UMIN-CTR Clinical Trial

Unique ID issued by UMIN UMIN000034801
Receipt number R000039592
Scientific Title Multicenter, parallel-group clinical trial of autologous cultured cartilage ACC-01 compared with intra-articular injection of sodium hyaluronate in patients with knee osteoarthritis
Date of disclosure of the study information 2018/11/07
Last modified on 2024/02/28 14:28:46

* This page includes information on clinical trials registered in UMIN clinical trial registed system.
* We don't aim to advertise certain products or treatments


Basic information

Public title

Multicenter, parallel-group clinical trial of autologous cultured cartilage ACC-01 compared with intra-articular injection of sodium hyaluronate in patients with knee osteoarthritis

Acronym

Multicenter, parallel-group clinical trial of autologous cultured cartilage ACC-01 compared with intra-articular injection of sodium hyaluronate in patients with knee osteoarthritis

Scientific Title

Multicenter, parallel-group clinical trial of autologous cultured cartilage ACC-01 compared with intra-articular injection of sodium hyaluronate in patients with knee osteoarthritis

Scientific Title:Acronym

Multicenter, parallel-group clinical trial of autologous cultured cartilage ACC-01 compared with intra-articular injection of sodium hyaluronate in patients with knee osteoarthritis

Region

Japan


Condition

Condition

Knee osteoarthritis

Classification by specialty

Orthopedics

Classification by malignancy

Others

Genomic information

NO


Objectives

Narrative objectives1

The purpose of this study is to investigate the efficacy and safety of autologous cultured cartilage ACC-01 by multicenter, parallel-group clinical trial compared with intra-articular injection of sodium hyaluronate (HA) in patients with knee osteoarthritis.

Basic objectives2

Efficacy

Basic objectives -Others


Trial characteristics_1


Trial characteristics_2


Developmental phase



Assessment

Primary outcomes

1) Change in WOMAC score between pre and post treatment with the investigational products

Key secondary outcomes

Efficacy
1) Change in WOMAC subscale (pain, stiffness, physical function) between pre and post treatment
2) Change in Lysholm Knee Score (LKS) between pre and post treatment
3) MRI_T2 values
4) 3D MOCART score (MRI evaluation)
5) ICRS score *1 (arthroscopy)
6) Histological evaluation *2
7) Number of days using NSAIDs
8) Presence or absence of repair with hyaline cartilage-like tissues
*1 Patients who give written informed consent of arthroscopy
*2 Patients who give written informed consent of biopsy

Safety
1) Number and rate of adverse events and product-related adverse events
2) Number and rate of significant product-related adverse events
3) Product problem


Base

Study type

Interventional


Study design

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification


Dynamic allocation


Institution consideration


Blocking


Concealment



Intervention

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Maneuver

Interventions/Control_1

・Taking healthy cartilage tissue
・Transplantation of autologous cultured cartilage ACC-01

Interventions/Control_2

Intra-articular injection of sodium hyaluronate

Interventions/Control_3


Interventions/Control_4


Interventions/Control_5


Interventions/Control_6


Interventions/Control_7


Interventions/Control_8


Interventions/Control_9


Interventions/Control_10



Eligibility

Age-lower limit

20 years-old <=

Age-upper limit

75 years-old >=

Gender

Male and Female

Key inclusion criteria

1) Patients who are aged 20 years or older at the time of informed consent, and who can give written informed consent
2) Patients having a localized cartilage defect whose size is over 2 cm2
3) Patients diagnosed as osteoarthritis (Kellgren-Lawrence grade 2 or grade 3) by x-ray examination
4) Patients with knee pain
5) Patients who have had conservative therapy, including exercise therapy, for the last 3 months

Key exclusion criteria

1) Patients who participated in previous clinical trials of ACC-01, or patients who have undergone ACC-01 transplantation
2) Patients who are aged 75 years or older at the time of informed consent
3) Patients with BMI >= 30
4) Patients who have difficulty in fixation by collagen membrane or periosteum because of entire cartilage defects in the knee joint
5) Patients with severe knee deformation (FTA >=180 degrees, <=170 degrees)
6) Patients who underwent surgery or arthroscopy in the affected knee joint within the last 3 months
7) Patients with a meniscal tear requiring treatment in the affected knee joint, or patients who underwent surgical treatment to meniscal in the affected knee joint in the last 3 months
8) Patients with autoimmune disease (e.g., rheumatoid arthritis), or patients with a history of these diseases
9) Patients with or suspected of a malignancy or patients with a history of malignancy within the last 5 years
10) Patients who have complications in the affected knee joint or whole body and were judged difficult to be evaluated by physicians
11) Patients who have a history of hypersensitivity to antibiotics (gentamicin or amphotericin B), or to aminoglycoside antibiotic
12) Patients with allergy to bovine or swine
13) patient with uncontrolled diabetes
14) Patients with a history of anaphylactic reaction
15) Patients with a history of hypersensitive against atelocollagen
16) Patients who cannot have an MRI examination
17) Patients participating in other clinical trials at the time of consent acquisition and patients planning to participate in other clinical trials during the study participation
18) Pregnant women, lactating women and patients who may be pregnant, or patients who desire pregnancy during clinical studies
19) Patients determined to be inappropriate by physicians

Target sample size

58


Research contact person

Name of lead principal investigator

1st name Shigeaki
Middle name
Last name Hayashi

Organization

Japan Tissue Engineering Co., Ltd.

Division name

Clinical Development Dept.

Zip code

443-0022

Address

6-209-1 Miyakitadori, Gamagori, Aichi 443-0022, Japan

TEL

0533-66-2020

Email

shigeaki_hayashi@jpte.co.jp


Public contact

Name of contact person

1st name Akira
Middle name
Last name Sugimoto

Organization

Japan Tissue Engineering Co., Ltd.

Division name

Clinical Development Dept.

Zip code

443-0022

Address

6-209-1 Miyakitadori, Gamagori, Aichi 443-0022, Japan

TEL

0533-66-2020

Homepage URL


Email

shigeaki_hayashi@jpte.co.jp


Sponsor or person

Institute

Japan Tissue Engineering Co., Ltd.

Institute

Department

Personal name



Funding Source

Organization

None

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization



Other related organizations

Co-sponsor


Name of secondary funder(s)



IRB Contact (For public release)

Organization

Hiroshima University hospital IRB

Address

Kasumi 1-2-3 Minami-ku,Hiroshima-shi,Hiroshima

Tel

082-257-5596

Email

hugcp@hiroshima-u.ac.jp


Secondary IDs

Secondary IDs

NO

Study ID_1


Org. issuing International ID_1


Study ID_2


Org. issuing International ID_2


IND to MHLW



Institutions

Institutions



Other administrative information

Date of disclosure of the study information

2018 Year 11 Month 07 Day


Related information

URL releasing protocol


Publication of results

Published


Result

URL related to results and publications

https://ssl4.eir-parts.net/doc/7774/tdnet/2403844/00.pdf

Number of participants that the trial has enrolled

58

Results

1.Primary outcomes
It was statistically shown that, in terms of change in WOMAC score between pre and post treatment, ACC-01 group improved significantly compared to HA group. (P<0.0001 Student's t-test)

2.Key secondary outcomes
In ACC-01 group, the number of cartilage defect sites (CDS) was 38 sites, and 37 sites (97.4%) were repaired with hyaline cartilage-like tissue (HCT). In HA group, the number of CDS was 43 sites, and no repair with HCT was observed in any of the CDS.

Results date posted

2024 Year 02 Month 28 Day

Results Delayed


Results Delay Reason


Date of the first journal publication of results


Baseline Characteristics

In this clinical trial, 58 cases were registered as eligible after screening and as a result of the determination by the Independent Eligibility Committee.
27 of the registered cases were assigned to ACC-01 group. 25 of the transplant cases completed the primary assessment at 52 weeks post treatment. 31 of the registered cases were assigned to HA group, and 29 received doses. The number of FAS cases, which was the primary efficacy analysis set, was 26 in ACC-01 group, and 28 in HA group.

Participant flow


Adverse events

In ACC-01 group, after cartilage slices biopsy and before ACC-01 implantation, 7 adverse events (AE) with a non-negligible causal relationship occurred in 7 cases (25.9%), and 5 AE with a negligible causal relationship occurred in 5 cases (18.5%). All of them were non-serious events.
After implantation, 38 AE with a non-negligible causal relationship occurred in 24 cases (92.3%), and 37 AE with a negligible causal relationship in 18 cases (69.2%). All of them were non-serious events.
In HA group, after the first dose, 2 AE with a non-negligible causal relationship occurred in 1 case (3.4%) and 17 AE with a negligible causal relationship occurred in 11 cases (37.9%). All of them were non-serious events. There were 3 AE in 3 cases that occurred prior to the first dose, all of which were not causally related and non-serious.

Outcome measures

1. Primary outcomes
Change in WOMAC score between pre and post treatment with the investigational products
Change in WOMAC score at 52 weeks post treatment with missing values imputed using LOCF was -20.39 (SD 10.09) in ACC-01 group and -5.19 (SD 10.85) in HA group. The group difference in change in WOMAC score was -15.21, and the 95% confidence interval was -20.99~-9.42, indicating that, statistically, ACC-01 group improved significantly compared to HA group (P<0.0001 student's t-test).

2. Key secondary outcomes
1) Change in WOMAC subscale (pain, stiffness, physical function) between pre and post treatment
All subscales in both groups showed an improvement in WOMAC scores over time, with ACC-01 group showing better improvement compared to HA group.

2) Change in Lysholm Knee Score between pre and post treatment
Like the change in the WOMAC score at 52 weeks post treatment for the primary endpoint, ACC-01 group showed better improvement compared to HA group.

3) Number of days using NSAIDs
In ACC-01 group, the number increased up to 12 weeks post treatment but began to decrease after 24 weeks post treatment. In HA group, it was almost constant regardless of the passage of time.

4) Presence or absence of repair with HCT
The presence or absence of repair with HCT was determined by the independent data monitoring committee (IDMC), based on the results of MRIT2 value, the 3D magnetic resonance observation of cartilage repair tissue (MOCART) system, the International Cartilage Repair Society (ICRS) score, and histological evaluation.
The number of CDS in ACC-01 group was 38 in 26 cases. 37 sites (97.4%) in 25 cases were repaired with HCT. On the other hand, 1 site (2.6%) in 1 case showed no repair with HCT.
The number of CDS in HA group was 43 in 27 cases, and no repair with HCT was observed in any of the CDS.

Plan to share IPD


IPD sharing Plan description



Progress

Recruitment status

Completed

Date of protocol fixation

2018 Year 07 Month 27 Day

Date of IRB

2018 Year 09 Month 18 Day

Anticipated trial start date

2019 Year 04 Month 24 Day

Last follow-up date

2023 Year 07 Month 14 Day

Date of closure to data entry


Date trial data considered complete


Date analysis concluded

2024 Year 01 Month 16 Day


Other

Other related information



Management information

Registered date

2018 Year 11 Month 07 Day

Last modified on

2024 Year 02 Month 28 Day



Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000039592


Research Plan
Registered date File name

Research case data specifications
Registered date File name

Research case data
Registered date File name