Phase 1 Study to Assess Safety and Efficacy of ANG003

Study Overview
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Brief Summary
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Randomized, parallel, active-treatment Phase 1 study of a single dose of orally administered ANG003 with a test meal in adult subjects with cystic fibrosis-related exocrine pancreatic insufficiency. The study's overall objectives are to evaluate the safety, tolerability and effect of four dose levels of ANG003.

Detailed Description
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The Phase 1 study was designed to compare a 24h Baseline Substrate Absorption Challenge Test (SACT) period with no enzymes to a 24h ANG003 SACT period with enzymes. Eligible subjects will be randomly assigned with equal allocation to one of four active dose levels of lipase, protease and amylase. Approximately 48 to 60 eligible subjects are planned to be enrolled in the study with 12 to 15 subjects assigned to each dose level from up to 21 investigational sites.

Official Title
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A Phase 1 Open-Label, Multicenter Study to Assess the Safety and Efficacy of ANG003 in Patients With Exocrine Pancreatic Insufficiency Due to Cystic Fibrosis

Conditions
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Exocrine Pancreatic Insufficiency

Intervention / Treatment
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* Drug: ANG003


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects 18 years of age or older. Confirmed diagnosis of CF defined as: a) CF signs and symptoms AND b) Two CF-causing mutations on genetic testing or sweat chloride >60 mEq/L. Documented history of fecal elastase <100 µg/g stool. EPI clinically controlled with minimal clinical symptoms and on a stable dose of PERT for 90 days before screening as determined by the Investigator. Adequate nutritional status measured by body mass index ≥20kg/m2 for adult subjects. Exclusion Criteria: Subjects with diabetes mellitus who are unable to refrain from short-acting and rapid-acting insulin on Days 1 and 5 for a daily total of 6 hours. Involuntary loss of ≥10% of usual body weight within last 6 months or involuntary loss of >5% of body weight within 1 month. Requires use of naso-gastric, J-tube, G-tube, and/or enteral feeding for the study duration. CF pulmonary exacerbation within 30 days prior to the Baseline SACT Period (Visit 2). Subjects who cannot discontinue omega-3 supplements >500 mg of DHA and EPA daily. Subjects unable to tolerate missing a dose of PERT.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ANG003 Dose Level 1<br>Single administration starting dose contains lipase, protease and amylase. | Drug: ANG003<br>* To evaluate four possible combinations of lipase, protease and amylase.<br>* Other names: Dose Level 1, Dose Level 2, Dose Level 3, and Dose Level 4.;|
| Experimental: ANG003 Dose Level 2<br>Single administration dose contains 2x lipase, 2x protease and 2x amylase starting dose. | Drug: ANG003<br>* To evaluate four possible combinations of lipase, protease and amylase.<br>* Other names: Dose Level 1, Dose Level 2, Dose Level 3, and Dose Level 4.;|
| Experimental: ANG003 Dose Level 3<br>Single administration dose contains 4x lipase, 2x protease and 2x amylase starting dose. | Drug: ANG003<br>* To evaluate four possible combinations of lipase, protease and amylase.<br>* Other names: Dose Level 1, Dose Level 2, Dose Level 3, and Dose Level 4.;|
| Experimental: ANG003 Dose Level 4<br>Single administration dose contains 6x lipase, 3x protease and 3x amylase starting dose. | Drug: ANG003<br>* To evaluate four possible combinations of lipase, protease and amylase.<br>* Other names: Dose Level 1, Dose Level 2, Dose Level 3, and Dose Level 4.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events (AE), Serious Adverse Events (SAE), and AEs Leading to Study Discontinuation | AE, SAE, and AEs leading to study discontinuation measured by frequency and severity during study. | Assessed through study completion, up to 9 days (Day 1 thru Day 9). | 
| Malabsorption Symptoms | Severity of malabsorption symptoms (e.g., abdominal discomfort or pain, bloating, heartburn, regurgitation or reflux, retching, stomach fullness, and vomiting) by patient reported outcome scale (0=None; 1=Very Mild; 2=Mild; 3=Moderate; 4=Severe; 5=Very Severe). Measured by 20 questions contained in Acute Patient Assessment of Gastrointestinal Symptoms (Acute PAGI-SYM) questionnaire. | Acute PAGI-SYM is based upon 7-day recall. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fat Absorption | Measured by concentration and percent of plasma fatty acids. | Assessed through study completion, up to 9 days (Day 1 thru Day 9). | 
| Protein Absorption | Measured by changes in plasma concentration of amino acids. | Assessed through study completion, up to 9 days (Day 1 thru Day 9). | 
| Carbohydrate Absorption | Changes in glucose (mg/dL) as measured by continuous glucose monitoring. | Assessed through study completion, up to 9 days (Day 1 thru Day 9). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cystic Fibrosis