Clinical Trial on the Efficacy and Safety of ALT001 in Osteoarthritis

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.

This clinical trial is developed in response to the urgent clinical need for safe and effective interventions in the treatment of knee osteoarthritis. In accordance with the principles of evidence-based medicine, a rigorous controlled study protocol has been designed. Through standardized trial procedures and a unified evaluation system, this trial will systematically and comprehensively assess the clinical application value of ALT001, manufactured by Darwin Starting Point (Hubei) Biopharmaceutical Co., Ltd., in patients with knee osteoarthritis. The study will focus on core efficacy endpoints including the degree of pain relief, improvement in joint motor function and enhancement of quality of life in patients. Meanwhile, key safety indicators such as the incidence of various adverse events after administration, the severity and duration of adverse reactions will be closely monitored. A multi-dimensional and multi-level comprehensive assessment will be conducted to clarify the clinical benefit characteristics and safety risks of the study product ALT001, thereby providing scientific, detailed and reliable evidence-based medical data to optimize clinical treatment guidelines and formulate individualized treatment regimens for knee osteoarthritis.

This clinical trial is conducted in response to the urgent clinical need for safe and effective interventions in the treatment of knee osteoarthritis. In accordance with the principles of evidence-based medicine, a rigorous controlled study protocol has been designed. Through standardized trial procedures and a unified evaluation system, this study will systematically and comprehensively assess the clinical efficacy of ALT001, manufactured by Darwin Starting Point (Hubei) Biopharmaceutical Co., Ltd., in patients with knee osteoarthritis. The trial will focus on core efficacy endpoints including the relief of pain intensity, improvement of joint motor function and enhancement of patients' quality of life. Meanwhile, it will strictly monitor key safety indicators such as the occurrence of various adverse events following medication administration, as well as the severity and duration of adverse reactions, and conduct a multi-dimensional and multi-level comprehensive assessment. The aim is to clarify the clinical benefit profile and safety risks of the investigational product ALT001, and to 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.

Inclusion criteria

• 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.

Exclusion criteria

• 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.