Phase II/III Randomized Trial of UC-MSC Secretome vs Sodium Hyaluronate in Knee Osteoarthritis (SECRET-OA)

A Phase II/III Randomized Double-Blind Multicenter Study Comparing UC-MSC-Derived Secretome and Sodium Hyaluronate on Pain and Function in Patients With Kellgren-Lawrence Grade 2-3 Knee Osteoarthritis

This study is a randomized, double-blind, multicenter Phase II/III clinical trial designed to evaluate the effectiveness and safety of umbilical cord-derived mesenchymal stem cell (UC-MSC) secretome compared with sodium hyaluronate in patients with knee osteoarthritis. Knee osteoarthritis is a common degenerative joint disease that causes chronic pain and functional limitation. Participants will be randomly assigned to receive intra-articular injections of either UC-MSC-derived secretome or sodium hyaluronate. The study aims to assess improvements in knee pain, physical function, and overall clinical outcomes, as well as to evaluate the safety of the interventions over the study period.

Study Overview

• Status: Not yet recruiting
• Conditions: Knee Osteoarthritis (Knee OA)
• Intervention / Treatment: Drug: Sodium Hyaluronate (Hyalein); Biological: UC-MSC-Derived Secretome

Detailed Description

This multicenter, randomized, double-blind Phase II/III clinical study aims to compare the efficacy and safety of intra-articular UC-MSC-derived secretome with sodium hyaluronate in patients with Kellgren-Lawrence grade 2-3 knee osteoarthritis. Eligible participants will be randomly allocated to one of two treatment arms. Clinical outcomes will be evaluated using validated pain and functional assessment tools at predefined time points. Safety assessments will include monitoring of adverse events throughout the study period. The results of this study are expected to provide evidence regarding the potential role of UC-MSC-derived secretome as an alternative therapeutic option for knee osteoarthritis.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Rudi Erwin Kurniawan, MD, MH; Phone Number: +6282166114111; Email: dr.rudierwin@gmail.com

Study Locations

• Indonesia
  • South Sumatera
    • Palembang, South Sumatera, Indonesia
      • RSUP Dr. Mohammad Hoesin Palembang
      • Contact: Radiyati Umi Partan, MD, PhD; Phone Number: +62812-7811-6601; Email: radiyati.u.p@fk.unsri.ac.id

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosed with primary OA in one or both knees based on American College of Rheumatology (Clinical and Rheumatology criteria). If both knees have OA, the knee with the OA grade that falls within the inclusion criteria (grade 2-3) will be selected. If both knees meet the inclusion criteria, the knee with the highest grade and the one that is most uncomfortable will be chosen.
2. Males or females in the age range 40-70 years
3. Symptomatic knee OA (defined by pain at the affected joint for at least 3 months before inclusion and visual analog scale 40 - 70 mm on a 100 mm Visual Analog Scale (VAS).
4. Radiographic evidence of grade 2 to 3 osteoarthritis (OA) based on Kellgren and Lawrence radiographic criteria.
5. Body mass index between 18 - 30 kg/m2
6. Female participants of childbearing age who agreed to use accepted methods of contraception during the course of the study.
7. Ability to provide written informed consent and willing to participate the study

Exclusion Criteria:

1. Participants who, based on physical examination and clinical history (anamnesis), are in the active or acute phase of cardiac, pulmonary, hematological, hepatic, renal, systemic autoimmune, immunodeficiency, or coagulation disorders that may interfere with the administration of the study drug (Secretome or Sodium Hyaluronate) will be excluded,
2. Diagnosed with a meniscal rupture based on clinical history (anamnesis) and physical examination. If the anamnesis and physical examination show symptoms and signs of a meniscal rupture, further evaluation will be performed using ultrasound (USG),
3. Participants with significant axial deviation, defined by valgus or varus deformity observed during physical examination, will be excluded,
4. Participants with other pathological lesions on knee X-rays from the screening examination will also be excluded,
5. History of any form of secondary arthritis in the knee due to trauma,
6. History of surgery or major trauma to the knee joint
7. Has knee effusion,
8. Has any other inflammatory disorder of the knee joint
9. Diagnosed with active malignancy.
10. History of stem cell or secretome therapy.
11. Intra-articular injection of corticosteroid and/or prior treatment with Sodium Hyaluronate and/or platelet rich plasma (PRP) in past 3 months.
12. Use of NSAIDs and/or chondroprotective supplements, such as glucosamine and chondroitin sulfate, within 7 days before the trial, whether used orally, topically, or via injection,
13. Undergoing immunosuppressive therapy, or anticoagulant therapy, or corticosteroid therapy.
14. For women of child-bearing potential: positive pregnancy test or lactating (females who were planning pregnancy within the next year were excluded).
15. Enrolled in any other clinical trials within the past four weeks.
16. The principal investigator considers that the participant is ineligible for the clinical trial due to any reasons other than those listed above

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: UC-MSC-Derived Secretome; Participants receive intra-articular injection of UC-MSC-derived secretome	Drug: Sodium Hyaluronate (Hyalein); Sodium hyaluronate administered via intra-articular injection as an active comparator.; Other Names: Sodium Hyaluronate
Active Comparator: Sodium Hyaluronate; Participants receive intra-articular injection of sodium hyaluronate	Biological: UC-MSC-Derived Secretome; Umbilical cord-derived mesenchymal stem cell secretome administered via intra-articular injection according to the study protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in WOMAC Pain Subscale Score	Change from baseline in knee pain assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale.	Baseline to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in WOMAC Total Score	Change from baseline in overall knee pain, stiffness, and physical function assessed using WOMAC total score.	Baseline to Week 12

Collaborators and Investigators

• Sponsor: Universitas Sriwijaya
• Collaborators: PT Bifarma Adiluhung
• Investigators: Study Chair: Radiyati Umi Partan, MD, PhD, Universitas Sriwijaya

Study record dates

Study Major Dates

• Study Start (Estimated): August 30, 2026
• Primary Completion (Estimated): September 16, 2026
• Study Completion (Estimated): December 24, 2027

Study Registration Dates

• First Submitted: January 1, 2026
• First Submitted That Met QC Criteria: January 1, 2026
• First Posted (Actual): January 13, 2026

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Randomized Controlled Trial; Knee Osteoarthritis; Intra-articular Injection; Sodium Hyaluronate; UC-MSC Secretome
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Osteoarthritis; Osteoarthritis, Knee; Carbohydrates; Glycosaminoglycans; Polysaccharides; Hyaluronic Acid
• Other Study ID Numbers: PML-BFA-04-2024 (Other Grant/Funding Number: PT Bifarma Adiluhung)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data underlying the primary and secondary outcome measures, including demographic characteristics, baseline clinical data, outcome scores, and adverse event data, will be shared. All data will be fully anonymized, with no direct identifiers, in accordance with applicable ethical and regulatory requirements.
• IPD Sharing Time Frame: De-identified individual participant data and supporting documents will be available beginning 6 months after publication of the primary study results and will remain available for up to 5 years.
• IPD Sharing Access Criteria: Access to de-identified IPD will be granted to qualified researchers who submit a methodologically sound research proposal. Requests will be reviewed by the study steering committee. Data will be shared under a data use agreement to ensure participant confidentiality and appropriate use of the data.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No