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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05082051




Registration number
NCT05082051
Ethics application status
Date submitted
7/09/2021
Date registered
18/10/2021
Date last updated
20/09/2024

Titles & IDs
Public title
Oral CDX-7108 in Healthy Adults and EPI Subjects
Scientific title
A 3-part, Phase 1a/1b, First-in-human, Randomized, Double-blind, Placebo-controlled Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of Oral CDX-7108 in Healthy Adult Subjects and to Evaluate Proof-of-concept Via Pharmacodynamics of a Single Dose of Oral CDX-7108 in Subjects with Exocrine Pancreatic Insufficiency
Secondary ID [1] 0 0
21.02.CLI
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Exocrine Pancreatic Insufficiency 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Part A
Treatment: Drugs - Part B
Treatment: Drugs - Part C

Active comparator: CDX-7108 - 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

Placebo comparator: Placebo - Excipients only


Treatment: Drugs: Part A
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.

Treatment: Drugs: Part B
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.

Treatment: Drugs: Part C
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Adverse events
Timepoint [1] 0 0
Up to 9 weeks
Primary outcome [2] 0 0
Changes in haematology from baseline
Timepoint [2] 0 0
Up to 5 weeks
Primary outcome [3] 0 0
Changes in coagulation tests from baseline
Timepoint [3] 0 0
Up to 5 weeks
Primary outcome [4] 0 0
Changes in clinical chemistry from baseline
Timepoint [4] 0 0
Up to 5 weeks
Primary outcome [5] 0 0
Changes in urinalysis from baseline
Timepoint [5] 0 0
Up to 5 weeks
Primary outcome [6] 0 0
Changes in Systolic Blood Pressure from baseline
Timepoint [6] 0 0
Up to 5 weeks
Primary outcome [7] 0 0
Changes in Diastolic Blood Pressure from baseline
Timepoint [7] 0 0
Up to 5 weeks
Primary outcome [8] 0 0
Changes in Pulse Rate vital signs from baseline
Timepoint [8] 0 0
Up to 5 weeks
Primary outcome [9] 0 0
Changes in Respiratory Rate vital signs from baseline
Timepoint [9] 0 0
Up to 5 weeks
Primary outcome [10] 0 0
Changes in Body Temperature vital signs from baseline
Timepoint [10] 0 0
Up to 5 weeks
Primary outcome [11] 0 0
Changes in 12-lead electrocardiogram (ECG) Heart Rate from baseline
Timepoint [11] 0 0
Up to 5 weeks
Primary outcome [12] 0 0
Changes in 12-lead electrocardiogram (ECG) PR Interval from baseline
Timepoint [12] 0 0
Up to 5 weeks
Primary outcome [13] 0 0
Changes in 12-lead electrocardiogram (ECG) QRS duration from baseline
Timepoint [13] 0 0
Up to 5 weeks
Primary outcome [14] 0 0
Changes in 12-lead electrocardiogram (ECG) QT Interval from baseline
Timepoint [14] 0 0
Up to 5 weeks
Primary outcome [15] 0 0
Changes in 12-lead electrocardiogram (ECG) QTcF Interval from baseline
Timepoint [15] 0 0
Up to 5 weeks
Primary outcome [16] 0 0
Changes in physical examination from baseline: Head
Timepoint [16] 0 0
Up to 5 weeks
Primary outcome [17] 0 0
Changes in physical examination from baseline: Ears
Timepoint [17] 0 0
Up to 5 weeks
Primary outcome [18] 0 0
Changes in physical examination from baseline: Eyes
Timepoint [18] 0 0
Up to 5 weeks
Primary outcome [19] 0 0
Changes in physical examination from baseline: Nose
Timepoint [19] 0 0
Up to 5 weeks
Primary outcome [20] 0 0
Changes in physical examination from baseline: Throat
Timepoint [20] 0 0
Up to 5 weeks
Primary outcome [21] 0 0
Changes in physical examination from baseline: Neck
Timepoint [21] 0 0
Up to 5 weeks
Primary outcome [22] 0 0
Changes in physical examination from baseline: General Appearance
Timepoint [22] 0 0
Up to 5 weeks
Primary outcome [23] 0 0
Changes in physical examination from baseline: Cardiovascular system
Timepoint [23] 0 0
Up to 5 weeks
Primary outcome [24] 0 0
Changes in physical examination from baseline: Respiratory system
Timepoint [24] 0 0
Up to 5 weeks
Primary outcome [25] 0 0
Changes in physical examination from baseline: GI system
Timepoint [25] 0 0
Up to 5 weeks
Primary outcome [26] 0 0
Changes in physical examination from baseline: Musculoskeletal system
Timepoint [26] 0 0
Up to 5 weeks
Primary outcome [27] 0 0
Changes in physical examination from baseline: Lymph nodes
Timepoint [27] 0 0
Up to 5 weeks
Primary outcome [28] 0 0
Changes in physical examination from baseline: Nervous system
Timepoint [28] 0 0
Up to 5 weeks
Secondary outcome [1] 0 0
Concentration-time profile of CDX-7108
Timepoint [1] 0 0
Up to 7 days
Secondary outcome [2] 0 0
Lipase activity
Timepoint [2] 0 0
Day 1
Secondary outcome [3] 0 0
CO2 excretion rate
Timepoint [3] 0 0
Up to 43 days

Eligibility
Key inclusion criteria
All subjects:

1. 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.
2. Body mass index (BMI) between 18.0 and 30.0 kg/m2.
3. 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:

1. Must agree to stay abstinent (where abstinence is the preferred and usual lifestyle of the subject), OR
2. Male subjects with a female partner of childbearing potential must agree to use highly effective contraception consisting of 2 forms of birth control.
3. 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.
4. These requirements do not apply to subjects in a same sex relationship.
4. 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.
5. Female subjects of childbearing potential are eligible to participate if they meet the following criteria:

1. Must agree not to become pregnant during the clinical study period and for 30 days after IP administration.
2. Must have a negative serum pregnancy test at Screening and Day -1.
3. 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
4. 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.
5. These requirements do not apply to subjects in a same sex relationship.
6. Female subjects of non-childbearing potential are eligible to participate if 1 of the following conditions apply:

1. Must have a confirmed clinical history of sterility (documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy, as confirmed by review of the subject's medical records, medical examination, or medical history interview)
2. Must be postmenopausal as defined as: amenorrhea for at least 1 year prior to Screening and a laboratory confirmed serum follicle-stimulating hormone (FSH) level =40 mIU/mL. Female subjects on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use 1 of the non-estrogen hormonal highly effective contraception methods (Appendix 3) from Screening (signing the ICF) until at and continuing throughout the clinical study period, and for 30 days after IP administration if they wish to continue their HRT during the study.
7. Female subjects must agree not to donate ova starting at Screening (signing the ICF) and continuing throughout the clinical study period, and for 30 days after IP administration.
8. Subject agrees not to participate in another interventional study while participating in the present clinical study.

Parts A (Single Ascending Dose Study) and B (Multiple Ascending Dose Study)
9. Healthy male and female, non-smoking, subjects between the ages of 18 and 55 years, inclusive, at the time of Screening. In each cohort, at least 2 male subjects and 2 female subjects should be enrolled.
10. Appropriate general health, as determined by an experienced physician based on a medical evaluation including detailed medical history, clinical laboratory tests, vital signs, 12-lead ECG, and full physical examination (and neurological assessment).

Part C (Proof-of-Concept Study)
11. Male and female subjects between the ages of 18 and 75 years (inclusive) who have undergone total or partial pancreatectomy or have an established diagnosis of CP, as confirmed by fecal pancreatic elastase-1 <100 µg/g in formed stools within 12 months of the Screening visit.
12. Subjects with clinically well controlled EPI under the regular use of PERT (remission or adequate improvement of steatorrhea on PERT), as determined by an experienced physician based on a medical evaluation including detailed medical history, clinical laboratory tests, vital signs, 12-lead ECG, and full physical examination (and neurological assessment).
13. 150min percentage 13CO2 excretion rate <4.4% dose/h using the Pancreo-Lip breath test at Screening.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
All subjects

1. Female subject who has been pregnant within the 6 months prior to Screening or breastfeeding within the 3 months prior to Screening.
2. Treatment with any antiplatelet and/or anticoagulant medication, except low-dose aspirin.
3. 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.
4. 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.
5. Known active infection with COVID-19, or a suspected infection with severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2]).
6. Chronic alcoholic intoxication that would preclude compliance with the study procedures.
7. 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.
8. Drug addiction that would preclude participation and compliance with study procedures.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. Known allergy or adverse reaction history to any component of the CDX-7108 oral dose formulation.

Part A (Single Ascending Dose Study) and Part B (Multiple Ascending Dose Study)
15. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies and childhood asthma) at time of Screening or IP administration, that in the opinion of the Investigator may put the subject at greater safety risk, influence response to study drug, or interfere with study assessments.
16. Current or chronic history of GI disorders or conditions interfering with normal GI anatomy or function. Examples include GI bypass surgery, partial or total gastrectomy, gastric band surgery, major (>1 m) small bowel resection, vagotomy, malabsorption, Crohn's disease, ulcerative colitis, irritable bowel syndrome, celiac sprue, and small intestinal bacterial overgrowth.
17. A positive Screening test for use of drugs (amphetamines, cocaine, marijuana, opiates, barbiturates, benzodiazepines, methadone, and methamphetamines) and alcohol (breath test). However, there is the option to re-screen once during the Screening period at the discretion of the Investigator or delegate in the case of a positive result at Screening for a prescribed medication, eg, codeine.
18. Subject has any clinically significant abnormalities in hematology, coagulation, clinical chemistry, or urinalysis at Screening as judged by the Investigator, including aspartate aminotransferase (AST) or ALT >1.5 times above the ULN. Repeat measurements are allowed at the discretion of the Investigator.
19. Use of any prescribed or nonprescribed medication in the 2 weeks preceding the first dose of IP. EXCEPTION: Subjects who have received approved vaccines (including approved COVID-19 vaccines) may be allowed if these vaccines are taken no less than 72 hours prior to the IP dose at the discretion of the Investigator.

Part C (Proof-of-Concept Study)
20. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies and childhood asthma) at time of Screening or IP administration, that in the opinion of the Investigator may put the subject at greater safety risk, influence response to study drug, or interfere with study assessments. NOTE: Subjects with treated diabetes secondary to CP or pancreatectomy are allowed.
21. Subject has any clinically significant abnormalities in hematology, coagulation, clinical chemistry, or urinalysis at Screening as judged by the Investigator, including AST or ALT >1.5 times above the ULN, or cholesterol or triglycerides >400 mg/dL. Repeat measurements are allowed at the discretion of the Investigator.
22. Current or chronic history of GI disorders or conditions interfering with normal GI anatomy or motility, with the exception of pancreatic insufficiency due to pancreatectomy, including pancreaticoduodenectomy, or CP
23. Use of any prescribed or nonprescribed medication potentially interfering with gastric pH, intestinal motility, or fat absorption, including herbal and dietary supplements and antacids; these medications shall be stopped for a minimum of 5 times their half-life before IP administration if, in the opinion of the Investigator, this does not represent a risk for the subject's wellbeing. EXCEPTIONS:

Histamine H2 receptor antagonists, PPI, insulin, analgesics, and chronic pain medications.

Oral contraceptives, paracetamol, or multivitamins. Subjects who have received approved vaccines (including approved COVID-19 vaccines) may be allowed if these vaccines are taken no less than 72 hours prior to the IP dose at the discretion of the Investigator.
24. Use of antibiotics within 8 days before the Pancreo-Lip breath test at Screening or Day 1.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/10/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
16/03/2023
Sample size
Target
Accrual to date
Final
54
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
CMAX Clinical Research - Adelaide
Recruitment postcode(s) [1] 0 0
SA 5000 - Adelaide
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
North Island
Country [2] 0 0
New Zealand
State/province [2] 0 0
South Island
Country [3] 0 0
New Zealand
State/province [3] 0 0
Wellington

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Société des Produits Nestlé (SPN)
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/study/NCT05082051
Trial related presentations / publications
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.
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.
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.
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.
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.
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.
Investigator's Brochure for CDX-7108. Edition 1.0, Release Date 31 March 2021.
CREON®. The United States Prescribing Information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020725s000lbl.pdf. Accessed on: 23 March 2021.
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.
Food and Drug Administration. Guidance for industry drug-induced liver injury: premarketing clinical evaluation. CDER. 2009.
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.
Aygen S, inventor; Infai Institut fur Biomedizinische Analytik und NMR Imaging GmbH, assignee. Method for measuring pancreatic metabolism. International Patent, WO2004043498. 27 May 2004.
Aygen S, inventor; Infai Institut fur Biomedizinische Analytik und NMR Imaging GmbH, assignee. Method for measuring pancreatic metabolism. European Patent, EP1560603. 07 March 2007.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Chris Wynne
Address 0 0
New Zealand Clinical Research
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05082051