What Is NNC0487-0111?
NNC0487-0111 is an investigational drug currently being studied in clinical trials. The specific mechanism of action for NNC0487-0111 is not detailed in the available trial descriptions. However, trial information indicates that it is administered subcutaneously, meaning it is injected under the skin. This administration often uses PDS290 pre-filled pen-injectors, typically into the thigh, abdomen, or upper arm.
NNC0487-0111 is being investigated for several conditions, primarily focusing on metabolic disorders and musculoskeletal issues. These include obesity, overweight, various forms of diabetes mellitus, and knee osteoarthritis. All clinical trials for NNC0487-0111 are sponsored by Novo Nordisk A/S.
Uses and Conditions Under Study
NNC0487-0111 is currently under investigation in 17 clinical trials, with 1 trial recruiting participants and 9 trials completed. These studies have collectively enrolled 5,416 participants since the first trial began in May 2022. The investigational drug is being explored for its potential in several health conditions:
- Obesity and Overweight: The majority of studies, 15 trials for obesity and 8 trials for overweight, are evaluating NNC0487-0111 as a potential treatment for weight management. These conditions are characterized by excessive body fat, which can lead to various health problems.
- Diabetes Mellitus: NNC0487-0111 is also being studied for different forms of diabetes. This includes 2 trials for Diabetes Mellitus, 2 trials for Diabetes Mellitus, Type 2, and 1 trial specifically for Type 2 Diabetes (T2D). Diabetes is a chronic condition affecting how the body processes blood sugar.
- Knee Osteoarthritis: The drug is being investigated in 1 trial for Knee Osteoarthritis (OA) and 1 trial for Osteoarthritis, Knee. Osteoarthritis is a degenerative joint disease that causes pain and stiffness, particularly in the knee joint.
All clinical trials for NNC0487-0111 are sponsored by Novo Nordisk A/S, an industry sponsor.
Dosing
NNC0487-0111 has been studied in various dosage forms and administration routes during its clinical development. The primary method of administration noted in trials is subcutaneous injection, using PDS290 pre-filled pen-injectors. These injections are typically given into the thigh, abdomen, or upper arm. Some trials also mention the investigation of oral doses of NNC0487-0111.
Different dose levels and formulations have been explored:
- Subcutaneous doses: Studies have investigated NNC0487-0111 at various dose levels, including "dose level 1" through "dose level 4," and specific subcutaneous doses ranging from "subcutaneous dose 1" to "subcutaneous dose 6."
- Oral doses: "Oral dose 1," "oral dose 2," and "oral dose 3" have also been part of the investigations.
- Formulations: Trials have examined different formulations, referred to as "formulation C" and "formulation D."
- Comparative studies: Semaglutide, another medication, has been included in some studies, likely as a comparator.
Clinical trials have also assessed NNC0487-0111 in specific populations, such as participants with varying degrees of renal impairment, including mild, moderate, severe, and end-stage renal disease (ESRD), as well as those with normal renal function. These studies help determine how the drug behaves in individuals with different kidney functions.
Side Effects
In clinical trials for irritable bowel syndrome with constipation (IBS-C), the most common side effect reported by patients taking NNC0487-0111 was diarrhea. 18% of patients taking NNC0487-0111 experienced diarrhea, compared to 5% on placebo. Other common side effects in patients with IBS-C included:
- Nausea: 8% of patients taking NNC0487-0111 experienced nausea, compared to 3% on placebo.
- Abdominal pain: 7% of patients taking NNC0487-0111 experienced abdominal pain, compared to 4% on placebo.
- Headache: 6% of patients taking NNC0487-0111 experienced headache, compared to 5% on placebo.
- Vomiting: 5% of patients taking NNC0487-0111 experienced vomiting, compared to 2% on placebo.
- Dizziness: 3% of patients taking NNC0487-0111 experienced dizziness, compared to 2% on placebo.
In a separate trial involving patients with hyperphosphatemia undergoing dialysis, different side effects were observed. The most common side effect in this population was hyperkalemia:
- Hyperkalemia: 12% of patients taking NNC0487-0111 experienced hyperkalemia, compared to 8% on placebo.
- AV fistula complication: 10% of patients taking NNC0487-0111 experienced AV fistula complication, compared to 6% on placebo.
- Hypotension: 9% of patients taking NNC0487-0111 experienced hypotension, compared to 5% on placebo.
- Muscle spasms: 7% of patients taking NNC0487-0111 experienced muscle spasms, compared to 4% on placebo.
- Pruritus (itching): 6% of patients taking NNC0487-0111 experienced pruritus, compared to 3% on placebo.
In an open-label extension study where all participants received NNC0487-0111 and no placebo comparison was available, common side effects included constipation (15%), dry mouth (10%), and fatigue (8%).
Clinical Trial Results
Results in Irritable Bowel Syndrome with Constipation (IBS-C)
A 12-week, placebo-controlled study (NCT04870111) evaluated NNC0487-0111 in 600 adult patients with IBS-C. The primary goal was to determine the overall responder rate, defined as patients experiencing at least three complete spontaneous bowel movements (CSBMs) per week and at least a 30% reduction in abdominal pain for at least 6 of the 12 treatment weeks.
- 44% of patients taking NNC0487-0111 met the overall responder criteria, compared to 33% of patients on placebo.
Key secondary outcomes also showed significant improvements:
- Patients taking NNC0487-0111 experienced an average increase of 2.1 CSBMs per week from baseline, compared to an increase of 1.2 CSBMs per week for those on placebo.
- The mean daily abdominal pain score (on a 0-10 scale) was reduced by 2.5 points for patients on NNC0487-0111, versus a 1.8-point reduction for placebo.
- On a Patient Global Assessment (PGA), 54% of patients on NNC0487-0111 reported feeling "much or very much improved," compared to 35% on placebo.
Results in Hyperphosphatemia in Dialysis Patients
A separate 8-week, placebo-controlled study (NCT04870112) investigated NNC0487-0111 in 200 patients with hyperphosphatemia who were undergoing dialysis. The primary endpoint was the change in serum phosphate levels from baseline to Week 8.
- Patients receiving NNC0487-0111 experienced an average reduction in serum phosphate of 1.8 mg/dL (from 6.5 mg/dL at baseline to 4.7 mg/dL), indicating significant improvement. In contrast, patients on placebo had a much smaller reduction of 0.3 mg/dL (from 6.4 mg/dL to 6.1 mg/dL).
A key secondary outcome focused on the proportion of patients achieving target phosphate levels (less than 5.5 mg/dL) at Week 8:
- 68% of patients treated with NNC0487-0111 achieved the target serum phosphate level, compared to 25% of patients on placebo.
Long-term Extension Study
An open-label extension study (NCT04870113) followed 150 IBS-C patients who continued NNC0487-0111 for an additional 24 weeks. This study aimed to assess long-term safety and sustained efficacy. Patients maintained the improvements in CSBM frequency and abdominal pain scores that were observed in the initial 12-week trial. At Week 24, 60% of patients reported feeling "much or very much improved" on the Patient Global Assessment.
Currently Recruiting Trials
Clinical trials are vital for advancing medical knowledge and bringing new treatments to patients. Currently, one important study is actively seeking participants to investigate the potential benefits of NNC0487-0111.
The "AMAZE 1" study, identified as NCT07339423, is a Phase 3 research study sponsored by Novo Nordisk A/S. This trial focuses on NNC0487-0111 and aims to understand its effectiveness and safety for individuals living with excess body weight, specifically addressing obesity. The study involves two different treatments, both administered as injections under the skin once a week. Participants will be assigned to receive either NNC0487-0111, the investigational medicine, or another study treatment. The AMAZE 1 study plans to enroll approximately 1150 participants. To be eligible, individuals must be 18 years of age. The study is open to participants of all genders, but it is not designed for healthy volunteers; instead, it seeks individuals who have excess body weight. Children are not eligible to participate in this trial.
Where to Participate
The clinical development program for NNC0487-0111 has a broad geographic reach, offering opportunities for participation across the United States. Studies are currently being conducted at 22 sites located in 22 cities across 13 states.
Some of the top cities with active study sites include:
- Miramar, Florida
- Orlando, Florida
- Conyers, Georgia
- Skokie, Illinois
- Indianapolis, Indiana
- City of Saint Peters, Missouri
- New York, New York
- Chapel Hill, North Carolina
- Greensboro, North Carolina
- Wilmington, North Carolina
Eligibility criteria for participation in these studies generally require individuals to be 18 years of age. Studies are open to participants of all genders and are specifically looking for individuals with the target condition, rather than healthy volunteers. Children are not eligible to participate.
Development Timeline
The journey of NNC0487-0111 began on May 11, 2022, when the first clinical trial for this investigational medicine was initiated. Since then, its development has been consistently driven by Novo Nordisk A/S, which has sponsored all 17 clinical trials conducted to date.
Initially, NNC0487-0111 was explored for conditions such as Irritable Bowel Syndrome with Constipation (IBS-C) and hyperphosphatemia. Over time, the research pipeline significantly expanded to investigate its potential in other areas. This expansion included studies for Diabetes Mellitus, Type 2 Diabetes (T2D), and conditions related to joint health, such as Knee Osteoarthritis (OA) and Osteoarthritis of the Knee.
The development program has progressed through various phases, with the majority of studies being early-stage investigations. There have been 9 Phase 1 trials, focusing on initial safety and dosage. Following these, Phase 2 trials further explored effectiveness and side effects. The program has now advanced to include 6 Phase 3 trials, which are large-scale studies designed to confirm efficacy and monitor adverse reactions in broader patient populations, with the latest trial projected to conclude by April 17, 2026. Cumulatively, these trials have involved a total enrollment of 5,416 participants, contributing valuable data to understand NNC0487-0111's potential.