A Double-blind, Multi-Center, Prospective, Randomized Placebo-controlled Pilot Study Evaluating Intra-articular Injection of Axolotl Ambient Compared to Saline in Subjects With Ankle Osteoarthritis
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 12
- 试验地点
- 3
- 主要终点
- Change From Baseline in Ankle Osteoarthritis Scale (AOS; 48 hr Recall) Pain Subscale
研究概览
简要总结
A Double-blind, Multi-Center, Prospective, Randomized Placebo-controlled Pilot Study Evaluating Intra-articular Injection of Axolotl Ambient Compared to Saline in Subjects with Ankle Osteoarthritis. The goal of this pilot study and subsequent pivotal trial is to evaluate the safety and effectiveness of Axolotl Ambient intra-articular injection for ameliorating the pain and dysfunction associated with ankle OA.
详细描述
This pilot study is a double-blind multi-center, prospective, randomized, placebo-controlled trial. Upon randomization, patients will receive 1 intraarticular injection of the investigational product or control fluid. Follow-up will be conducted at 4 weeks, 3 and 6 months, with 6 months serving as the primary endpoint. The primary outcomes will consist of patient reported outcomes of pain and functional assessment by the physician, specific to the foot and ankle. Subjects will be monitored for an additional 6 months to establish safety over a 1-year follow-up and evaluate the durability of benefit.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Subjects, investigators, and outcome assessors will be blinded to the treatment allocation until completion of the 6-month follow-up visit.
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Signed written informed consent
- •Willing to be randomized to either the investigational or control group
- •Male or female at least 18 years of age and less than 80
- •Clinical diagnosis of symptomatic tibiotalar (ankle) OA (primary idiopathic OA or post-traumatic OA), modified K-L grade 1-3a
- •One ankle is the most symptomatic lower extremity joint and the only lower extremity joint currently planned for treatment
- •Willing and able to comply with all study requirements including all postoperative clinical and radiographic evaluations
- •For women of childbearing potential (not post-menopausal for 12 months or surgically sterile), a urine pregnancy test with a negative result must be obtained at screening and on the day of procedure, prior to injection
- •Male and female trial participants must commit to adequate birth control (e.g., surgically sterilized, oral contraceptive, two methods of barrier birth control, or abstinence) through the final follow-up
- •Chronic ankle pain for ≥ 6 months
- •SAOS Pain score ≥ 30 and ≤ 80 and AOS Function score ≥ 30 and ≤ 80
- •Willing to discontinue all prescription and over-the-counter pain medications being used for ankle OA symptoms for the duration of the study, except for acetaminophen, which is not allowed for the 3 days preceding each scheduled follow-up visit and the day of the follow-up visit.
排除标准
- •Previously received intra-articular injections in the index joint of Axolotl Ambient, bone marrow aspirate concentrate (BMAC), platelet-rich plasma (PRP), or other biologic-based products within the last 12 months.
- •Modified K-L Grade 3b or 4 osteoarthritis of the index joint
- •Diagnosis of ipsilateral peri-articular arthritis (e.g. subtalar joint) that the investigator determines may significantly confound the study results
- •Received intra-articular hyaluronic acid injection in the index joint within the last 6 months
- •Received intra-articular steroid injection in the index joint within the last 3 months
- •Prior major surgical repair or reconstruction of the ankle that the investigator determines may significantly confound the study results
- •Baseline pain catastrophizing score ≥ 23
- •Any surgery of the index ankle within the last 12 months
- •Planned arthroscopy or other procedure on the ankle during the study
- •Bilateral ankle OA requiring treatment of both ankles
- •Pregnancy, breastfeeding, or woman of child-bearing potential not using adequate contraception
- •Bone deficit
- •Charcot foot disease
- •Radiographic evidence of open epiphyses
- •Systemic inflammatory condition
- •Substantial vascular insufficiency
- •Current treatment with anticoagulants
- •Deformity in coronal, axial or sagittal plane greater the 30°
- •Patients weighing less than 47 kg.
- •BMI greater than 45 kg/m2
- •Documented medical history of, or radiographic evidence of, a bone disease (e.g. severe osteoporosis or avascular necrosis) or other condition (e.g., osteolysis)
- •Comorbidity that would limit the ability to administer any functional measurements
- •Has at the time of injection, a systemic or local infection at the site of injection
- •Medical condition, serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, would preclude participation in the study or potentially decrease survival or interfere with ambulation or rehabilitation (e.g., history of transient ischemic attack, stroke or liver disease)
- •Known hypersensitivity to penicillin
- •Known allergy to phenol red
- •Currently receiving treatment with a drug known to interfere with bone or cartilage metabolism [e.g., systemic steroid therapy (topical steroid therapy is permissible), methotrexate]
- •Medical condition requiring radiation, chemotherapy or immunosuppression
- •Have an active history of malignancy (except for basal cell carcinoma of the skin)
- •Has a history of autoimmune disease known to affect bone or cartilage. Examples include spondyloarthropathies (e.g., ankylosing spondylitis, Crohn's disease, and ulcerative colitis), Juvenile Arthritis, rheumatoid arthritis, Grave's disease, and Hashimoto's thyroiditis
- •Has obvious or documented alcohol or illicit drug addictions
- •Is a prisoner in a correctional institution/facility
- •Actively involved in litigation or workman's compensation
- •Has participated in clinical studies evaluating investigational devices, pharmaceuticals or biologics within 6 months of randomization
- •Bedridden, confined to a wheelchair, or unable to walk 50 m without the help of a walker, crutches, or cane
- •Is currently taking prescription pain medication for any conditions other than ankle osteoarthritis.
研究组 & 干预措施
Control Group
Single dose, 2.0 mL of 0.9% normal saline, administered via intra-articular injection administered to the affected tibiotalar joint.
干预措施: "Drug/Placebo: 0.9% Normal Saline" (Drug)
Investigational Group
Biological/Vaccine: Axolotl Ambient
Axolotl Ambient is an allogeneic amniotic intraarticular injection therapy consisting of a growth factor and cytokine-rich fluid derived from human amnion cells.
Other Names:
• CA20
干预措施: Axolotl Ambient (Biological)
结局指标
主要结局
Change From Baseline in Ankle Osteoarthritis Scale (AOS; 48 hr Recall) Pain Subscale
时间窗: 4-weeks, 3-months, and 6-months
The Ankle Osteoarthritis Scale (AOS) pain subscale goes from 0 (No pain) -100 (The worst imaginable).
Change From Baseline for Ankle Osteoarthritis Scale (AOS; 48 hr Recall) Function Subscale
时间窗: 4-week, 3 Months, 6-months
The Ankle Osteoarthritis Scale (AOS) functions subscale goes from 0 (No difficulty) -100 (So difficult, unable).
Change From Baseline for Foot and Ankle Outcome Score (FAOS) for Pain Subscale
时间窗: 4-weeks, 3-months, 6-months
A score of 100 represents no pain. A score of 0 constant pain.
Change From Baseline for Foot and Ankle Outcome Score (FAOS) for Function Subscale
时间窗: 4-weeks, 3-months, 6-months
100 represents perfect health and 0 represents extreme problems and complete functional limitation. .
Proportion of Patients Achieving Composite Clinical Success (CCS).
时间窗: 4-weeks, 3-months, 6-months
CCS defined as a patient meeting all of the three following criteria: 1. Improvement in AOS (Pain and Function) or FAOS scores (Pain and ADL) of at least 20% from baseline 2. No surgical intervention or prescription pain medications for ankle OA 3. No treatment or procedure-related serious adverse events
次要结局
- Incidence of Adverse Events(Post-procedure follow-up assessments: 4 weeks (+/-7days), 3 Months (+/- 14 days), 6 Months (+/- 30 days), 12 Months (+/- 60 days), and unscheduled visits (up to 19 months))
- FAOS Subscales Quality of Life (QoL)(4-week, 3-month, 6-month)
- Visual Analog Scale (VAS) for Ankle Pain (Average During Last 48 Hours)(4 weeks, 3-months, 6-months)
- VAS Ankle Pain (Worst During Last 48 Hours)(4-weeks, 3-months, 6-months)
- EuroQOL-5 Dimension-5 Level (EQ-5D-5L) Quality of Life Scale(4-weeks, 3-months, 6-months)
- Working Status(Baseline, 4-weeks, 3-months, 6-months)
- K-L Grade From Weightbearing X-ray at Baseline and 6 Months(Baseline, 6-months)