A Phase 2a, Randomized, Open-Label, Active-Controlled, Crossover Study to Evaluate Safety and Explore Efficacy of Different Doses of New Lipase NHS7108 Administered Orally in Participants With Exocrine Pancreatic Insufficiency- EPIC

Summary

The purpose of this study is to measure the safety and explore the efficacy of 4 different doses of the new lipase NHS7108 in participants with EPI. In this study, all participants will take NHS7108 daily for 14 days and a matching dose of standard-of-care, pancrelipase (Zenpep®) for 14 days according to Treatment Sequence assignment. Both NHS7108 and Zenpep® are oral capsules that will be taken with each of the daily 3 meals and 2 snacks. Participants will interrupt all of their usual pancrelipase/pancreatin treatment for up to 8 days during screening and for the entire 2 treatment periods, where participants will take either the new lipase NHS7108 or a matching dose of the standard-of-care pancrelipase (Zenpep®). Participants will be asked to stay in a setting that allows controlled diet and 72-hour stool collection for approximately 7 days during the screening period and again for approximately 7 days at the end of each treatment period. During these 3 supervised periods, participants will receive a standardized diet with a predefined amount of fat and protein, stools will be collected in special containers and during the last day of the treatment period, blood samples will be obtained to measure fat absorption. These are essential to ensure valid assessment of participants' fat and protein absorption. Outside the 3 supervised periods, participants will be provided with guidelines and recommendations to create their own home-controlled meals and snacks according to their preferences for the remainder of the study duration. Number of Participants: The aim is to have 56 participants completing the study. Assuming approximately 14% drop-out rate, approximately 66 participants will be randomized to study intervention. Study Arms and Duration: The total study duration for each participant will be about 100 days (approximately 14 weeks), including: * A screening period of up to approximately 28 days (might be extended up to a total of 56 days) prior to the first dose administration. * A crossover treatment period (2 treatment periods: approximately 14 days each, with no washout in between). For each treatment period, study intervention will be administered 5 times a day (with 3 main meals and 2 snacks). After completion of Treatment Period 1, the participant will receive and start the new treatment for Treatment Period 2. * An end of treatment/early discontinuation visit within approximately 7 days of the last study intervention dose. * An end-of-study safety follow-up visit at 14 (±2) days after the last dose administration. Very low dose group: 10 mg NHS7108 (approximately 25,000 LU)/main meal and snack; 25,000 LU Zenpep/main meal and snack (50 mg NHS7108 \[approximately 125,000 LU\] per day; 125,000 LU Zenpep per day) Low dose group: 20 mg NHS7108 (approximately 50,000 LU)/main meal and 10 mg NHS7108 (approximately 25,000 LU)/snack; 50,000 LU Zenpep/main meal and 25,000 LU Zenpep/snack (80 mg NHS7108 \[approximately 200,000 LU\] per day; 200,000 LU Zenpep per day) Medium dose group: 40 mg NHS7108 (approximately 100,000 LU)/main meal and 20 mg (approximately 50,000 LU) NHS7108/snack; 100,000 LU Zenpep/main meal and 50,000 LU Zenpep/snack (160 mg \[approximately 400,000 LU\] NHS7108 per day; 400,000 LU Zenpep per day) High dose group: 60 mg NHS7108 (approximately 150,000 LU)/main meal and 30 mg NHS7108 (approximately 75,000 LU)/snack; 150,000 LU Zenpep/main meal and 75,000 LU Zenpep/snack (240 mg NHS7108 \[approximately 600,000 LU\] per day; 600,000 LU Zenpep per day). The dose for participants \< 60 kg who are assigned to the high dose group will need to be weight-adjusted to ensure that they receive no more than 10,000 LU/kg/day.

Eligibility

Age range

18–85 years

Sex

All

Healthy volunteers

No

Interventions

• Drug
  NHS7108

  NHS7108 is the experimental drug. It is a recombinant, modified version of a triacylglycerol lipase enzyme derived from the bacteria Bacillus thermoamylovorans and produced by fermentation of recombinant Escherichia coli. Unit dose strength: 10 mg (approximately 25,000 LU) per capsule.

• Drug
  Zenpep®

  Zenpep® is the active comparator. It is a combination of lipases, proteases, and amylases. Unit dose strength: 25,000 LU per capsule.

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