Phase 2 Combination Study With Escalating Doses of MS1819-SD on Top of a Stable Dose of PPEs

NCT04302662 | Completed Phase 2

• 1 other identifier: MS1819/18/02
• Study Type: interventional
• Target: 20
• Locations: 2 countries
• Sites: 10

Brief Summary

This is a Phase 2 study sponsored by AzurRx SAS and involves testing of a new medication for the compensation of exocrine pancreatic insufficiency (EPI) caused by cystic fibrosis (CF). 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 efficacy and safety of escalating doses of study drug on top of a stable dose of PPEs in CF patients who are not fully compensated by PPEs only. This enzyme has demonstrated an appropriate profile to compensate the pancreatic lipase (enzyme) deficiency that is common in CP (chronic pancreatitis) and CF patients. The design of the study is open-label, meaning that all eligible patients will receive the study drug MS1819-SD. The study drug dose will increase throughout the study during dose escalation visits in each treatment period; study includes a total of three treatment periods. The total duration of the MS1819-SD treatment phase is of 39-51 days. The total duration of patient participation in the study is of 69-81 days. Approximately 24 patients will be enrolled in this study.

Conditions

Cystic Fibrosis; Cystic Fibrosis Gastrointestinal Disease; Cystic Fibrosis of Pancreas

Keywords

Exocrine Pancreatic Insufficiency

Outcome Measures

Primary Outcomes (2)

• Coefficient of fat absorption

  determination of fat absorption based on fat intake and fat excretion over 3 days on high fat meal

  15 days

• Adverse Events

  AE, SAE, SUSAR, immunoallergic reactions

  81 days

Secondary Outcomes (6)

• Weight of stools

  15 days

• number of daily evacuations

  15 days

• Steatorrhea,

  15 days

• Creatorrhea

  15 days

• Body weight

  15 days

Interventions

MS1819-SD DRUG

Patients will receive increasing doses from the lowest to a maximum dose of MS1819-SD on top of a stable dose of PPEs. The total treatment phase will range from 39 to 51 days.

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated informed consent form.
• Age \> 12 years at the time of screening
• Male or female.
• Under stable dose of PPE ≥ 1 month. Stable dose is defined as dose of medication not changed during this time period and the medication must be commercially available and be administered in the recommended dose range.
• A nutritional status as defined by:
• BMI ≤ 22.0 kg/m2 for female patients
• BMI ≤ 23.0 kg/m2 for male patients
• BMI ≤ 50th percentile for patients 12 to \< 18 years of age.
• Cystic fibrosis, based on 2 clinical features consistent with CF in the opinion of the investigator AND sweat chloride concentration \> 60 mmol/L by pilocarpine iontophoresis.
• Faecal pancreatic elastase-1 \< 100 µg/g of stools at screening.
• Baseline CFA \< 80% with a maximum daily dose of 10,000 lipase units/kg/day.
• Clinically stable with no documented evidence of significant respiratory symptoms that would require administration of intravenous antibiotics, oxygen supplementation, or hospitalization within the 30 days of screening.
• Male and female patients, if of childbearing potential, must use a reliable method of contraception during the study. A reliable method of birth control is defined as one of the following: oral or injectable contraceptives, intrauterine device, contraceptive implants, tubal ligation, hysterectomy, or a double-barrier method (diaphragm with spermicidal foam or jelly, or a condom), abstinence or vasectomy. Periodic abstinence (calendar, symptothermal, or post-ovulation methods) is not an acceptable method of contraception. The preferred and usual lifestyle of the patient must also be evaluated in determining if sexual abstinence is a reliable method of birth control.
• Be considered as reliable and capable of adhering to the protocol, according to the judgment of the investigator.

You may not qualify if:

• Established or suspected fibrosing colonopathy.
• Total or partial gastrectomy.
• A history of solid organ transplant or significant surgical resection of the bowel; significant resection of the bowel is defined as any resection of the terminal ileum or ileocecal valve. Patients who have had qualitative, long-term changes in nutritional status after any other bowel resection (eg, increased of new need for pancreatic enzyme supplementation compared with preoperative status to maintain the same nutritional status) should also be excluded.
• Any chronic diarrheal illness unrelated to pancreatic insufficiency (eg, infectious gastroenteritis, sprue, inflammatory bowel disease)
• Known hypersensitivity or other severe reaction to any ingredient of the investigational medicinal product (IMP).
• Bilirubin \> 1.5 times upper limit normal (ULN).
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 5 times ULN.
• Alkaline phosphatase (ALP) \> 5 times ULN.
• Gamma glutamyltransferase (GGT) \> 5 times ULN.
• Signs and/or symtoms of liver cirrhosis or portal hypertension (eg, splenomegaly, ascites, esophageal varices), or documented liver disease unrelated to CF
• Patients with a known allergy to the stool marker.
• Feeding via an enteral tube during 6 months before screening
• Routine use of anti-diarrheals, anti-spasmodics, or cathartic laxatives, or a change in chronic osmotic laxatives (eg, polyethylene glycol) regimen in the previous laxative therapy within the last 12 months before screening
• History of severe constipation with \< 1 evacuation/week under appropriate laxative therapy within the last 12 months before screening.
• Documentation of distal intestinal pseudo-obstruction syndrome within the last 12 months before screening.

Sponsors & Collaborators

• AzurRx SAS: lead

Study Sites (10)

Országos Korányi TBC és Pulmonológiai Intézet Cisztás Fibrózis Részleg

Budapest, 1122, Hungary

Location

Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Oktatókórház, Gyermekegészségügyi Központ

Miskolc, 3526, Hungary

Location

Somogy Megyei Kaposi Mór Oktató Kórház, Mosdósi telephelye Mosdósi Gyermekrehabilitációs és Gyermekpulmonológiai Egység

Mosdós, 7257, Hungary

Location

Tüdőgyógyintézet Törökbálint Gyermekpulmonológiai Osztály és Szakrendelés

Törökbálint, 2045, Hungary

Location

Çukurova University School of Medicine

Adana, Turkey (Türkiye)

Location

Hacettepe University School of Medicine

Ankara, Turkey (Türkiye)

Location

Akdeniz University School of Medicine

Antalya, Turkey (Türkiye)

Location

Cerrahpasa University School of Medicine

Istanbul, Turkey (Türkiye)

Location

Mamara University School of Medicine

Istanbul, Turkey (Türkiye)

Location

Necmettin Erbakan University,Meram School of Medicine

Konya, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Cystic Fibrosis; Exocrine Pancreatic Insufficiency

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Sequential assignment: eligible patients will be receiving increased doses from lower, middle to upper range of MS1819-SD on top of a stable dose of PPEs

Study Record Dates

• First Submitted: March 4, 2020
• First Posted: March 10, 2020
• Study Start: June 27, 2019
• Primary Completion: June 3, 2021
• Study Completion: June 3, 2021
• Last Updated: August 19, 2021

Record last verified: 2021-08

Locations

HU (4); TU (6)