Phase 1 Study to Assess Safety and Efficacy of ANG003

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

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.

Study Overview

• Status: Completed
• Conditions: Exocrine Pancreatic Insufficiency
• Intervention / Treatment: Drug: ANG003

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Long Beach, California, United States, 90806
      • Long Beach Memorial Medical Center
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Children's Research Institute affiliated with University of Louisville School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital,
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Medical Center
    • Detroit, Michigan, United States, 48201
      • Harper University Hospital / Wayne State University
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical College
    • Valhalla, New York, United States, 10595
      • New York Medical College at Westchester Medical Center
  • Ohio
    • Akron, Ohio, United States, 44308
      • Akron Childrens Hospital
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44106
      • University Hospitals of Cleveland Medical Center
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • UPMC Children's Hospital of Pittsburgh
  • Texas
    • Dallas, Texas, United States, 75235
      • University of Texas Southwestern Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male and female subjects 18 years of age or older.
2. 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.
3. Documented history of fecal elastase <100 µg/g stool.
4. EPI clinically controlled with minimal clinical symptoms and on a stable dose of PERT for 90 days before screening as determined by the Investigator.
5. Adequate nutritional status measured by body mass index ≥20kg/m2 for adult subjects.

Exclusion Criteria:

1. 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.
2. Involuntary loss of ≥10% of usual body weight within last 6 months or involuntary loss of >5% of body weight within 1 month.
3. Requires use of naso-gastric, J-tube, G-tube, and/or enteral feeding for the study duration.
4. CF pulmonary exacerbation within 30 days prior to the Baseline SACT Period (Visit 2).
5. Subjects who cannot discontinue omega-3 supplements >500 mg of DHA and EPA daily.
6. Subjects unable to tolerate missing a dose of PERT.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ANG003 Dose Level 1; Single administration dose contains 20 mg lipase, 25 mg protease and 40 mg amylase.	Drug: ANG003; To evaluate four possible combinations of lipase, protease and amylase.; Other Names: Dose Level 1, Dose Level 2, Dose Level 3, and Dose Level 4.
Experimental: ANG003 Dose Level 2; Single administration dose contains 40 mg lipase, 50 mg protease and 80 mg amylase.	Drug: ANG003; To evaluate four possible combinations of lipase, protease and amylase.; Other Names: Dose Level 1, Dose Level 2, Dose Level 3, and Dose Level 4.
Experimental: ANG003 Dose Level 3; Single administration dose contains 80 mg lipase, 50 mg protease and 80 mg amylase.	Drug: ANG003; To evaluate four possible combinations of lipase, protease and amylase.; Other Names: Dose Level 1, Dose Level 2, Dose Level 3, and Dose Level 4.
Experimental: ANG003 Dose Level 4; Single administration dose contains 120 mg lipase, 75 mg protease and 120 mg amylase.	Drug: ANG003; To evaluate four possible combinations of lipase, protease and amylase.; Other Names: Dose Level 1, Dose Level 2, Dose Level 3, and Dose Level 4.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and AEs Leading to Study Discontinuation	AE, SAEs and AEs leading to study discontinuation measured by number of participants during study.	Assessed through study completion, up to 9 days (Day 1 thru Day 9).

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).

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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).
Fat Absorption Assessed as Cmax of DHA+EPA	Measured by concentration of plasma fatty acids.	DHA+EPA measured at baseline t0, 1h, 2h, 4h, 6h, 8h, 10-12h, and 24h post on Baseline SACT (Day 1) and ANG003 SACT (Day 5)
Fat Absorption Assessed as Area Under the Curve (AUC-24hr) of Plamsa Docosahexaenoic Acid (DHA) and Eicosapentaenoic Acid (EPA)	Measured by concentration of plasma fatty acids.	DHA+EPA measured at baseline t0, 1h, 2h, 4h, 6h, 8h, 10-12h, and 24h post on Baseline SACT (Day 1) and ANG003 SACT (Day 5)

Collaborators and Investigators

• Sponsor: Anagram Therapeutics, Inc.
• Investigators: Principal Investigator: Meghana Sathe, MD, University of Texas

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2023
• Primary Completion (Actual): July 8, 2024
• Study Completion (Actual): July 8, 2024

Study Registration Dates

• First Submitted: August 9, 2023
• First Submitted That Met QC Criteria: September 18, 2023
• First Posted (Actual): September 25, 2023

Study Record Updates

• Last Update Posted (Actual): April 27, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Cystic Fibrosis
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cystic Fibrosis; Exocrine Pancreatic Insufficiency
• Other Study ID Numbers: ANG003-22-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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