First Research Study to Look at How Two Medicines, NNC0480-0389 and Semaglutide, Work Together in Healthy People, in People With High Body Weight and in People With Diabetes

NCT ID: NCT04259801

Last Updated: 2023-11-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 152 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-17
• Study Completion Date: 2022-03-16

Brief Summary

The purpose of this study is to investigate how safe, and how well tolerated, the new study drug NNC0480-0389 is when it is given together with semaglutide. This will be investigated in healthy participants, participants with high bodyweight and participants with type 2 diabetes (T2D). NNC0480-0389 has not been given to humans before. It has been previously tested in the laboratory and on animals. NNC0480-0389 will be tested at various dose levels. Semaglutide is a new approved drug and is already available on the market for treatment of diabetes. It will also be investigated how quickly and to what extent NNC0480-0389 and semaglutide are taken up and eliminated from the body. This is called pharmacokinetics. The effect of NNC0480-0389 given together with semaglutide will also be investigated on body weight and glucose levels in the blood. This is called pharmacodynamics. The effects of NNC0480-0389 and/or semaglutide will be compared to the effects of a placebo. A placebo is a "dummy" medicine without any active medicine. Placebo looks like NNC0480-0389 and/or semaglutide. There are 4 possibilities for which treatment participants will get; participants will receive NNC0480-0389 and semaglutide or NNC0480-0389 and placebo or placebo with semaglutide, or placebo with placebo. Participants and the responsible doctor will not know which combination participants will be given. This is called a double-blinded study. However, this information can be looked up during the study if it is important for participants' health. The study medicines will be given as injections under the skin. Participants will be in the study for about 25 weeks.

Conditions

Healthy Volunteers; Overweight; Obesity; Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

NNC0480-0389 and semaglutide

Part 1: 6 subjects will receive a single subcutaneous (s.c., under the skin) dose of NNC0480-0389 co-administered with s.c. semaglutide.

Part 2: 12 subjects will receive 4 doses of s.c. NNC0480-0389 co-administered with s.c. semaglutide, after 8 weeks of dosing with s.c semaglutide.

Group Type: EXPERIMENTAL

NNC0480-0389

Intervention Type: DRUG

Part 1: A single dose of NNC0480-0389, dose increased in each cohort. Part 2: Weekly doses (for 4 weeks) of NNC0480-0389, dose increased in each cohort.

Semaglutide

Intervention Type: DRUG

Part 1: Single dose of semaglutide (0.5 mg). Part 2: Weekly doses of semaglutide alone for 8 weeks (2 x 0.25 mg, 2 x 0.5 mg and 4 x 1 mg) followed by weekly fixed doses of 1 mg semaglutide for 4 weeks.

NNC0480-0389 and placebo (semaglutide)

Part 1: 4 subjects will receive a single dose of s.c. NNC0480-0389 co-administered with semaglutide placebo.

Part 2: 4 subjects will receive 4 doses of s.c. NNC0480-0389, co-administered with semaglutide placebo after 8 weeks of dosing with semaglutide placebo.

Group Type: EXPERIMENTAL

NNC0480-0389

Intervention Type: DRUG

Part 1: A single dose of NNC0480-0389, dose increased in each cohort. Part 2: Weekly doses (for 4 weeks) of NNC0480-0389, dose increased in each cohort.

Placebo (NNC0480-0389)

Intervention Type: DRUG

Placebo for NNC0480-0389. Part 1: A single dose of placebo (NNC0480-0389), dose increased in each cohort. Part 2: Weekly doses (for 4 weeks) of placebo A, dose increased in each cohort.

Placebo (NNC0480-0389) with semaglutide

Part 1: 2 subjects will receive a single dose of placebo (NNC0480-0389), co-administered with s.c. semaglutide.

Part 2: 4 subjects will receive 4 doses of placebo (NNC0480-0389), co-administered with s.c. semaglutide, after 8 weeks of dosing with s.c. semaglutide

Group Type: ACTIVE_COMPARATOR

Semaglutide

Intervention Type: DRUG

Part 1: Single dose of semaglutide (0.5 mg). Part 2: Weekly doses of semaglutide alone for 8 weeks (2 x 0.25 mg, 2 x 0.5 mg and 4 x 1 mg) followed by weekly fixed doses of 1 mg semaglutide for 4 weeks.

Placebo (semaglutide)

Intervention Type: DRUG

Part 1: Single dose of placebo (semaglutide) (0.5 mg). Part 2: Weekly doses of placebo (semaglutide) alone for 8 weeks (2 x 0.25 mg, 2 x 0.5 mg and 4 x 1 mg) followed by weekly fixed doses of 1 mg semaglutide for 4 weeks.

Placebo (NNC0480-0389) with placebo (semaglutide)

Part 1: 3 subjects will receive a single dose of placebo (NNC0480-0389), co-administered with semaglutide placebo.

Part 2: 2 subjects will receive 4 doses of placebo (NNC0480-0389), co-administered with semaglutide placebo, after 8 weeks of dosing with semaglutide placebo.

Group Type: PLACEBO_COMPARATOR

Placebo (NNC0480-0389)

Intervention Type: DRUG

Placebo for NNC0480-0389. Part 1: A single dose of placebo (NNC0480-0389), dose increased in each cohort. Part 2: Weekly doses (for 4 weeks) of placebo A, dose increased in each cohort.

Placebo (semaglutide)

Intervention Type: DRUG

Part 1: Single dose of placebo (semaglutide) (0.5 mg). Part 2: Weekly doses of placebo (semaglutide) alone for 8 weeks (2 x 0.25 mg, 2 x 0.5 mg and 4 x 1 mg) followed by weekly fixed doses of 1 mg semaglutide for 4 weeks.

Interventions

NNC0480-0389

Part 1: A single dose of NNC0480-0389, dose increased in each cohort. Part 2: Weekly doses (for 4 weeks) of NNC0480-0389, dose increased in each cohort.

Intervention Type: DRUG

Semaglutide

Part 1: Single dose of semaglutide (0.5 mg). Part 2: Weekly doses of semaglutide alone for 8 weeks (2 x 0.25 mg, 2 x 0.5 mg and 4 x 1 mg) followed by weekly fixed doses of 1 mg semaglutide for 4 weeks.

Intervention Type: DRUG

Placebo (NNC0480-0389)

Placebo for NNC0480-0389. Part 1: A single dose of placebo (NNC0480-0389), dose increased in each cohort. Part 2: Weekly doses (for 4 weeks) of placebo A, dose increased in each cohort.

Intervention Type: DRUG

Placebo (semaglutide)

Part 1: Single dose of placebo (semaglutide) (0.5 mg). Part 2: Weekly doses of placebo (semaglutide) alone for 8 weeks (2 x 0.25 mg, 2 x 0.5 mg and 4 x 1 mg) followed by weekly fixed doses of 1 mg semaglutide for 4 weeks.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Part 1:

• Male aged 18-45 years (both inclusive) at the time of signing informed consent.
• Body mass index between 20.0 kg/m^2 and 29.9 kg/m^2 (both inclusive).
• 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.

Part 2 (not applicable for proof-of-concept (PoC) cohort):

• Body mass index between 20.0 kg/m^2 and 39.9 kg/m^2 (both inclusive).
• Female of non-childbearing potential or male aged 18-55 years (both inclusive) at the time of signing informed consent.
• Considered to be eligible 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.

Part 2 (only applicable for PoC cohort):

• Body mass index between 25.0 kg/m^2 and 39.9 kg/m^2 (both inclusive). Overweight or obesity should be due to excess adipose tissue, as judged by the investigator.
• Female of non-childbearing potential or male aged 18-64 years (both inclusive) at the time of signing informed consent.
• Considered to be eligible 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.
• Diagnosed with type 2 diabetes at least 90 days prior to the day of screening.
• Subjects treated with diet and exercise as monotherapy or in combination with 1-2 of the following anti-diabetic drug(s) at a stable dose for at least 30 days prior to screening: metformin, sulfonylureas, meglitinides, DPP-4 inhibitors, alpha-glucosidase inhibitors, thiazolidinediones, GLP-1 receptor agonists or SLGT-2 inhibitors. The metformin dose should be between 1500 mg to 3000 mg or maximum tolerated or effective dose documented in subject's medical record.
• Glycosylated haemoglobin (HbA1c) in the range of 6.5% (inclusive) and 10% (non-inclusive).

Exclusion Criteria

Part 1:

• Any disorder which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol.
• HbA1c equal to or above 6.5 % (48 mmol/mol) at screening.
• Use of prescription medicinal products or non-prescription drugs, except routine vitamins, occasional use of acetaminophen, ibuprofen and acetylsalicylic acid, or topical medication not reaching systemic circulation within 14 days prior to the day of screening. Presence or history of any clinically relevant respiratory, metabolic, renal, hepatic, cardiovascular, gastrointestinal, or endocrinological conditions.

Part 2 (not applicable for PoC cohort):

• Any disorder (except for conditions associated with T2D for the PoC cohort) which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol.
• Presence or history of any clinically relevant respiratory, metabolic, renal, hepatic, cardiovascular, gastrointestinal, or endocrinological conditions (except conditions associated with T2D for PoC Cohort).
• Use of prescription medicinal products or non-prescription drugs, except routine vitamins, occasional use of acetaminophen, ibuprofen and acetylsalicylic acid, or topical medication not reaching systemic circulation within 14 days prior to the day of screening.
• HbA1c equal to or above 6.5 % (48 mmol/mol) at screening.

Part 2 (only applicable for PoC cohort):

• Any disorder (except for conditions associated with T2D for the PoC cohort) which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol.
• Presence or history of any clinically relevant respiratory, metabolic, renal, hepatic, gastrointestinal, or endocrinological conditions (except conditions associated with T2D for PoC Cohort).
• Use of any prohibited medications as listed in the protocol within 14 days of screening.
• Use of prescribed medications at the time of screening at a dose that had not been stable within 30 days prior to screening.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Novo Nordisk A/S

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Reporting Anchor & Disclosure (1452)

Role: STUDY_DIRECTOR

Novo Nordisk A/S

Locations

Novo Nordisk Investigational Site

Groningen, , Netherlands

Countries

Netherlands

Other Identifiers

2019-002857-44

Identifier Type: REGISTRY

Identifier Source: secondary_id

U1111-1236-4114

Identifier Type: OTHER

Identifier Source: secondary_id

NN9389-4536

Identifier Type: -

Identifier Source: org_study_id