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

Trial Summary

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.

What data supports the effectiveness of the drug dapagliflozin for kidney amyloidosis?

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 cardiovascular benefits. While these findings are not specific to kidney amyloidosis, they suggest potential benefits for kidney health. ^{1 2 3 4 5}

Is dapagliflozin generally safe for humans?

Dapagliflozin is generally well tolerated in humans, with a low risk of low blood sugar (hypoglycemia) and common side effects being genital infections, especially in women. It is not recommended for people with moderate or severe kidney problems. ^{1 2 6 7 8}

How is the drug dapagliflozin unique for treating kidney amyloidosis?

Dapagliflozin is unique because it is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that not only helps manage blood sugar levels in type 2 diabetes but also reduces the risk of kidney disease progression and cardiovascular events in patients with chronic kidney disease, regardless of diabetes status. This dual benefit of managing both kidney and heart health makes it a novel option for conditions like kidney amyloidosis, where standard treatments may not exist. ^{1 2 3 7 9}

What is the purpose of this trial?

The goal of this clinical trial is to learn if an oral drug called dapagliflozin is safe and can reduce high protein levels in the urine of patients with renal amyloid light-chain (AL) amyloidosis using a decentralized study design. Participants will be: * screened for the trial via an online platform * contacted by study personal to obtain electronic consent * enrolled in the trial if eligible and consented * contacted by study personal for further instructions and directions * sent dapagliflozin oral medication (supplied by the site pharmacy) * followed up regularly with the study team via telemedicine or other online avenues * monitored using lab work, inquiries about side effects and assessment of protocol adherence at 1 month, 3 months and 6 months * continue treatment for 6 months

Research Team

Jeffrey Zonder, M.D.

Principal Investigator

Barbara Ann Karmanos Cancer Institute

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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, 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]

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 (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 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]

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]

References

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

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

2. Belgium pubmed.ncbi.nlm.nih.gov

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

3. Spain pubmed.ncbi.nlm.nih.gov

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

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

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

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

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

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

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

7. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics and clinical efficacy of dapagliflozin for the treatment of type 2 diabetes. [2021]

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

Dapagliflozin: A Sodium Glucose Cotransporter 2 Inhibitor for the Treatment of Diabetes Mellitus. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Inhibition of Sodium-Glucose Cotransporter 2 with Dapagliflozin in Han: SPRD Rats with Polycystic Kidney Disease. [2021]