A Phase IIa Study With Escalating Dose of MS1819-SD

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

This is a Phase IIa study sponsored by AzurRx SAS and Syneos Health is a local representative sponsor and involves testing of a new medication for the compensation of exocrine pancreatic insufficiency (EPI) caused by chronic pacreatitis (CP) and/or distal pancreatectomy. The new medication is called MS1819 Spray Dried (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.

Approximately twelve patients will be enrolled in this study.

Study Overview

• Status: Completed
• Conditions: Chronic Pancreatitis; Distal Pancreatectomy
• Intervention / Treatment: Drug: MS1819-SD

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Mackay, Queensland, Australia, 4740
      • Mackay Institute of Research and Innovation
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • CMAX
  • Western Australia
    • Perth, Western Australia, Australia, 6009
      • Linear Research
• France
  • Marseille, France, 13385
    • Hôpital Timone Adulte (CIC-CPCET)
• New Zealand
  • Christchurch, New Zealand, 8011
    • Christchurch Clinical Studies Trust
  • Wellington, New Zealand, 6242
    • P3 Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed and dated informed consent form,
2. Age >18 years,
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 <100 μg/g of stools at screening or within one month of the screening visit,
7. CFA measurement ≤ 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.

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 ≥1 meter length, etc.,
6. Acute pancreatitis or exacerbation of CP ≤3 months,
7. Pancreatectomy for exocrine or endocrine cancer ≤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. Bilirubin >3 times ULN (upper limit normal),

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigate safety of escalating doses of MS1819-SD as measured by number of participants with adverse events including clinical or laboratory abnormalities	Safety variables will be monitored by physical examination with particular attention paid to immunoallergic events and digestive symptomatology. In addition, laboratory tests will include haematology and biochemistry.	60 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigate the efficacy of MS1819-SD in patients by the Coefficient of Fat Absorption change from baseline	The primary efficacy endpoint is the Coefficient Fat Absorption (CFA) change from baseline.The secondary efficacy endpoints are the number of daily evacuations per day, the consistency of stools assessed by the Bristol scale (from Type 1 to Type 7) and the weight of stools during the stool collection period.	60 days

Collaborators and Investigators

• Sponsor: AzurRx SAS

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2017
• Primary Completion (Actual): June 29, 2018
• Study Completion (Actual): June 29, 2018

Study Registration Dates

• First Submitted: March 6, 2018
• First Submitted That Met QC Criteria: March 22, 2018
• First Posted (Actual): March 29, 2018

Study Record Updates

• Last Update Posted (Actual): September 28, 2018
• Last Update Submitted That Met QC Criteria: September 27, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Exocrine Pancreatic Insufficiency
• Additional Relevant MeSH Terms: Digestive System Diseases; Pancreatic Diseases; Pancreatitis; Pancreatitis, Chronic; Exocrine Pancreatic Insufficiency
• Other Study ID Numbers: MS1819/16/01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No