A Double-Blind, Placebo-Controlled Assessment of the Tolerability and Efficacy of XT-150 for the Treatment of Moderate to Severe Pain Due to Osteoarthritis of the Knee
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 289
- 试验地点
- 6
- 主要终点
- Stage A: Number of Participants Achieving 30% Improvement From Baseline in Western Ontario and McMasters Arthritis Index (WOMAC) Pain Score
研究概览
简要总结
This is a Phase 2 safety and efficacy study of XT-150 in adult participants experiencing moderate to severe pain due to osteoarthritis of the knee.
详细描述
In this Phase 2 study, Baseline (Day 0) confirmation of study eligibility will be completed the day before or day of study drug administration.
Study drug will be administered by intra-articular (IA) injection into the joint space of the index knee (knee selected for treatment).
Up to 270 participants will be randomly enrolled into 1 of 6 treatment sequences (45 participants/ group). Treatment Groups:
- 0.15 mg/mL XT-150 (1mL), 0.15 mg/mL XT-150 (1mL)
- 0.15 mg/mL XT-150 (1mL), 0.45 mg/mL XT-150 (1mL)
- 0.45 mg/mL XT-150 (1mL), 0.15 mg/mL XT-150 (1mL)
- 0.45 mg/mL XT-150 (1mL), 0.45 mg/mL XT-150 (1mL)
- Placebo (1mL), 0.15 mg/mL XT-150 (1mL)
- Placebo (1mL), 0.45 mg/mL XT-150 (1mL)
The study will be conducted in 2 stages, A and B. Participants will be randomized at Day 0 to a treatment regimen, one treatment assignment for Stage A and one treatment assignment for Stage B:
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 45 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Symptomatic disease due to osteoarthritis, defined as a WOMAC Pain score ≥ 8 (worst possible = 20)
- •Focused Analgesia Selection Test will be used to determine whether patients can report pain with sufficient consistency to enter the clinical trial
- •Males and females between 45 and 85 years of age, inclusive
- •Kellgren-Lawrence grading of 2 or 3 within the last 6 months
- •Stable analgesic regimen during the 4 weeks prior to enrollment
- •In the judgment of the Investigator, acceptable general medical condition
- •Life expectancy >6 months
- •Male and female participants who are heterosexually active and not surgically sterile must agree to use effective contraception, including abstinence, for the duration of the study
- •Have suitable knee joint anatomy for intra-articular injection
- •Willing and able to return for the follow-up (FU) visits
- •Able to read and understand study instructions, and willing and able to comply with all study procedures
排除标准
- •Hypersensitivity, allergy, or significant reaction to any ingredient of the study drug, including double-stranded DNA, mannose, and sucrose
- •Previously received XT-150 injection(s)
- •Scheduled partial or complete knee replacement within 6 months; participant agrees not to schedule a knee replacement during Stage A of the study
- •History of knee arthroplasty on the Index Knee, i.e., selected for study injection(s)
- •History of rheumatoid arthritis or other inflammatory disease
- •History of immunosuppressive therapy; systemic steroids in the last 3 months
- •Received knee injection with hyaluronic acid or stem-cells in the last 6 months
- •Knee injection of glucocorticoid in the last 3 months
- •Current treatment with systemic immunosuppressive (systemic corticosteroid therapy or other strong immunosuppressant)
- •Currently receiving systemic chemotherapy or radiation therapy for malignancy
- •Clinically significant hepatic disease as indicated by clinical laboratory results ≥3 times the upper limit of normal for any liver function test (e.g., aspartate aminotransferase, alanine aminotransferase)
- •Severe anemia (Grade 3; hemoglobin <8.0 g/dL, <4.9 mmol/L, <80 g/L; transfusion indicated), Grade 1 white cell counts (lymphocytes <LLN - 800/mm^3; <LLN - 0.8 x 109 /L, neutrophils <LLN - 1500/mm^3; <LLN - 1.5 x 109 /L), LLN=Lower Limit Normal Range
- •Positive serology for human immunodeficiency virus, hepatitis B virus, or hepatitis C virus
- •Significant neuropsychiatric conditions; dementia, major depression, or altered mental state that in the opinion of the Investigator will interfere with study participation
- •Current treatment with systemic antibiotics or antivirals (EXCEPTION: topical treatments)
- •Current anticoagulant or anti-platelet treatment (e.g., warfarin, heparins, factor X inhibitors, clopidogrel, prasugrel, ticagrelor, or dipyridamole). Low-dose (≤ 325 mg/day) aspirin is permitted
- •Known or suspected history of active alcohol or intravenous/oral drug abuse within 1 year before the screening visit
- •Use of any investigational drug or device within 3 months before enrollment or current participation in a trial that included intervention with a drug or device; or currently participating in an investigational drug or device study
- •Any condition that, in the opinion of the Investigator, could compromise the safety of the participant, the participant's ability to communicate with the study staff, or the quality of the data
研究组 & 干预措施
Stage A: Placebo, Stage B: 0.15 mg/mL XT-150
Inactive comparator in Stage A, low dose active in Stage B
干预措施: XT-150 (Biological)
Stage A: 0.15 mg/mL XT-150, Stage B: 0.15 mg/mL XT-150
Low dose active in Stage A and Stage B
干预措施: XT-150 (Biological)
Stage A: 0.15 mg/mL XT-150, Stage B: 0.45 mg/mL XT-150
Low dose active in Stage A, high dose active in Stage B
干预措施: XT-150 (Biological)
Stage A: 0.45 mg/mL XT-150, Stage B: 0.15 mg/mL XT-150
High dose active in Stage A, low dose active in Stage B
干预措施: XT-150 (Biological)
Stage A: 0.45 mg/mL XT-150, Stage B: 0.45 mg/mL XT-150
High dose active in Stage A and Stage B
干预措施: XT-150 (Biological)
Stage A: Placebo, Stage B: 0.15 mg/mL XT-150
Inactive comparator in Stage A, low dose active in Stage B
干预措施: Placebo (Drug)
Stage A: Placebo, Stage B: 0.45 mg/mL XT-150
Inactive comparator in Stage A, high dose active in Stage B
干预措施: XT-150 (Biological)
Stage A: Placebo, Stage B: 0.45 mg/mL XT-150
Inactive comparator in Stage A, high dose active in Stage B
干预措施: Placebo (Drug)
结局指标
主要结局
Stage A: Number of Participants Achieving 30% Improvement From Baseline in Western Ontario and McMasters Arthritis Index (WOMAC) Pain Score
时间窗: Day 180
The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score will be obtained from the Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire which is a validated, commonly used instrument to assess the participant's opinion about their knee and associated problems. Each item is answered on a 5-point Likert scale. The score for pain category ranges from 0 (no pain) to 20 (maximum pain); higher score indicates worse outcomes. Baseline is defined as the Day 0 value.
Stage A: Change From Baseline in WOMAC Pain Score at Day 180
时间窗: Day 180
The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score will be obtained from the Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire which is a validated, commonly used instrument to assess the participant's opinion about their knee and associated problems. Each item is answered on a 5-point Likert scale. The score for pain category ranges from 0 (no pain) to 20 (maximum pain); higher score indicates worse outcomes. Baseline is defined as the Day 0 value.
Stage A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Prior to second dose (Up to Day 180-Day 330)
Adverse events were collected from the time of informed consent through the last study visit on Day 360 (1 year). Treatment Emergent Adverse Events (TEAEs) occurred from the time of study drug treatment on Day 0 through end of study (Day 360) or early termination. This analysis reports any AEs/SAEs that occurred prior to the second dose.
Stage B: Number of Participants With AEs and SAEs
时间窗: Post Second Dose (Day 180-Day 330 through Day 360)
Adverse events were collected from the time of informed consent through the last study visit on Day 360 (1 year). Treatment Emergent Adverse Events occurred from the time of study drug treatment on Day 0 through end of study (Day 360) or early termination. This analysis reports any AEs/SAEs that occurred after the second dose.
次要结局
- Stage B: Change From Baseline in WOMAC Pain Score at Day 360(Day 360)
- Stage B: Change From Baseline in WOMAC Function Score(At Day 360)
- Stage A: Change From Baseline in Brief Pain Inventory (BPI) of Interference Score(Day 180)
- Stage A: Change From Baseline in Patients Overall Assessment (POA)(Day 180)
- Stage A and B: Number of Participants With Presence of Anti-interleukin (IL)-10 Antibody(Up to Day 360)