Phase 1b Open-Label, Multi-Center, Randomized Trial to Evaluate the Safety of PEP and EUFLEXXA for the Treatment of Subjects With Knee Osteoarthritis (KOA)
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- Rion Inc.
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Long Term Safety Follow-Up Occurrence of DLTs From Day 91 to Day 365
研究概览
简要总结
Evaluate the safety and exploratory efficacy of single intra-articular injections of PEP reconstituted with 0.9% Normal Saline at a low dose (one vial PEP) and high dose (two vials PEP), with and without EUFLEXXA, for the treatment of Knee Osteoarthritis
详细描述
Study Plan (with Dose Escalation): Arm 1 and Arm 2 will run in parallel such that initially 3 subjects will be enrolled in Arm 1a (PEP Low Dose) and 3 subjects will be enrolled in Arm 2a (PEP-EUFLEXXA Low Dose). After all 6 subjects complete the 30 day follow up and there was not more than 1 AE grade 3 or higher per Arm, a further 9 subjects will be enrolled in Arm 1b (PEP High Dose) and a further 9 subjects will be enrolled in Arm 2b (PEP-EUFLEXXA High Dose).
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
- None
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age: Adults aged 18-90 years of age
- •Type of Participant and Disease Characteristics:
- •Diagnosis of unilateral or bilateral symptomatic KOA of at least 6 months duration (meets American College of Rheumatology/Arthritis [ACR] criteria)
- •Daily knee pain in the more symptomatic knee of ≥ 30 and ≤ 80 on a 100-point VAS for greater than 6 months
- •Kellgren Lawrence Grade 2 to 3 osteoarthritis in the more symptomatic knee based on standard knee radiographs
- •Failed conservative management including at least 2 of the following:
- •Lack of improvement with attempted weight loss in the past year if body mass index (BMI) > 30 kg/m2;
- •Lack of response to a 4-week trial in the past year of oral acetaminophen or NSAIDs taken as needed;
- •Lack of response to a 4-week trial in the past year of topical NSAIDs or capsaicin applied as needed;
- •Lack of improvement after injection therapy with cortisone, PRP or hyaluronic acid;
- •Lack of improvement after a 4-week course of physical therapy in the past year; or
- •Lack of improvement after a 4-week trial of quadriceps strengthening home exercise program in the past year.
- •Requesting injection therapy for pain management
- •Contraceptive use by participants and their partners should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •o A serum pregnancy test (human chorionic gonadotropin [hCG]) should be done for all women of childbearing potential (WOCBP) at Screening, and a urine pregnancy test should be done on Day 1, prior to injection, with results reviewed before injection to confirm the participant's eligibility. Participants who have positive pregnancy test result will not be permitted to continue in the study (see Section 5.2, Exclusion criteria 18 and 19).
- •Signed informed consent as described in Appendix 1 (Section 10.1) which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
- •Ability to comply with protocol.
排除标准
- •Steroid or viscosupplement injection in the planned treatment knee(s) within the past 3 months.
- •PRP injection in the planned treatment knee(s) within the past 6 months.
- •History of documented allergy to intra-articular EUFLEXXA.
- •History of cancer including melanoma (with the exception of localized skin cancer) in the past 2 years.
- •HIV positive participants.
- •BMI > 40 kg/m
- •Arthroscopic debridement in the planned treatment knee(s) in the last 6 months.
- •Cartilage restoration procedure in the planned treatment knee(s) in the last 5 years.
- •History of gout or pseudogout.
- •History of or evidence of active rheumatologic disease, severe peripheral neuropathy, clinically evident cardiac or respiratory disease that interferes with functional status.
- •Poorly controlled diabetes defined as a glycated hemoglobin (HbA1c) concentration of ≥ 8.0%.
- •Currently taking any cancer treatment regimen (including aromatase inhibitors).
- •Calcium pyrophosphate deposition disease (CPPD) evident on X-ray.
- •Systemic (oral, intravenous, or intramuscular) steroids in the last 3 months.
- •Concurrent participation in another investigational drug or device study or participation in the last 30 days prior to enrollment.
- •Evidence of recent alcohol or drug abuse, or history of medication misuse or addiction.
- •Female participants who are pregnant, breast feeding, or trying to become pregnant.
- •Women unwilling to use approved contraception method for 3 months after receiving dose of investigational drug.
- •Unwilling or unable to comply with Telehealth visits (eg, ability to access internet, on camera capabilities, etc).
研究组 & 干预措施
1A PEP Low Dose
1A PEP Low Dose in Saline
干预措施: PEP (Drug)
1B PEP High Dose
1B PEP High Dose in Saline
干预措施: PEP (Drug)
2a PEP-EUFLEXXA Low Dose
2A PEP-EUFLEXXA Low Dose
干预措施: PEP/Euflexxa (Combination Product)
2b PEP-EUFLEXXA High Dose
2B PEP-EUFLEXXA High Dose
干预措施: PEP/Euflexxa (Combination Product)
结局指标
主要结局
Long Term Safety Follow-Up Occurrence of DLTs From Day 91 to Day 365
时间窗: Day 365
The long-term safety after treatment with a single intra-articular injection of PEP, with or without EUFLEXXA as assessed from the incidence of DLTs during the Day 91 through Day 365 follow up period.
Primary Safety Follow up 90 Days post injection occurrence of DLTs
时间窗: First 90 days
The safety of a single intra-articular injection of PEP, with or without EUFLEXXA, through the initial 90-day treatment period as assessed by the occurrence of DLTs with severity grading based on the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI CTCAE).
次要结局
- Exploratory Endpoints of Efficacy-Radiographic Response(Day 365)
- Exploratory Endpoints of Efficacy-Participant-Reported responses:(Day 365)