CagriSema for Chronic Kidney Disease and Type 2 Diabetes in Obesity

Recruiting in Palo Alto (17 mi)

+209 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Novo Nordisk A/S

Must be taking: Ace inhibitors, Arbs

Must not be taking: Glp-1ra, Amylin analogues

Disqualifiers: Pregnancy, Hereditary kidney diseases, Dialysis, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing a new medicine called CagriSema to see if it can reduce kidney damage in people with chronic kidney disease, type 2 diabetes, and who are overweight or obese. The study will compare CagriSema to two other medicines.

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 must be on a stable dose of an ACE inhibitor or ARB for at least 30 days before screening. You cannot have used certain diabetes medications like GLP-1 receptor agonists within 60 days before screening.

Is CagriSema safe for humans?

Semaglutide, a component of CagriSema, has been shown to be safe and well-tolerated in people with type 2 diabetes and chronic kidney disease. It has a good safety profile, with benefits like weight loss and reduced cardiovascular risks, and is generally well-tolerated with a low risk of low blood sugar (hypoglycemia). ^{1 2 3 4 5}

What makes the drug CagriSema unique for treating chronic kidney disease and type 2 diabetes in obesity?

CagriSema combines semaglutide, a glucagon-like peptide-1 receptor agonist, with cagrilintide, potentially enhancing weight loss and glycemic control while also offering cardiovascular and renal protection. This combination may provide a novel approach for patients with chronic kidney disease and type 2 diabetes, especially those who are obese, by addressing multiple aspects of the disease with a single treatment. ^{1 3 6 7 8}

Research Team

Clinical Transparency (dept. 2834)

Principal Investigator

Novo Nordisk A/S

Eligibility Criteria

Adults over 18 with chronic kidney disease, type 2 diabetes, and a BMI of at least 27 can join this study. They must have some kidney function left (eGFR ≥15 to <90), not be on dialysis, and have been treated with specific blood pressure meds for at least a month. Pregnant women or those planning pregnancy are excluded.

Inclusion Criteria

You have a high level of albumin in your urine, as tested by the central laboratory at the start of the study.

I am 18 years old or older.

I was diagnosed with type 2 diabetes more than 6 months ago.

Exclusion Criteria

I haven't used GLP-1 receptor agonists or amylin analogues in the last 60 days.

I have a genetic or autoimmune kidney disease, like polycystic kidney disease or glomerulonephritis.

I have been on dialysis in the last 90 days.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants undergo a dose escalation period to reach the target dose of study medication

16 weeks

Maintenance Treatment

Participants receive the assigned study medication or placebo once weekly

10 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

Treatment Details

Interventions

• Cagrilintide (Other)
• CagriSema (Other)
• Placebo (Other)
• Semaglutide (Other)

Trial Overview The trial is testing CagriSema against Semaglutide, Cagrilintide, and placebo in reducing kidney damage for people with CKD and T2D who are overweight. Treatments are assigned randomly like flipping a coin, and neither participants nor doctors know which one they get.

Participant Groups

Group I: Semaglutide Experimental Treatment 2 Interventions

Participants will receive semaglutide and placebo matched to cagrilintide subcutaneously once-weekly after a dose escalation period of 16 weeks during the maintenance period for 10 weeks.

Group II: Cagrilintide Experimental Treatment 2 Interventions

Participants will receive cagrilintide and placebo matching to semaglutide subcutaneously once-weekly after a dose escalation period of 16 weeks during the maintenance period for 10 weeks.

Group III: CagriSema Experimental Treatment 2 Interventions

Participants will receive cagrilintide and semaglutide subcutaneously once-weekly after a dose escalation period of 16 weeks during the maintenance period for 10 weeks.

Group IV: Placebo Placebo Group 1 Intervention

Participants will receive placebo matched to cagrilintide and placebo matched to semaglutide subcutaneously once weekly for 26 weeks.

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

Sodium-glucose cotransporter type 2 (SGLT2) inhibitors provide cardiovascular and renal protection for patients with diabetic kidney disease, but there is still a high residual risk and limited effectiveness in moderate to severe chronic kidney disease (CKD).

Oral semaglutide, a GLP-1 receptor agonist, offers a promising alternative with potent antihyperglycemic effects, low risk of hypoglycemia, and cardiovascular and renal benefits, potentially improving early treatment options for patients with type 2 diabetes and diabetic kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucagon-like peptide 1(GLP-1) receptor agonists in the management of the patient with type 2diabetes mellitus and chronic kidney disease: an approach for the nephrologist. Cases, A.[2023]

Oral semaglutide (Rybelsus®), a GLP-1 receptor agonist, not only helps lower blood sugar levels in people with type 2 diabetes but also promotes significant weight loss and has a lower risk of causing hypoglycemia.

Clinical studies indicate that GLP-1 receptor agonists are safe for individuals with type 2 diabetes and chronic kidney disease, and they may offer additional benefits such as protecting kidney function and reducing the risk of major cardiovascular events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Peptide in a Pill - Oral Semaglutide in the Management of Type 2 Diabetes. Selvarajan, R., Subramanian, R.[2023]

Subcutaneous semaglutide (Ozempic®), a GLP-1 receptor agonist, has shown significant efficacy in improving glycemic control and reducing HbA1c, albuminuria, and blood pressure in patients with advanced diabetic kidney disease (DKD) during a 6-month follow-up study involving patients on maintenance hemodialysis.

The treatment not only aids in weight loss and appetite suppression but also helps preserve residual kidney function, potentially improving patient outcomes and facilitating their inclusion on kidney transplant waiting lists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Semaglutide, a Glucagon-Like Peptide-1 Receptor Agonist in Real-Life: A Case Series of Patients in Maintenance Incremental Hemodialysis. De la Flor, JC., Lorenzo, JD., Marschall, A., et al.[2022]

Oral semaglutide (Rybelsus®) has been shown to provide better glycaemic control and promote weight loss in patients with type 2 diabetes (T2DM) compared to standard oral glucose-lowering medications, based on data from the PIONEER clinical trial program involving 9543 patients.

The safety profile of oral semaglutide is similar to other GLP-1 receptor agonists, and it demonstrated cardiovascular safety comparable to placebo in high-risk patients, making it a viable option for T2DM management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Oral semaglutide, first oral GLP-1 receptor agonist (Rybelsus®)]. Paquot, N.[2022]

In a study involving 486 type 2 diabetes patients, semaglutide was found to be effective in improving glycemic control and achieving weight loss, with no significant differences in efficacy between patients with chronic kidney disease (CKD) and those without.

The treatment was safe for all patients, and CKD severity did not notably affect the treatment response, suggesting that semaglutide can be effectively used in managing type 2 diabetes in patients with varying levels of kidney function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of chronic kidney disease and its severity on the efficacy of semaglutide in type 2 diabetes patients: a multicenter real-world study. García de Lucas, MD., Caballero, I., Fernández-García, JC., et al.[2023]

In the STEP 2 trial involving 1,205 participants, semaglutide (both 1.0 mg and 2.4 mg) significantly improved kidney function as measured by urine albumin-to-creatinine ratio (UACR), with reductions of -14.8% and -20.6% respectively, compared to an increase of +18.3% in the placebo group.

Across pooled data from STEP 1-3, semaglutide did not affect estimated glomerular filtration rate (eGFR) decline in participants with normal kidney function, indicating its safety in terms of kidney function preservation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Semaglutide on Albuminuria and Kidney Function in People With Overweight or Obesity With or Without Type 2 Diabetes: Exploratory Analysis From the STEP 1, 2, and 3 Trials. Heerspink, HJL., Apperloo, E., Davies, M., et al.[2023]

Oral semaglutide significantly improved glycaemic control and reduced body weight in patients with type 2 diabetes and moderate renal impairment, showing a mean decrease in HbA1c of -1.0 percentage points compared to -0.2 with placebo over 26 weeks.

While more patients experienced adverse events with oral semaglutide (74%) compared to placebo (65%), the safety profile was consistent with other GLP-1 receptor agonists, indicating it may be a viable treatment option for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment (PIONEER 5): a placebo-controlled, randomised, phase 3a trial. Mosenzon, O., Blicher, TM., Rosenlund, S., et al.[2020]

References

1. Spain pubmed.ncbi.nlm.nih.gov

Glucagon-like peptide 1(GLP-1) receptor agonists in the management of the patient with type 2diabetes mellitus and chronic kidney disease: an approach for the nephrologist. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

A Peptide in a Pill - Oral Semaglutide in the Management of Type 2 Diabetes. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Semaglutide, a Glucagon-Like Peptide-1 Receptor Agonist in Real-Life: A Case Series of Patients in Maintenance Incremental Hemodialysis. [2022]

4. Belgium pubmed.ncbi.nlm.nih.gov

[Oral semaglutide, first oral GLP-1 receptor agonist (Rybelsus®)]. [2022]

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

Achieving glycaemic control without weight gain, hypoglycaemia, or gastrointestinal adverse events in type 2 diabetes in the SUSTAIN clinical trial programme. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Influence of chronic kidney disease and its severity on the efficacy of semaglutide in type 2 diabetes patients: a multicenter real-world study. [2023]

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

Effects of Semaglutide on Albuminuria and Kidney Function in People With Overweight or Obesity With or Without Type 2 Diabetes: Exploratory Analysis From the STEP 1, 2, and 3 Trials. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment (PIONEER 5): a placebo-controlled, randomised, phase 3a trial. [2020]