Efficacy and Safety Study of Intra-Articular Injections of Autologous Peripheral Blood Stem Cells Following Subchondral Drilling Surgery for the Treatment of Articular Cartilage Injury in the Knee

Multicenter, Randomized, Open-Label, Standard Treatment-Controlled Parallel Group Phase 2 Study to Evaluate Efficacy and Safety of Intra-Articular Injections of Autologous Peripheral Blood Stem Cells and Hyaluronic Acid Adjuvant Therapy Following Subchondral Drilling Surgery for the Treatment of Articular Cartilage Injury in the Knee With an Optional Open-Label Extension for the Standard Treatment-Controlled Group

This is a 24-month, multicenter, randomized, open-label, standard treatment-controlled, parallel-group, Phase 2 study for adults with large or complicated knee articular cartilage lesions and are candidates for knee joint cartilage repair surgery. The safety and efficacy of intra-articular injections of peripheral blood stem cells (PBSCs) together with hyaluronic acid (HA) after subchondral drilling surgery will be evaluated to determine whether PBSC therapy can improve functional outcome and reduce pain of the knee joint better than a standard treatment (HA injections and physiotherapy regimen).

Study Overview

• Status: Completed
• Conditions: Articular Cartilage Disorder of Knee; Articular Cartilage; Degeneration
• Intervention / Treatment: Biological: Autologous peripheral blood stem cells and hyaluronic acid; Other: Hyaluronic acid

Detailed Description

This is a 24-month, multicenter, randomized, open-label, standard treatment-controlled, parallel-group, Phase 2 study for adults with large or complicated knee articular cartilage lesions and are candidates for knee joint cartilage repair surgery. The safety and efficacy of intra-articular injections of peripheral blood stem cells (PBSCs) together with hyaluronic acid (HA) after subchondral drilling surgery will be evaluated to determine whether PBSC therapy can improve functional outcome and reduce pain of the knee joint better than a standard treatment (HA injections and physiotherapy regimen).

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• Malaysia
  • Kuala Lumpur, Malaysia
    • Kuala Lumpur Sports Medicine Centre
• United States
  • Florida
    • Gulf Breeze, Florida, United States, 32561
      • Andrews Research & Education Foundation (AREF)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged between 18 to 55 years at screening (20 to 57 years for the open-label extension)
• Present for evaluation and treatment of knee pain, knee swelling, or knee mechanical symptoms due to cartilage lesions
• Provide written informed consent
• International Cartilage Repair Society (ICRS) Grade 3 or 4 lesions diagnosis from MRI scans of the target knee

• All subjects must also satisfy at least 1 of the following inclusion criteria:

  • Isolated knee articular cartilage lesion (single lesion) estimated to be ≥3 cm2 as demonstrated on MRI scanning. Multiple knee articular cartilage lesions (multiple lesions) with at least 1 lesion estimated to be ≥3 cm2 as demonstrated on MRI scanning. Bipolar cartilage defects demonstrated on MRI scanning with at least 1 articular surface lesion to be ≥3 cm2. One or more cartilage defects involving the patello-femoral joint as demonstrated on MRI scanning with at least 1 lesion ≥3 cm2. One or more cartilage defects involving the tibio-femoral joint as demonstrated on MRI scanning with at least 1 lesion to be ≥3 cm2. Previously failed cartilage repair procedures (i.e., microfracture, osteochondral autograft transplantation surgery (OATS), ACI)

Exclusion Criteria:

• Three or more previous surgical interventions on the knee in question.
• Preoperative flexion deformity greater than 10 degrees.
• Presence of ligamentous injury which would require reconstruction, varus or valgus deformity requiring osteotomy, or cases that require complex surgery prior to cartilage regeneration

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Subjects randomized to the intervention group will undergo subchondral drilling surgery according to standard protocol, and will also receive a regimen of PBSC and HA intra-articular injections and postoperative physiotherapy.	Biological: Autologous peripheral blood stem cells and hyaluronic acid; Regimen of intra-articular PBSC and HA injections and postoperative physiotherapy
Active Comparator: Standard treatment; Subjects randomized to the standard treatment-controlled parallel group will receive intra-articular HA injections and a physiotherapy regimen.	Other: Hyaluronic acid; Regimen of intra-articular HA injections and postoperative physiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
International Knee Documentation Committee (IKDC) score	Subjective IKDC core as a measure of joint function	24 months
Knee injury and Osteoarthritis Outcome (KOOS) pain subdomain	KOOS pain subdomain score as a measure of joint pain	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Numeric Rating Scale (NRS) for pain	Numeric Rating Scale (NRS) for pain	24 months

Other Outcome Measures

Outcome Measure	Time Frame
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	up to 24 months

Collaborators and Investigators

• Sponsor: KLSMC Stem Cells, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2015
• Primary Completion (Actual): July 1, 2022
• Study Completion (Actual): July 1, 2022

Study Registration Dates

• First Submitted: March 24, 2017
• First Submitted That Met QC Criteria: April 3, 2017
• First Posted (Actual): April 4, 2017

Study Record Updates

• Last Update Posted (Actual): August 16, 2022
• Last Update Submitted That Met QC Criteria: August 15, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Connective Tissue Diseases; Cartilage Diseases; Physiological Effects of Drugs; Immunologic Factors; Protective Agents; Adjuvants, Immunologic; Viscosupplements; Hyaluronic Acid
• Other Study ID Numbers: KLSMC-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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