Clinical trial NCT05979428: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Dyslipidaemia
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2023-08-07
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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%.

Primary outcomes:
measure: Part A (SAD): Number of treatment emergent adverse events (TEAEs)
timeFrame: From pre-dose (Day 1) to end of study (Day 110)
measure: Part B (MAD): Number of treatment emergent adverse events (TEAEs)
timeFrame: From pre-dose (Day 1) to end of study (Day 131)
measure: Part C (SAD): Number of treatment emergent adverse events (TEAEs)
timeFrame: From pre-dose (Day 1) to end of study (Day 110)
Secondary outcomes:
measure: Part A (SAD): AUC0-∞, SD; the area under the NNC0491-6075 serum concentration-time curve from 0 to infinity after a single dose
timeFrame: From pre-dose (Day 1) to end of study (Day 110)
measure: Part A (SAD): Cmax, SD; the maximum serum concentration of NNC0491-6075 after a single dose
timeFrame: From pre-dose (Day 1) to end of study (Day 110)
measure: Part A (SAD): t½, SD; the terminal half-life of NNC0491-6075 after a single dose
timeFrame: From pre-dose (Day 1) to end of study (Day 110)
measure: Part A (SAD): tmax, SD; The time to maximum concentration of NNC0491-6075 after a single-dose (only from subcutaneous administration)
timeFrame: From pre-dose (Day 1) to end of study (Day 110)
measure: 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
timeFrame: From pre-dose (Day 22) to 168 hours after last dose (Day 29)
measure: Part B (MAD): Cmax, MD; the maximum serum concentration of NNC0491-6075 after last dose
timeFrame: From pre-dose (Day 22) to end of study (Day 131)
measure: Part B (MAD): t½, MD; the terminal half-life of NNC0491-6075 after last dose
timeFrame: From pre-dose (Day 22) to end of study (Day 131)
measure: Part B (MAD): tmax, MD; The time to maximum concentration of NNC0491-6075 after last dose
timeFrame: From pre-dose (Day 22) to end of study (Day 131)
measure: Part C (SAD): AUC0-∞, SD; the area under the NNC0491-6075 serum concentration-time curve from 0 to infinity after a single dose
timeFrame: From pre-dose (Day 1) to end of study (Day 110)
measure: Part C (SAD): Cmax, SD; the maximum serum concentration of NNC0491-6075 after a single dose
timeFrame: From pre-dose (Day 1) to end of study (Day 110)
measure: Part C (SAD): t½, SD; the terminal half-life of NNC0491-6075 after a single dose
timeFrame: From pre-dose (Day 1) to end of study (Day 110)
measure: Part C (SAD): tmax, SD; The time to maximum concentration of NNC0491-6075 after a single-dose (only from subcutaneous administration)
timeFrame: From pre-dose (Day 1) to end of study (Day 110)
Other outcomes:
Locations:
city: Cypress
country: United States
facility: Altasciences Clinical LA, Inc.
state: California
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency dept. 2834
role: STUDY_DIRECTOR
References: