NNC4004-0002 for High Uric Acid

Recruiting at 1 trial location

Overseen By Novo Nordisk

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Novo Nordisk A/S

Must not be taking: Uric acid medications

Disqualifiers: Gout, Cardiovascular, Hepatic, others

Compensation: Varies

Number of Visits: 14

Duration: 1 day

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will evaluate an investigational drug called NNC4004-0002. "Investigational" means NNC4004-0002 has not been approved for sale/ for clinical use or for the use described in this study/ by any regulatory authority. Its use in this study is experimental. This will be the first time that NNC4004-0002 will be given to human. This study will be testing the ability of the study medicine to lower serum uric acid. The main aim of this study will be to see if the new study medicine is safe and tolerated by the body after a single dose of study medicine in adults with asymptomatic hyperuricemia. Participants will either get NNC4004-0002 (the study medicine), or saline. Which treatment the participant get will be decided by chance. The participant will get the medicine as an injection under their skin. Depending on the dose they will receive, participant may need more than one injection. The study will last for about 19 months in total. The participant will take part in the study for about 7 months. Participant will have approximately 14 visits to the clinic and one of them will be a 4 night in-house stay.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you have used serum uric acid lowering medication before.

What data supports the effectiveness of the drug NNC4004-0002 for high uric acid?

Research shows that increasing the dose of allopurinol, a drug used to lower uric acid, is effective and safe for patients with gout, even those with kidney issues. This suggests that similar treatments targeting uric acid levels can be effective in managing conditions like high uric acid. ^{1 2 3 4 5}

Research Team

Clinical Transparency (dept. 2834)

Principal Investigator

Novo Nordisk A/S

Eligibility Criteria

This study is for adults with asymptomatic hyperuricemia, which means they have high uric acid levels but no symptoms. Participants should be generally healthy and willing to receive injections under their skin. They'll need to commit to a 7-month study period with around 14 clinic visits, including a 4-night stay.

Inclusion Criteria

Considered to be generally healthy based on 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

Body mass index (BMI) 20 to 35 kilogram per meter square (kg/m2) at screening

Serum uric acid levels ≥ 6.8 miligram per decileter (mg/dL) to ≤ 12 mg/dL on 2 consecutive screening samples (the first at the screening visit [V1], and the second taken at V2 [day -1]; samples at least 7 days apart)

Exclusion Criteria

Screening alanine transaminase (ALT) or aspartate aminotransferase (AST) values > 2× upper limit normal (ULN) or total bilirubin >1.5× ULN

I do not have serious heart, liver, past cancers, or chronic debilitating diseases.

I have or had chronic kidney disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of NNC4004-0002 or placebo injected subcutaneously

1 day

1 visit (in-person), 4-night in-house stay

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 weeks

Approximately 13 visits (in-person)

Treatment Details

Interventions

• NNC4004-0002

Trial Overview The trial is testing NNC4004-0002, an investigational drug not yet approved by the FDA. It's given as an injection and compared against saline (placebo) to see if it can safely lower serum uric acid after just one dose in participants.

Participant Groups

Group I: NNC4004-0002 Experimental Treatment 1 Intervention

Participants will receive a single dose of NNC4004-0002 injected subcutaneously. Trial will include up to 6 ascending single-dose cohorts.

Group II: Placebo Placebo Group 1 Intervention

Participants in each cohort will receive placebo matched to NNC4004-0002 injected subcutaneously.

Who Is Running the Clinical Trial?

Novo Nordisk A/S

Lead Sponsor

Trials

1,578

Recruited

3,813,000+

Lars Fruergaard Jørgensen

Novo Nordisk A/S

Chief Executive Officer since 2017

MSc in Finance and Business Administration, Aarhus School of Business, Aarhus University, Denmark

Martin Holst Lange

Novo Nordisk A/S

Chief Medical Officer since 2021

MD from University of Copenhagen

Findings from Research

In a study of 90 patients with gout, increasing the dose of allopurinol above the standard recommendations resulted in a significant reduction in serum urate levels, with about 89% of patients achieving the target level of <0.36 mmoles/liter after 12 months.

The study found that higher doses of allopurinol did not lead to increased toxicity, even in patients with renal impairment, indicating that dose escalation can be a safe and effective strategy for managing gout.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using allopurinol above the dose based on creatinine clearance is effective and safe in patients with chronic gout, including those with renal impairment. Stamp, LK., O'Donnell, JL., Zhang, M., et al.[2013]

In a study of 292,270 individuals with gout, initiating urate-lowering therapy (ULT) was linked to a higher risk of hospitalizations for gout flares within the first 6 months (adjusted Hazard Ratio of 4.54), but this risk decreased significantly after 12 months.

Achieving a serum urate level of less than 360 micromol/l within the first year of ULT initiation was associated with a 43% reduction in the risk of hospitalizations, highlighting the importance of reaching treatment targets for long-term management of gout.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treat-to-target urate-lowering therapy and hospitalizations for gout: results from a nationwide cohort study in England. Russell, MD., Roddy, E., Rutherford, AI., et al.[2023]

In a study of 102 gout patients, 78% achieved the recommended serum uric acid target of <360 μmol/L, while 65% met the stricter target of <300 μmol/L, indicating effective management of gout with current therapies.

The majority of patients (84%) were treated with allopurinol, suggesting that adherence to uric acid-lowering therapy is high, and a treat-to-target approach may enhance patient outcomes in gout management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence to uric acid treatment guidelines in a rheumatology clinic. Conway, R., Coughlan, RJ., Carey, JJ.[2021]

In a 12-week study of Chinese patients with gout receiving benzbromarone, 60.5% of those classified as renal underexcretors achieved the target serum urate level (<360 μmol/L), compared to only 39.0% of patients in the unclassified group, indicating that hyperuricemia classification can improve treatment outcomes.

Patients in the underexcretion group also showed lower blood glucose and cholesterol levels without a significant difference in the frequency of gout attacks, suggesting that targeting treatment based on hyperuricemia classification may enhance overall health outcomes for gout patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Clinical Typing on Serum Urate Targets of Benzbromarone in Chinese Gout Patients: A Prospective Cohort Study. Xue, X., Yuan, X., Han, L., et al.[2022]

In a study of 230 gout patients, 73% successfully achieved their target serum urate levels with urate lowering therapy, indicating that the treatment is generally effective.

The primary reason for the 27% of patients who did not reach their target was non-adherence to the treatment regimen, highlighting the importance of patient compliance in managing gout effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Achieving serum urate targets in gout: an audit in a gout-oriented rheumatology practice. Corbett, EJM., Pentony, P., McGill, NW.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Using allopurinol above the dose based on creatinine clearance is effective and safe in patients with chronic gout, including those with renal impairment. [2013]

2. England pubmed.ncbi.nlm.nih.gov

Treat-to-target urate-lowering therapy and hospitalizations for gout: results from a nationwide cohort study in England. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

Adherence to uric acid treatment guidelines in a rheumatology clinic. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Effect of Clinical Typing on Serum Urate Targets of Benzbromarone in Chinese Gout Patients: A Prospective Cohort Study. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Achieving serum urate targets in gout: an audit in a gout-oriented rheumatology practice. [2018]