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

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04259801
• Collaborator: (none)
• Enrollment: 152
• Location: 1
• Arms: 4
• Actual Duration (Months): 24.9
• Patients Per Site Per Month: 6.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers; Overweight; Obesity; Diabetes Mellitus, Type 2	Drug: NNC0480-0389; Drug: Semaglutide; Drug: Placebo (NNC0480-0389); Drug: Placebo (semaglutide)	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 152 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Part 1: Single ascending dose Part 2: Multiple ascending dosePart 1: Single ascending dose Part 2: Multiple ascending dose
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Sponsor staff involved in the clinical trial is masked according to company standard procedures.
• Primary Purpose: Treatment
• Official Title: Investigation of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of NNC0480-0389 in Combination With Semaglutide s.c.
• Actual Study Start Date: Feb 17, 2020
• Actual Primary Completion Date: Mar 16, 2022
• Actual Study Completion Date: Mar 16, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: 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.; 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.
Experimental: 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.	Drug: 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.; 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.
Active Comparator: 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	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.; 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.
Placebo Comparator: 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.	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.; 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.

Outcome Measures

Primary Outcome Measures

1. Number of treatment emergent adverse events (TEAE) in Part 1 [From time of dosing (day 1) until completion of follow-up visit (day 71)]

   Number of events

2. Number of treatment emergent adverse events (TEAE) in Part 2 [From first combination dosing (day 57) until completion of follow-up visit (day 148)]

   Number of events

Secondary Outcome Measures

1. Area under the NNC0480-0389 plasma concentration-time curve from time [From baseline (day 1) to post treatment follow-up (day 71)]

   h∙nmol/L

2. Maximum plasma concentration of NNC0480-0389 after administration of a single dose [From baseline (day 1) to post treatment follow-up (day 71)]

   nmol/L

3. Area under the semaglutide plasma concentration time curve from time of dosing to infinity after administration of a single dose [From baseline (day 1) to post treatment follow-up (day 71)]

   h∙nmol/L

4. The maximum concentration of semaglutide after administration of a single dose [From baseline (day 1) to post treatment follow-up (day 71)]

   nmol/L

5. Area under the NNC0480-0389 plasma concentration-time curve from 0 to 168 hours after administration of the 4th dose of NNC0480-0389 in week 12 [From administration of dose in week 12 (day 78) to day 85]

   h∙nmol/L

6. Maximum plasma concentration of NNC0480-0389 after administration of the 4th dose of NNC0480-0389 in week 12 [From administration of dose in week 12 (day 78) to post treatment follow-up (day 148)]

   nmol/L

7. Area under the semaglutide plasma concentration-time curve from 0-168 hours after administration of the 12th dose of semaglutide [From administration of dose in week 12 (day 78) to day 85]

   h∙nmol/L

8. The maximum concentration of semaglutide after administration of the 12th dose of semaglutide [From administration of dose in week 12 (day 78) to post treatment follow-up (day 148)]

   nmol/L

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Groningen		Netherlands	9728 NZ

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

• Study Director: Clinical Reporting Anchor & Disclosure (1452), Novo Nordisk A/S

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT04259801
• Other Study ID Numbers: NN9389-4536; 2019-002857-44; U1111-1236-4114
• First Posted: Feb 6, 2020
• Last Update Posted: Mar 24, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Diabetes Mellitus, Type 2; Overweight

Study Results

No Results Posted as of Mar 24, 2022