Oral CDX-7108 in Healthy Adults and EPI Subjects

NCT05082051 | Completed Phase 1

• 1 other identifier: 21.02.CLI
• Study Type: interventional
• Target: 54
• Locations: 2 countries
• Sites: 4

Brief Summary

Phase 1a/1b single and multiple ascending dose study of oral CDX-7108 in healthy adult subjects and a single dose proof-of-concept study of oral CDX-7108 in subjects with exocrine pancreatic insufficiency. No clinical studies have yet been performed with CDX-7108 and its effects in humans are unknown. This is the first-in-human (FIH) study of CDX-7108, which aims to assess the safety, tolerability, pharmacokinetics (PK) of escalating single and multiple oral doses of CDX-7108 in healthy adult subjects and to evaluate the pharmacodynamics of a single dose of oral CDX-7108 in a proof-of-concept (POC) study in subjects with exocrine pancreatic insufficiency (EPI).

Conditions

Exocrine Pancreatic Insufficiency

Outcome Measures

Primary Outcomes (28)

• Adverse events

  Number and severity of adverse events

  Up to 9 weeks

• Changes in haematology from baseline

  Number of participants with changes in haematology measurements (erythrocyte count, thrombocyte count, haemoglobin, haematocrit, mean cell hemoglobin concertation) using immunoassays.

  Up to 5 weeks

• Changes in coagulation tests from baseline

  Number of participants with changes in coagulation factors (INR, prothrombin time, fibrogen, red blood cell indices and leukocyte count) using immunoassays.

  Up to 5 weeks

• Changes in clinical chemistry from baseline

  Number of participants with changes in clinical chemistry (bicarbonate, albumin, total protein, blood glucose, sodium, potassium, phosphate, calcium, urea creatine, chloride, creatine kinase, urate, AST, ALT, ALP, GGT, triglycerides, total cholesterol, lactate dehydrogenase, c-reactive protein, total bilirubin) using immunoassays.

  Up to 5 weeks

• Changes in urinalysis from baseline

  Number of participants with changes in leucocyte esterase, protein, urobilinogen, ketones, bilirubin, microscopy, blood, pH, nitrate, specific gravity, urobilinogen and glucose) using immunoassays.

  Up to 5 weeks

• Changes in Systolic Blood Pressure from baseline

  Changes in Systolic Blood Pressure from baseline

  Up to 5 weeks

• Changes in Diastolic Blood Pressure from baseline

  Changes in Diastolic Blood Pressure from baseline

  Up to 5 weeks

• Changes in Pulse Rate vital signs from baseline

  Changes in pulse rate from baseline

  Up to 5 weeks

• Changes in Respiratory Rate vital signs from baseline

  Changes in respiratory rate from baseline

  Up to 5 weeks

• Changes in Body Temperature vital signs from baseline

  Changes in body temperature from baseline

  Up to 5 weeks

• Changes in 12-lead electrocardiogram (ECG) Heart Rate from baseline

  Changes in ECG Heart rate from baseline

  Up to 5 weeks

• Changes in 12-lead electrocardiogram (ECG) PR Interval from baseline

  Changes in ECG PR interval from baseline

  Up to 5 weeks

• Changes in 12-lead electrocardiogram (ECG) QRS duration from baseline

  Changes in electrocardiogram QRS duration interval from baseline

  Up to 5 weeks

• Changes in 12-lead electrocardiogram (ECG) QT Interval from baseline

  Changes in ECG QT interval from baseline

  Up to 5 weeks

• Changes in 12-lead electrocardiogram (ECG) QTcF Interval from baseline

  Changes in ECG QTcF interval from baseline

  Up to 5 weeks

• Changes in physical examination from baseline: Head

  Changes in general appearance of the head from baseline

  Up to 5 weeks

• Changes in physical examination from baseline: Ears

  Changes in general appearance of the ears from baseline

  Up to 5 weeks

• Changes in physical examination from baseline: Eyes

  Changes in general appearance of the eyes from baseline

  Up to 5 weeks

• Changes in physical examination from baseline: Nose

  Changes in general appearance of the nose from baseline

  Up to 5 weeks

• Changes in physical examination from baseline: Throat

  Changes in general appearance of the throat from baseline

  Up to 5 weeks

• Changes in physical examination from baseline: Neck

  Changes in general appearance of the neck (including thyroid) from baseline

  Up to 5 weeks

• Changes in physical examination from baseline: General Appearance

  Changes in general appearance of the skin from baseline

  Up to 5 weeks

• Changes in physical examination from baseline: Cardiovascular system

  Changes in cardiovascular system from baseline

  Up to 5 weeks

• Changes in physical examination from baseline: Respiratory system

  Changes in respiratory system from baseline

  Up to 5 weeks

• Changes in physical examination from baseline: GI system

  Changes in GI system from baseline

  Up to 5 weeks

• Changes in physical examination from baseline: Musculoskeletal system

  Changes in musculoskeletal system from baseline

  Up to 5 weeks

• Changes in physical examination from baseline: Lymph nodes

  Changes in lymph nodes from baseline

  Up to 5 weeks

• Changes in physical examination from baseline: Nervous system

  Changes in nervous system from baseline

  Up to 5 weeks

Secondary Outcomes (3)

• Concentration-time profile of CDX-7108

  Up to 7 days

• Lipase activity

  Day 1

• CO2 excretion rate

  Up to 43 days

Other Outcomes (1)

• Immunogenicity Assessment

  Up to 5 weeks

Study Arms (2)

CDX-7108

ACTIVE COMPARATOR

CDX-7108, an oral recombinant lipase. It is a modified version of a triacylglycerol lipase enzyme derived from the bacteria Bacillus thermoamylovans (btLIP) and produced by fermentation of recombinant Escherichia coli.7

Drug: Part A; Drug: Part B; Drug: Part C

Placebo

PLACEBO COMPARATOR

Excipients only

Drug: Part A; Drug: Part B; Drug: Part C

Interventions

Part A DRUG

Randomized, double-blind, placebo-controlled dose escalation part to investigate the safety, tolerability, immunogenicity, and PK of CDX-7108 after single oral dose administration in healthy adult subjects. Single-dose administration of CDX-7108 at the following anticipated dose levels. 10 000, 50 000, 150 000, 250 000, and 500 000 lipase units will be evaluated in 5 sequential cohorts of 6 subjects each.

Also known as: Single Ascending Dose Study

CDX-7108; Placebo

Part B DRUG

Randomized, double-blind, placebo-controlled dose escalation parts to investigate the safety, tolerability, immunogenicity, and PK of CDX-7108 after multiple oral dose administration in healthy adult subjects. It will evaluate multiple dose administration of CDX-7108 at an appropriate low (50 000 lipase units), mid (150 000 lipase units), and high dose (250 000 lipase units) 4 times a day (QID) for 6 consecutive days in 3 sequential cohorts of 6 subjects each.

Also known as: Multiple Ascending Dose Study

CDX-7108; Placebo

Part C DRUG

Randomized, double-blind, placebo-controlled, single-dose, 2-way crossover part to assess POC of CDX-7108 in terms of PD as well as its safety, tolerability, and immunogenicity in subjects with EPI. Approximately 10 subjects with severe EPI from partial/total pancreatectomy or chronic pancreatitis will be enrolled. It is anticipated that Part C (POC study) will commence after completion of the third single-dose cohort from Part A (SAD study) and following SRC review of the data from this cohort.

Also known as: Proof-of-Concept Study

CDX-7108; Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects:
• Capable of giving signed informed consent prior to initiation of any protocol-specific procedures, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Body mass index (BMI) between 18.0 and 30.0 kg/m2.
• Nonsterilized male subjects are eligible to participate if they agree to ONE of the following starting at Screening and continuing throughout the clinical study period, and for 90 days after IP administration:
• Must agree to stay abstinent (where abstinence is the preferred and usual lifestyle of the subject), OR
• Male subjects with a female partner of childbearing potential must agree to use highly effective contraception consisting of 2 forms of birth control.
• Male subjects with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile penetration.
• These requirements do not apply to subjects in a same sex relationship.
• Male subjects must agree not to donate sperm starting at Screening and continuing throughout the clinical study period, and for 90 days after IP administration.
• Female subjects of childbearing potential are eligible to participate if they meet the following criteria:
• Must agree not to become pregnant during the clinical study period and for 30 days after IP administration.
• Must have a negative serum pregnancy test at Screening and Day -1.
• If heterosexually active, must agree to consistently use a form of highly effective birth control, in combination with a barrier method (as defined in Appendix 3) starting at Screening (signing the ICF) and continuing throughout the clinical study period, and for 30 days after IP administration, OR
• Must agree to stay abstinent (where abstinence is the preferred and usual lifestyle of the subject), starting at Screening (signing the ICF) and continuing throughout the clinical study period, and for 30 days after IP administration.
• These requirements do not apply to subjects in a same sex relationship.

You may not qualify if:

• All subjects
• Female subject who has been pregnant within the 6 months prior to Screening or breastfeeding within the 3 months prior to Screening.
• Treatment with any antiplatelet and/or anticoagulant medication, except low-dose aspirin.
• Evidence or history of specific food intolerance. Examples include gluten intolerance, lactose intolerance, or dairy food intolerance or any food/ingredient included in the standard breakfast provided at the study site.
• A positive result, on Screening, for serum hepatitis B surface antigen, hepatitis A virus antibodies, hepatitis C virus antibodies or antibodies to human immunodeficiency virus type 1 and/or type 2.
• Known active infection with COVID-19, or a suspected infection with severe acute respiratory syndrome coronavirus-2 \[SARS-CoV-2\]).
• Chronic alcoholic intoxication that would preclude compliance with the study procedures.
• Habitual use of nicotine products or smoking within 3 months (\>10 cigarettes per day) prior to Screening, and/or unwilling to refrain from smoking during the confinement period. Nicotine replacement therapy is allowed during the study.
• Drug addiction that would preclude participation and compliance with study procedures.
• Subject has a pulse rate \<40 or \>100 bpm; mean systolic blood pressure (SBP) \>150 mmHg; mean diastolic blood pressure (DBP) \>95 mmHg at Screening. Repeat measurements are allowed at the discretion of the Investigator.
• Subject has any clinically significant abnormalities at Screening in rhythm, conduction or morphology of the resting ECG and any clinically significant abnormalities in the 12-lead ECG, as considered by the Investigator, that may interfere with the interpretation of QTc interval changes including abnormal ST-T wave morphology.
• Subject has prolonged QTcF \>450 msec for male subjects or \>470 msec for female subjects or a family history of prolonged QT syndrome, at Screening.
• Plasma donation within the 14 days prior to the first dose of IP or any whole blood donation/significant blood loss \>500 mL during the 3 months prior to the first dose of IP.
• Treatment with any investigational drug or device/treatment within the 30 days or 5 half-lives of the drug (whichever is longer) prior to the administration of IP.
• Known allergy or adverse reaction history to any component of the CDX-7108 oral dose formulation.

Sponsors & Collaborators

• Société des Produits Nestlé (SPN): lead

Study Sites (4)

CMAX Clinical Research

Adelaide, New South Wales, SA 5000, Australia

Location

New Zealand Clinical Research

Auckland, North Island, 1010, New Zealand

Location

New Zealand Clinical Research

Christchurch, South Island, 8011, New Zealand

Location

P3 Research

Lower Hutt, Wellington Region, 5010, New Zealand

Location

Related Publications (15)

• Forsmark Chris E. Chronic pancreatitis In: Sleisenger M, Fordtran J, Feldman M, Brandt L, and Friedman L. eds. Sleisenger & Fordtran's Gastrointestinal and liver disease. 10th ed Philadelphia, PA: Saunders-Elsevier; 2016:1020.

  BACKGROUND

• Shandro BM, Nagarajah R, Poullis A. Challenges in the management of pancreatic exocrine insufficiency. World J Gastrointest Pharmacol Ther. 2018 Oct 25;9(5):39-46. doi: 10.4292/wjgpt.v9.i5.39.

  PMID: 30397535 BACKGROUND

• ASGE Standards of Practice Committee; Chandrasekhara V, Chathadi KV, Acosta RD, Decker GA, Early DS, Eloubeidi MA, Evans JA, Faulx AL, Fanelli RD, Fisher DA, Foley K, Fonkalsrud L, Hwang JH, Jue TL, Khashab MA, Lightdale JR, Muthusamy VR, Pasha SF, Saltzman JR, Sharaf R, Shaukat A, Shergill AK, Wang A, Cash BD, DeWitt JM. The role of endoscopy in benign pancreatic disease. Gastrointest Endosc. 2015 Aug;82(2):203-14. doi: 10.1016/j.gie.2015.04.022. Epub 2015 Jun 12. No abstract available.

  PMID: 26077456 BACKGROUND

• Saito T, Hirano K, Isayama H, Nakai Y, Saito K, Umefune G, Akiyama D, Watanabe T, Takagi K, Hamada T, Takahara N, Uchino R, Mizuno S, Kogure H, Matsubara S, Yamamoto N, Tada M, Koike K. The Role of Pancreatic Enzyme Replacement Therapy in Unresectable Pancreatic Cancer: A Prospective Cohort Study. Pancreas. 2017 Mar;46(3):341-346. doi: 10.1097/MPA.0000000000000767.

  PMID: 28099252 BACKGROUND

• Imrie CW, Connett G, Hall RI, Charnley RM. Review article: enzyme supplementation in cystic fibrosis, chronic pancreatitis, pancreatic and periampullary cancer. Aliment Pharmacol Ther. 2010 Nov;32 Suppl 1:1-25. doi: 10.1111/j.1365-2036.2010.04437.x.

  PMID: 21054452 BACKGROUND

• Keller J, Layer P. Human pancreatic exocrine response to nutrients in health and disease. Gut. 2005 Jul;54 Suppl 6(Suppl 6):vi1-28. doi: 10.1136/gut.2005.065946. No abstract available.

  PMID: 15951527 BACKGROUND

• Investigator's Brochure for CDX-7108. Edition 1.0, Release Date 31 March 2021.

  BACKGROUND

• CREON®. The United States Prescribing Information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020725s000lbl.pdf. Accessed on: 23 March 2021.

  BACKGROUND

• Food and Drug Administration. Guidance for industry: estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers. Center for Drug Evaluation and Research (CDER). 2005.

  BACKGROUND

• Food and Drug Administration. Guidance for industry drug-induced liver injury: premarketing clinical evaluation. CDER. 2009.

  BACKGROUND

• Loser C, Brauer C, Aygen S, Hennemann O, Folsch UR. Comparative clinical evaluation of the 13C-mixed triglyceride breath test as an indirect pancreatic function test. Scand J Gastroenterol. 1998 Mar;33(3):327-34. doi: 10.1080/00365529850170946.

  PMID: 9548629 BACKGROUND

• Aygen S, inventor; Infai Institut fur Biomedizinische Analytik und NMR Imaging GmbH, assignee. Method for measuring pancreatic metabolism. International Patent, WO2004043498. 27 May 2004.

  BACKGROUND

• Aygen S, inventor; Infai Institut fur Biomedizinische Analytik und NMR Imaging GmbH, assignee. Method for measuring pancreatic metabolism. European Patent, EP1560603. 07 March 2007.

  BACKGROUND

• Aygen S, inventor; Infai Institut fur Biomedizinische Analytik und NMR Imaging GmbH, assignee. Method for measuring pancreatic metabolism. United States patent US 7762957. 27 July 2010.

  BACKGROUND

• James LP, Letzig L, Simpson PM, Capparelli E, Roberts DW, Hinson JA, Davern TJ, Lee WM. Pharmacokinetics of acetaminophen-protein adducts in adults with acetaminophen overdose and acute liver failure. Drug Metab Dispos. 2009 Aug;37(8):1779-84. doi: 10.1124/dmd.108.026195. Epub 2009 May 13.

  PMID: 19439490 BACKGROUND

MeSH Terms

Conditions

Exocrine Pancreatic Insufficiency

Interventions

Medicare Part B; Medicare Part C

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Medicare; Medical Assistance; Public Assistance; Financing, Government; Financing, Organized; Economics; Health Care Economics and Organizations; Insurance, Health; Insurance; Legislation as Topic; Social Control, Formal; Legislation, Hospital

Study Officials

• Chris Wynne

  New Zealand Clinical Research

  PRINCIPAL INVESTIGATOR

• John Windsor

  New Zealand Clinical Research

  PRINCIPAL INVESTIGATOR

• Nam Nguyen

  CMAX Clinical Research

  PRINCIPAL INVESTIGATOR

• Richard Stubbs

  P3 Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 3-part study Parts A and B are randomized, double-blind, placebo-controlled dose escalation parts to investigate the safety, tolerability, immunogenicity, and PK of CDX-7108 after single and multiple oral dose administration in healthy adult subjects. Part C is a randomized, double-blind, placebo-controlled, single-dose, 2-way crossover part to assess POC of CDX-7108 in terms of PD as well as its safety, tolerability, and immunogenicity in subjects with EPI.

Study Record Dates

• First Submitted: September 7, 2021
• First Posted: October 18, 2021
• Study Start: October 11, 2021
• Primary Completion: March 16, 2023
• Study Completion: March 16, 2023
• Last Updated: September 20, 2024

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (3); AU (1)