Exocrine Pancreatic InsufficiencyPhase 1NCT05082051
Oral CDX-7108 in Healthy Adults and EPI Subjects
A Phase 1 study testing Part A, Part B and Part C in people with Exocrine Pancreatic Insufficiency, run by Société des Produits Nestlé (SPN) at 4 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Exocrine Pancreatic Insufficiency
- What is being tested?
- Part A, Part B and Part C
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 54 participants
- Where
- 4 sitesin 2 countries
- Study dates
- 11 Oct 2021to 16 Mar 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- Female subjects of non-childbearing potential are eligible to participate if 1 of the following conditions apply:
- 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)
- 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.
- 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.
- 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)
- 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.
- 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)
- 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.
- 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).
- 150min percentage 13CO2 excretion rate <4.4% dose/h using the Pancreo-Lip breath test at Screening.
Who cannot join
- 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]).
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- 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.
- Part A (Single Ascending Dose Study) and Part B (Multiple Ascending Dose Study)
- 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.
- 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.
- 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.
- 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.
- 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)
- 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.
- 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.
- 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
- 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.
- Use of antibiotics within 8 days before the Pancreo-Lip breath test at Screening or Day 1.
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
New Zealand3 sites
New Zealand Clinical Research
Auckland, North Island, 1010
New Zealand Clinical Research
Christchurch, South Island, 8011
P3 Research
Lower Hutt, Wellington Region, 5010
About this study
Official 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
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).
Read the detailed description
This is an integrated 3-part study to investigate the safety, tolerability, PK, and PD of CDX-7108. The 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. The study will commence with Part A (single ascending dose [SAD] study) and will progress to Part B (multiple ascending dose [MAD] study), and Part C (POC study)
- Conditions
- Exocrine Pancreatic Insufficiency
- Being tested
- Part A, Part B, Part C
- Medical subject headings
- Exocrine Pancreatic Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Part ADrug
Also called Single Ascending Dose Study
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.
Part BDrug
Also called Multiple Ascending Dose Study
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.
Part CDrug
Also called Proof-of-Concept Study
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Part A; Drug: Part B; Drug: Part C |
| Placebo | Placebo comparator | Excipients only Receives: Drug: Part A; Drug: Part B; Drug: Part C |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events
Number and severity of adverse events
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 5 weeks
Changes in Systolic Blood Pressure from baseline
Changes in Systolic Blood Pressure from baseline
Measured: Up to 5 weeks
Changes in Diastolic Blood Pressure from baseline
Changes in Diastolic Blood Pressure from baseline
Measured: Up to 5 weeks
Changes in Pulse Rate vital signs from baseline
Changes in pulse rate from baseline
Measured: Up to 5 weeks
Changes in Respiratory Rate vital signs from baseline
Changes in respiratory rate from baseline
Measured: Up to 5 weeks
Changes in Body Temperature vital signs from baseline
Changes in body temperature from baseline
Measured: Up to 5 weeks
Changes in 12-lead electrocardiogram (ECG) Heart Rate from baseline
Changes in ECG Heart rate from baseline
Measured: Up to 5 weeks
Changes in 12-lead electrocardiogram (ECG) PR Interval from baseline
Changes in ECG PR interval from baseline
Measured: Up to 5 weeks
Changes in 12-lead electrocardiogram (ECG) QRS duration from baseline
Changes in electrocardiogram QRS duration interval from baseline
Measured: Up to 5 weeks
Changes in 12-lead electrocardiogram (ECG) QT Interval from baseline
Changes in ECG QT interval from baseline
Measured: Up to 5 weeks
Changes in 12-lead electrocardiogram (ECG) QTcF Interval from baseline
Changes in ECG QTcF interval from baseline
Measured: Up to 5 weeks
Changes in physical examination from baseline: Head
Changes in general appearance of the head from baseline
Measured: Up to 5 weeks
Changes in physical examination from baseline: Ears
Changes in general appearance of the ears from baseline
Measured: Up to 5 weeks
Changes in physical examination from baseline: Eyes
Changes in general appearance of the eyes from baseline
Measured: Up to 5 weeks
Changes in physical examination from baseline: Nose
Changes in general appearance of the nose from baseline
Measured: Up to 5 weeks
Changes in physical examination from baseline: Throat
Changes in general appearance of the throat from baseline
Measured: Up to 5 weeks
Changes in physical examination from baseline: Neck
Changes in general appearance of the neck (including thyroid) from baseline
Measured: Up to 5 weeks
Changes in physical examination from baseline: General Appearance
Changes in general appearance of the skin from baseline
Measured: Up to 5 weeks
Changes in physical examination from baseline: Cardiovascular system
Changes in cardiovascular system from baseline
Measured: Up to 5 weeks
Changes in physical examination from baseline: Respiratory system
Changes in respiratory system from baseline
Measured: Up to 5 weeks
Changes in physical examination from baseline: GI system
Changes in GI system from baseline
Measured: Up to 5 weeks
Changes in physical examination from baseline: Musculoskeletal system
Changes in musculoskeletal system from baseline
Measured: Up to 5 weeks
Changes in physical examination from baseline: Lymph nodes
Changes in lymph nodes from baseline
Measured: Up to 5 weeks
Changes in physical examination from baseline: Nervous system
Changes in nervous system from baseline
Measured: Up to 5 weeks
Secondary outcomes (3)
Concentration-time profile of CDX-7108
Serum concentration-time profile of CDX-7108
Measured: Up to 7 days
Lipase activity
Serum Lipase activity
Measured: Day 1
CO2 excretion rate
CO2 excretion rate (% dose/h),
Measured: Up to 43 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2021
- Study start11 Oct 2021
- Primary completion16 Mar 2023
- Study completion16 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Exocrine Pancreatic InsufficiencyStudies of the same condition, open and under way.
- More trials run by Société des Produits Nestlé (SPN)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Société des Produits Nestlé (SPN)
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Chris Wynne, Principal investigator, New Zealand Clinical ResearchJohn Windsor, Principal investigator, New Zealand Clinical ResearchNam Nguyen, Principal investigator, CMAX Clinical ResearchRichard Stubbs, Principal investigator, P3 Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05082051
- Sponsor's protocol ID
- 21.02.CLI
- Status last verified
- Apr 2023
- First submitted
- 7 Sep 2021
- Last updated
- 20 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 30397535ASGE 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.
PubMed 26077456Saito 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.
PubMed 28099252Imrie 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.
PubMed 21054452Keller 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.
PubMed 15951527Investigator'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.
PubMed 9548629Aygen 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.
PubMed 19439490
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT05082051
- Acronym / sponsor ID
- 21.02.CLI
- Conditions
- Exocrine Pancreatic Insufficiency
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Société des Produits Nestlé (SPN)Industry (pharma, biotech, devices)
- Study start
- 11 Oct 2021 (actual)
- Primary completion
- 16 Mar 2023 (actual)
- Study completion
- 16 Mar 2023 (actual)
- First posted
- 18 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
This is an integrated 3-part study to investigate the safety, tolerability, PK, and PD of CDX-7108. The 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. The study will commence with Part A (single ascending dose [SAD] study) and will progress to Part B (multiple ascending dose [MAD] study), and Part C (POC study)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| CDX-7108 | Active comparator | Drug: Part A, Drug: Part B, Drug: Part CCDX-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 | Placebo comparator | Drug: Part A, Drug: Part B, Drug: Part CExcipients only |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- 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:
- 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:
Key exclusion criteria (29 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Part AAlso: Single Ascending Dose StudyRandomized, 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. | Drug | CDX-7108, Placebo |
| Part BAlso: Multiple Ascending Dose StudyRandomized, 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. | Drug | CDX-7108, Placebo |
| Part CAlso: Proof-of-Concept StudyRandomized, 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. | Drug | CDX-7108, Placebo |
Primary outcome
Adverse events
Time frame: Up to 9 weeks
Number and severity of adverse events
Changes in haematology from baseline
Time frame: Up to 5 weeks
Number of participants with changes in haematology measurements (erythrocyte count, thrombocyte count, haemoglobin, haematocrit, mean cell hemoglobin concertation) using immunoassays.
Changes in coagulation tests from baseline
Time frame: Up to 5 weeks
Number of participants with changes in coagulation factors (INR, prothrombin time, fibrogen, red blood cell indices and leukocyte count) using immunoassays.
Changes in clinical chemistry from baseline
Time frame: Up to 5 weeks
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.
Changes in urinalysis from baseline
Time frame: Up to 5 weeks
Number of participants with changes in leucocyte esterase, protein, urobilinogen, ketones, bilirubin, microscopy, blood, pH, nitrate, specific gravity, urobilinogen and glucose) using immunoassays.
Changes in Systolic Blood Pressure from baseline
Time frame: Up to 5 weeks
Changes in Systolic Blood Pressure from baseline
Changes in Diastolic Blood Pressure from baseline
Time frame: Up to 5 weeks
Changes in Diastolic Blood Pressure from baseline
Changes in Pulse Rate vital signs from baseline
Time frame: Up to 5 weeks
Changes in pulse rate from baseline
Changes in Respiratory Rate vital signs from baseline
Time frame: Up to 5 weeks
Changes in respiratory rate from baseline
Changes in Body Temperature vital signs from baseline
Time frame: Up to 5 weeks
Changes in body temperature from baseline
Changes in 12-lead electrocardiogram (ECG) Heart Rate from baseline
Time frame: Up to 5 weeks
Changes in ECG Heart rate from baseline
Changes in 12-lead electrocardiogram (ECG) PR Interval from baseline
Time frame: Up to 5 weeks
Changes in ECG PR interval from baseline
Changes in 12-lead electrocardiogram (ECG) QRS duration from baseline
Time frame: Up to 5 weeks
Changes in electrocardiogram QRS duration interval from baseline
Changes in 12-lead electrocardiogram (ECG) QT Interval from baseline
Time frame: Up to 5 weeks
Changes in ECG QT interval from baseline
Changes in 12-lead electrocardiogram (ECG) QTcF Interval from baseline
Time frame: Up to 5 weeks
Changes in ECG QTcF interval from baseline
Changes in physical examination from baseline: Head
Time frame: Up to 5 weeks
Changes in general appearance of the head from baseline
Changes in physical examination from baseline: Ears
Time frame: Up to 5 weeks
Changes in general appearance of the ears from baseline
Changes in physical examination from baseline: Eyes
Time frame: Up to 5 weeks
Changes in general appearance of the eyes from baseline
Changes in physical examination from baseline: Nose
Time frame: Up to 5 weeks
Changes in general appearance of the nose from baseline
Changes in physical examination from baseline: Throat
Time frame: Up to 5 weeks
Changes in general appearance of the throat from baseline
Changes in physical examination from baseline: Neck
Time frame: Up to 5 weeks
Changes in general appearance of the neck (including thyroid) from baseline
Changes in physical examination from baseline: General Appearance
Time frame: Up to 5 weeks
Changes in general appearance of the skin from baseline
Changes in physical examination from baseline: Cardiovascular system
Time frame: Up to 5 weeks
Changes in cardiovascular system from baseline
Changes in physical examination from baseline: Respiratory system
Time frame: Up to 5 weeks
Changes in respiratory system from baseline
Changes in physical examination from baseline: GI system
Time frame: Up to 5 weeks
Changes in GI system from baseline
Changes in physical examination from baseline: Musculoskeletal system
Time frame: Up to 5 weeks
Changes in musculoskeletal system from baseline
Changes in physical examination from baseline: Lymph nodes
Time frame: Up to 5 weeks
Changes in lymph nodes from baseline
Changes in physical examination from baseline: Nervous system
Time frame: Up to 5 weeks
Changes in nervous system from baseline
3 secondary outcomes
Concentration-time profile of CDX-7108
Time frame: Up to 7 days
Lipase activity
Time frame: Day 1
CO2 excretion rate
Time frame: Up to 43 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2024.
- BackgroundForsmark 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: PubMed 30397535Shandro 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.
- Background: PubMed 26077456ASGE 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.
- Background: PubMed 28099252Saito 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.
- Background: PubMed 21054452Imrie 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.
- Background: PubMed 15951527Keller 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.
- BackgroundInvestigator's Brochure for CDX-7108. Edition 1.0, Release Date 31 March 2021.
- BackgroundCREON®. The United States Prescribing Information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020725s000lbl.pdf. Accessed on: 23 March 2021.
- BackgroundFood 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.
- BackgroundFood and Drug Administration. Guidance for industry drug-induced liver injury: premarketing clinical evaluation. CDER. 2009.
- Background: PubMed 9548629Loser 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.
- BackgroundAygen S, inventor; Infai Institut fur Biomedizinische Analytik und NMR Imaging GmbH, assignee. Method for measuring pancreatic metabolism. International Patent, WO2004043498. 27 May 2004.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chris Wynne principal investigator
New Zealand Clinical Research
John Windsor principal investigator
New Zealand Clinical Research
Nam Nguyen principal investigator
CMAX Clinical Research
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Part A, Part B and Part C in people with Exocrine Pancreatic Insufficiency, run by Société des Produits Nestlé (SPN) at 4 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 27 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in New Zealand, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse events (time frame: Up to 9 weeks). The study lists 28 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05082051, which also lists 15 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Sep 2024.