Cell Therapy With Cellistem-OA for Symptomatic Knee Osteoarthritis

Cell Therapy for Patients With Symptomatic Knee Osteoarthritis: Phase I / II, Controlled, Randomized and Double-blind Clinical Trial

Symptomatic knee osteoarthritis is a serious public health problem in the world, it carries a high personal, social and economic impact. Currently, there are no drugs that modify the natural course of the disease. As analgesic therapy becomes insufficient, more invasive measures are applied, ultimately leading to arthroplasty.

The scientific community has joined efforts to develop new therapeutic approaches that allow the delay and regeneration of injured tissue in these patients. These include cell therapy with mesenchymal stem cells derived from different sources. Although most of the clinical studies carried out in different parts of the world with this therapy in patients with knee osteoarthritis have shown therapeutic benefit, it is necessary to develop clinical trials with high quality in our population.

The aim of this project is to evaluate the safety, tolerance and efficacy of Cellistem-OA (biological therapy based on mesenchymal stem cells derived from Wharton's jelly of umbilical cord) in patients with knee osteoarthritis in the Colombian population.

Investigators proposed to carry out an experimental (clinical trial), randomized, controlled and parallel with 30 participants with knee knee osteoarthritis of the medical complex Fundación Oftalmológica de Santander Clínica Carlos Ardila Lulle. The participants will be randomized into two groups: i) 15 patients who will receive a dose of 2 x 106 Cellistem-OA and ii) 15 patients who will receive an active comparator (acetonide of triamcinolone 10mg / mL), which will be administered by intra-articular injection in the superolateral aspect of the knee. The outcomes to be evaluated will be: (i) decrease in joint pain, (ii) increase in joint functionality, (iii) improvement in quality of life and (iv) improvement of articular cartilage. These parameters will be evaluated at weeks 1, 4, 8, 12, 24, 25, 28, 32, 36 and 52 post-treatments. Additionally, local and systemic adverse events will be recorded to establish whether or not there is an association between them and the intervention.

Study Overview

• Status: Not yet recruiting
• Conditions: Knee Osteoarthritis; Mesenchymal Stem Cells; Cell Therapy
• Intervention / Treatment: Drug: Triamcinolone acetonide; Biological: CELLISTEM-OA

Detailed Description

Type of study Controlled, randomized, double-blind clinical trial comparing CELLISTEM-OA and active comparator (triamcinolone acetonide).

Study population Patients from the Fundación Oftalmológica de Santander Clínica Carlos Ardila Lulle who consult the trauma and rheumatology service by knee osteoarthritis. Patients who show interest in participating will be cited to an interview with the researchers where both the objectives and the research procedures will be explained.

Sample size The sample size considered are 30 participants distributed in two groups.

Group 1 (control) active comparator: triamcinolone acetonide (10mg / mL) via intra-articular, 5 cc.

Group 2 (experimental): CELLISTEM-OA via intra-articular, doses of 2 x 106 cells in 5cc of saline solution.

The intra-articular puncture will be performed by an orthopedic doctor specializing in knee and hip treatments using sterile technique, after cooling the skin with local ice.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Martha L Arango, PhD; Phone Number: (57) 3226816547; Email: martha.arango@foscal.com.co
• Study Contact Backup: Name: Omar Amado, MD; Phone Number: (57)3108595352; Email: omaramado85@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 26 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients who / with:

• Osteoarthritis of the knee.
• Kellgren II or III to knee radiography.
• 30 to 75 years inclusive.
• Pain scale greater than 40 over 100 mm.
• MRI with G I, II or III chondral knee injury with or without stable degenerative meniscal injury.
• Stable knee.
• Examination of the rest of the normal limb.
• Willingness to participate in the study for 1 year.
• Ability to understand and willingness to sign the informed consent.

Exclusion Criteria:

Patients who / with:

• Symptomatic contralateral knee osteoarthritis.
• Significant knee trauma in the preceding 3 months.
• Wound or skin lesion in the knee studied.
• Anatomical valgus greater than 10º.
• Anatomical varus greater than 5º.
• Clinically significant joint effusion.
• Edema greater than 20% of the surface of the plateau or condyle in NMR.
• Previously known alterations in the hip and / or spine.
• Predominant patellofemoral pathology (radiographs with IWANO II osteoarthritis or more).
• Any type of inflammatory arthritis.
• History of active infections including HIV, HBV and HCV.
• Results of laboratory tests (hemogram and CRP) outside the normal ranges.
• Presence of fever on day -1 or day 0.
• Use of oral corticosteroids.
• Use of anticoagulants.
• Immunosuppression, uncontrolled diabetes mellitus, hyperthyroidism, psychiatric illnesses
• Active neoplasia or during the preceding 5 years.
• Pregnancy or breastfeeding (b-Hcg positive).
• Use of drugs or alcoholism.
• IA injections or knee surgeries in the last 180 days.
• BMI> 35.
• Any type of metallic implant susceptible to displacement with MRI.
• Use of pacemakers.
• History of severe allergy or anaphylactic shock.
• Significant alterations in the evaluation of the initial laboratory tests.
• Any factor that, in the opinion of the investigator, may affect the adequate follow-up of the patient during the study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group 1 (control-Triamcinolone acetonide); Triamcinolone acetonide (10mg / mL) via intra-articular, 5 cc, one dose (zero time).	Drug: Triamcinolone acetonide; The intra-articular puncture will be performed by an orthopedic doctor specializing in knee and hip treatments. The procedure will be carried out using sterile technique, after cooling the skin with local ice.; Other Names: Kenacort-A
Experimental: Group 2 (experimental- CELLISTEM-OA); CELLISTEM-OA via intra-articular, doses of 2 x 106 mesenchymal stem cells in 5cc of saline solution, one dose (zero time).	Biological: CELLISTEM-OA; The intra-articular puncture will be performed by an orthopedic doctor specializing in knee and hip treatments. The procedure will be carried out using sterile technique, after cooling the skin with local ice.; Other Names: Mesenchymal stem cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decrease in joint pain	Pain will be measured through visual analog scale (VAS).	12 months
Increased joint functionality	Joint functionality will be measured through the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).	12 months
Improvement in the quality of life	Quality of life will be measured through the Short Form 36 Health Survey Questionnaire (SF-36).	12 months
Imaging improvement of articular cartilage	The improvement of articular cartilage will be evaluated by nuclear magnetic resonance (NMR).	12 months

Collaborators and Investigators

• Sponsor: Fundación Oftalmológica de Santander Clínica Carlos Ardila Lulle
• Collaborators: Cells for Cells
• Investigators: Principal Investigator: Martha L Arango, PhD, Fundación Oftalmológica de Santander Clínica Carlos Ardila Lulle

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2021
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): June 30, 2022

Study Registration Dates

• First Submitted: April 20, 2021
• First Submitted That Met QC Criteria: April 23, 2021
• First Posted (Actual): April 28, 2021

Study Record Updates

• Last Update Posted (Actual): April 28, 2021
• Last Update Submitted That Met QC Criteria: April 23, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; Triamcinolone diacetate
• Other Study ID Numbers: OA-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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