A Study to Look at How Safe a New Medicine (NNC0491-6075) is in Healthy People and in Participants With High Levels of Fat in the Blood

Healthy Volunteers Clinical Trial

Official title:

A Phase I, Randomised, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of NNC0491-6075 Following Single Dose Administration to Healthy Participants and Multiple Doses to Participants With Dyslipidaemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05979428
• Other study ID #: NN6491-4973
• Secondary ID: U1111-1285-1575
• Status: Recruiting
• Phase: Phase 1
• Start date: August 7, 2023
• Est. completion date: March 10, 2025

Study information

• Verified date: August 2023
• Source: Novo Nordisk A/S
• Contact: Novo Nordisk
• Phone: (+1) 866-867-7178
• Email: clinicaltrials[@]novonordisk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study is testing a new study medicine to treat people with high levels of fat in the blood. The main aim of the study is to see if the new study medicine is safe and how it works in the body. Participants will either get NNC0491-6075 (the new study medicine) or placebo (a "dummy medicine" without active ingredients). Which treatment participants get is decided by chance. NNC0491-6075 is a new medicine which cannot be prescribed by doctors. The study has 3 parts (Part A, Part B and Part C). In Part A, investigators look at the effect of the study medicine after a single dose in healthy participants. Participants will get the study medicine either as injection(s) under the skin or as an infusion into a vein by the study staff. In Part B, investigators look at the effect of receiving the study medicine once weekly for four weeks in participants with high levels of fat in the blood but who are otherwise healthy. Participants will get the study medicine as injections under the skin by the study staff. In Part C, investigators look at the effect of the study medicine after a single dose in healthy participants of Japanese origin. Participants will get the study medicine either as injection(s) under the skin or as an infusion into a vein by the study staff. The study will last for about 18 months in total for Part A, Part B and Part C. Participants in Part A and Part C will be in the study for about 139 days each, from screening to the final visit while in Part B they will be in the study for about 160 days from screening to the final visit.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 106
• Est. completion date: March 10, 2025
• Est. primary completion date: February 3, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

Part A:

• Men or women of non-childbearing potential

• Aged 18-55 years (both inclusive) at the time of signing informed consent

• Considered to be generally healthy based on the medical history, physical examination, and the results of vital signs, electrocardiogram and clinical laboratory tests (presence of dyslipidaemia [example hypertriglyceridemia] is allowed) performed during the screening visit, as judged by the investigator

• Body mass index (BMI) between 18.5 and 34.9 kilograms per square meter (kg/m^2) (both inclusive) at screening

• Non-Japanese defined as not meeting inclusion criteria for Part C

Part B:

• Men or women of non-childbearing potential

• Aged 18-64 years (both inclusive) at the time of signing informed consent

• Dyslipidaemia at screening defined as all the below: Fasting serum triglycerides (TGs) greater than or equal to 150 milligrams per deciliter (mg/dL) and less than or equal to 500 mg/dL. Participants must have two measurements performed for eligibility. Both measurements must be greater than or equal to 135 mg/dL and at least one must be greater than or equal to 150 mg/dL. One of the measurements may be based on medical records or pre-screening results if the test is no more than 90 days old. If TGs are measured twice during the screening period, the tests must be performed with at least 4 days apart. TGs measured in the screening period must be after a 10 hour fast

• Fasting low-density lipoprotein cholesterol (LDL-C) greater than or equal to 50 mg/dL and less than 190 mg/dL

• Considered to be generally healthy based on the medical history, physical examination, and the results of vital signs, electrocardiogram and clinical laboratory tests performed during the screening visit, as judged by the investigator

• BMI between 18.5 and 34.9 kg/m^2 (both inclusive) at screening

• If on statin therapy the dose must have been stable for at least 8 weeks before screening and must be intended to remain stable throughout the study

Part C:

• Men or women of non-childbearing potential

• Aged 18-55 years (both inclusive) at the time of signing informed consent

• Considered to be generally healthy based on the medical history, physical examination, and the results of vital signs, electrocardiogram and clinical laboratory tests (presence of dyslipidaemia [example, hypertriglyceridemia] is allowed) performed during the screening visit, as judged by the investigator

• BMI between 18.5 and 34.9 kg/m^2 (both inclusive) at screening

• Japanese defined as both biological parents of Japanese descent

Exclusion Criteria:

Part A,B and C:

• Known or suspected hypersensitivity to study intervention(s) or related products

• Any disorder, which in the investigator's opinion might jeopardise participant's safety or compliance with the protocol

• Use of prescription or non-prescription medicinal products within 14 days before screening. Exceptions are: Topical medications; occasional use of over-the-counter acetaminophen or Non-steroidal anti-inflammatory drugs (NSAIDs) at their labelled doses for mild pain; and statin therapy in Part B only if the dose has been stable for at least 8 weeks prior to screening and is intended to remain stable throughout the trial

• Any laboratory safety parameters at screening outside the below laboratory ranges, see designated reference range documents for specific values: Alanine aminotransferase greater than upper limit of normal (ULN) +50 percentage (%), Aspartate aminotransferase greater than ULN +50%, Total Bilirubin greater than ULN +20%, Creatine kinase greater than ULN +50%.

Related Conditions & MeSH terms

• Dyslipidaemia
• Dyslipidemias
• Healthy Volunteers

Intervention

Drug:
• NNC0491-6075
NNC0491-6075 will be administered as a subcutaneous injection in a skinfold in the abdomen or intravenously into a vein in the wrist, elbow, or the back of the hand.
• Placebo
Placebo matched to NNC0491-6075 will be administered as a subcutaneous injection in a skinfold in the abdomen or intravenously into a vein in the wrist, elbow, or the back of the hand.

Locations

Country	Name	City	State
United States	Novo Nordisk Investigational Site	Cypress	California

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A (SAD): Number of treatment emergent adverse events (TEAEs)	Measured as count of events. An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. A TEAE is defined as an AE that either has onset time after first trial product administration and no later than the end of study visit or Is present before first trial product administration and increases in severity during the treatment period and no later than the end of study visit.	From pre-dose (Day 1) to end of study (Day 110)
Primary	Part B (MAD): Number of treatment emergent adverse events (TEAEs)	Measured as count of events. An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. A TEAE is defined as an AE that either has onset time after first trial product administration and no later than the end of study visit or Is present before first trial product administration and increases in severity during the treatment period and no later than the end of study visit.	From pre-dose (Day 1) to end of study (Day 131)
Primary	Part C (SAD): Number of treatment emergent adverse events (TEAEs)	Measured as count of events. An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. A TEAE is defined as an AE that either has onset time after first trial product administration and no later than the end of study visit or Is present before first trial product administration and increases in severity during the treatment period and no later than the end of study visit.	From pre-dose (Day 1) to end of study (Day 110)
Secondary	Part A (SAD): AUC0-8, SD; the area under the NNC0491-6075 serum concentration-time curve from 0 to infinity after a single dose	Measured as hours*nanomoles per liter (h*nmol/L)	From pre-dose (Day 1) to end of study (Day 110)
Secondary	Part A (SAD): Cmax, SD; the maximum serum concentration of NNC0491-6075 after a single dose	Measured as nanomoles per liter (nmol/L)	From pre-dose (Day 1) to end of study (Day 110)
Secondary	Part A (SAD): t½, SD; the terminal half-life of NNC0491-6075 after a single dose	Measured as hours (h)	From pre-dose (Day 1) to end of study (Day 110)
Secondary	Part A (SAD): tmax, SD; The time to maximum concentration of NNC0491-6075 after a single-dose (only from subcutaneous administration)	Measured as hours	From pre-dose (Day 1) to end of study (Day 110)
Secondary	Part B (MAD): AUC0-168h, MD; the area under the NNC0491-6075 serum concentration-time curve from time 0 to 168 hours after last dose	Measured as h*nmol/L	From pre-dose (Day 22) to 168 hours after last dose (Day 29)
Secondary	Part B (MAD): Cmax, MD; the maximum serum concentration of NNC0491-6075 after last dose	Measured as nmol/L	From pre-dose (Day 22) to end of study (Day 131)
Secondary	Part B (MAD): t½, MD; the terminal half-life of NNC0491-6075 after last dose	Measured as hours	From pre-dose (Day 22) to end of study (Day 131)
Secondary	Part B (MAD): tmax, MD; The time to maximum concentration of NNC0491-6075 after last dose	Measured as hours	From pre-dose (Day 22) to end of study (Day 131)
Secondary	Part C (SAD): AUC0-8, SD; the area under the NNC0491-6075 serum concentration-time curve from 0 to infinity after a single dose	Measured as h*nmol/L	From pre-dose (Day 1) to end of study (Day 110)
Secondary	Part C (SAD): Cmax, SD; the maximum serum concentration of NNC0491-6075 after a single dose	Measured as nmol/L	From pre-dose (Day 1) to end of study (Day 110)
Secondary	Part C (SAD): t½, SD; the terminal half-life of NNC0491-6075 after a single dose	Measured as hours	From pre-dose (Day 1) to end of study (Day 110)
Secondary	Part C (SAD): tmax, SD; The time to maximum concentration of NNC0491-6075 after a single-dose (only from subcutaneous administration)	Measured as hours	From pre-dose (Day 1) to end of study (Day 110)