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Trial registered on ANZCTR


Registration number
ACTRN12616000962437
Ethics application status
Approved
Date submitted
27/06/2016
Date registered
21/07/2016
Date last updated
26/02/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
MS1819-SD phase IIa clinical trial for patients with exocrine pancreatic insufficiency (EPI) caused by chronic pancreatitis (CP) and/or distal pancreatectomy.
Scientific title
A multicentre open-label phase IIa study with escalating dose of MS1819-SD, to investigate the efficacy and safety of a Yarrowia lipolytica lipase preparation for the compensation of exocrine pancreatic insufficiency caused by chronic pancreatitis and/or distal pancreatectomy.
Secondary ID [1] 289438 0
AZUR RX Number MS1819/16/01
Universal Trial Number (UTN)
Trial acronym
MS1819SD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Exocrine pancreatic insufficiency (EPI) caused by chronic pancreatitis (CP) 299130 0
Exocrine pancreatic insufficiency (EPI) caused by distal pancreatectomy. 299131 0
Condition category
Condition code
Metabolic and Endocrine 299150 299150 0 0
Other endocrine disorders
Oral and Gastrointestinal 299463 299463 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a Phase IIa study, testing a new medication for the compensation of exocrine pancreatic insufficiency caused by chronic pacreatitis and/or distal pancreatectomy. The new medication is called MS1819-SD which is a lipase produced by the LIP2 gene of Yarrowia lipolytica using recombinant DNA technology.

The primary purpose of this study is to investigate the safety of escalating doses of study drug MS1819-SD in people with chronic pancreatitis. This enzyme has demonstrated an appropriate profile to compensate the pancreatic lipase (enzyme) deficiency that is common with CP patients. The deficiency in this enzyme can be responsible of greasy diarrhea, fecal urge and weight loss.

The design of the study is open-label, meaning that all eligible participants will receive the study drug MS1819-SD. The MS1819-SD dose will increase throughout the study during dose escalation visits in each treatment period; study includes a total of four treatment periods.

The total duration of the MS1819-SD treatment phase is of 48-60 days, The total duration of patient participation in the study is of 74-93 days. Patient will receive increasing doses from the lowest dose of MS1819-SD to a maximum dose of MS1819-SD. The total treatment phase will range from 48 days to 60 days.
Intervention code [1] 295036 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 298630 0
The primary objective of this Phase IIa study is to investigate the safety of escalating doses of MS1819SD, a spraydried yarrowia lipolytica lipase preparation in people with chronic pancreatitis.
Timepoint [1] 298630 0
At the end of each treatment phase, safety variables will be monitored by physical examination with particular attention paid to immunoallergic events and digestive symptomatology. In addition, laboratory tests will include immunogenic assessment for circulating levels of LIP2, antibodies against LIP2, hematology and biochemistry.
Secondary outcome [1] 324808 0
The secondary objective for this study is to investigate the efficacy of MS1819SD
in patients with chronic pancreatitis by analysis of coefficient of fat absorption (CFA)and change from baseline.
Timepoint [1] 324808 0
Key secondary endpoints such as the number of evacuations, stools consistency and stools weight during the stools collection period will be assessed.

Eligibility
Key inclusion criteria
1. Signed and dated informed consent form,
2. Age 18 years and older,
3. Male or female,
4. Body weight within the range [50-100 Kg] for males or [40-90 Kg] for females,
5. Distal pancreatectomy for any disorder (e.g. acute pancreatitis or its complications, CP or its complications, pancreatic endocrine or exocrine cancer, or others) and/or CP of any etiology (e.g. alcohol, genetics, hypercalcemia, or others) of grade 2 or higher (Cambridge classification),
6. Faecal pancreatic elastase-1 less than 100 micro g/g at screening or within one month of the screening visit,
7. CFA measurement less than or equal to 75% at washout,
8. Female patients must be post-menopausal (defined as at least 12 months post cessation of menses), surgically sterile or, if of childbearing potential, using a reliable method of contraception during the study.
9. Being considered as reliable and capable of adhering to the protocol, according to the judgment of the investigator.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Cystic fibrosis,
2. Total or partial gastrectomy,
3. Cephalic or total duodenopancreatectomy,
4. Documented fibrosing colonopathy,
5. Any small bowel disease possibly responsible for malabsorption, including small intestinal bacterial overgrowth, celiac disease, small bowel resection greater than or equal to 1 meter length, etc.,
6. Acute pancreatitis or exacerbation of CP less than or equal to 3 months,
7. Pancreatectomy for exocrine or endocrine cancer less than or equal to 1 year,
8. Metastatic or locally recurrent exocrine pancreatic cancer,
9. Known hypersensitivity or other severe reaction to any ingredient of the investigational medicinal product,
10. Lactation or known pregnancy or positive pregnancy test at both screening and baseline for women of childbearing potential,

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
Type of endpoint/s
Statistical methods / analysis
This study is a phase IIa trial, aiming to primarily investigate the safety and to provide exploratory information on the efficacy of different MS1819 doses.
Twelve patients are considered sufficient to assess the safety of doses administered during the escalating dose Phase C within the range of doses evaluated. To account for an anticipated 20% withdrawal rate, approximately 15 patients are planned to be enrolled.

No power calculation has been performed. The sets used for safety and efficacy analyses will include the following:
Safety Set:
A. The safety set is defined as all patients who receive at least one dose of MS1819-SD. Patients will be analysed according to the treatment actually received.
Efficacy Analysis Sets:
A. Full analysis set (FAS): is defined as all patients receiving at least one dose of treatment and with some efficacy assessment available on treatment. The FAS is considered as the primary set for the efficacy analysis.
B. Per-Protocol set (PP): is a subset of the FAS comprising all patients who do not violate the terms of the protocol in a way that would affect the study outcome significantly, as determined by the study clinician.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
28/11/2016
Actual
27/01/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
13
Accrual to date
9
Final
Recruitment in Australia
Recruitment state(s)
SA,WA
Recruitment hospital [1] 5984 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 5986 0
Linear Clinical Research - Nedlands
Recruitment hospital [3] 8747 0
Mackay Base Hospital - Mackay
Recruitment postcode(s) [1] 13407 0
5000 - Adelaide
Recruitment postcode(s) [2] 13408 0
6009 - Nedlands
Recruitment postcode(s) [3] 16867 0
4740 - Mackay
Recruitment outside Australia
Country [1] 7960 0
New Zealand
State/province [1] 7960 0
Wellington
Country [2] 7961 0
New Zealand
State/province [2] 7961 0
Christchurch
Country [3] 9627 0
France
State/province [3] 9627 0

Funding & Sponsors
Funding source category [1] 293832 0
Commercial sector/Industry
Name [1] 293832 0
AzurRx
Country [1] 293832 0
France
Primary sponsor type
Commercial sector/Industry
Name
INC Research Australia Pty Ltd
Address
159 Port Road Hindmarsh
South Australia 5007
Australia
Country
Australia
Secondary sponsor category [1] 292661 0
None
Name [1] 292661 0
Address [1] 292661 0
Country [1] 292661 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295259 0
Human Research Ethics Committee (The Queen Elizabeth Hospital)
Ethics committee address [1] 295259 0
Basil Hetzel Institute DX465101
The Queen Elizabeth Hospital
28 Woodville Road
Woodville South SA 5011
Ethics committee country [1] 295259 0
Australia
Date submitted for ethics approval [1] 295259 0
17/05/2016
Approval date [1] 295259 0
18/07/2016
Ethics approval number [1] 295259 0
Ethics committee name [2] 295517 0
Central Health and Disability Ethics Committee
Ethics committee address [2] 295517 0
Ministry of Health
Ethics Department
Freyberg Building
Reception – Ground Floor
20 Aitken Street
Wellington
Ethics committee country [2] 295517 0
New Zealand
Date submitted for ethics approval [2] 295517 0
26/07/2016
Approval date [2] 295517 0
27/09/2016
Ethics approval number [2] 295517 0
Ethics committee name [3] 295518 0
Bellberry Human Research Ethics Committee
Ethics committee address [3] 295518 0
129 Glen Osmond Road Eastwood South Australia 5063
Ethics committee country [3] 295518 0
Australia
Date submitted for ethics approval [3] 295518 0
27/07/2016
Approval date [3] 295518 0
06/09/2016
Ethics approval number [3] 295518 0

Summary
Brief summary
This is a Phase IIa study, testing a new medication for chronic pancreatitis. The new medication is called MS1819-SD which is a modified version of a naturally occurring enzyme made in the pancreas.

The primary purpose of this study is to investigate the safety of escalating doses of study drug MS1819-SD in people with chronic pancreatitis. This enzyme has demonstrated an appropriate profile to compensate the pancreatic lipase (enzyme) deficiency that is common with CP patients. The deficiency in this enzyme can be responsible of greasy diarrhea, fecal urge and weight loss.

The design of the study is open-label, meaning that all eligible participants will receive the study drug MS1819-SD. The MS1819-SD dose will increase throughout the study during dose escalation visits in each treatment period; study includes a total of four treatment periods that ranges from low, medium, to higher doses. The total duration of the MS1819-SD treatment phase is of 48-60 days, Participants will be required to complete five day stool collections following high fat meals at the end of the washout period and at the end of each treatment phase. The total duration of patient participation in the study is of 74-93 days.

Safety will be assessed at throughout the study that will include physical examinations and pathology testing to determine immunoallergic effects, Digestive symptoms will also be assessed and evaluated throughout the study.

This study is being sponsored by AzurRx (the Sponsor). The Sponsor will fund researchers who conduct this research for the use of their facilities and to conduct this study.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 66574 0
A/Prof Quoc Nam Nguyen
Address 66574 0
Department of Gastroenterology
Royal Adelaide Hospital
North Terrace
Adelaide SA 5000
Country 66574 0
Australia
Phone 66574 0
+61 8 7088 7900
Fax 66574 0
Email 66574 0
[email protected]
Contact person for public queries
Name 66575 0
Pawel Waszka
Address 66575 0
Crown Square Building Przyokopowa 31, 9th floor, Warsaw
Country 66575 0
Poland
Phone 66575 0
+48222564220
Fax 66575 0
Email 66575 0
[email protected]
Contact person for scientific queries
Name 66576 0
Hans-Juergen Gruss
Address 66576 0
River View The Meadows Business Park Station Approach, Camberley, Surrey
Country 66576 0
United Kingdom
Phone 66576 0
+441276481331
Fax 66576 0
Email 66576 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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