A Study Evaluating the Efficacy of a Single Injection Autologous Adipose Derived Mesenchymal Stromal Cells in Patients With Knee Osteoarthritis (ADIPOA-2)

A Phase IIb, Prospective, Multicentre, Double-blind, Triple-arm, Randomized Versus Placebo Trial, to Assess the Efficacy of a Single Injection of Either 2 or 10 x 106 Autologous Adipose Derived Mesenchymal Stromal Cells (ASC) in the Treatment of Mild to Moderate Osteoarthritis (OA) of the Knee, Active and Unresponsive to Conservative Therapy for at Least 12 Months

ASCs will be administered via intra-articular use into the knee joint affected by OA where they are expected to exert their therapeutic effects.

The objective of this clinical trial is to generate efficacy and tolerability profiles of single injections of 2 dosages of autologous ASCs versus standard of care (placebo), when administered locally into a knee joint affected by OA after in vitro cell expansion. The potential of ASC to lead to a disease-modifying therapeutic option for the treatment of this chronic and debilitating disease will be assessed by MRI after 1 and 2 years.

This will be a phase IIb, multi-centre, prospective, randomized, double-blind study, comparing culture-expanded autologous ASC with placebo.

Study Overview

• Status: Active, not recruiting
• Conditions: Osteoarthritis
• Intervention / Treatment: Biological: Injection (2x106 ASC/5ml).; Biological: Injection (10x106 ASC/5ml).; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34295
    • UH Montpellier

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Symptomatic mild to moderate osteoarthritis (OA) of the index knee as defined by the American college of Rheumatology (ACR)
• Must meet pain criteria at the time of screening/baseline visit since at least half of the days in the previous month
• NSAID washout of at least 2 days before screening/baseline

Exclusion Criteria:

• Previous treatments acting on cartilage or bone metabolism
• Received intra-articular injection of corticosteroids, platelet rich plasma or hyaluronic acid within the previous 6 months,
• Significant trauma or surgery to the index knee within the last year or arthroscopy of the index knee within 12 months of screening.
• Kellgren-Lawrence Grade 1 or 4 in the index knee on any incidences.
• Osteoarthritis causing significant pain in any joint other than the identified knee, i.e., pain in hip, or contralateral knee (≥ 20 mm pain) as confirmed by a separate VAS at baseline for any other painful joint concerned
• History of joint replacement of the knee or hip within the previous 12 months

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 2x106 ASC intra-articular injection; Injection of Autologous adipose derived stem cells (2x106 ASC/5ml). The patient of this group will receive one single administration of the cells and will be followed for 12 months. A final follow up visit will occur at Month 24.	Biological: Injection (2x106 ASC/5ml).; Injection of Autologous adipose derived stem cells (2x106 ASC/5ml). The patient of this group will receive one single administration of the cells and will be followed for 12 months. A final follow up visit will occur at Month 24.
Experimental: 10x106 ASC intra-articular injection; Injection of Autologous adipose derived stem cells (10x106 ASC/5ml). The patient of this group will receive one single administration of the cells and will be followed for 12 months. A final follow up visit will occur at Month 24.	Biological: Injection (10x106 ASC/5ml).; Injection of Autologous adipose derived stem cells (10x106 ASC/5ml). The patient of this group will receive one single administration of the cells and will be followed for 12 months. A final follow up visit will occur at Month 24.
Placebo Comparator: Placebo; 0.5% glucose in saline with 4.5% albumin	Other: Placebo; Injection of placebo 0.5% glucose in saline with 4.5% alb/5ml The patient of this group will receive one single administration and will be followed for 12 months. A final follow up visit will occur at Month 24.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement of pain or physical function	evaluate the efficacy of ASC in mild to moderate knee OA (KL 2-3) based on increase in the number of "strict" responders defined by improvements from baseline in WOMAC pain or physical function subscores 50% with absolute changes 20 mm at 6 month, compared to placebo	Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disability (WOMAC)	assessed by WOMAC questionnaire	Months 1, 3, 6, 12 and 24
Disability (KOOS)	assessed by KOOS (Knee injury and Osteoarthritis Outcome Score questionnaire)	Months 1, 3, 6, 12 and 24
Disability (SAS)	assessed by SAS questionnaire (The Short Arthritis Assessment Scale)	Months 1, 3, 6, 12 and 24
Change in Quality of life	assessed by SF-36 questionnaire	Months 1, 3, 6, 12 and 24
painkillers consumption	Changes from baseline (Day 0) to months 1, 3, 6, 12 and 24 in use of painkillers	Months 1, 3, 6, 12 and 24
Structural changes (X-Ray)	Changes from baseline (Day 0) to months 12 and 24 in femorotibial joint space of the index knee on X-ray	Months 12 and 24
Structural changes (MRI)	Changes from baseline (Day 0) to months 12 and 24 by MOAKS (MRI Osteoarthritis Knee score)	Months 12 and 24

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Collaborators: Assistance Publique - Hôpitaux de Paris; Institut National de la Santé Et de la Recherche Médicale, France; Cambridge University Hospitals NHS Foundation Trust; University of Padova; Istituto Ortopedico Rizzoli; National University of Ireland, Galway, Ireland; University Hospital, Toulouse; Etablissement Français du Sang; University of Ulm; Centre National de la Recherche Scientifique, France; Stichting Katholieke Universiteit; European Clinical Research Infrastructure Network; HUMAN MED AG (HM); SPORTS SURGERY CLINIC LIMITED; EVANGELISCHES WALDKRANKENHAUS SPANDAU KRANKENHAUSBETRIEBS GGMBH (EWK); PINTAIL LTD (PT); Aries srl (ARIES)
• Investigators: Principal Investigator: Christian Jorgensen, MD, PhD, University Hospital, Montpellier

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2016
• Primary Completion (Actual): September 1, 2022
• Study Completion (Estimated): March 1, 2024

Study Registration Dates

• First Submitted: June 13, 2016
• First Submitted That Met QC Criteria: July 15, 2016
• First Posted (Estimated): July 20, 2016

Study Record Updates

• Last Update Posted (Actual): August 16, 2023
• Last Update Submitted That Met QC Criteria: August 11, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis
• Other Study ID Numbers: UF 9494

Plan for Individual participant data (IPD)

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