Dapagliflozin for Kidney Amyloidosis

(FLORAL Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Jeffrey Zonder, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Jeffrey Zonder

Must not be taking: SGLT2 inhibitors

Disqualifiers: Multiple myeloma, Diabetes, Liver disease, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 3 Jurisdictions

Trial Summary

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

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.

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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.

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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.

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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 am 18 years old or older.

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

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.

Trial 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)

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Karmanos Cancer Institute Detroit, MI

Who Is Running the Clinical Trial?

Jeffrey Zonder Lead Sponsor

Barbara Ann Karmanos Cancer Institute Lead Sponsor

References

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

Antidiabetic Drug Approved to Reduce Risk of Kidney Disease. [2023] Dapagliflozin (Farxiga) is now approved to reduce the risk of declining kidney function, kidney failure, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease with or without type 2 diabetes.

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

[Dapagliflozin (forxiga®) : SGLT 2 cotransporter inhibitor as glucose-lowering agent in type 2 diabetes]. [2021] Dapagliflozin, a specific inhibitor of sodium-glu¬cose cotransporters type 2 (SGLT2, inhibits glucose reabsorp¬tion in renal tubules and thus promotes glucosuria. This effect results in a reduction in fasting and postprandial glycaemia and a decrease of glycated haemoglobin (HbA1c), with a minor risk of hypoglycaemia, a weight reduction and a reduction in arterial blood pressure. The efficacy of empagliflozin on HbA1c reduction increases according to the level of hyper¬glycaemia but decreases in patients with renal insufficiency. Mycotic genital infections occur more frequently, especially in women, while a negligible increase in mild urinary tract infections may be observed. Dapagliflozin (Forxiga®), 10 mg once daily, is indicated for the treatment of T2DM and reim¬bursed in Belgium with conditions as add-on to a background glucose-lowering therapy (either metformin or sulfonylurea/ repaglinide or metformin plus sulfonylurea/repaglinide or basal insulin plus at least one of these oral glucose-lowering agents). Preliminary results suggest some cardiovascular and renal protection. These results should be confirmed in an ongoing large prospective controlled trial (DECLARE) in type 2 diabetic patients at high cardiovascular risk.

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

An update on dapagliflozin for chronic kidney disease. [2022] Dapagliflozin is an oral agent for type 2 diabetes mellitus (T2DM) belonging to the sodium/glucose cotransporter 2 inhibitor (SGLT2-I) class of antihyperglycemic medications. In clinical trials, dapagliflozin has also been shown to reduce cardiovascular and major renal events. In the DAPA-CKD trial, dapagliflozin significantly reduced the composite renal outcome in patients with chronic kidney disease (CKD). Dapagliflozin represents a new pharmacologic option for reducing CKD progression in patients with and without diabetes.

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] Label="SOURCE CITATION">Heerspink HJ, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383:1436-46. 32970396.

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

Dapagliflozin: A Review in Symptomatic Heart Failure with Reduced Ejection Fraction. [2022] Dapagliflozin [Farxiga® (USA); Forxiga® (EU)], a sodium-glucose cotransporter 2 (SGLT2) inhibitor, was recently approved in the USA and the EU for the treatment of adults with symptomatic heart failure with reduced ejection fraction (HFrEF). The cardiovascular (CV) benefits of dapagliflozin were first observed in the DECLARE-TIMI 58 trial, in which dapagliflozin 10 mg/day significantly reduced the risk of CV death or hospitalization for HF in patients with type 2 diabetes mellitus (T2DM) who had or were at risk for atherosclerotic CV disease. In the subsequent DAPA-HF trial, dapagliflozin 10 mg/day in addition to standard of care was associated with a significantly lower risk of worsening HF or CV death than placebo in patients with HFrEF, regardless of the presence or absence of T2DM. The benefits of dapagliflozin also remained consistent regardless of background HF therapies. Dapagliflozin was generally well tolerated, with an overall safety profile consistent with its known safety profile in other indications. In conclusion, dapagliflozin is an effective and generally well-tolerated treatment that represents a valuable new addition to the options available for symptomatic HFrEF.

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

Dapagliflozin: a review of its use in patients with type 2 diabetes. [2022] Dapagliflozin (Forxiga(®), Farxiga(®)) is an orally administered sodium-glucose co-transporter-2 (SGLT2) inhibitor used in the management of patients with type 2 diabetes. Dapagliflozin reduces renal glucose reabsorption by inhibiting the transporter protein SGLT2 in the renal proximal tubule, thereby increasing urinary glucose excretion and reducing blood glucose levels. Its mechanism of action is independent of insulin secretion or action; therefore, dapagliflozin provides complementary therapy when used in combination with other antihyperglycaemic drugs. This article updates an earlier review of dapagliflozin and focuses on longer-term efficacy and tolerability data (e.g. from extensions of earlier clinical trials), as well as data from studies in special patient populations (e.g. history of cardiovascular disease). Numerous well-designed clinical trials with dapagliflozin, primarily as add-on therapy for 24 weeks (but also as monotherapy or initial combination therapy), have consistently demonstrated reductions in glycosylated haemoglobin, fasting plasma glucose levels and bodyweight. Extensions of these trials show the effects are maintained over longer-term follow-up periods of ≈1-4 years and dapagliflozin is generally well tolerated. Dapagliflozin has a low risk of hypoglycaemia, although the incidence varies depending on background therapy, and genital mycotic infections (particularly in women) are the most common adverse events. Dapagliflozin is not recommended in patients with moderate or severe renal impairment. In view of its unique mechanism of action and now well-established efficacy and tolerability profile, dapagliflozin is a useful treatment option in the management of type 2 diabetes, although its effects on diabetic complications remain to be evaluated.

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

Pharmacokinetics, pharmacodynamics and clinical efficacy of dapagliflozin for the treatment of type 2 diabetes. [2021] Dapagliflozin (DAPA) (Farxiga or Forxiga) is a sodium glucose cotransporter 2 (SGLT2) inhibitor approved for type 2 diabetes mellitus(T2DM) treatment.

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

Dapagliflozin: A Sodium Glucose Cotransporter 2 Inhibitor for the Treatment of Diabetes Mellitus. [2021] To review clinical evidence for the efficacy, safety, and tolerability of dapagliflozin (Farxiga-AstraZeneca), a sodium glucose cotransporter 2 inhibitor, as monotherapy or in combination with other hypoglycemic agents for the treatment of type 2 diabetes.

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

Inhibition of Sodium-Glucose Cotransporter 2 with Dapagliflozin in Han: SPRD Rats with Polycystic Kidney Disease. [2021] Dapagliflozin (DAPA) is a selective inhibitor of the sodium-glucose cotransporter 2 (SGLT2) which induces glucosuria and osmotic diuresis. The therapeutic effect of DAPA in progressing stages of polycystic kidney disease (PKD) has not been studied.