Dapagliflozin for Kidney Amyloidosis

(FLORAL Trial)

Overseen By Jeffrey Zonder, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Jeffrey Zonder

Must not be taking: SGLT2 inhibitors

Disqualifiers: Multiple myeloma, Diabetes, Liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 6 months

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether dapagliflozin, an oral medication, is safe and can reduce high protein levels in the urine for individuals with kidney amyloidosis. In this condition, an abnormal protein accumulates in the kidneys, causing damage. Participants will take the medication daily for six months and have regular online check-ins with the study team. This trial suits individuals in Michigan with a confirmed diagnosis of kidney amyloidosis and significant protein in their urine. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

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 recently started or changed the dose of certain blood pressure medications (ACE inhibitors or ARBs) within 3 months before joining. It's best to discuss your current medications with the study team.

Is there any evidence suggesting that dapagliflozin is likely to be safe for humans?

Research has shown that dapagliflozin is generally safe and well-tolerated in people with amyloidosis, a condition where proteins accumulate in organs. In earlier studies, patients taking dapagliflozin experienced a lower risk of kidney failure and heart-related deaths, which is promising for those with kidney issues.

Another study using real-world data found dapagliflozin to be a safe option for people with diabetes, a condition often accompanying kidney problems. Some animal studies have indicated risks to developing kidneys, but these involved young rats. In adults, the medication maintains a good safety record.

Overall, these findings suggest that dapagliflozin is likely safe for use in this trial. As with any medication, side effects may occur, so regular check-ups will be part of the study. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for kidney amyloidosis, which often focus on managing symptoms and slowing disease progression, dapagliflozin offers a novel approach by targeting the disease at a metabolic level. Dapagliflozin is a type of medication known as an SGLT2 inhibitor, typically used for diabetes management, which works by promoting the excretion of excess glucose through urine. Researchers are excited about dapagliflozin because it has shown potential to not only improve kidney function but also reduce amyloid deposits, offering a dual benefit that current options do not provide. This innovative mechanism could represent a significant breakthrough in treating kidney amyloidosis.

What evidence suggests that dapagliflozin might be an effective treatment for kidney amyloidosis?

Research has shown that dapagliflozin, the investigational treatment in this trial, can slow the decline of kidney function and lower the risk of kidney failure. Studies have found that this drug improves health outcomes for people with chronic kidney disease, regardless of whether they have type 2 diabetes. It blocks a protein in the kidneys that typically aids in sugar reabsorption, thereby protecting the kidneys. Although dapagliflozin is not specifically approved for kidney amyloidosis, it may help by reducing protein levels in urine and improving kidney health. Overall, evidence supports its potential effectiveness in managing kidney problems. ^{1 3 4 6 7}

Who Is on the Research Team?

Jeffrey Zonder, M.D.

Principal Investigator

Barbara Ann Karmanos Cancer Institute

Are You a Good Fit for This Trial?

This trial is for patients with renal AL amyloidosis, a condition where abnormal proteins build up in the kidneys. Participants must be comfortable using online platforms and telemedicine for screening, consent, instructions, medication delivery, and follow-ups.

Inclusion Criteria

My kidney condition has not improved for at least 3 months.

I can care for myself and am up and about more than 50% of my waking hours.

I agree to follow the study rules, including using apps and attending virtual meetings.

Exclusion Criteria

My kidney function is very low.

I have used SGLT2 inhibitors for my diabetes.

I am currently undergoing or have recently completed my first round of treatment for my blood cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (virtual)

Treatment

Participants receive dapagliflozin 10mg orally, daily for 6 months

6 months

Regular telemedicine visits and lab work at 1, 3, and 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Dapagliflozin

Trial Overview The FLORAL study is testing if dapagliflozin taken orally can lower protein levels in urine of renal AL amyloidosis patients. The trial involves remote monitoring over six months with lab work and side effect assessments at set intervals.

How Is the Trial Designed?

Group I: Dapagliflozin Experimental Treatment 1 Intervention

Dapagliflozin 10mg orally, daily for 6 months

Dapagliflozin is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Forxiga for:

• Type 2 diabetes
• Heart failure
• Chronic kidney disease

Approved in United States as Farxiga for:

• Type 2 diabetes
• Heart failure
• Chronic kidney disease

Approved in Canada as Farxiga for:

• Type 2 diabetes
• Heart failure
• Chronic kidney disease

Who Is Running the Clinical Trial?

Jeffrey Zonder

Lead Sponsor

Trials

1

Recruited

20+

Barbara Ann Karmanos Cancer Institute

Lead Sponsor

Trials

166

Recruited

9,300+

Published Research Related to This Trial

Dapagliflozin (Farxiga) is approved for reducing the risk of declining kidney function and kidney failure in adults with chronic kidney disease, regardless of whether they have type 2 diabetes.

It also helps lower the risk of cardiovascular death and hospitalization for heart failure, highlighting its efficacy in managing both kidney and heart health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antidiabetic Drug Approved to Reduce Risk of Kidney Disease. Aschenbrenner, DS.[2023]

Dapagliflozin effectively lowers blood sugar levels and glycated hemoglobin (HbA1c) in patients with type 2 diabetes, with a low risk of hypoglycemia and additional benefits like weight loss and reduced blood pressure.

While it is generally safe, dapagliflozin can increase the risk of genital infections, particularly in women, and its efficacy may be reduced in patients with kidney issues; ongoing trials are investigating its potential cardiovascular and renal protective effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Dapagliflozin (forxiga®) : SGLT 2 cotransporter inhibitor as glucose-lowering agent in type 2 diabetes]. Scheen, AJ.[2021]

In a study involving male Han: SPRD rats with polycystic kidney disease, dapagliflozin (DAPA) treatment for 5 weeks significantly improved renal function and reduced albuminuria compared to the control group.

However, DAPA did not affect cyst growth in the kidneys, indicating that while it has some beneficial effects on kidney function, its impact on the progression of polycystic kidney disease may be limited compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of Sodium-Glucose Cotransporter 2 with Dapagliflozin in Han: SPRD Rats with Polycystic Kidney Disease. Rodriguez, D., Kapoor, S., Edenhofer, I., et al.[2021]

Dapagliflozin is an effective SGLT2 inhibitor for managing type 2 diabetes, showing consistent reductions in blood glucose levels and body weight over long-term follow-up periods of 1-4 years across various clinical trials.

It has a low risk of causing hypoglycemia and is generally well tolerated, although it can lead to genital infections, particularly in women, and is not recommended for patients with moderate to severe renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin: a review of its use in patients with type 2 diabetes. Plosker, GL.[2022]

Dapagliflozin is an effective treatment for type 2 diabetes, proven through multiple controlled clinical trials that assess its efficacy, safety, and tolerability.

It is approved by the FDA for use as a standalone therapy or in combination with other glucose-lowering medications, including insulin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin: A Sodium Glucose Cotransporter 2 Inhibitor for the Treatment of Diabetes Mellitus. Davis, PN., Ndefo, UA., Oliver, A.[2021]

Dapagliflozin, an SGLT2 inhibitor, is effective in treating type 2 diabetes and has been shown to significantly reduce cardiovascular and major renal events in clinical trials.

In the DAPA-CKD trial, dapagliflozin notably decreased the risk of kidney disease progression in patients with chronic kidney disease, making it a valuable treatment option for both diabetic and non-diabetic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on dapagliflozin for chronic kidney disease. Kelly, MS.[2022]

Dapagliflozin has been shown to significantly improve kidney outcomes in patients with chronic kidney disease, demonstrating its efficacy in reducing the risk of kidney disease progression.

The study involved a large cohort of patients, providing robust evidence for the safety and effectiveness of dapagliflozin in managing chronic kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In CKD, dapagliflozin reduced a composite of eGFR decline, end-stage kidney disease, or CV or renal mortality. Molony, DA., LeMaistre, FI.[2021]

Dapagliflozin (DAPA) is an effective SGLT2 inhibitor for treating type 2 diabetes, showing favorable pharmacokinetics and pharmacodynamics that help lower blood sugar levels while having beneficial effects on other metabolic risk factors.

While DAPA is generally safe, it carries an increased risk of genital and urinary infections, and concerns about bladder cancer and cardiovascular safety remain, prompting the FDA to seek further data on these issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics and clinical efficacy of dapagliflozin for the treatment of type 2 diabetes. Maranghi, M., Carnovale, A., Durante, C., et al.[2021]

Dapagliflozin, an SGLT2 inhibitor, has been shown to significantly reduce the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure with reduced ejection fraction (HFrEF), regardless of whether they have type 2 diabetes.

In the DAPA-HF trial, dapagliflozin was well tolerated and demonstrated a lower risk of worsening heart failure or cardiovascular death compared to placebo, making it a valuable treatment option for adults with symptomatic HFrEF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin: A Review in Symptomatic Heart Failure with Reduced Ejection Fraction. Blair, HA.[2022]

Citations

1. withpower.com withpower.com/trial/phase-2-immunoglobulin-light-chain-amyloidosis-4-2024-95774

Dapagliflozin for Kidney Amyloidosis (FLORAL Trial) Dapagliflozin has been shown to reduce the risk of kidney function decline and kidney failure in people with chronic kidney disease, and it also offers ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10780141/

Safety and Tolerability of SGLT2 Inhibitors in Cardiac ... Sodium-glucose transport protein 2 inhibitors (SGLT2i) slow the progression of renal dysfunction and improve the prognosis of patients with ...

3. jacc.org jacc.org/doi/10.1016/j.jchf.2021.06.017

Effects of Dapagliflozin in Patients With Kidney Disease ... Dapagliflozin reduced the risk of kidney failure and cardiovascular death/HF hospitalization and prolonged survival in CKD patients with or without type 2 ...

4. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2023/202293Orig1s026.pdf

CENTER FOR DRUG EVALUATION AND RESEARCH Juvenile rats directly exposed to dapagliflozin showed risk to the developing kidney (renal pelvic and tubular dilatations) during maturation.

5. pharmacytimes.com pharmacytimes.com/view/dapagliflozin-improves-outcomes-in-patients-with-chronic-kidney-disease-regardless-of-presence-of-diabetes

Dapagliflozin Improves Outcomes in Patients With Chronic ... Dapagliflozin was found to lower the risk for prolonged hospitalization or death (HR, 0.83; 95% CI, 0.72-0.95), the composite of first ...

6. hfsa.org hfsa.org/farxiga-demonstrated-unprecedented-reduction-risk-kidney-failure-and-cardiovascular-or-renal-death

Farxiga demonstrated unprecedented reduction in the risk ... Farxiga demonstrated unprecedented reduction in the risk of kidney failure and cardiovascular or renal death in patients with chronic kidney disease in the ...

7. drugtopics.com drugtopics.com/view/real-world-data-show-dapagliflozin-empagliflozin-are-safe-options-for-diabetes

Real-World Data Show Dapagliflozin, Empagliflozin Are ... The primary outcome—sustained eGFR decline of 30% or more, end-stage renal disease, hospitalization for heart failure, or all-cause death— ...