DapagliFLOzin in Renal AL Amyloidosis (FLORAL)

• Participants are recruited by one of the following methods:

• Self-referral through the website
• Receiving recruitment materials from their provider.
• Participant visits the prescreening website.

• High level prescreening questions are answered by the participant.
• If appropriate based on answers to the questions, the participant may provide their contact information for follow up by the study team.
• Study team contacts potential participants to review the study and explain next steps
• Participant is provided with the link and password to view the video and sign the consent via Adobe Sign
• An investigator will meet virtually with the participant to obtain medical history information, concomitant medications, and performance status (screening visit)
• 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
• The lab will fax results to the site
• After review of eligibility and the study team will proceed with enrolling the participant if appropriate
• 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.
• The participant is approved to begin dosing by the investigator
• The site will dispense via mail the following:

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

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).