DapagliFLOzin in Renal AL Amyloidosis (FLORAL) (FLORAL)

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

Study Overview

• Status: Recruiting
• Conditions: Renal AL Amyloidosis
• Intervention / Treatment: Drug: Dapagliflozin

Detailed Description

1. Participants are recruited by one of the following methods:

   1. Self-referral through the website
   2. Receiving recruitment materials from their provider.

2. Participant visits the prescreening website.

   1. High level prescreening questions are answered by the participant.
   2. If appropriate based on answers to the questions, the participant may provide their contact information for follow up by the study team.
3. Study team contacts potential participants to review the study and explain next steps
4. Participant is provided with the link and password to view the video and sign the consent via Adobe Sign
5. An investigator will meet virtually with the participant to obtain medical history information, concomitant medications, and performance status (screening visit)
6. Once the participant passes screening in step 5, an order will be sent to the participant for the remaining screening labs to be done at a local laboratory that is covered by their insurance
7. The lab will fax results to the site
8. After review of eligibility and the study team will proceed with enrolling the participant if appropriate
9. The participant will proceed to the baseline visit (telehealth for any portion that can be done via phone/video and order for lab tests as previously described) if needed to comply with the protocol calendar/window.
10. The participant is approved to begin dosing by the investigator

11. The site will dispense via mail the following:

    1. 4 month's supply of Dapagliflozin
    2. A self-addressed envelope for return of the diary and pill bottles at the end of the dosing period
    3. A weighing scale (if required)
12. Dosing compliance will be checked during initial study treatment via sharing of pill accountability data or screenshot of paper pill diary
13. If clinically indicated, labs will be ordered and run more frequently to assess for toxicity.
14. Visits 3, 4, and 5 will be conducted in the same manner as described above.
15. All pill bottles and diaries (if paper version is used) will be returned via the provided envelope

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Christiane Houde; Phone Number: 3135768673; Email: Houdec@karmanos.org
• Study Contact Backup: Name: Jeffrey Zonder, M.D.; Phone Number: 3135768732; Email: zonderj@karmanos.org

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Karmanos Cancer Institute
      • Contact: Christiane Houde; Phone Number: 3135768673; Email: Houdec@karmanos.org
      • Contact: Jeffrey Zonder; Phone Number: 3135768732; Email: zonderj@karmanos.org
      • Contact: Jeffrey Zonder, M.D.
      • Contact: Andrew Kin, M.D.
      • Contact: Aditi Sharma, M.D.
      • Contact: Joel Topf, M.D.
      • Contact: Craig Cole, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Provision of signed and dated informed consent form.
• Stated willingness to comply with study procedures, including remote telehealth consultations with the study team, confirming availability, and agreeing to use mobile/web applications for study purposes.
• Age ≥18 years.
• Histopathologic diagnosis of renal AL amyloidosis confirmed by biopsy of any tissue and evidence of >1.0 g/day proteinuria without any other identifiable cause.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1 or 2.
• Plateau in any renal response (i.e., reduction in proteinuria) for at least 3 months prior to enrollment, as determined by the enrolling physician.
• Residence in the state of Michigan.

Exclusion Criteria:

• Either ongoing first line induction with anti-plasma cell therapy or ongoing post- induction maintenance for <6 months prior to enrollment.
• Diagnosis of symptomatic multiple myeloma, including presence of lytic bone disease, plasmacytomas, ≥60% plasma cells in the bone marrow, or hypercalcemia, either currently or in the past.
• Women of child-bearing potential (i.e., those who have not undergone chemical or surgical sterilization or are not postmenopausal) and who are unwilling to use a medically accepted and reliable form of contraception while participating in the study and for 2 weeks following the last dose of study medication, as determined by the investigator, or have a positive pregnancy test at the time of enrolment or are currently breastfeeding.
• Known allergic reactions to components of the dapagliflozin.
• Treatment requiring type 1 or type 2 diabetes mellitus.
• Baseline eGFR <25 mL/min/1.73m2.
• Acute or chronic liver disease with severe impairment of liver function (e.g., ascites, esophageal varices or coagulopathy)
• Current or previous use of any SGLT2i.
• Initiation or dose modification of angiotensin converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers (ARBs) <3 months prior to enrollment.
• Active malignancy requiring treatment (other than AL amyloidosis and non-melanoma skin cancers).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dapagliflozin; Dapagliflozin 10mg orally, daily for 6 months	Drug: Dapagliflozin; 10mg orally once daily; Other Names: BMS-512148; Forxiga® / Farxiga®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients achieving 30% reduction in daily proteinuria.	A patient will be considered to have achieved the desired urine protein reduction if a 30% reduction in 24-hour albuminuria occurs at any point during the six-month period from the initiation of dapagliflozin therapy. The proportion of patients achieving this reduction will be calculated as the ratio of the total number of patients who experienced the reduction to the total number of evaluable patients.	Up to Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Completion rate of tele-visits	The completion rate of tele-visits, including post-trial feedback, will be calculated as the ratio of completed tele-visits to scheduled tele-visits.	Up to Month 6

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients experiencing any of the following: (1) sustained decline in eGFR, (2) onset of ESRD, or (3) death from a renal disease-related or cardiovascular cause.	A patient's status will be recorded as 'yes' if any of the following three events occur at any time during the 6 months of study therapy: a sustained ≥50% decline in estimated glomerular filtration rate (eGFR); the onset of dialysis-requiring end- stage renal disease (ESRD); or death from a renal disease-related or cardiovascular cause. Otherwise, the status will be marked as 'no'.	Up to Month 6
Incidence rate of developing dialysis dependent ESRD in patients with Pavia Renal AL Stage II or III involvement.	The onset of ESRD in patients with Pavia Renal Stage II or III involvement will be recorded as binary (yes vs. no).	Up to Month 6

Collaborators and Investigators

• Sponsor: Barbara Ann Karmanos Cancer Institute
• Investigators: Principal Investigator: Jeffrey Zonder, M.D., Barbara Ann Karmanos Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2024
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: May 14, 2024
• First Submitted That Met QC Criteria: May 14, 2024
• First Posted (Actual): May 17, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 7, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Metabolic Diseases; Immune System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Paraproteinemias; Proteostasis Deficiencies; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Sodium-Glucose Transporter 2 Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Dapagliflozin
• Other Study ID Numbers: 2023-074

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No