UMIN-CTR Clinical Trial

Public title

Clinical study of minimally invasive transplantation of autologous chondrocytes products (ACP) for cartilage repair for the knee joint

Acronym

Clinical study of minimally invasive transplantation of autologous chondrocytes products (ACP) for cartilage repair for the knee joint

Scientific Title

Clinical study of minimally invasive transplantation of autologous chondrocytes products (ACP) for cartilage repair for the knee joint

Scientific Title:Acronym

Clinical study of minimally invasive transplantation of autologous chondrocytes products (ACP) for cartilage repair for the knee joint

Region

Japan

Condition

Focal cartilage defect of the knee joint caused by trauma and/or early osteoarthritis

Classification by specialty

Orthopedics

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

The objective of this study is to evaluate the safety and study evaluation criteria for a focal cartilage defect repair of the knee joint caused by trauma and/or early osteoarthritis using minimally invasive transplantation of autologous chondrocytes products (ACP).

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Developmental phase

Phase I

Primary outcomes

Clinical evaluation (Improvement of KOOS (Knee injury and Osteoarthritis Outcome Score) from baseline)

Key secondary outcomes

Clinical evaluation, MRl, Arthroscopy, Pathological evaluation and Activity evaluation. Frequency and content of adverse events.

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Device,equipment

Interventions/Control_1

Chondrocytes are obtained from unloaded part of patient's cartilage and cultured through passaging. The chondrocytes mixed with hydrogel are transplanted under arthroscopy or minimal open surgery.

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

16

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

Patients with symptomatic pain of the knee who has focal chondral defect detectable by MRI.
Patients with chondral defect of ICRS III/IV or Outerbridge-Brittberg III/IV.
The size of chondral defect:2-9cm2.

Key exclusion criteria

Patients with
1.advanced osteoarthritis KL grade II and above with narrowing of the gap of knee joint,
2.arthritis with autoimmune disease such as Rheumatoid arthritis,
3.abnormal alignment of lower extremity,
4.infectious disease (HIV/HBV/HCV/HTLV etc.).

Target sample size

6

Name of lead principal investigator

1st name	Ken
Middle name
Last name	Nakata

Organization

Osaka University Graduate School of Medicine

Division name

Medicine for Sports and Performing Arts

Zip code

565-0871

Address

2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan

TEL

0662108439

Email

takanamoto@hss.osaka-u.ac.jp

Name of contact person

1st name	Takashi
Middle name
Last name	Kanamoto

Organization

Osaka University Graduate School of Medicine

Division name

Medicine for Sports and Performing Arts

Zip code

565-0871

Address

2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan

TEL

0662108439

Homepage URL

Email

takanamoto@hss.osaka-u.ac.jp

Institute

Department of Orthopaedics, Osaka University
Graduate School of Medicine

Institute

Department

Personal name

Organization

Interstem Co., Ltd.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Department of Orthopaedics, Osaka University Graduate School of Medicine

Address

2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan

Tel

0662108439

Email

takanamoto@hss.osaka-u.ac.jp

Secondary IDs

YES

Study ID_1

jRCTb050190105

Org. issuing International ID_1

Japan Registry of Clinical Trials

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2018

Year

12

Month

10

Day

URL releasing protocol

https://jrct.niph.go.jp/latest-detail/jRCTb050190105

Publication of results

Published

URL related to results and publications

https://jrct.niph.go.jp/latest-detail/jRCTb050190105

Number of participants that the trial has enrolled

6

Results

In 6 patients who underwent ACP, there were 11 adverse events, but none were serious.
The primary endpoint, the change from baseline in KOOS 5 at Week 52, showed significant improvement, and ACP can be estimated to be effective.
The secondary endpoints KOOS-symptoms and KOOS-pain showed significant improvement from baseline, with an improvement in scores above the MCID on the average of all five items.
Based on the mean of 14 ICRSII items, it was determined that an estimate of efficacy could be made.

Results date posted

2024

Year

01

Month

04

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

The six patients who were deemed eligible for cell transplantation in this study and enrolled in the secondary enrollment consisted of four males (66.7%) and two females (33.3%), who were 52.8 plus (or) minus 7.5 years old at the time consent was obtained.
The primary disease was early osteoarthritis of the knee in 5 patients (83.3%) and other (right knee PF articular cartilage damage) in 1 patient (16.7%). 3 patients (50.0%) had right-sided and 3 patients (50.0%) had left-sided knees, and none of them received surgical treatment or physical therapy related to this treatment.

Participant flow

Consent was obtained from 8 patients and screening tests were performed.
Two cases did not reach secondary enrollment.
One was considered ineligible before the secondary enrollment because the patient did not meet the inclusion criteria, and one was considered ineligible before the first enrollment because the patient did not meet the exclusion criteria.
There were six patients who underwent autologous cultured chondrocyte transplantation(ACP) after secondary enrollment, all of whom completed the 52-week observation period specified for this study.
One of 6 patients was last observed at 130 weeks after transplantation because the patient requested to refrain from visiting the clinic due to concerns about COVID-19 infection resulting from the visit, following the spread of COVID-19 infection after the 26-week postoperative visit.

Adverse events

Eleven cell transplantation related adverse events occurred in all six patients treated with this therapy.
There were no cases of infections suspected to have been caused by the provision of regenerative medicine.
Two adverse events that were considered to have a direct causal relationship to this treatment, autologous chondrocyte transplantation, were partial cartilage loss and cartilage hyperplasia in one patient.
Other nine adverse events judged to be weakly related to this treatment included six cases of postoperative pain, one case of left plantar numbness, two cases of postoperative swelling.

Outcome measures

The change from baseline (at screening) in KOOS 5 at 52 weeks, the primary efficacy endpoint, was showing a marked improvement.
The MCID (Minimal Clinically Important Difference, clinically relevant minimum change) of the KOOS subscore used as a secondary efficacy endpoint was 8 -10, and of the five items, KOOS-symptoms and KOOS-pain were recognized as notable improvements from the time of screening, and all five items showed improvements in scores above the MCID on average.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2018

Year

10

Month

30

Day

Date of IRB

2018

Year

10

Month

30

Day

Anticipated trial start date

2019

Year

02

Month

14

Day

Last follow-up date

2022

Year

09

Month

30

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2018

Year

12

Month

06

Day

Last modified on

2024

Year

01

Month

04

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000039049