ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12618001883202

Ethics application status

Approved

Date submitted

23/10/2018

Date registered

20/11/2018

Date last updated

16/04/2024

Date data sharing statement initially provided

20/11/2018

Date results provided

16/04/2024

Type of registration

Prospectively registered

Titles & IDs

Public title

Amnion cell therapy for fistulising perianal Crohn's disease

Scientific title

A human pilot study evaluating the safety of locally administered allogeneic human amnion epithelial cells for the treatment of refractory perianal fistulising Crohn's disease

Secondary ID [1]

Nil known

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Crohn's Disease

Perianal fistulas

Condition category

Condition code

Inflammatory and Immune System

Autoimmune diseases

Oral and Gastrointestinal

Inflammatory bowel disease

Oral and Gastrointestinal

Crohn's disease

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Update (made prior to enrolment commencement)
This intervention requires a single local injection of human amnion epithelial cells into perianal fistula sites. This will occur during the examination under anaesthesia surgical procedure performed by a specialist colorectal surgeon in an operating theatre. The dose of the human amnion epithelial cells is 40 million cells per fistula, with up to 3 fistulas treated per participant (maximum 120 million cells). Prior to fistula injection, all perianal setons must be removed and the internal opening of the fistula sutured closed to allow healing.

Intervention code [1]

Treatment: Other

Intervention code [2]

Treatment: Surgery

Comparator / control treatment

No control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

The primary outcome is safety with an adverse event defined as any of the following 1) worsening (change in nature, severity or frequency) of Crohn's disease present at the time of the study based on the Perianal Disease Activity Index (PDAI), 2) intercurrent illness based on patient self-reporting, 3) abnormal laboratory values (FBE, UEC, LFT, CRP) defined as clinically significant shifts from baseline within the range of normal that the investigator considers to be clinically significant or 4) clinically significant abnormalities in physical examination, vital signs, weight and drainage for the perianal fistulas. A causality assessment will be perfomed regarding AEs and defined as one of the following: unrelated, unlikely, possible or probable.

The severity of AEs will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), v4.0. A serious adverse event (SAE) is any untoward medical occurrence that occurs at any dose. An AE in a clinical trial is designated to be serious if it results in death, is life-threatening, requires inpatient hospitalisation, or prolongs existing hospitalisation, results in persistent or significant disability or incapacity.

Timepoint [1]

Week 24 after intervention

Secondary outcome [1]

1. Feasibility of route of stem cell administration based on a specifically designed questionnaire for investigator completion

Timepoint [1]

Week 24 after intervention

Secondary outcome [2]

2. Efficacy of treatment
This will be measured by assessing fistula closure on physical examination and with MRI.
i. Clinical assessment defined as absence of drainage (spontaneous or with gentle compression)
ii. Closure of all treated external openings based on visual inspection upon clinical perianal examination
iii. Radiographic response assessed by MRI

A partial clinical response is defined as closure of >50% of all treated external openings

Timepoint [2]

Week 24 after intervention

Secondary outcome [3]

3. Health-related quality of life based on the IBD-Q (validated questionnaire)

Timepoint [3]

Week 24 after intervention

Eligibility

Key inclusion criteria

1. Adult participant
2. Non-active or mildly active luminal Crohn's for over 6 months (defined by CDAI less than 220)
3. Presence of complex perianal fistulas as classified by the American Gastroenterological Association (AGA)
4. More than 1 of the following: high intersphincteric, high trans-sphincteric, extra-sphincteric, supra-sphincteric, more than 2 external openings or associated collections
5. Fistulas with a maximum of 2 internal and 3 external openings
6. Fistulas draining for more than 6 weeks prior to inclusion
7. Refractory to more than 1 of the following treatments: antibiotics with no response after 1 month, immunomodulators with no response after 3 months, anti-TNF induction or maintenance. Definition of lack of response will assessed as per the Perianal Disease Activity Index (PDAI).

Minimum age

18 Years

Maximum age

80 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

1. Rectal or anal stenosis
2. Active severe proctitis (presence of superficial or deep ulcers)
3. Diverting stomas
4. Abscess or collection more than 2 cm size that were not properly drained
5. Corticosteroid use within the previous 4 weeks
6. Inability to tolerate or comply with trial requirements
7. Current pregnancy

Study design

Purpose of the study

Treatment

Allocation to intervention

Non-randomised trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Who is / are masked / blinded?

Intervention assignment

Other design features

Phase

Not Applicable

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

There is no planned formal statistical analysis of this phase I trial, but descriptive and inferential statistical analysis will be conducted as appropriate.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

7/01/2019

Actual

24/06/2020

Date of last participant enrolment

Anticipated

7/12/2020

Actual

9/06/2021

Date of last data collection

Anticipated

1/12/2021

Actual

28/06/2023

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Monash Medical Centre - Clayton campus - Clayton

Recruitment hospital [2]

Dandenong Hospital - Dandenong

Recruitment hospital [3]

Casey Hospital - Berwick

Recruitment postcode(s) [1]

3168 - Clayton

Recruitment postcode(s) [2]

3175 - Dandenong

Recruitment postcode(s) [3]

3806 - Berwick

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Gastroenterological Society of Australia

Address [1]

Suite 1, Level 1
517 Flinders Lane
Melbourne Vic 3000

Country [1]

Australia

Primary sponsor type

Hospital

Name

Monash Health

Address

Monash Medical Centre
264 Clayton Road, Clayton
Victoria, 3168

Country

Australia

Secondary sponsor category [1]

University

Name [1]

Monash University

Address [1]

Wellington Road, Clayton
Victoria, 3800

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Monash Health Human Research Ethics Committee

Ethics committee address [1]

Level 2, I Block, Monash Medical Centre
246 Clayton Road, Clayton
Vic, 3168

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

18/04/2018

Approval date [1]

05/12/2018

Ethics approval number [1]

Monash Health Ref: 18-0000-225A

Summary

Brief summary

Effective treatments for complex perianal Crohn's disease remains an important unmet area of need in inflammatory bowel disease. Perianal fistulas affect over one third of Crohn's disease with severe cases requiring surgery and long-term immune-modifying treatments with side effects.

Local injection of mesenchymal stem cells has been the only effective new treatment since the anti-tumour necrosis factor drugs over a decade ago. Fistula healing effects of stem cells have been shown last even at 1 year after treatment. Human amnion epithelial cells are a non-embryonic adult stem cell which is easily obtained from healthy human placentas (after delivery of a healthy baby) which would otherwise be discarded. Compared with mesenchymal stem cells, amnion stem cells are obtained much faster, produce much greater amounts and theoretically should be safer. This gives them a greater advantage.

This study is a pilot study aiming to recruit 10 adults with complex perianal Crohn's fistulas who have previously failed one conventional treatment. Participants will receive one injection of amnion stem cells while undergoing examination under anaesthesia, which is a common procedure performed for those suffering this condition. 

The primary purpose of this study is to establish safety of the amnion stem cells with secondary goals to assess feasibility of treatment, effectiveness in fistula healing and improvement in quality of life. These will be measured at 24 weeks after treatment with stem cells. The total duration of the trial is approximately 28 weeks, however we would like to assess longer term with a final visit at 1 year.

We hypothesise that human amnion epithelial cell therapy will be a safe, tolerable and effective treatment.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Gregory Moore

Address

Department of Gastroenterology, Monash Medical Centre
264 Clayton Road, Clayton
Victoria 3168

Country

Australia

Phone

+61 3 9594 3177

Fax

Charlotte.Keung@monashhealth.org

Contact person for public queries

Name

Charlotte Keung

Address

Department of Gastroenterology, Monash Medical Centre
264 Clayton Road, Clayton
Victoria 3168

Country

Australia

Phone

+61 3 9594 3177

Fax

Charlotte.Keung@monashhealth.org

Contact person for scientific queries

Name

Charlotte Keung

Address

Department of Gastroenterology, Monash Medical Centre
264 Clayton Road, Clayton
Victoria 3168

Country

Australia

Phone

+61 3 9594 3177

Fax

Charlotte.Keung@monashhealth.org

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

Individual participant data (IPD) for this trial will not be publicly available to protect participant confidentiality due to the small numbers of participants in this trial who may become identifiable with line-by-line data collection.

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
5948	Informed consent form			charlotte.keung@monashhealth.org
5949	Ethical approval			charlotte.keung@monashhealth.org

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Dimensions AI	Crescentic Glomerulonephritis: Pathogenesis and Therapeutic Potential of Human Amniotic Stem Cells	2021	https://doi.org/10.3389/fphys.2021.724186
Dimensions AI	Amniotic fluid characteristics and its application in stem cell therapy: A review	2022	https://doi.org/10.18502/ijrm.v20i8.11752
Embase	Local fistula injection of allogeneic human amnion epithelial cells is safe and well tolerated in patients with refractory complex perianal Crohn's disease: a phase I open label study with long-term follow up.	2023	https://dx.doi.org/10.1016/j.ebiom.2023.104879

N.B. These documents automatically identified may not have been verified by the study sponsor.

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