Table 1.

SBI-101-01 SCHEDULE OF Events

Module/visit	Screen A	Screen B	Predose baseline	Day
	Post-AKI diagnosis, before initiation of CRRT	After starting on CRRT		Day 0 time 0−24 h (or before removal)	Day 0 time 24 h or removal of SBI-101	Day 1 + 1 post-treatment	Day 3 + 1	Day 7 ± 1	Day 14 ± 2	Day 21 ± 3	Day 28 ± 3	D/C	Day 90 ± 14	Day 180 ± 14 or WD
	1	2	3	4	5	6	7	8	9	10	11	12	13	14
Informed consenta	X	X
Inclusion/exclusionb	X	X	X
Randomizationc		X
Demographics		X
Medical history	X	X
PE or limited PAd		X	X		X	X	X	X	X	X	X	X	X	X
Vital signse	X	X	X	X	X	X	X	X	X	X	X	X	X	X
Concomitant therapiesf		X	X	X	X	X	X	X	X	X	X	X	X
Clinical labsg,r	X	X	X	X		X	X	X	X	X	X	X	X	X
Urine testsh	X	X	X		X	X	X	X	X	X	X	X	X	X
Fluid input and output monitoringi			X	X	X	X	X	X
ECGj			X		X
SBI-101 Administrationk				X Initiation	X Complete
Research samplingl	X	X	X	X	X	X	X	X	X			X	X	X
Adverse eventsm		X	X	X	X	X	X	X	X	X	X	X*
UADEsn				X	X	X
Dischargeo												X
SAEsp				X	X	X	X	X	X	X	X	X	X	X
Outcomesq						X	X	X	X	X	X	X		X

AKI, acute kidney injury; CRRT, continuous renal replacement therapy; ECG, electrocardiogram; HEENT, head, eyes, ears, nose, and throat; PA, limited physical assessment; PE, physical examination; SAE, serious adverse event; UADE, unanticipated adverse device effect; WD, withdrawal.

^aInformed consent will be obtained before the conduct of any study procedures. For subjects undergoing screen A (in which subjects are identified following an AKI diagnosis but before the initiation of CRRT), and for subjects undergoing screen B, consent may be obtained directly from the study subject or from their legally authorized representative. The institutional review board will dictate which individuals shall be considered legally authorized to render consent for a subject.

^bEligibility will be assessed for all subjects by the investigator before randomization of a subject into the study.

^cSubjects will be randomized 2:1 (8 low-dose cohort + 4 sham), and 2:1 (8 high-dose cohort + 4 sham).

^dFull physical examinations will be conducted at screening and at required visits through day 7 (module 8). Thereafter, physical examinations may be limited but should include cardiac, respiratory, HEENT, and gastrointestinal systems.

^eVital signs include measurement of respiration, pulse, and blood pressure collected before start of treatment, then after start of SBI-101 or sham therapy at 1, 5, 10, 15, 30, and 60 minutes, then at 2, 4, 6, 8, 12, 16, 20, and 24 hours, until completion of SBI-101 or sham therapy. In addition, vitals will be collected at the time of removal from SBI-101 or sham therapy, and at 4, 6, and 12 hours postremoval. Temperature will be collected at 30 minutes and at 2, 4, 6, 8, 12, 16, 20, and 24 hours.

^fConcomitant therapies will be collected for 3 days before investigational product administration through day 28. Concomitant medications will be collected at the discharge day if it occurs within 28 days of completion of SBI-101 or sham therapy.

^gClinical laboratory assessments will include chemistry panel, hematology panel (coagulation tests), and pregnancy testing for women of child-bearing potential at screen B.

^hUrine tests will include urinalysis (urine tests).

ⁱFluid input/output monitoring: ins and outs will be collected for 12 hours before initiation of SBI-101 or sham therapy, out to a maximum of 7 days as long as the subject has an indwelling catheter and data are available.

^jA 12-lead ECG will be recorded at predose baseline, within 1 hour of completion of SBI-101 or sham therapy. Additional ECGs should be collected for study purposes if subject has chest pain, palpitations and/or syncope, or other symptoms or arrhythmia or signs of cardiac malfunction.

^kI.p. administration will be initiated by the insertion of SBI-101 or sham control into the CRRT circuit.

^lResearch sampling will occur at the following timepoints: screen A (as applicable) and screen B; predose baseline (venous sampling and urine collection, and a sample from the device ultrafiltrate compartment after integration with i.p. but before subject hookup); and during SBI-101 or sham administration at 30 minutes, and at 6, 12, 18, and 24 hours (or before removal); for these timepoints, only plasma will be collected and will come directly from the device. Additional research samples will be collected from venous sampling at timepoints outlined in the table, following completion of treatment. Urine collection for research will also be collected at screen A (as applicable), screen B, and at least once during SBI-101 and/or sham administration. Additional urine research samples will be collected at conclusion of treatment, and at days 1, 3, 7, 14, 21, and 28 posttreatment.

^mAdverse events (AEs) will be collected from before SBI-101 and/or sham administration (predose baseline) through day 28 follow-up. AEs will be collected at the discharge day if it occurs within 28 days of completion of SBI-101 or sham therapy.

ⁿUADEs will be collected from the time of SBI-101 and/or sham administration through 12 hours postremoval.

^oHospital discharge; this visit may come at any time in the time course of study visits (may be before day 28 or after); if discharge happens on the same date as an already defined study visit, then only the study visit module should be completed.

^pSAEs will be collected from the time of SBI-101 and/or sham administration (predose baseline) through day 180.

^qOutcomes including survival, time to cessation of CRRT, intensive care unit length of stay, and need for on-going renal replacement therapy will be assessed at all postdose study visits out to day 28.

^rAntibodies against allogeneic mesenchymal stromal cells only at baseline, 3, and 6 months.