Trial Outcomes & Findings for An Open-Label Multiple Dose Study of RZ358 in Patients With Congenital Hyperinsulinism (NCT NCT04538989)

Last Updated: 2025-05-28

Results Overview

The median of average daily percent time within the glucose target range 70-180 mg/dL (3.9-10 mmol/L) by CGM at Baseline and End of Treatment (EOT) is reported.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

23 participants

Primary outcome timeframe

8 weeks

Results posted on

2025-05-28

Participant Flow

Sites were recruited based on cHI professional expertise and sufficient patient panels and advocacy referrals.

NA; open-label study

Participant milestones

Participant milestones
Measure	RZ358 Cohort 1 RZ358 Sequential Group Cohort 1: IV infusion for 8 weeks (3 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 2 RZ358 Sequential Group Cohort 2: IV infusion for 8 weeks (6 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 3 RZ358 Sequential Group Cohort 3: IV infusion for 8 weeks (9 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 4 RZ358 Sequential Group Cohort 4: IV infusion for 8 weeks (bi-weekly fixed dose-titration from 3 to 9 mg/kg for the first 4 weeks, followed by a fixed 9 mg/kg dose amount thereafter for the remaining 4 weeks)
Overall Study STARTED	4	8	8	3
Overall Study COMPLETED	4	8	8	3
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

An Open-Label Multiple Dose Study of RZ358 in Patients With Congenital Hyperinsulinism

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	RZ358 Cohort 1 n=4 Participants RZ358 Sequential Group Cohort 1: IV infusion for 8 weeks (3 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 2 n=8 Participants RZ358 Sequential Group Cohort 2: IV infusion for 8 weeks (6 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 3 n=8 Participants RZ358 Sequential Group Cohort 3: IV infusion for 8 weeks (9 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 4 n=3 Participants RZ358 Sequential Group Cohort 4: IV infusion for 8 weeks (bi-weekly fixed dose-titration from 3 to 9 mg/kg for the first 4 weeks, followed by a fixed 9 mg/kg dose amount thereafter for the remaining 4 weeks)	Total n=23 Participants Total of all reporting groups
Age, Categorical <=18 years	4 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants	3 Participants n=4 Participants	22 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Continuous	5.8 years STANDARD_DEVIATION 4.35 • n=5 Participants	9.3 years STANDARD_DEVIATION 6.88 • n=7 Participants	5.8 years STANDARD_DEVIATION 5.12 • n=5 Participants	4.0 years STANDARD_DEVIATION 2.00 • n=4 Participants	6.7 years STANDARD_DEVIATION 5.50 • n=21 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	5 Participants n=7 Participants	3 Participants n=5 Participants	1 Participants n=4 Participants	13 Participants n=21 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants	2 Participants n=4 Participants	10 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants	3 Participants n=4 Participants	21 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants	3 Participants n=4 Participants	20 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Region of Enrollment Turkey	0 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants	0 participants n=4 Participants	7 participants n=21 Participants
Region of Enrollment United States	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants
Region of Enrollment Denmark	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants
Region of Enrollment United Kingdom	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	0 participants n=4 Participants	2 participants n=21 Participants
Region of Enrollment Georgia	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants
Region of Enrollment Israel	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants
Region of Enrollment Bulgaria	3 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	3 participants n=21 Participants
Region of Enrollment Germany	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants
Region of Enrollment Russia	0 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants	3 participants n=4 Participants	5 participants n=21 Participants
Region of Enrollment Spain	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants

PRIMARY outcome

Timeframe: 8 weeks

Population: Per Protocol Population

The median of average daily percent time within the glucose target range 70-180 mg/dL (3.9-10 mmol/L) by CGM at Baseline and End of Treatment (EOT) is reported.

Outcome measures

Outcome measures
Measure	RZ358 Cohort 4 n=3 Participants RZ358 Sequential Group Cohort 4: IV infusion for 8 weeks (bi-weekly fixed dose-titration from 3 to 9 mg/kg for the first 4 weeks, followed by a fixed 9 mg/kg dose amount thereafter for the remaining 4 weeks)	RZ358 Pooled n=22 Participants RZ358 Total Participants	RZ358 Cohort 1 n=4 Participants RZ358 Sequential Group Cohort 1: IV infusion for 8 weeks (3 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 2 n=8 Participants RZ358 Sequential Group Cohort 2: IV infusion for 8 weeks (6 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 3 n=7 Participants RZ358 Sequential Group Cohort 3: IV infusion for 8 weeks (9 mg/kg bi-weekly for 8 weeks)
Median of Average Daily Percent Time Within a Glucose Target Range of 70-180 mg/dL (3.9-10 mmol/L) by CGM at Baseline (BL) and End of Treatment (EOT) Median of Average Daily Percent Time in 70-180 mg/dL at BL	59.3 Daily Percent Time Interval 25.7 to 110.0	76.9 Daily Percent Time Interval 65.3 to 80.7	81.7 Daily Percent Time Interval 70.5 to 92.5	72.9 Daily Percent Time Interval 67.5 to 80.9	83.4 Daily Percent Time Interval 43.2 to 94.8
Median of Average Daily Percent Time Within a Glucose Target Range of 70-180 mg/dL (3.9-10 mmol/L) by CGM at Baseline (BL) and End of Treatment (EOT) Median of Average Daily Percent Time in 70-180 mg/dL at 8 weeks (EOT)	70.8 Daily Percent Time Interval 50.9 to 93.9	79.1 Daily Percent Time Interval 72.0 to 83.9	84.8 Daily Percent Time Interval 71.6 to 100.3	78.5 Daily Percent Time Interval 61.1 to 88.6	82.9 Daily Percent Time Interval 67.1 to 91.6

PRIMARY outcome

Timeframe: 8 weeks

Population: Per Protocol Population

The average daily percent time within the glucose target range (70-180 mg/dL) is compared from baseline to end of treatment (EOT) and the median percent change of that difference is reported.

Outcome measures

Outcome measures
Measure	RZ358 Cohort 4 n=3 Participants RZ358 Sequential Group Cohort 4: IV infusion for 8 weeks (bi-weekly fixed dose-titration from 3 to 9 mg/kg for the first 4 weeks, followed by a fixed 9 mg/kg dose amount thereafter for the remaining 4 weeks)	RZ358 Pooled n=22 Participants RZ358 Total Participants	RZ358 Cohort 1 n=4 Participants RZ358 Sequential Group Cohort 1: IV infusion for 8 weeks (3 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 2 n=8 Participants RZ358 Sequential Group Cohort 2: IV infusion for 8 weeks (6 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 3 n=7 Participants RZ358 Sequential Group Cohort 3: IV infusion for 8 weeks (9 mg/kg bi-weekly for 8 weeks)
Median Percent Change of Average Daily Percent Time Within a Glucose Target Range of 70-180 mg/dL (3.9-10 mmol/L) by CGM From Baseline (BL)	9.07 Percent Change Interval -29.6 to 48.4	4.59 Percent Change Interval -16.7 to 65.1	6.19 Percent Change Interval -2.8 to 13.6	0.31 Percent Change Interval -19.7 to 24.2	5.52 Percent Change Interval -82.3 to 215.2

PRIMARY outcome

Timeframe: Pre dose Weeks 1,3,5,7, 1-hr post dose Week 1 and Week 7, and Follow up on Days 14, Day 28, Day 42, and Day 105

Population: PK Population; Data from Cohort 1, 2 and 4 was not collected during Pre-dose Week 1.

All patients who received RZ358 and for whom the primary PK data was considered to be sufficient and interpretable were to be included in the PK analyses. Individual and mean plasma concentration data is summarized descriptively at the specified timepoints. The results of this study may be combined with those of other studies for analysis and modeling (e.g., population PK and PK-PD), and therefore the PK parameters are reported separately, as part of an iterative population PK approach.

Outcome measures

Outcome measures
Measure	RZ358 Cohort 4 n=3 Participants RZ358 Sequential Group Cohort 4: IV infusion for 8 weeks (bi-weekly fixed dose-titration from 3 to 9 mg/kg for the first 4 weeks, followed by a fixed 9 mg/kg dose amount thereafter for the remaining 4 weeks)	RZ358 Pooled n=23 Participants RZ358 Total Participants	RZ358 Cohort 1 n=4 Participants RZ358 Sequential Group Cohort 1: IV infusion for 8 weeks (3 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 2 n=8 Participants RZ358 Sequential Group Cohort 2: IV infusion for 8 weeks (6 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 3 n=8 Participants RZ358 Sequential Group Cohort 3: IV infusion for 8 weeks (9 mg/kg bi-weekly for 8 weeks)
Repeat Dose Pharmacokinetics of RZ358 Pre dose Week 1	—	55648 ng/mL Interval 55648.0 to 55648.0	—	—	55648 ng/mL Interval 55648.0 to 55648.0
Repeat Dose Pharmacokinetics of RZ358 Post dose (1hr) Wk1/D1	43593 ng/mL Interval 36330.0 to 53742.0	89333 ng/mL Interval 1308.0 to 250230.0	29093 ng/mL Interval 1308.0 to 96685.0	120368 ng/mL Interval 74257.0 to 190700.0	164047 ng/mL Interval 73398.0 to 250230.0
Repeat Dose Pharmacokinetics of RZ358 Pre dose Week 3	8961 ng/mL Interval 7244.0 to 10613.0	28999 ng/mL Interval 7244.0 to 83824.0	38951 ng/mL Interval 15363.0 to 83824.0	28397 ng/mL Interval 21187.0 to 35857.0	41512 ng/mL Interval 19816.0 to 60351.0
Repeat Dose Pharmacokinetics of RZ358 Pre dose Week 5	34243 ng/mL Interval 26150.0 to 42212.0	64808 ng/mL Interval 20692.0 to 376850.0	20692 ng/mL Interval 20692.0 to 20692.0	82646 ng/mL Interval 36116.0 to 376850.0	74457 ng/mL Interval 51606.0 to 99696.0
Repeat Dose Pharmacokinetics of RZ358 Pre dose Week 7	55532 ng/mL Interval 48740.0 to 68459.0	67823 ng/mL Interval 29669.0 to 123120.0	31902 ng/mL Interval 31902.0 to 31902.0	56919 ng/mL Interval 29669.0 to 82349.0	95721 ng/mL Interval 55202.0 to 123120.0
Repeat Dose Pharmacokinetics of RZ358 Post dose (1hr) Week 7	245905 ng/mL Interval 181540.0 to 434760.0	217295 ng/mL Interval 94593.0 to 527410.0	94593 ng/mL Interval 94593.0 to 94593.0	178090 ng/mL Interval 123230.0 to 245640.0	280843 ng/mL Interval 141480.0 to 527410.0
Repeat Dose Pharmacokinetics of RZ358 Follow-Up Day 14/EOT	110134 ng/mL Interval 93403.0 to 127370.0	82683 ng/mL Interval 42139.0 to 129580.0	59542 ng/mL Interval 42139.0 to 76282.0	70990 ng/mL Interval 48766.0 to 99871.0	105005 ng/mL Interval 78798.0 to 129580.0
Repeat Dose Pharmacokinetics of RZ358 Follow-up Day 28	52039 ng/mL Interval 48235.0 to 57834.0	50125 ng/mL Interval 26997.0 to 125040.0	46751 ng/mL Interval 27504.0 to 125040.0	39385 ng/mL Interval 26997.0 to 59121.0	63201 ng/mL Interval 45579.0 to 108180.0
Repeat Dose Pharmacokinetics of RZ358 Follow-up Day 42	37394 ng/mL Interval 30944.0 to 50353.0	31066 ng/mL Interval 13552.0 to 60868.0	23166 ng/mL Interval 14390.0 to 29879.0	24226 ng/mL Interval 13552.0 to 37256.0	43034 ng/mL Interval 26741.0 to 60868.0
Repeat Dose Pharmacokinetics of RZ358 Follow-up Day 105	4194 ng/mL Interval 3297.0 to 6469.0	4857 ng/mL Interval 1105.0 to 15651.0	2307 ng/mL Interval 1201.0 to 3412.0	4231 ng/mL Interval 1105.0 to 15651.0	9269 ng/mL Interval 3743.0 to 14616.0

SECONDARY outcome

Timeframe: 8 weeks

Population: Per Protocol Population; For efficacy outcomes, the PP Population included 20 participants for BGM-based glycemic endpoints due to endpoint-specific exclusions. One participant in Cohort 1 and one in Cohort 4 were excluded from the PP population BGM-based analyses because they failed to meet pre-specified minimum testing frequency by glucometer. One participant in Cohort 3 was also excluded from the PP population BGM analyses for stopping background SOC therapy after starting RZ358 in the study

The median of average weekly number of overall hypoglycemia events (\<70 mg/dL \[3.9mmol/L\], moderate hypoglycemia events (\<60 mg/dL \[3.3 mmol/L\] and severe hypoglycemia events (\<50 mg/dL \[2.8mmol/L\]) by SMBG at baseline (BL) and end of treatment (EOT) is reported.

Outcome measures

Outcome measures
Measure	RZ358 Cohort 4 n=2 Participants RZ358 Sequential Group Cohort 4: IV infusion for 8 weeks (bi-weekly fixed dose-titration from 3 to 9 mg/kg for the first 4 weeks, followed by a fixed 9 mg/kg dose amount thereafter for the remaining 4 weeks)	RZ358 Pooled n=20 Participants RZ358 Total Participants	RZ358 Cohort 1 n=3 Participants RZ358 Sequential Group Cohort 1: IV infusion for 8 weeks (3 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 2 n=8 Participants RZ358 Sequential Group Cohort 2: IV infusion for 8 weeks (6 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 3 n=7 Participants RZ358 Sequential Group Cohort 3: IV infusion for 8 weeks (9 mg/kg bi-weekly for 8 weeks)
Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT) Median Overall Hypoglycemia Events (<70 mg/dL; <3.9 mmol/L) at BL	9.30 Hypoglycemia Events Interval -6.02 to 24.6	11.5 Hypoglycemia Events Interval 9.43 to 19.5	10.1 Hypoglycemia Events Interval 2.46 to 17.7	12.5 Hypoglycemia Events Interval 2.94 to 28.9	13.0 Hypoglycemia Events Interval 9.15 to 23.2
Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT) Median Overall Hypoglycemia Events (<70 mg/dL; <3.9 mmol/L) at 8 Weeks (EOT)	7.60 Hypoglycemia Events Interval -19.0 to 34.2	5.00 Hypoglycemia Events Interval 4.12 to 10.7	9.92 Hypoglycemia Events Interval 1.85 to 15.4	6.60 Hypoglycemia Events Interval 2.4 to 15.6	1.87 Hypoglycemia Events Interval -2.7 to 12.8
Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT) Median Moderate Hypoglycemia Events (<60 mg/dL; <3.3 mmol/L) at BL	3.69 Hypoglycemia Events Interval -5.08 to 12.5	5.99 Hypoglycemia Events Interval 4.8 to 13.7	3.06 Hypoglycemia Events Interval -0.84 to 8.05	6.69 Hypoglycemia Events Interval 0.158 to 21.2	9.00 Hypoglycemia Events Interval 4.18 to 19.0
Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT) Median Severe Hypoglycemia Events (<50 mg/dL; <2.8 mmol/L) at 8 Weeks (EOT)	0.52 Hypoglycemia Events Interval 0.27 to 0.77	0.49 Hypoglycemia Events Interval 0.45 to 1.88	1.17 Hypoglycemia Events Interval -3.47 to 6.97	0.94 Hypoglycemia Events Interval 0.15 to 2.34	0.00 Hypoglycemia Events Interval -0.74 to 2.77
Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT) Median Moderate Hypoglycemia Events (<60 mg/dL; <3.3 mmol/L) at 8 Weeks (EOT)	4.18 Hypoglycemia Events Interval -4.4 to 12.8	2.75 Hypoglycemia Events Interval 2.08 to 6.89	6.42 Hypoglycemia Events Interval -1.52 to 12.9	3.17 Hypoglycemia Events Interval 0.945 to 9.0	0.47 Hypoglycemia Events Interval -3.13 to 10.1
Median of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG at Baseline (BL) and End of Treatment (EOT) Median Severe Hypoglycemia Events (<50 mg/dL; <2.8 mmol/L) at BL	0.91 Hypoglycemia Events Interval -4.24 to 6.05	1.90 Hypoglycemia Events Interval 1.35 to 6.1	1.31 Hypoglycemia Events Interval 0.32 to 2.58	2.59 Hypoglycemia Events Interval -0.71 to 10.4	3.50 Hypoglycemia Events Interval -0.2 to 8.66

SECONDARY outcome

Timeframe: 8 weeks

The average weekly number overall hypoglycemia events (\<70 mg/dL \[3.9mmol/L\], moderate hypoglycemia events (\<60 mg/dL \[3.3 mmol/L\] and severe hypoglycemia events (\<50 mg/dL \[2.8mmol/L\]) by SMBG is compared from baseline (BL) to end of treatment (EOT) and the median percent changes of those differences are reported.

Outcome measures

Outcome measures
Measure	RZ358 Cohort 4 n=2 Participants RZ358 Sequential Group Cohort 4: IV infusion for 8 weeks (bi-weekly fixed dose-titration from 3 to 9 mg/kg for the first 4 weeks, followed by a fixed 9 mg/kg dose amount thereafter for the remaining 4 weeks)	RZ358 Pooled n=20 Participants RZ358 Total Participants	RZ358 Cohort 1 n=3 Participants RZ358 Sequential Group Cohort 1: IV infusion for 8 weeks (3 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 2 n=8 Participants RZ358 Sequential Group Cohort 2: IV infusion for 8 weeks (6 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 3 n=7 Participants RZ358 Sequential Group Cohort 3: IV infusion for 8 weeks (9 mg/kg bi-weekly for 8 weeks)
Median Percent Change of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG From Baseline (BL) Median Percent Change of Overall Hypoglycemia Events (<70 mg/dL; <3.9 mmol/L) from BL	-19.9 Percent Change Interval -174.0 to 135.0	-58.9 Percent Change Interval -65.9 to -27.9	-1.6 Percent Change Interval -138.0 to 131.0	-47.7 Percent Change Interval -71.9 to -17.6	-84.4 Percent Change Interval -101.0 to -50.3
Median Percent Change of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG From Baseline (BL) Median Percent Change of Moderate Hypoglycemia Events (<60 mg/dL; <3.3 mmol/L) from BL	20.8 Percent Change Interval -499.0 to 540.0	-64.4 Percent Change Interval -74.1 to 7.3	14.6 Percent Change Interval -314.0 to 498.0	-65.3 Percent Change Interval -84.5 to -18.8	-94.8 Percent Change Interval -106.0 to -58.0
Median Percent Change of Average Weekly Overall, Moderate, and Severe Hypoglycemia Events by SMBG From Baseline (BL) Median Percent Change of Severe Hypoglycemia Events (<50 mg/dL; <2.8 mmol/L) from BL	-26.9 Percent Change Interval -471.0 to 417.0	-78.2 Percent Change Interval -89.3 to -4.32	-40.3 Percent Change Interval -459.0 to 550.0	-78.2 Percent Change Interval -107.0 to 4.93	-100 Percent Change Interval -105.0 to -70.2

SECONDARY outcome

Timeframe: 8 weeks

Population: Per Protocol Population

The median of average daily percent time in overall (\<70 mg/dL \[\<3.9 mmol/L\]), moderate (\<60 mg/dL \[3.3 mmol/L\]), and severe (\<50 mg/dL \[2.8 mmol/L\]) hypoglycemia at baseline (BL) and end of treatment (EOT) is reported.

Outcome measures

Outcome measures
Measure	RZ358 Cohort 4 n=3 Participants RZ358 Sequential Group Cohort 4: IV infusion for 8 weeks (bi-weekly fixed dose-titration from 3 to 9 mg/kg for the first 4 weeks, followed by a fixed 9 mg/kg dose amount thereafter for the remaining 4 weeks)	RZ358 Pooled n=22 Participants RZ358 Total Participants	RZ358 Cohort 1 n=4 Participants RZ358 Sequential Group Cohort 1: IV infusion for 8 weeks (3 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 2 n=8 Participants RZ358 Sequential Group Cohort 2: IV infusion for 8 weeks (6 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 3 n=7 Participants RZ358 Sequential Group Cohort 3: IV infusion for 8 weeks (9 mg/kg bi-weekly for 8 weeks)
Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT) Median Daily Percent Time in Moderate Hypoglycemia (<60 mg/dL; <3.3 mmol/L) at 8 Weeks (EOT)	7.35 Daily Percent Time Interval -0.43 to 13.9	3.81 Daily Percent Time Interval 3.06 to 6.73	5.13 Daily Percent Time Interval 0.05 to 9.39	3.25 Daily Percent Time Interval 1.31 to 7.6	1.79 Daily Percent Time Interval -0.72 to 10.1
Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT) Median Daily Percent Time in Severe Hypoglycemia (<50 mg/dL; < 2.8 mmol/L) at 8 Weeks (EOT)	1.27 Daily Percent Time Interval -0.67 to 3.93	1.15 Daily Percent Time Interval 1.01 to 2.33	1.27 Daily Percent Time Interval -0.216 to 3.04	1.05 Daily Percent Time Interval 0.49 to 3.02	0.61 Daily Percent Time Interval -0.17 to 3.65
Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT) Median Daily Percent Time in Overall Hypoglycemia (<70mg/dL; <3.9 mmol/L) at BL	34.4 Daily Percent Time Interval -11.4 to 69.8	16.2 Daily Percent Time Interval 15.2 to 31.2	16.3 Daily Percent Time Interval 7.83 to 24.8	20.3 Daily Percent Time Interval 14.3 to 29.1	13.7 Daily Percent Time Interval -1.17 to 53.7
Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT) Median Daily Percent Time in Overall Hypoglycemia (<70mg/dL; <3.9 mmol/L) at 8 Weeks (EOT)	20.4 Daily Percent Time Interval -6.4 to 38.9	8.54 Daily Percent Time Interval 6.73 to 14.6	12.3 Daily Percent Time Interval 1.28 to 19.6	6.68 Daily Percent Time Interval 3.05 to 16.0	5.42 Daily Percent Time Interval -1.3 to 20.6
Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT) Median Daily Percent Time in Moderate Hypoglycemia (<60 mg/dL; <3.3 mmol/L) at BL	19.5 Daily Percent Time Interval -9.22 to 37.9	7.31 Daily Percent Time Interval 6.19 to 18.4	6.85 Daily Percent Time Interval 1.53 to 11.5	8.75 Daily Percent Time Interval 6.38 to 17.3	5.22 Daily Percent Time Interval -6.3 to 36.8
Median of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT) Median Daily Percent Time in Severe Hypoglycemia (<50 mg/dL; < 2.8 mmol/L) at BL	3.03 Daily Percent Time Interval -4.08 to 11.2	2.56 Daily Percent Time Interval 1.76 to 6.84	1.97 Daily Percent Time Interval -0.09 to 3.72	3.57 Daily Percent Time Interval 2.12 to 8.17	1.12 Daily Percent Time Interval -3.7 to 13.9

SECONDARY outcome

Timeframe: 8 weeks

Population: Per Protocol Population

The average daily percent time in overall (\<70 mg/dL \[\<3.9 mmol/L\]), moderate (\<60 mg/dL \[3.3 mmol/L\]), and severe (\<50 mg/dL \[2.8 mmol/L\]) hypoglycemia is compared from baseline (BL) to end of treatment (EOT) and the median percent changes of those differences are reported.

Outcome measures

Outcome measures
Measure	RZ358 Cohort 4 n=3 Participants RZ358 Sequential Group Cohort 4: IV infusion for 8 weeks (bi-weekly fixed dose-titration from 3 to 9 mg/kg for the first 4 weeks, followed by a fixed 9 mg/kg dose amount thereafter for the remaining 4 weeks)	RZ358 Pooled n=22 Participants RZ358 Total Participants	RZ358 Cohort 1 n=4 Participants RZ358 Sequential Group Cohort 1: IV infusion for 8 weeks (3 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 2 n=8 Participants RZ358 Sequential Group Cohort 2: IV infusion for 8 weeks (6 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 3 n=7 Participants RZ358 Sequential Group Cohort 3: IV infusion for 8 weeks (9 mg/kg bi-weekly for 8 weeks)
Median Percent Change of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL) Median Percent Change in Daily Percent Time in Moderate Hypoglycemia (<60mg/dL; <3.3 mmol/L) from BL	-53.9 Percent Change Interval -130.0 to 56.2	-60.2 Percent Change Interval -65.9 to -19.9	-19.3 Percent Change Interval -103.0 to 66.5	-65.9 Percent Change Interval -94.9 to -8.67	-75.9 Percent Change Interval -107.0 to 7.76
Median Percent Change of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL) Median Percent Change in Daily Percent Time in Overall Hypoglycemia (<70mg/dL; <3.9 mmol/L) from BL	-46.6 Percent Change Interval -53.1 to -36.2	-53.5 Percent Change Interval -65.5 to -36.6	-31.1 Percent Change Interval -84.0 to 6.0	-64.6 Percent Change Interval -83.7 to -22.4	-61.0 Percent Change Interval -95.2 to -22.0
Median Percent Change of Average Daily Percent Time With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL) Median Percent Change in Daily Percent Time in Severe Hypoglycemia (<50 mg/dL; < 2.8 mmol/L) from BL	-60.7 Percent Change Interval -213.0 to 173.0	-64.8 Percent Change Interval -66.6 to 68.8	-21.9 Percent Change Interval -299.0 to 447.0	-74.4 Percent Change Interval -120.0 to 54.0	-85.0 Percent Change Interval -164.0 to 178.0

SECONDARY outcome

Timeframe: 8 weeks

Population: Per Protocol Population

The median of average duration (minutes) in overall (\<70 mg/dL \[\<3.9 mmol/L\]), moderate (\<60 mg/dL \[3.3 mmol/L\] ), and severe (\<50 mg/dL \[2.8 mmol/L\]) hypoglycemia by CGM at baseline (BL) and end of treatment (EOT) is reported.

Outcome measures

Outcome measures
Measure	RZ358 Cohort 4 n=3 Participants RZ358 Sequential Group Cohort 4: IV infusion for 8 weeks (bi-weekly fixed dose-titration from 3 to 9 mg/kg for the first 4 weeks, followed by a fixed 9 mg/kg dose amount thereafter for the remaining 4 weeks)	RZ358 Pooled n=22 Participants RZ358 Total Participants	RZ358 Cohort 1 n=4 Participants RZ358 Sequential Group Cohort 1: IV infusion for 8 weeks (3 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 2 n=8 Participants RZ358 Sequential Group Cohort 2: IV infusion for 8 weeks (6 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 3 n=7 Participants RZ358 Sequential Group Cohort 3: IV infusion for 8 weeks (9 mg/kg bi-weekly for 8 weeks)
Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT) Median Daily Duration (min) of Overall Hypoglycemia (<70 mg/dL; 3.9 mmol/L) at BL	472 Daily Minutes in Hypoglycemia Interval -177.0 to 966.0	214 Daily Minutes in Hypoglycemia Interval 202.0 to 402.0	204 Daily Minutes in Hypoglycemia Interval 107.0 to 301.0	266 Daily Minutes in Hypoglycemia Interval 185.0 to 379.0	180 Daily Minutes in Hypoglycemia Interval 8.77 to 675.0
Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT) Median Daily Duration (min) of Moderate Hypoglycemia (<60 mg/dL; 3.3 mmol/L) at BL	257 Daily Minutes in Hypoglycemia Interval -134.0 to 513.0	97.5 Daily Minutes in Hypoglycemia Interval 83.7 to 232.0	90.5 Daily Minutes in Hypoglycemia Interval 21.8 to 141.0	113 Daily Minutes in Hypoglycemia Interval 80.6 to 226.0	67.9 Daily Minutes in Hypoglycemia Interval -62.9 to 449.0
Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT) Median Daily Duration (min) of Moderate Hypoglycemia (<60 mg/dL; 3.3 mmol/L) at 8 Weeks (EOT)	105 Daily Minutes in Hypoglycemia Interval -6.03 to 195.0	46.0 Daily Minutes in Hypoglycemia Interval 39.3 to 90.6	65.8 Daily Minutes in Hypoglycemia Interval -4.32 to 130.0	35.7 Daily Minutes in Hypoglycemia Interval 13.6 to 93.9	25.3 Daily Minutes in Hypoglycemia Interval -10.8 to 144.0
Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT) Median Daily Duration (min) of Severe Hypoglycemia (<50 mg/dL; 2.8 mmol/L) at BL	39.3 Daily Minutes in Hypoglycemia Interval -61.1 to 152.0	32.7 Daily Minutes in Hypoglycemia Interval 24.1 to 83.1	26.1 Daily Minutes in Hypoglycemia Interval -0.28 to 46.7	46.3 Daily Minutes in Hypoglycemia Interval 26.1 to 105.0	14.3 Daily Minutes in Hypoglycemia Interval -37.5 to 159.0
Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT) Median Daily Duration (min) of Overall Hypoglycemia (<70 mg/dL; 3.9 mmol/L) at 8 Weeks (EOT)	287 Daily Minutes in Hypoglycemia Interval -93.6 to 554.0	99.1 Daily Minutes in Hypoglycemia Interval 89.5 to 200.0	158 Daily Minutes in Hypoglycemia Interval 10.1 to 268.0	84.1 Daily Minutes in Hypoglycemia Interval 36.5 to 208.0	76.7 Daily Minutes in Hypoglycemia Interval -19.5 to 293.0
Median of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM at Baseline (BL) and End of Treatment (EOT) Median Daily Duration (min) of Severe Hypoglycemia (<50 mg/dL; 2.8 mmol/L) at 8 Weeks (EOT)	16.7 Daily Minutes in Hypoglycemia Interval -9.13 to 53.6	14.8 Daily Minutes in Hypoglycemia Interval 12.2 to 29.0	15.00 Daily Minutes in Hypoglycemia Interval -5.07 to 41.2	14.8 Daily Minutes in Hypoglycemia Interval 6.14 to 30.1	8.67 Daily Minutes in Hypoglycemia Interval -2.36 to 50.9

SECONDARY outcome

Timeframe: 8 weeks

Population: Per Protocol Population

The average duration (minutes) in overall (\<70 mg/dL \[\<3.9 mmol/L\]), moderate (\<60 mg/dL \[3.3 mmol/L\] ), and severe (\<50 mg/dL \[2.8 mmol/L\]) hypoglycemia by CGM is compared from baseline (BL) to end of treatment (EOT) and the median percent changes of those differences are reported.

Outcome measures

Outcome measures
Measure	RZ358 Cohort 4 n=3 Participants RZ358 Sequential Group Cohort 4: IV infusion for 8 weeks (bi-weekly fixed dose-titration from 3 to 9 mg/kg for the first 4 weeks, followed by a fixed 9 mg/kg dose amount thereafter for the remaining 4 weeks)	RZ358 Pooled n=22 Participants RZ358 Total Participants	RZ358 Cohort 1 n=4 Participants RZ358 Sequential Group Cohort 1: IV infusion for 8 weeks (3 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 2 n=8 Participants RZ358 Sequential Group Cohort 2: IV infusion for 8 weeks (6 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 3 n=7 Participants RZ358 Sequential Group Cohort 3: IV infusion for 8 weeks (9 mg/kg bi-weekly for 8 weeks)
Median Percent Change of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL) Median Percent Change in Daily Duration (min) of Moderate Hypoglycemia (<60mg/dL; 3.3mmol/L) from BL	-52.8 Percent Change Interval -147.0 to 89.9	-58.1 Percent Change Interval -65.5 to -20.5	9.19 Percent Change Interval -97.7 to 69.9	-65.8 Percent Change Interval -92.9 to -23.8	-70.9 Percent Change Interval -106.0 to 9.37
Median Percent Change of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL) Median Percent Change in Daily Duration (min) of Overall Hypoglycemia (<70mg/dL; 3.9 mmol/L) from BL	-40.2 Percent Change Interval -47.5 to -34.8	-49.1 Percent Change Interval -64.4 to -36.1	-22.2 Percent Change Interval -83.4 to 13.0	-63.7 Percent Change Interval -82.0 to -30.1	-57.5 Percent Change Interval -94.3 to -18.2
Median Percent Change of Average Daily Duration (Minutes) With Overall, Moderate, and Severe Hypoglycemia by CGM From Baseline (BL) Median Percent Change in Daily Duration (min) of Severe Hypoglycemia (<50 mg/dL; 2.8 mmol/L) from BL	-59.8 Percent Change Interval -325.0 to 357.0	-63.0 Percent Change Interval -66.2 to 61.3	-18.6 Percent Change Interval -272.0 to 400.0	-77.0 Percent Change Interval -107.0 to 7.36	-81.2 Percent Change Interval -160.0 to 171.0

SECONDARY outcome

Timeframe: 8 Weeks

Population: Per Protocol Population

The occurrence of hypoglycemia during a 12 Hour fasting challenge.

Outcome measures

Outcome measures
Measure	RZ358 Cohort 4 n=3 Participants RZ358 Sequential Group Cohort 4: IV infusion for 8 weeks (bi-weekly fixed dose-titration from 3 to 9 mg/kg for the first 4 weeks, followed by a fixed 9 mg/kg dose amount thereafter for the remaining 4 weeks)	RZ358 Pooled n=22 Participants RZ358 Total Participants	RZ358 Cohort 1 n=4 Participants RZ358 Sequential Group Cohort 1: IV infusion for 8 weeks (3 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 2 n=8 Participants RZ358 Sequential Group Cohort 2: IV infusion for 8 weeks (6 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 3 n=7 Participants RZ358 Sequential Group Cohort 3: IV infusion for 8 weeks (9 mg/kg bi-weekly for 8 weeks)
Occurrence of Hypoglycemia During Fasting Challenge Number of patients able to complete fast at Baseline (n)	0 participants	5 participants	3 participants	2 participants	0 participants
Occurrence of Hypoglycemia During Fasting Challenge Number of patients able to complete fast at EOT (n)	1 participants	7 participants	3 participants	1 participants	2 participants

SECONDARY outcome

Timeframe: 8 weeks

Population: Per Protocol Population

The median of average hypoglycemia events per day at each of the specified glucose thresholds \[\<70, \<60, and \<50 mg/dL (3.9, 3.3, and 2.8 mmol/L)\], by CGM at baseline (BL) and end of treatment (EOT) is reported.

Outcome measures

Outcome measures
Measure	RZ358 Cohort 4 n=3 Participants RZ358 Sequential Group Cohort 4: IV infusion for 8 weeks (bi-weekly fixed dose-titration from 3 to 9 mg/kg for the first 4 weeks, followed by a fixed 9 mg/kg dose amount thereafter for the remaining 4 weeks)	RZ358 Pooled n=22 Participants RZ358 Total Participants	RZ358 Cohort 1 n=4 Participants RZ358 Sequential Group Cohort 1: IV infusion for 8 weeks (3 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 2 n=8 Participants RZ358 Sequential Group Cohort 2: IV infusion for 8 weeks (6 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 3 n=7 Participants RZ358 Sequential Group Cohort 3: IV infusion for 8 weeks (9 mg/kg bi-weekly for 8 weeks)
Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT) Median of Average Hypoglycemia Events Per Day <70mg/dL (3.9mmol/L) at BL	4.47 Hypoglycemia Events Per Day Interval 2.18 to 6.22	3.37 Hypoglycemia Events Per Day Interval 2.77 to 3.91	3.00 Hypoglycemia Events Per Day Interval 1.71 to 4.25	3.50 Hypoglycemia Events Per Day Interval 2.4 to 4.3	2.46 Hypoglycemia Events Per Day Interval 1.49 to 4.84
Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT) Median of Average Hypoglycemia Events Per Day <70mg/dL (3.9mmol/L) at 8 Weeks (EOT)	3.33 Hypoglycemia Events Per Day Interval -1.05 to 8.11	2.23 Hypoglycemia Events Per Day Interval 1.72 to 3.37	2.37 Hypoglycemia Events Per Day Interval 0.78 to 3.88	1.70 Hypoglycemia Events Per Day Interval 0.93 to 3.78	2.33 Hypoglycemia Events Per Day Interval 0.09 to 4.83
Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT) Median of Average Hypoglycemia Events Per Day <60 mg/dL (3.3mmol/L) at 8 Weeks (EOT)	2.07 Hypoglycemia Events Per Day Interval -0.86 to 5.84	1.50 Hypoglycemia Events Per Day Interval 1.15 to 2.48	1.54 Hypoglycemia Events Per Day Interval 0.6 to 2.53	1.06 Hypoglycemia Events Per Day Interval 0.5 to 2.92	1.60 Hypoglycemia Events Per Day Interval -0.14 to 3.72
Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT) Median Average Hypoglycemia Events Per Day <50mg/dL(2.8mmol/L) at BL	1.67 Hypoglycemia Events Per Day Interval -0.62 to 3.27	1.13 Hypoglycemia Events Per Day Interval 0.77 to 1.47	0.91 Hypoglycemia Events Per Day Interval 0.08 to 1.69	1.29 Hypoglycemia Events Per Day Interval 0.61 to 2.33	0.79 Hypoglycemia Events Per Day Interval 0.3 to 1.25
Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT) Median Average Hypoglycemia Events Per Day <50mg/dL(2.8mmol/L) at 8 Weeks (EOT)	1.00 Hypoglycemia Events Per Day Interval -0.12 to 2.2	0.64 Hypoglycemia Events Per Day Interval 0.54 to 1.09	0.74 Hypoglycemia Events Per Day Interval 0.2 to 1.18	0.53 Hypoglycemia Events Per Day Interval 0.23 to 1.4	0.60 Hypoglycemia Events Per Day Interval 0.03 to 1.55
Median of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM at Baseline (BL) and End of Treatment (EOT) Median of Average Hypoglycemia Events Per Day <60 mg/dL (3.3mmol/L) at BL	3.07 Hypoglycemia Events Per Day Interval 0.3 to 5.53	2.00 Hypoglycemia Events Per Day Interval 1.85 to 2.8	1.73 Hypoglycemia Events Per Day Interval 1.11 to 2.62	2.22 Hypoglycemia Events Per Day Interval 1.59 to 3.52	1.77 Hypoglycemia Events Per Day Interval 0.92 to 3.23

SECONDARY outcome

Timeframe: 8 weeks

Population: Per Protocol Population

The average hypoglycemia events per day at each of the specified glucose thresholds \[\<70, \<60, and \<50 mg/dL (3.9, 3.3, and 2.8 mmol/L)\], by CGM is compared from baseline (BL) to end of treatment (EOT) and the median net changes of those differences are reported.

Outcome measures

Outcome measures
Measure	RZ358 Cohort 4 n=3 Participants RZ358 Sequential Group Cohort 4: IV infusion for 8 weeks (bi-weekly fixed dose-titration from 3 to 9 mg/kg for the first 4 weeks, followed by a fixed 9 mg/kg dose amount thereafter for the remaining 4 weeks)	RZ358 Pooled n=22 Participants RZ358 Total Participants	RZ358 Cohort 1 n=4 Participants RZ358 Sequential Group Cohort 1: IV infusion for 8 weeks (3 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 2 n=8 Participants RZ358 Sequential Group Cohort 2: IV infusion for 8 weeks (6 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 3 n=7 Participants RZ358 Sequential Group Cohort 3: IV infusion for 8 weeks (9 mg/kg bi-weekly for 8 weeks)
Median Net Change of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM From Baseline (BL) Median Net Change of Average Hypoglycemia Events Per Day <70 mg/dL (3.9mmol/L) from BL	-1.14 Events Per Day Interval -3.48 to 2.14	-1.05 Events Per Day Interval -1.67 to 0.08	-0.47 Events Per Day Interval -1.98 to 0.69	-1.41 Events Per Day Interval -2.04 to 0.04	-1.49 Events Per Day Interval -3.76 to 2.34
Median Net Change of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM From Baseline (BL) Median Net Change of Average Hypoglycemia Events Per Day <60 mg/dL (3.3mmol/L) from BL	-0.39 Events Per Day Interval -1.82 to 0.97	-0.61 Events Per Day Interval -1.14 to 0.12	-0.32 Events Per Day Interval -1.48 to 0.89	-0.82 Events Per Day Interval -1.57 to -0.13	-0.63 Events Per Day Interval -2.48 to 1.9
Median Net Change of Average Hypoglycemia Events Per Day at Each of the Specified Glucose Thresholds by CGM From Baseline (BL) Median Net Change of Average Hypoglycemia Events Per Day <50mg/dL(2.8mmol/L) from BL	-0.35 Events Per Day Interval -2.33 to 1.76	-0.30 Events Per Day Interval -0.63 to 0.01	-0.28 Events Per Day Interval -0.94 to 0.54	-0.98 Events Per Day Interval -1.24 to -0.08	-0.06 Events Per Day Interval -0.72 to 0.76

SECONDARY outcome

Timeframe: 8 weeks

Population: Per Protocol Population

The median of average 8-hour overnight (12am-8am) percent time within the glucose target range (70-180 mg/dL) at baseline (BL) and end of treatment (EOT) is reported.

Outcome measures

Outcome measures
Measure	RZ358 Cohort 4 n=3 Participants RZ358 Sequential Group Cohort 4: IV infusion for 8 weeks (bi-weekly fixed dose-titration from 3 to 9 mg/kg for the first 4 weeks, followed by a fixed 9 mg/kg dose amount thereafter for the remaining 4 weeks)	RZ358 Pooled n=22 Participants RZ358 Total Participants	RZ358 Cohort 1 n=4 Participants RZ358 Sequential Group Cohort 1: IV infusion for 8 weeks (3 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 2 n=8 Participants RZ358 Sequential Group Cohort 2: IV infusion for 8 weeks (6 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 3 n=7 Participants RZ358 Sequential Group Cohort 3: IV infusion for 8 weeks (9 mg/kg bi-weekly for 8 weeks)
Median of Average 8-hour Overnight Percent Time in Glucose Target Range of 70-180mg/dL by CGM at Baseline (BL) and End of Treatment (EOT) Median of Average 8h Overnight Percent Time in 70-180 mg/dL at 8 Weeks (EOT)	73.8 8-hour Overnight Percent Time Interval 51.0 to 91.4	80.1 8-hour Overnight Percent Time Interval 69.9 to 85.6	84.4 8-hour Overnight Percent Time Interval 68.2 to 103.0	81.1 8-hour Overnight Percent Time Interval 55.7 to 94.1	89.2 8-hour Overnight Percent Time Interval 62.5 to 96.0
Median of Average 8-hour Overnight Percent Time in Glucose Target Range of 70-180mg/dL by CGM at Baseline (BL) and End of Treatment (EOT) Median of Average 8h Overnight Percent Time in 70-180 mg/dL at BL	48.0 8-hour Overnight Percent Time Interval -1.33 to 121.0	75.0 8-hour Overnight Percent Time Interval 63.1 to 83.1	80.8 8-hour Overnight Percent Time Interval 60.2 to 103.0	75.0 8-hour Overnight Percent Time Interval 70.1 to 86.6	82.1 8-hour Overnight Percent Time Interval 36.4 to 99.6

SECONDARY outcome

Timeframe: 8 weeks

Population: Per Protocol Population

The average 8-hour overnight (12am-8am) percent time within the glucose target range (70-180 mg/dL) is compared from baseline (BL) to end of treeatment (EOT) and the median percent change of that difference is reported.

Outcome measures

Outcome measures
Measure	RZ358 Cohort 4 n=3 Participants RZ358 Sequential Group Cohort 4: IV infusion for 8 weeks (bi-weekly fixed dose-titration from 3 to 9 mg/kg for the first 4 weeks, followed by a fixed 9 mg/kg dose amount thereafter for the remaining 4 weeks)	RZ358 Pooled n=22 Participants RZ358 Total Participants	RZ358 Cohort 1 n=4 Participants RZ358 Sequential Group Cohort 1: IV infusion for 8 weeks (3 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 2 n=8 Participants RZ358 Sequential Group Cohort 2: IV infusion for 8 weeks (6 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 3 n=7 Participants RZ358 Sequential Group Cohort 3: IV infusion for 8 weeks (9 mg/kg bi-weekly for 8 weeks)
Median Percent Change of Average 8-hour Overnight Percent Time in Glucose Target Range of 70-180mg/dL by CGM From Baseline (BL)	44.1 Percent Change Interval -58.7 to 116.0	4.22 Percent Change Interval -11.1 to 66.9	7.59 Percent Change Interval -4.71 to 15.8	3.67 Percent Change Interval -28.6 to 22.4	-2.64 Percent Change Interval -59.1 to 211.0

Adverse Events

RZ358 Cohort 1

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

RZ358 Cohort 2

Serious events: 2 serious events

Other events: 7 other events

Deaths: 0 deaths

RZ358 Cohort 3

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

RZ358 Cohort 4

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	RZ358 Cohort 1 n=4 participants at risk RZ358 Sequential Group Cohort 1: IV infusion for 8 weeks (3 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 2 n=8 participants at risk RZ358 Sequential Group Cohort 2: IV infusion for 8 weeks (6 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 3 n=8 participants at risk RZ358 Sequential Group Cohort 3: IV infusion for 8 weeks (9 mg/kg bi-weekly for 8 weeks)	RZ358 Cohort 4 n=3 participants at risk RZ358 Sequential Group Cohort 4: IV infusion for 8 weeks (bi-weekly fixed dose-titration from 3 to 9 mg/kg for the first 4 weeks, followed by a fixed 9 mg/kg dose amount thereafter for the remaining 4 weeks)
Endocrine disorders Hypoglycemia with LOC	0.00% 0/4 • 8 weeks Any untoward medical occurrence \[i.e., any unfavorable and unintended sign (including abnormal lab findings), symptom or disease\] which is either new or pre-existing but worsened in severity or frequency, whether or not it has a causal relationship to the study investigational (medicinal) products or procedures. Includes events w/ onset from the time of providing written informed consent until the EOS visit. AE may or may not be temporally or causally associated w/ the use of a study drug.	12.5% 1/8 • Number of events 1 • 8 weeks Any untoward medical occurrence \[i.e., any unfavorable and unintended sign (including abnormal lab findings), symptom or disease\] which is either new or pre-existing but worsened in severity or frequency, whether or not it has a causal relationship to the study investigational (medicinal) products or procedures. Includes events w/ onset from the time of providing written informed consent until the EOS visit. AE may or may not be temporally or causally associated w/ the use of a study drug.	0.00% 0/8 • 8 weeks Any untoward medical occurrence \[i.e., any unfavorable and unintended sign (including abnormal lab findings), symptom or disease\] which is either new or pre-existing but worsened in severity or frequency, whether or not it has a causal relationship to the study investigational (medicinal) products or procedures. Includes events w/ onset from the time of providing written informed consent until the EOS visit. AE may or may not be temporally or causally associated w/ the use of a study drug.	0.00% 0/3 • 8 weeks Any untoward medical occurrence \[i.e., any unfavorable and unintended sign (including abnormal lab findings), symptom or disease\] which is either new or pre-existing but worsened in severity or frequency, whether or not it has a causal relationship to the study investigational (medicinal) products or procedures. Includes events w/ onset from the time of providing written informed consent until the EOS visit. AE may or may not be temporally or causally associated w/ the use of a study drug.
Nervous system disorders Tonic-Clonic Seizure	0.00% 0/4 • 8 weeks Any untoward medical occurrence \[i.e., any unfavorable and unintended sign (including abnormal lab findings), symptom or disease\] which is either new or pre-existing but worsened in severity or frequency, whether or not it has a causal relationship to the study investigational (medicinal) products or procedures. Includes events w/ onset from the time of providing written informed consent until the EOS visit. AE may or may not be temporally or causally associated w/ the use of a study drug.	0.00% 0/8 • 8 weeks Any untoward medical occurrence \[i.e., any unfavorable and unintended sign (including abnormal lab findings), symptom or disease\] which is either new or pre-existing but worsened in severity or frequency, whether or not it has a causal relationship to the study investigational (medicinal) products or procedures. Includes events w/ onset from the time of providing written informed consent until the EOS visit. AE may or may not be temporally or causally associated w/ the use of a study drug.	12.5% 1/8 • Number of events 1 • 8 weeks Any untoward medical occurrence \[i.e., any unfavorable and unintended sign (including abnormal lab findings), symptom or disease\] which is either new or pre-existing but worsened in severity or frequency, whether or not it has a causal relationship to the study investigational (medicinal) products or procedures. Includes events w/ onset from the time of providing written informed consent until the EOS visit. AE may or may not be temporally or causally associated w/ the use of a study drug.	0.00% 0/3 • 8 weeks Any untoward medical occurrence \[i.e., any unfavorable and unintended sign (including abnormal lab findings), symptom or disease\] which is either new or pre-existing but worsened in severity or frequency, whether or not it has a causal relationship to the study investigational (medicinal) products or procedures. Includes events w/ onset from the time of providing written informed consent until the EOS visit. AE may or may not be temporally or causally associated w/ the use of a study drug.
Blood and lymphatic system disorders Eosinophilic Leukocytosis	0.00% 0/4 • 8 weeks Any untoward medical occurrence \[i.e., any unfavorable and unintended sign (including abnormal lab findings), symptom or disease\] which is either new or pre-existing but worsened in severity or frequency, whether or not it has a causal relationship to the study investigational (medicinal) products or procedures. Includes events w/ onset from the time of providing written informed consent until the EOS visit. AE may or may not be temporally or causally associated w/ the use of a study drug.	12.5% 1/8 • Number of events 1 • 8 weeks Any untoward medical occurrence \[i.e., any unfavorable and unintended sign (including abnormal lab findings), symptom or disease\] which is either new or pre-existing but worsened in severity or frequency, whether or not it has a causal relationship to the study investigational (medicinal) products or procedures. Includes events w/ onset from the time of providing written informed consent until the EOS visit. AE may or may not be temporally or causally associated w/ the use of a study drug.	0.00% 0/8 • 8 weeks Any untoward medical occurrence \[i.e., any unfavorable and unintended sign (including abnormal lab findings), symptom or disease\] which is either new or pre-existing but worsened in severity or frequency, whether or not it has a causal relationship to the study investigational (medicinal) products or procedures. Includes events w/ onset from the time of providing written informed consent until the EOS visit. AE may or may not be temporally or causally associated w/ the use of a study drug.	0.00% 0/3 • 8 weeks Any untoward medical occurrence \[i.e., any unfavorable and unintended sign (including abnormal lab findings), symptom or disease\] which is either new or pre-existing but worsened in severity or frequency, whether or not it has a causal relationship to the study investigational (medicinal) products or procedures. Includes events w/ onset from the time of providing written informed consent until the EOS visit. AE may or may not be temporally or causally associated w/ the use of a study drug.

Other adverse events

Additional Information

Chief Medical Officer (Dr. Brian Roberts)

Rezolute

Phone: 650-206-4507

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60