Phase I Clinical Trial of UC-MSCs in the Treatment of Knee Osteoarthritis

NCT06463847 | Recruiting Phase 1 DMC

• 1 other identifier: UHCT240051
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

In recent years, the incidence rate and disability rate of osteoarthritis have continued to grow, and it has become a common chronic disease of elderly patients, second only to the "three highs", and poses a continuous threat to China's medical and health system and public health system. Knee osteoarthritis is the main type of osteoarthritis, ranking 11th in global disability diseases and 38th in disability adjusted life year loss, causing significant economic burden to patients, families, and society. At present, most of the treatment methods for KOA have limited efficacy, only relieving pain symptoms and cannot prevent cartilage damage and other tissue damage in the joints. Due to the limitations of adverse events, there is still no optimal treatment plan for KOA. Most studies believe that autologous mesenchymal stem cell transplantation is a new treatment method with good efficacy and good repair effect for mild to moderate cartilage defects. Given that there is currently no optimal treatment plan for KOA, human umbilical cord mesenchymal stem cell injection has potential development value and is of great significance for the treatment of KOA patients.

Conditions

Knee Osteoarthritis

Keywords

Knee Osteoarthritis; UC-MSCs; Cell Therapy; Safety; DLT; Efficiency

Outcome Measures

Primary Outcomes (1)

• Adverse Events

  Incidence and severity of adverse events after administration (CTCAE 5.0)

  From Baseline (0 W) to 4 weeks after treatment

Secondary Outcomes (5)

• WOMAC (Western Ontario and McMaster Universities Arthritis Index，with the minimum value 0, and the maximum value 240, and higher scores mean a worse outcome)

  From Baseline (0 W) to 24 hours, 4 weeks, 12 weeks, 24 weeks, 48 weeks after treatment

• VAS (Visual Analogue Scale,with the minimum value 0, and the maximum value 10, and higher scores mean a worse outcome)

  From Baseline (0 W) to 24 hours, 4 weeks, 12 weeks, 24 weeks, 48 weeks after treatment

• Changes in knee joint range of motion from baseline

  From Baseline (0 W) to 4 weeks, 12 weeks, 24 weeks, 48 weeks after treatment]

• Changes in X-Kellgren-Lawrence grading and minimum joint space width (mJSW) from baseline

  From Baseline (0 W) to 24 weeks, 48 weeks after treatment

• Changes of MRI-Roberts cartilage repair score, cartilage thickness and synovial inflammation score (reference MOAKS) compared with baseline

  From Baseline (0 W) to 24 weeks, 48 weeks after treatment

Study Arms (3)

1UC-MSCs Treatment Group

EXPERIMENTAL

Participants will receive conventional treatment plus 1 time of UC-MSCs (5×10\^6 UC-MSCs/2.5mL, single injection into the knee cavity).

Drug: UC-MSCs

2UC-MSCs Treatment Group

EXPERIMENTAL

Participants will receive conventional treatment plus 1 time of UC-MSCs (1×10\^7 UC-MSCs/2.5mL, single injection into the knee cavity).

Drug: UC-MSCs

3UC-MSCs Treatment Group

EXPERIMENTAL

Participants will receive conventional treatment plus 1 time of UC-MSCs (2×10\^7 UC-MSCs/2.5mL, single injection into the knee cavity).

Drug: UC-MSCs

Interventions

UC-MSCs DRUG

In this study, three dose groups are preset, which are low-dose group: 5×10\^6 cells/2.5mL; medium-dose group: 1×10\^7 cells/2.5mL; high-dose group: 2×10\^7cells/2.5mL, 9 to 18 subjects will be recruited, and will be sequential from the low-dose group to the high-dose group according to the "3+3" dose escalation principle. At least 3 subjects are enrolled in each group for the safety and tolerability test of single administration. After the last subject in each dose group completes the DLT observation period, the sponsor and the researcher jointly confirm the safety tolerance of the subjects in the previous dose group, and only after the safe tolerance is determined can the subjects enter the next dose group, so as to evaluate the safety and tolerance of human umbilical cord mesenchymal stem cell injection in the treatment of knee osteoarthritis. Recommend appropriate cell therapy dose (RP2D) for Phase II clinical trials.

1UC-MSCs Treatment Group; 2UC-MSCs Treatment Group; 3UC-MSCs Treatment Group

Eligibility Criteria

• Age: 50 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Prior to conducting any assessment, written informed consent must be obtained;
• Able to communicate well with researchers during screening, understand and comply with experimental requirements;
• Age range from 50 to 70 years old (including threshold), regardless of gender;
• Male weight ≥ 50 kg, female weight ≥ 45 kg, body mass index (BMI) within the range of 18-26 kg/m2 (including critical values);
• According to the diagnostic criteria for knee osteoarthritis in the "Guidelines for the Diagnosis and Treatment of Osteoarthritis (2018 Edition)", subjects diagnosed with knee osteoarthritis (see Annex 1 for details); The course of knee osteoarthritis is more than 4 weeks;
• The target knee joint X-ray Kellgren Lawrence radiological grading (K-L IV grade) is II-III grade. Patients diagnosed with knee osteoarthritis on both sides should have non target knee joint symptoms, signs, and grading that do not exceed the target knee joint;
• MRI examination shows partial or full layer damage to the cartilage of the knee joint;
• A VAS score of ≥ 5 and ≤ 7 for knee joint pain at least 48 hours after discontinuing the use of all painkillers during screening;
• Patients who use analgesic therapy (taking paracetamol/acetaminophen) to control local pain in the target knee joint agree to discontinue the use of similar analgesics 2 weeks prior to administration, and only allow NSAID as a rescue drug; Patients who use glucosamine, chondroitin, opioid drugs, or diacetate, glucosamine, etc. must agree to discontinue such drugs from 2 weeks prior to administration.

You may not qualify if:

• Individuals with a history of knee joint infection, surgery, and radiation therapy within 6 months prior to administration;
• Combined instability of the knee joint (anterior and posterior cruciate ligaments, medial and lateral collateral ligaments), rupture, relaxation, or external deformity of the knee joint;
• According to researchers, diseases that may interfere with knee joint function assessment, such as symptomatic lower back pain, lumbar disc herniation, and hip joint pain in the target knee joint;
• According to the judgment of researchers, local diseases that may confuse knee joint function assessment include but are not limited to septic arthritis, reactive arthritis, clinically recurrent pseudogout, chondrocalcinosis, or joint fractures;
• Within 3 months prior to administration, any medication injection treatment (including intra-articular injection of growth factors, hormones, or sodium hyaluronate) or lavage surgery has been received in the knee joint (target side) cavity;
• Merge intra-articular or periarticular tumors (such as knee synovial chondroma, pigmented nodular synovitis, etc.);
• Various serious systemic diseases such as neurological disorders, respiratory disorders, heart diseases (NYHA grade III and above), and liver dysfunction (ALT\>3) × ULN or AST\>3 × ULN, renal dysfunction (Cr\>2) × ULN or BUN\>2 × ULN, coagulation dysfunction (INR\>1.5), or severe hematological disorders (such as grade 3 or above anemia, hemoglobin (Hb)\<8 g/dL, grade 2 or above thrombocytopenia, PLT\<75) × 10 \^ 9/L);
• Diagnosed as systemic inflammatory arthritis or connective tissue disease, including but not limited to rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, gout, Paget's disease, systemic lupus erythematosus, or other systemic diseases that may confuse KOA assessment (such as fibromyalgia);
• Subjects who receive long-term (\>14 days) oral corticosteroids\>5 mg/day within 3 months prior to administration, or who require long-term glucocorticoid treatment during the trial period;
• Previously received stem cell therapy;
• Uncontrolled hypertension is defined as systolic blood pressure (SBP)\>160 mmHg or diastolic blood pressure (DBP)\>100 mmHg during screening;
• Having a history of tumors, mental illness, severe autoimmune diseases, hematological diseases, and long-term use of immunosuppressants;
• Have a history of alcohol and prohibited drug abuse;
• Has a history of hypersensitivity to protein drugs;
• There are contraindications to MRI examination or unwillingness to undergo MRI examination;

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead
• Wuhan Hamilton Biotechnology Co., Ltd: collaborator
• Guangzhou Hamilton Biotechnology Co., Ltd.: collaborator

Study Sites (1)

Wuhan Union Hospital

Wuhan, Hubei, 430000, China

RECRUITING

MeSH Terms

Conditions

Osteoarthritis, Knee

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Central Study Contacts

Hongtao Tian, MD

CONTACT

18627171618; tianhongtao@me.com

Wei Tong, MD

CONTACT

13437105155; tongwei312@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2024
• First Posted: June 18, 2024
• Study Start: June 30, 2024
• Primary Completion: October 30, 2024
• Study Completion (Estimated): October 30, 2026
• Last Updated: July 1, 2024

Record last verified: 2023-09

Locations

CN (1)