AzTrials
AzTrials

Cartilage DamagePhase 3IMPACT2NCT04236739

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

A Phase 3 study testing Instant MSC Product accompanying Autologous Chondron Transplantation in people with Cartilage Damage, run by R.J.H. Custers at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 45 years
Conditions the study is for
Cartilage Damage
What is being tested?
Instant MSC Product accompanying Autologous Chondron Transplantation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
1 siteNetherlands
Study dates
23 Jul 2019to 3 Sep 2025
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 45 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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.
Show all 9Show fewer
  • 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).

Who cannot join

  • 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.
  • Any surgery in the knee joint 6 months prior to study inclusion.
  • 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.

Trial locations and contacts

1 site in 1 country.

Netherlands1 site
  • University Medical Center Utrecht

    Utrecht, Utrecht, 3584 CX

Other trials in Netherlands

About this study

Official title: Randomized Controlled Trial Comparing Clinical Outcomes of Instant MSC Product Accompanying Autologous Chondron Transplantation (IMPACT) for Focal Articular Cartilage Lesions of the Knee to Conservative Treatment

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.

Read the detailed description

IMPACT is designed as a one-stage cell-based regenerative therapy for isolated articular cartilage lesions. The investigational product consists of two cell types. Firstly, allogeneic MSCs, which are an "off-the-shelf" ATMP and also being used in a clinical trial for the treatment of steroid-resistant Graft versus Host Disease. Secondly, defect derived autologous chondrons that are reinserted into the defect in combination with MSCs within one procedure. During surgery, the autologous defect derived chondrons will be combined with allogeneic cryopreserved and thawed MSCs to enhance cartilage formation. Cells will be combined at a ratio of 10% chondrons and 90% MSCs and mixed in Tisseel® which will act as a cell carrier scaffold. In the phase I-II trial we showed no significant differences in clinical outcome between these dosages. Tisseel® is a registered widely used two-component adhesive containing fibrinogen and thrombin concentrate. When mixed, these components mimic the final steps of blood coagulation and form a stable physiological fibrin clot. The ATMP will be applied to the cartilage defect in a concentration of approximately 2 million cells per ml of fibrin glue, 0,5 to 0,7 ml per cm^2 will be administered. The amount of MSCs and chondrons is thus dependant of the size of the lesion. The cells will be applied in a ratio of 10:90 autologous chondrons: allogeneic MSCs.

To evaluate the clinical status/ improvement of the participants treated with the IMPACT therapy, the included participants will be asked to complete the Knee injury and Osteoarthritis Outcome Scoring (KOOS) and the EuroQoL 5-Dimension Health Questionnaire (EQ5D) at baseline (before IMPACT therapy) and at 3, 6, 9, 12 and 18 months follow-up.

To evaluate work leave and medical consumption a modified version iMTA Productivity cost questionnaire and iMTA Medical Consumption Questionnaire will be used.

A cost-effectiveness analysis will be performed to evaluate the extent to which IMPACT therapy affects costs compared to current treatment techniques. The costs of the procedures that are performed (i.e. IMPACT or current practice), as well as the costs of the product that is used (materials, operation theatre etc.), and the duration of the accompanying hospitalization episode, will be determined using the UMC Utrecht administrative data and study budget. In addition, the results of the iMTA Medical Consumption Questionnaire and the iMTA Productivity cost questionnaire will be used to collect data on respectively resource use and productivity loss during the rehabilitation period. All resource use will be multiplied with cost prizes, which will be obtained from the Dutch Healthcare Authority or from the Dutch manual for performing health economic evaluations, to calculate total societal costs. These costs will be combined with the QoL outcome measures (as described previously), to obtain an estimate of the cost-effectiveness of IMPACT as compared to current practice.

Being tested
Instant MSC Product accompanying Autologous Chondron Transplantation
Keywords
Cartilage, Cartilage damage, Cell therapy, MSC, ATMP, Knee, IMPACT, ACI, Chondrons
Medical subject headings
Tooth, Impacted

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Instant MSC Product accompanying Autologous Chondron TransplantationDrug

    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.

Study groups in NCT04236739
Study groupRoleWhat they receive
IMPACTExperimentalApplication of a mixture of allogenic MSC's and autologous chondrons with a fibrin cell carrier (Tisseel®) during one surgical procedure.
Receives: Drug: Instant MSC Product accompanying Autologous Chondron Transplantation
ControlNo interventionOptional physical therapy or pain medication, according to participants' desire for 9 months.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Clinical change on scale of 0-100

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

    Measured: At baseline, 3, 6 and 9 months

  2. 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.)

    Measured: At baseline, 3, 6 and 9 months

Secondary outcomes (1)
  1. Structural change of the cartilage tissue

    MRI-scan

    Measured: At baseline, 6 and 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Jan 2020
  2. Study start23 Jul 2019
  3. Primary completion3 Sep 2025
  4. Study completion3 Sep 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Model description
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.
Masking
None (open label)
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04236739
Sponsor's protocol ID
19-455
Other IDs
NL67161.000.18, 2018-003470-27, 2018
Acronym
IMPACT2
Status last verified
Sep 2025
First submitted
15 Jan 2020
Last updated
27 Mar 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes

Publications

  • 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.

    PubMed 27507787
  • 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.

    PubMed 28600828
  • 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.

    PubMed 33036661
  • 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.

    PubMed 33591794

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Instant MSC Product accompanying Autologous Chondron Transplantation in people with Cartilage Damage, run by R.J.H. Custers at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clinical change on scale of 0-100 (time frame: At baseline, 3, 6 and 9 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04236739, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2026.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in