Single-Center, Randomized, Double-Blind, Parallel-Controlled Clinical Trial to Evaluate the Efficacy and Safety of ALT001 for Osteoarthritis
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Change in the WOMAC Pain Score of the target knee joint at 24 weeks (14 weeks after the last injection) compared with the baseline.
研究概览
简要总结
This clinical trial will focus on the core efficacy endpoints including relief of pain intensity, improvement of joint motor function and enhancement of quality of life in patients. Meanwhile, it will strictly monitor key safety indicators such as the occurrence of various adverse events after medication, the severity and duration of adverse reactions, and conduct a multi-dimensional and multi-level comprehensive assessment. The study aims to clarify the clinical benefit profile and safety risks of the investigational product ALT001, and provide scientific, detailed and reliable evidence-based medical data to support the optimization of clinical treatment guidelines and the formulation of individualized treatment regimens for knee osteoarthritis.
Patients enrolled in the trial will receive investigational product treatment on the basis of conventional therapy. They will be randomly assigned to the placebo group, low-dose group and high-dose group at a ratio of 1:1:1. For each treatment course, patients in all groups will receive an injection of 2 vials of the investigational product into a single knee joint (for bilateral knee osteoarthritis, both knees may be injected, with one fixed knee joint selected for subsequent assessments). The injection will be administered once every 2 weeks for a total of 6 administrations.
详细描述
This is a single-center, randomized, double-blind, placebo-controlled clinical trial. Patients will be enrolled after signing the informed consent form and meeting the inclusion/exclusion criteria, with a planned enrollment of 30 participants.
All enrolled patients will receive the study drug on the basis of conventional treatment, and be randomly assigned to the placebo group, low-dose group and high-dose group at a ratio of 1:1:1 (see Table 1 for details). Patients in each group will receive an injection of 2 vials of the study product into a single knee joint per treatment session (for bilateral osteoarthritis, both knees may be injected, while a fixed knee joint will be selected for subsequent assessments). Injections will be administered once every 2 weeks for a total of 6 times.
Follow-up assessments will be conducted concomitantly with injections at 2, 4, 6, 8 and 10 weeks after the first injection, and all safety and efficacy data will be collected during these visits.
The entire study consists of the following phases: Screening Period (Day -7 to Day 0), Treatment Visit 1 (first injection, Day 0), Treatment Visit 2 (second injection, Week 2 ±3 days), Treatment Visit 3 (third injection, Week 4 ±3 days), Treatment Visit 4 (fourth injection, Week 6 ±3 days), Treatment Visit 5 (fifth injection, Week 8 ±3 days), Treatment Visit 6 (sixth injection, Week 10 ±3 days), Follow-up Visit 7 (Week 12 ±5 days), Follow-up Visit 8 (Week 18 ±7 days) and Follow-up Visit 9 (Week 24 ±7 days).
The outcome measures of this clinical trial are based on the participants' subjective evaluations. To avoid bias in trial results caused by participants' subjective perceptions, a blinded design is applied to all participants. A double-blind design is also adopted, with follow-up investigators masked, to prevent the investigators' subjective judgments from influencing participants during follow-up. This trial uses a placebo-controlled design, where the trial conditions, clinical observation items and evaluation criteria are consistent between the experimental and control groups. In addition, participants in the two groups are assigned in accordance with the randomization principle.
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
- 50 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 50 to 75 years old (inclusive), gender unrestricted;
- •Body Mass Index (BMI) within the range of 18 ≤ BMI ≤ 35;
- •Meets the diagnostic criteria for osteoarthritis (OA) in Chinese Guidelines for the Diagnosis and Treatment of Osteoarthritis (2021 Edition) [1]. A diagnosis of knee osteoarthritis can be made if criterion ① plus any 2 of criteria ②, ③, ④, ⑤ are satisfied:
- •① Recurrent knee pain within the past 1 month;
- •② X-ray (standing or weight-bearing position) shows narrowed joint space, subchondral bone sclerosis and/or cystic changes, and osteophyte formation at the joint margin;
- •③ Aged ≥ 50 years;
- •④ Morning stiffness duration ≤ 30 minutes;
- •⑤ Crepitus (sensation or sound) during joint movement;
- •Kellgren-Lawrence grade of Grade Ⅰ to Ⅲ for at least one knee joint on anteroposterior and lateral (stress) X-ray of bilateral knee joints within 6 months;
- •A score of 4 to 8 points (inclusive) for pain on flat ground walking or stair climbing in the WOMAC Pain Score of at least one knee joint;
- •For participants who have been taking glucosamine or diacerein-containing drugs before the screening period, the dosage must be kept stable throughout the entire clinical trial;
- •Discontinued all analgesic drugs for more than 2 weeks before the screening period, and agreed not to use any other analgesic drugs except rescue medication throughout the entire study;
- •Willing to cooperate with the clinical trial and able to sign the informed consent form.
排除标准
- •With other diseases that cause knee pain and dysfunction (e.g., autoimmune arthritis, infectious arthritis, gouty arthritis, knee joint tumors, etc.);
- •With pain in other body parts exceeding knee pain, which may interfere with the assessment of the knee joint;
- •With significantly narrowed joint space or bony ankylosis due to bone bridge formation between joints;
- •With lower extremity pain caused by lumbar spinal stenosis or lumbar disc herniation;
- •With systemic infection or severe local infection;
- •With clinically significant abnormalities in any item of the four infectious disease screening tests;
- •With a history of knee joint surgery, open trauma within 1 year, or intra-articular injection, radiotherapy, or arthroscopy within 6 months;
- •With intra-articular corticosteroid block therapy for the knee joint or long-term (continuous ≥2 weeks) use of corticosteroids or immunosuppressants within 6 months;
- •With a history of taking Chinese herbal decoctions or proprietary Chinese medicines for knee pain within 1 month;
- •With physical therapy or topical medication (e.g., electromagnetic therapy, cupping, acupuncture, plasters, fumigation, etc.) on the knee joint within 1 week;
- •With severe diseases of the heart, brain, liver, kidney, hematologic, endocrine, or immune systems (e.g., AST/ALT or creatinine ≥2.0×ULN, glycosylated hemoglobin ≥8%, hemophilia, etc.);
- •With malignant tumors;
- •Planning to undergo elective knee joint surgery during the study period;
- •With obvious knee joint effusion (significant joint swelling or bulging) or severe venous/lymphatic stasis of the lower extremities;
- •Requiring long-term use of warfarin or other anticoagulants (except for a stable daily dose of aspirin ≤100 mg and/or clopidogrel);
- •With consciousness disturbance or mental illness, unable to complete self-assessment;
- •With a history of drug abuse or alcoholism;
- •With a history of allergy to the raw materials of the study product and control product, or atopic diathesis (previous allergy to protein-based drugs or food);
- •With a positive pregnancy test, pregnant/lactating women, those with recent childbearing plans, or those unable to take reliable contraceptive measures during the study;
- •Having participated in other clinical trials of drugs, biological agents, or medical products within 3 months;
- •Other circumstances deemed inappropriate for participation in this clinical trial by the investigator.
研究组 & 干预措施
Placebo Group
2 vials per administration, once every 2 weeks, intra-articular injection.
干预措施: Placebo (Other)
ALT001 Low-Dose Group
1 vial per administration, once every 2 weeks, intra-articular injection.
干预措施: ALT001 (Drug)
ALT001 High-Dose Group
2 vials per administration, once every 2 weeks, intra-articular injection.
干预措施: ALT001 (Drug)
结局指标
主要结局
Change in the WOMAC Pain Score of the target knee joint at 24 weeks (14 weeks after the last injection) compared with the baseline.
时间窗: 24 weeks (14 weeks after the last injection)
The WOMAC Index (Western Ontario and McMaster Universities Osteoarthritis Index) is a commonly used assessment tool for evaluating symptom severity and joint function in patients with knee joint disorders \[6\]. It comprises three dimensions: pain, stiffness, and physical function. Through the assessment of these three dimensions, the degree of pain, joint mobility, and difficulty in performing daily activities in patients' daily lives can be objectively evaluated. The WOMAC score is a composite rating of the patient's subjective experience within the 48 hours prior to each assessment. WOMAC Pain Score includes five items: pain when walking on a flat surface, climbing up or down stairs, pain at night, pain when sitting or lying down, and pain when standing upright. For detailed scoring criteria, see Annex 1. During the treatment period and the final follow-up period, the pain assessment is based on the patient's experience within the 48 hours prior to the current visit.
Changes in the levels of inflammatory factors IL-1β, IL-6, and TNF-α in the synovial fluid of the target knee joint during treatment and at 14 weeks post-treatment compared with the baseline.
时间窗: 14 weeks
IL-1β, IL-6, and TNF-α, the three cytokines, can promote the production of other inflammatory factors by activating the NF-κB and MAPK signaling pathways, thereby exacerbating the degree of inflammatory response. Although this interaction can trigger a more robust immune response, it may also induce chronic inflammation and tissue damage. The levels of IL-1β, IL-6, and TNF-α serve as important predictive markers for monitoring the disease progression of osteoarthritis (OA). (For patients from whom synovial fluid cannot be aspirated, irrigate the joint cavity with 5 ml of sterile water for injection first before aspiration; the entire procedure must be performed under strict aseptic conditions.)
次要结局
- Changes in the WOMAC Physical Function Score of the target knee joint at 2, 4, 6, 8, 10, 12, 18 (non-mandatory) and 24 weeks compared with the baseline.(2, 4, 6, 8, 10, 12, 18(non-mandatory))
- Changes in the WOMAC Total Score of the target knee joint at 2, 4, 6, 8, 10, 12, 18 (non-mandatory) and 24 weeks compared with the baseline.(2, 4, 6, 8, 10, 12, 18 (non-mandatory) and 24 weeks)
- Changes in the VAS Pain Score of the target knee joint at 2, 4, 6, 8, 10, 12, 18 (non-mandatory) and 24 weeks compared with the baseline.(2, 4, 6, 8, 10, 12, 18 (non-mandatory) and 24 weeks)
- Deep proteomics indicators(During treatment and at 14 weeks post-treatment)