Trial Review

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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 information initially provided
29/10/2021
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] 295566 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Crohn's Disease 310156 0
Perianal fistulas 310157 0
Condition category
Condition code
Inflammatory and Immune System 308907 308907 0 0
Autoimmune diseases
Oral and Gastrointestinal 309184 309184 0 0
Inflammatory bowel disease
Oral and Gastrointestinal 309185 309185 0 0
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] 312735 0
Treatment: Other
Intervention code [2] 312736 0
Treatment: Surgery
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 307875 0
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] 307875 0
Week 24 after intervention
Secondary outcome [1] 353190 0
1. Feasibility of route of stem cell administration based on a specifically designed questionnaire for investigator completion
Timepoint [1] 353190 0
Week 24 after intervention
Secondary outcome [2] 353191 0
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] 353191 0
Week 24 after intervention
Secondary outcome [3] 353192 0
3. Health-related quality of life based on the IBD-Q (validated questionnaire)
Timepoint [3] 353192 0
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?
No
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
10
Accrual to date
Final
10
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 12249 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [2] 12250 0
Dandenong Hospital - Dandenong
Recruitment hospital [3] 12251 0
Casey Hospital - Berwick
Recruitment postcode(s) [1] 24435 0
3168 - Clayton
Recruitment postcode(s) [2] 24436 0
3175 - Dandenong
Recruitment postcode(s) [3] 24437 0
3806 - Berwick

Funding & Sponsors
Funding source category [1] 300142 0
Charities/Societies/Foundations
Name [1] 300142 0
Gastroenterological Society of Australia
Country [1] 300142 0
Australia
Primary sponsor type
Hospital
Name
Monash Health
Address
Monash Medical Centre
264 Clayton Road, Clayton
Victoria, 3168
Country
Australia
Secondary sponsor category [1] 299544 0
University
Name [1] 299544 0
Monash University
Address [1] 299544 0
Wellington Road, Clayton
Victoria, 3800
Country [1] 299544 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300975 0
Monash Health Human Research Ethics Committee
Ethics committee address [1] 300975 0
Level 2, I Block, Monash Medical Centre
246 Clayton Road, Clayton
Vic, 3168
Ethics committee country [1] 300975 0
Australia
Date submitted for ethics approval [1] 300975 0
18/04/2018
Approval date [1] 300975 0
05/12/2018
Ethics approval number [1] 300975 0
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 85482 0
Dr Gregory Moore
Address 85482 0
Department of Gastroenterology, Monash Medical Centre
264 Clayton Road, Clayton
Victoria 3168
Country 85482 0
Australia
Phone 85482 0
+61 3 9594 3177
Fax 85482 0
Email 85482 0
Charlotte.Keung@monashhealth.org
Contact person for public queries
Name 85483 0
Dr Charlotte Keung
Address 85483 0
Department of Gastroenterology, Monash Medical Centre
264 Clayton Road, Clayton
Victoria 3168
Country 85483 0
Australia
Phone 85483 0
+61 3 9594 3177
Fax 85483 0
Email 85483 0
Charlotte.Keung@monashhealth.org
Contact person for scientific queries
Name 85484 0
Dr Charlotte Keung
Address 85484 0
Department of Gastroenterology, Monash Medical Centre
264 Clayton Road, Clayton
Victoria 3168
Country 85484 0
Australia
Phone 85484 0
+61 3 9594 3177
Fax 85484 0
Email 85484 0
Charlotte.Keung@monashhealth.org

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
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.TypeCitationLinkEmailOther DetailsAttachment
5948Informed consent form  charlotte.keung@monashhealth.org
5949Ethical approval  charlotte.keung@monashhealth.org



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Online Dec 1st 2023, EBioMedicine Keung C, Nguy... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseLocal 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.2023https://dx.doi.org/10.1016/j.ebiom.2023.104879
Dimensions AIAmniotic fluid characteristics and its application in stem cell therapy: A review2022https://doi.org/10.18502/ijrm.v20i8.11752
Dimensions AICrescentic Glomerulonephritis: Pathogenesis and Therapeutic Potential of Human Amniotic Stem Cells2021https://doi.org/10.3389/fphys.2021.724186
N.B. These documents automatically identified may not have been verified by the study sponsor.