Comparing Clinical Outcomes of the One-step Cartilage Transplantation in Cartilage Defects of the Knee With Conservative Treatment

NCT04236739 | Completed Phase 3

• 3 other identifiers: 19-455NL67161.000.182018-003470-27
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Articular cartilage defects in the knee have poor intrinsic healing capacity and may lead to functional disability and osteoarthritis. Cartilage cell therapy using autologous chondrocyte implantation has been established as the first advanced treatment therapy medicinal product. Although this technique has achieved good mid-term results, it is a costly and extensive two-stage procedure. 'Instant MSC Product accompanying Autologous Chondron Transplantation' (IMPACT) combines autologous recycled chondrons (chondrocytes surrounded by pericellular matrix) with MSCs for one-stage treatment of cartilage defects. IMPACT was successfully executed in a first-in-man phase I/II clinical trial in which 35 participants with cartilage defects were treated. The results showed a good safety profile, proper feasibility and good initial clinical efficacy at 18 months follow-up. Also good outcome at 24 and 36 months was shown in ongoing post study surveying of the participants. Consequently a new study with IMPACT was designed; IMPACT2. The objective of IMPACT2 is to compare clinical outcomes of 30 individual participants with cartilage defects treated with IMPACT to 30 participants treated with standard care for 9 months (consisting of optional physical therapy and pain medication). Participants should be aged 18-45 years with a symptomatic Modified Outerbridge Grade III or IV cartilage lesion of the knee ranging in size 2-8 cm\^2. After enrolment, participants will be allocated (randomized) to either group A in which case they receive IMPACT-treatment, or group B that will receive standard care. Standard care consists of optional physical therapy and pain medication. After 9 months, participants in group B can receive the IMPACT-procedure as well.

Conditions

Cartilage Damage

Keywords

Cartilage; Cartilage damage; Cell therapy; MSC; ATMP; Knee; IMPACT; ACI; Chondrons

Outcome Measures

Primary Outcomes (2)

• Clinical change on scale of 0-100

  KOOS-questionnaire (Knee injury and Osteoarthritis Outcome Score, 100 indicating no symptoms and 0 indicating extreme symptoms)

  At baseline, 3, 6 and 9 months

• Quality of life change on scale of 0-100

  EQ-5d-questionnaire (The EQ-5D-5L has 5 dimensions, each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome that reflect the patient's own judgement.)

  At baseline, 3, 6 and 9 months

Secondary Outcomes (1)

• Structural change of the cartilage tissue

  At baseline, 6 and 18 months

Other Outcomes (1)

• Change in healtcare use and costs

  At baseline, 3, 6, 9, 12 and 18 months

Study Arms (2)

IMPACT

EXPERIMENTAL

Application of a mixture of allogenic MSC's and autologous chondrons with a fibrin cell carrier (Tisseel®) during one surgical procedure.

Drug: Instant MSC Product accompanying Autologous Chondron Transplantation

Control

NO INTERVENTION

Optional physical therapy or pain medication, according to participants' desire for 9 months.

Interventions

Instant MSC Product accompanying Autologous Chondron Transplantation DRUG

Application of a mixture of allogenic MSC's and autologous chondrons with a fibrin cell carrier (Tisseel®) in the cartilage defect of the knee during one surgical procedure.

IMPACT

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Participants must meet the following criteria to be eligible for the study:
• Provides written informed consent, is able to understand the content of the study, understands the requirements for follow-up visits and is willing to provide the required information at follow-up visits and in the questionnaires.
• Symptomatic articular cartilage lesion of the knee (femoral condyles or trochlea).
• Age \>18 and \<45 years old
• Participants must meet the following secondary criteria to be eligible for the study:
• Modified Outerbridge Grade III or IV isolated cartilage lesion of the knee.
• A post-debridement size of the cartilage lesion \> 2cm2 and ≤ 8 cm2
• At least 50% of functional meniscus remaining. Meniscal repair or resection is allowed during the IMPACT surgery provided that the surgeon is able to confirm that at least 50% of functional meniscus remains.
• Stable knee ligaments (i.e. anterior and posterior cruciate ligaments).

You may not qualify if:

• Malalignment of \>5 degrees
• (History of) osteoarthritis, defined as Kellgren-Lawrence grade \>3 as determined from appropriate X-ray.
• Concomitant inflammatory disease that affects the joint (rheumatoid arthritis, metabolic bone disease, psoriasis, gout, symptomatic chondrocalcinosis)
• (History of) Septic arthritis.
• (History of) Total meniscectomy in the target knee joint.
• Risk groups for MRI scanning due to the magnetic field like participants with pacemakers, nerve stimulators, metal particles, stents, clips or implants, (possible) pregnancy or breast feeding.

Sponsors & Collaborators

• R.J.H. Custers: lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator

Study Sites (1)

University Medical Center Utrecht

Utrecht, Utrecht, 3584 CX, Netherlands

Location

Related Publications (4)

• de Windt TS, Vonk LA, Slaper-Cortenbach IC, van den Broek MP, Nizak R, van Rijen MH, de Weger RA, Dhert WJ, Saris DB. Allogeneic Mesenchymal Stem Cells Stimulate Cartilage Regeneration and Are Safe for Single-Stage Cartilage Repair in Humans upon Mixture with Recycled Autologous Chondrons. Stem Cells. 2017 Jan;35(1):256-264. doi: 10.1002/stem.2475. Epub 2016 Aug 29.

  PMID: 27507787 BACKGROUND

• de Windt TS, Vonk LA, Slaper-Cortenbach ICM, Nizak R, van Rijen MHP, Saris DBF. Allogeneic MSCs and Recycled Autologous Chondrons Mixed in a One-Stage Cartilage Cell Transplantion: A First-in-Man Trial in 35 Patients. Stem Cells. 2017 Aug;35(8):1984-1993. doi: 10.1002/stem.2657. Epub 2017 Jun 23.

  PMID: 28600828 BACKGROUND

• Korpershoek JV, Vonk LA, Kester EC, Creemers LB, de Windt TS, Kip MMA, Saris DBF, Custers RJH. Efficacy of one-stage cartilage repair using allogeneic mesenchymal stromal cells and autologous chondron transplantation (IMPACT) compared to nonsurgical treatment for focal articular cartilage lesions of the knee: study protocol for a crossover randomized controlled trial. Trials. 2020 Oct 9;21(1):842. doi: 10.1186/s13063-020-04771-8.

  PMID: 33036661 BACKGROUND

• Saris TFF, de Windt TS, Kester EC, Vonk LA, Custers RJH, Saris DBF. Five-Year Outcome of 1-Stage Cell-Based Cartilage Repair Using Recycled Autologous Chondrons and Allogenic Mesenchymal Stromal Cells: A First-in-Human Clinical Trial. Am J Sports Med. 2021 Mar;49(4):941-947. doi: 10.1177/0363546520988069. Epub 2021 Feb 16.

  PMID: 33591794 BACKGROUND

MeSH Terms

Conditions

Tooth, Impacted

Condition Hierarchy (Ancestors)

Tooth Diseases; Stomatognathic Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This is a randomized controlled trial. At baseline, participants will be randomized with variable block randomisation method to either group A in which case they receive IMPACT-treatment, or group B that will receive standard care. Standard care consists of optional physical therapy and pain medication. After 9 months, participants in group B can receive the intervention as well.

Study Record Dates

• First Submitted: January 15, 2020
• First Posted: January 22, 2020
• Study Start: July 23, 2019
• Primary Completion: September 3, 2025
• Study Completion: September 3, 2025
• Last Updated: March 27, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

NL (1)