screening (e.g. steroid, anesthetic), or sodium hyaluronate by IA intervention of the target knee within 6 months prior to screening.
- •Administered systemic immunosuppressive agent, systemic antiinflammatory drug, systemic steroid, systemic analgesics (except acetaminophen, and tramadol as rescue medications), duloxetine, or over-the-counter medications contain analgesics (e.g. cold medicine) within 2 weeks prior to screening. Administered systemic herbal, homeopathic, or naturopathic remedies for knee OA within 2 weeks prior to screening. A subject requiring routine use of low-dose Aspirin for preventing thrombosis (≤ 100 mg/day) will not be excluded from this study
- •Administered local immunosuppressive agent, local anti-inflammatory drug, local steroid, local analgesics, over-the-counter medications contain analgesics, herbal, homeopathic, or naturopathic remedies for knee OA within 2 weeks prior to screening.
- •Has participated in other investigational studies within 4 weeks prior to screening.
- •Administered monoamine oxidase inhibitor, selective serotonin reuptake inhibitor, serotonin-norepinephrine reuptake inhibitors, benzodiazepine, or tricyclic antidepressants within 4 weeks prior to screening.
- •With joint diseases expect knee OA that is considered not eligible to enter the study by the investigator.
- •Systemic diseases that may affect joints, including but not limited to inflammatory joint diseases, reactive arthritis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and fibromyalgia.
- •Known or suspected infection around the target knee joint.
Arms & Interventions
ELIXCYTE
Subjects will be intra-articular (IA) injected with 4 mL of ELIXCYTE (containing 32×10\^6 ADSCs) at the target knee once
Intervention: ELIXCYTE
Placebo control (Saline)
Subjects will be intra-articular (IA) injected with 4 mL of saline at the target knee once
Intervention: Saline
Outcomes
Primary Outcomes
Change of WOMAC pain score on the target knee
Time Frame: 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 Outcomes
- Functional subscale of WOMAC(Screening visit, Day 1, Week 2, 4, 12, 24, 36 and 48)
- Total used amount of rescue medications used(Screening, through Day 1 to Week 24, through Day 1 to Week 48)
- Time to the first consumption of rescue medications after treatment(through study completion, an average of 1 year)
- Incidence of Adverse event (AE) and serious adverse event (SAE)(through study completion, an average of 1 year)
- Percentage of pain responders (WOMAC pain score)(Week 24 and Week 48)
- Total scores of WOMAC(Screening visit, Day 1, Week 2, 4, 12, 24, 36 and 48)
- Stiffness subscale of WOMAC(Screening visit, Day 1, Week 2, 4, 12, 24, 36 and 48)
- Objective knee score of Knee Society Knee Scoring System (KSS)(Screening visit, Day 1, Week 2, 4, 12, 24, 36 and 48)
- Percentage of subjects using the rescue medication(s)(Screening, through Day 1 to Week 24, through Day 1 to Week 48)
- Incidence of immediate AE(Day 1)
- Pain subscale of WOMAC(Screening visit, Day 1, Week 2, 4, 12, 24, 36 and 48)
- Functional knee score of Knee Society Knee Scoring System (KSS)(Screening visit, Day 1, Week 2, 4, 12, 24, 36 and 48)
- Number of subjects with abnormal findings in laboratory tests(Screening Visit, Day 1, Week 2, 4, 12, 24, 36 and 48)
- Number of subjects with abnormal findings in physical examination(Screening Visit, Day 1, Week 2, 4, 12, 24, 36 and 48)
- Visual Analogue Scale (VAS) for pain(Screening visit, Day 1, Week 2, 4, 12, 24, 36 and 48)
- Total score of Knee Injury and Osteoarthritis Outcome Score (KOOS)(Screening visit, Day 1, Week 2, 4, 12, 24, 36 and 48)
- Total score of Whole-Organ Magnetic Resonance Imaging Score (WORMS)(Screening, Week 24 and Week 48)
- Cartilage thickness in the total femorotibial joint(Screening, Week 24 and Week 48)
- Number of days of rescue medications consumption(Screening, through Day 1 to Week 24, through Day 1 to Week 48)
- Incidence of AE of special interest (AESI)(through study completion, an average of 1 year)
- Number of subjects with abnormal vital signs(Screening Visit, Day 1, Week 2, 4, 12, 24, 36 and 48)