Trial Outcomes & Findings for A Study of Zetomipzomib (KZR-616) in Patients With Autoimmune Hepatitis (PORTOLA) (NCT NCT05569759)

Last Updated: 2026-01-13

Results Overview

The number of patients who achieve complete biochemical response (CR), defined as normal ALT, AST, and IgG values (if IgG level is elevated at Baseline) with glucocorticoid dose not higher than starting dose (at Baseline), by Week 24 of the Double-Blind Treatment Period. Analyses were also conducted at Week 12, Week 16, and Week 20.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

24 participants

Primary outcome timeframe

Week 12, Week 16, Week 20, and Week 24

Results posted on

2026-01-13

Participant Flow

The randomization stratification factor for the study was use of glucocorticoids at Screening (ie, glucocorticoid use, no glucocorticoid use at Screening).

Participant milestones

Participant milestones
Measure	Zetomipzomib + Standard-of-care (Glucocorticoids) Participants received an initial 30 mg dose of zetomipzomib, followed by weekly 60 mg doses of zetomipzomib, for the remaining 23 weeks of the treatment period in addition to standard of care. Participants who completed the double blind treatment period could elect to continue in the open-label extension (OLE) period of the study. Participants who enrolled in the OLE period received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib in addition to standard of care, for up to a total of 24 additional weeks of treatment. zetomipzomib: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Placebo + Standard-of-care (Glucocorticoids) Participants received an initial 30 mg dose of placebo (sterile water for injection), followed by weekly 60 mg doses of placebo, for the remaining 23 weeks of the treatment period in addition to standard of care. placebo: Subcutaneous injection of placebo Participants who completed the double blind treatment period could elect to continue in the open-label extension (OLE) period of the study. Participants who enrolled in the OLE period received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib in addition to standard of care, for up to a total of 24 additional weeks of treatment.
Double Blind Treatment Period STARTED	16	8
Double Blind Treatment Period COMPLETED	13	7
Double Blind Treatment Period NOT COMPLETED	3	1
Optional Open-Label Extension STARTED	9	5
Optional Open-Label Extension COMPLETED	4	3
Optional Open-Label Extension NOT COMPLETED	5	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

This is the subset of participants with abnormal baseline IgG values.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Zetomipzomib + Standard-of-care (Glucocorticoids) n=16 Participants Participants received an initial 30 mg dose of zetomipzomib, followed by weekly 60 mg doses of zetomipzomib, for the remaining 23 weeks of the double-blind treatment period in addition to standard of care. Participants who completed the double-blind treatment period could elect to continue in the open-label extension (OLE) period of the study. Participants who enrolled in the OLE period received an initial 30 mg dose of zetomipzomib at the OLE Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib in addition to standard of care, for up to a total of 24 additional weeks of treatment. zetomipzomib: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Placebo + Standard-of-care (Glucocorticoids) n=7 Participants Participants received an initial 30 mg dose of placebo (sterile water for injection), followed by weekly 60 mg doses of placebo, for the remaining 23 weeks of the double-blind treatment period in addition to standard of care. placebo: Subcutaneous injection of placebo Participants who completed the double-blind treatment period could elect to continue in the open-label extension (OLE) period of the study. Participants who enrolled in the OLE period received an initial 30 mg dose of zetomipzomib at the OLE Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib in addition to standard of care, for up to a total of 24 additional weeks of treatment.	Total n=23 Participants Total of all reporting groups
Age, Continuous	54.4 years STANDARD_DEVIATION 15.6 • n=16 Participants	48.9 years STANDARD_DEVIATION 19.7 • n=7 Participants	52.7 years STANDARD_DEVIATION 16.7 • n=23 Participants
Sex: Female, Male Female	8 Participants n=16 Participants	5 Participants n=7 Participants	13 Participants n=23 Participants
Sex: Female, Male Male	8 Participants n=16 Participants	2 Participants n=7 Participants	10 Participants n=23 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=16 Participants	1 Participants n=7 Participants	3 Participants n=23 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	14 Participants n=16 Participants	6 Participants n=7 Participants	20 Participants n=23 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=16 Participants	0 Participants n=7 Participants	0 Participants n=23 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=16 Participants	0 Participants n=7 Participants	0 Participants n=23 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=16 Participants	1 Participants n=7 Participants	2 Participants n=23 Participants
Race/Ethnicity, Customized Native Hawaiian	0 Participants n=16 Participants	0 Participants n=7 Participants	0 Participants n=23 Participants
Race/Ethnicity, Customized White	13 Participants n=16 Participants	6 Participants n=7 Participants	19 Participants n=23 Participants
Race/Ethnicity, Customized Asian Indian	0 Participants n=16 Participants	0 Participants n=7 Participants	0 Participants n=23 Participants
Race/Ethnicity, Customized Chinese	0 Participants n=16 Participants	0 Participants n=7 Participants	0 Participants n=23 Participants
Race/Ethnicity, Customized Filipino	0 Participants n=16 Participants	0 Participants n=7 Participants	0 Participants n=23 Participants
Race/Ethnicity, Customized Japanese	0 Participants n=16 Participants	0 Participants n=7 Participants	0 Participants n=23 Participants
Race/Ethnicity, Customized Korean	0 Participants n=16 Participants	0 Participants n=7 Participants	0 Participants n=23 Participants
Race/Ethnicity, Customized Vietnamese	0 Participants n=16 Participants	0 Participants n=7 Participants	0 Participants n=23 Participants
Race/Ethnicity, Customized Other Asian	0 Participants n=16 Participants	0 Participants n=7 Participants	0 Participants n=23 Participants
Race/Ethnicity, Customized Guamanian or Chamorro	0 Participants n=16 Participants	0 Participants n=7 Participants	0 Participants n=23 Participants
Race/Ethnicity, Customized Samoan	0 Participants n=16 Participants	0 Participants n=7 Participants	0 Participants n=23 Participants
Race/Ethnicity, Customized Other Pacific Islander	0 Participants n=16 Participants	0 Participants n=7 Participants	0 Participants n=23 Participants
Race/Ethnicity, Customized Other	2 Participants n=16 Participants	0 Participants n=7 Participants	2 Participants n=23 Participants
Race/Ethnicity, Customized Multi-Racial	0 Participants n=16 Participants	0 Participants n=7 Participants	0 Participants n=23 Participants
Baseline ALT	106.7 U/L STANDARD_DEVIATION 49.0 • n=16 Participants	143.4 U/L STANDARD_DEVIATION 75.2 • n=7 Participants	117.9 U/L STANDARD_DEVIATION 59.0 • n=23 Participants
Baseline AST	79.5 U/L STANDARD_DEVIATION 50.4 • n=16 Participants	107.0 U/L STANDARD_DEVIATION 40.6 • n=7 Participants	87.8 U/L STANDARD_DEVIATION 48.4 • n=23 Participants
Baseline IgG	1865.3 mg/dL STANDARD_DEVIATION 842.5 • n=16 Participants	1985.1 mg/dL STANDARD_DEVIATION 579.2 • n=7 Participants	1901.7 mg/dL STANDARD_DEVIATION 760.7 • n=23 Participants
Baseline IgG (Abnormal at Baseline)	2396.7 mg/dL STANDARD_DEVIATION 751.8 • n=9 Participants • This is the subset of participants with abnormal baseline IgG values.	2213.0 mg/dL STANDARD_DEVIATION 514.5 • n=5 Participants • This is the subset of participants with abnormal baseline IgG values.	2331.1 mg/dL STANDARD_DEVIATION 661.5 • n=14 Participants • This is the subset of participants with abnormal baseline IgG values.
Duration of AIH	5.5 years STANDARD_DEVIATION 5.9 • n=16 Participants	8.3 years STANDARD_DEVIATION 7.6 • n=7 Participants	6.3 years STANDARD_DEVIATION 6.4 • n=23 Participants
Glucocorticoid Dose at Baseline	21.3 mg/day STANDARD_DEVIATION 3.4 • n=16 Participants	20.0 mg/day STANDARD_DEVIATION 0.0 • n=7 Participants	20.9 mg/day STANDARD_DEVIATION 2.9 • n=23 Participants

PRIMARY outcome

Timeframe: Week 12, Week 16, Week 20, and Week 24

Population: The Intent to Treat (ITT) Set included all randomized participants (N=24).

Outcome measures

Outcome measures
Measure	Double-blind Treatment Period: Zetomipzomib + Standard-of-care (Glucocorticoids) n=16 Participants Participants received an initial 30 mg dose of zetomipzomib, followed by weekly 60 mg doses of zetomipzomib, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. zetomipzomib: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Double-blind Treatment Period: Placebo + Standard-of-care (Glucocorticoids) n=8 Participants Participants received an initial 30 mg dose of placebo (sterile water for injection), followed by weekly 60 mg doses of placebo, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. placebo: Subcutaneous injection of placebo	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Zetomipzomib in DBTP) Participants, who received zetomipzomib in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received zetomipzomib during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Placebo in DBTP) Participants, who received placebo in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received placebo during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly
Patients Who Achieved Complete Biochemical Response Week 24	8 Participants	3 Participants	—	—
Patients Who Achieved Complete Biochemical Response Week 12	6 Participants	3 Participants	—	—
Patients Who Achieved Complete Biochemical Response Week 16	7 Participants	3 Participants	—	—
Patients Who Achieved Complete Biochemical Response Week 20	8 Participants	3 Participants	—	—

PRIMARY outcome

Timeframe: Baseline through end of study visit (DBTP, Week 28 and OLE, Up to Week 24)

Population: The Safety Set (N=23) includes all participants who received at least one dose of IMP and were analyzed as randomized to treatment.

Proportion of participants who experience AEs (adverse events) and SAEs (serious adverse events) during the double-blind treatment period (DBTP) and the open-label extension (OLE).

Outcome measures

Outcome measures
Measure	Double-blind Treatment Period: Zetomipzomib + Standard-of-care (Glucocorticoids) n=16 Participants Participants received an initial 30 mg dose of zetomipzomib, followed by weekly 60 mg doses of zetomipzomib, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. zetomipzomib: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Double-blind Treatment Period: Placebo + Standard-of-care (Glucocorticoids) n=7 Participants Participants received an initial 30 mg dose of placebo (sterile water for injection), followed by weekly 60 mg doses of placebo, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. placebo: Subcutaneous injection of placebo	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Zetomipzomib in DBTP) n=9 Participants Participants, who received zetomipzomib in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received zetomipzomib during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Placebo in DBTP) n=5 Participants Participants, who received placebo in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received placebo during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly
The Safety and Tolerability of Zetomipzomib Adverse events	16 participants	7 participants	9 participants	5 participants
The Safety and Tolerability of Zetomipzomib Serious adverse events	2 participants	1 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: Start of open-label extension (OLE) period through End of Study (EOS) up to OLE Week 25

Population: Participants who enrolled in the optional open-label extension following their completion of the double-blind treatment period of the study and achieved a complete response during the double-blind treatment period.

Proportion of participants experiencing a disease flare among the participants who achieved a complete biochemical response (CR) during the double-blind treatment period.

Outcome measures

Outcome measures
Measure	Double-blind Treatment Period: Zetomipzomib + Standard-of-care (Glucocorticoids) n=5 Participants Participants received an initial 30 mg dose of zetomipzomib, followed by weekly 60 mg doses of zetomipzomib, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. zetomipzomib: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Double-blind Treatment Period: Placebo + Standard-of-care (Glucocorticoids) n=2 Participants Participants received an initial 30 mg dose of placebo (sterile water for injection), followed by weekly 60 mg doses of placebo, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. placebo: Subcutaneous injection of placebo	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Zetomipzomib in DBTP) Participants, who received zetomipzomib in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received zetomipzomib during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Placebo in DBTP) Participants, who received placebo in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received placebo during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly
Proportion of Participants Experiencing a Disease Flare Among the Participants Who Achieved a CR During the Double-blind Treatment Period	0 participants Interval 0.0 to 52.2	0 participants Interval 0.0 to 84.2	—	—

SECONDARY outcome

Timeframe: Weeks 12, 16, 20, and 24

Population: The Intent to Treat (ITT) Set included all randomized participants (N=24).

Changes from baseline in alanine aminotransferase (ALT) during the double-blind treatment period.

Outcome measures

Outcome measures
Measure	Double-blind Treatment Period: Zetomipzomib + Standard-of-care (Glucocorticoids) n=16 Participants Participants received an initial 30 mg dose of zetomipzomib, followed by weekly 60 mg doses of zetomipzomib, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. zetomipzomib: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Double-blind Treatment Period: Placebo + Standard-of-care (Glucocorticoids) n=8 Participants Participants received an initial 30 mg dose of placebo (sterile water for injection), followed by weekly 60 mg doses of placebo, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. placebo: Subcutaneous injection of placebo	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Zetomipzomib in DBTP) Participants, who received zetomipzomib in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received zetomipzomib during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Placebo in DBTP) Participants, who received placebo in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received placebo during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly
Alanine Aminotransferase (ALT) Week 12	-49.8 U/L Standard Deviation 67.1	-47.3 U/L Standard Deviation 116.5	—	—
Alanine Aminotransferase (ALT) Week 20	-29.4 U/L Standard Deviation 100.8	-33.3 U/L Standard Deviation 113.4	—	—
Alanine Aminotransferase (ALT) Week 24	-22.8 U/L Standard Deviation 103.5	-80.6 U/L Standard Deviation 58.0	—	—
Alanine Aminotransferase (ALT) Week 16	-46.4 U/L Standard Deviation 70.4	-65.8 U/L Standard Deviation 81.7	—	—

SECONDARY outcome

Timeframe: Weeks 12, 16, 20, and 24

Population: The Intent to Treat (ITT) Set included all randomized participants (N=24).

Proportion of participants who achieved a partial response (PR) during the double-blind treatment period of the study.

Outcome measures

Outcome measures
Measure	Double-blind Treatment Period: Zetomipzomib + Standard-of-care (Glucocorticoids) n=16 Participants Participants received an initial 30 mg dose of zetomipzomib, followed by weekly 60 mg doses of zetomipzomib, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. zetomipzomib: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Double-blind Treatment Period: Placebo + Standard-of-care (Glucocorticoids) n=8 Participants Participants received an initial 30 mg dose of placebo (sterile water for injection), followed by weekly 60 mg doses of placebo, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. placebo: Subcutaneous injection of placebo	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Zetomipzomib in DBTP) Participants, who received zetomipzomib in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received zetomipzomib during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Placebo in DBTP) Participants, who received placebo in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received placebo during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly
Partial Response Week 12	4 Participants	2 Participants	—	—
Partial Response Week 16	1 Participants	0 Participants	—	—
Partial Response Week 20	1 Participants	0 Participants	—	—
Partial Response Week 24	2 Participants	1 Participants	—	—

SECONDARY outcome

Timeframe: Baseline through Week 24

Population: The Intent to Treat (ITT) Set included all randomized participants (N=24).

Time to complete response (CR), defined as the duration from first dose of study drug (zetomipzomib or placebo) to first CR, during the double-blind treatment period was measured using the Kaplan-Meier method. Due to the small sample size, not enough events of participants achieving CR were observed to provide Kaplan-Meier estimates for the 25th percentile, median, and 75th percentile time to CR.

Outcome measures

Outcome measures
Measure	Double-blind Treatment Period: Zetomipzomib + Standard-of-care (Glucocorticoids) n=16 Participants Participants received an initial 30 mg dose of zetomipzomib, followed by weekly 60 mg doses of zetomipzomib, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. zetomipzomib: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Double-blind Treatment Period: Placebo + Standard-of-care (Glucocorticoids) n=8 Participants Participants received an initial 30 mg dose of placebo (sterile water for injection), followed by weekly 60 mg doses of placebo, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. placebo: Subcutaneous injection of placebo	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Zetomipzomib in DBTP) Participants, who received zetomipzomib in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received zetomipzomib during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Placebo in DBTP) Participants, who received placebo in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received placebo during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly
Time to Complete Response	NA weeks Interval 8.14 to Not evaluable due to the small number of participants who achieved complete response as participants who did not achieve a CR were considered non-responders and were censored from analysis.	NA weeks Interval 4.14 to Not evaluable due to the small number of participants who achieved complete response as participants who did not achieve a CR were considered non-responders and were censored from analysis.	—	—

SECONDARY outcome

Timeframe: Week 24

Population: The Intent to Treat (ITT) Set included all randomized participants (N=24).

Proportion of participants who experienced a disease flare after complete response (CR) during the double-blind treatment period.

Outcome measures

Outcome measures
Measure	Double-blind Treatment Period: Zetomipzomib + Standard-of-care (Glucocorticoids) n=16 Participants Participants received an initial 30 mg dose of zetomipzomib, followed by weekly 60 mg doses of zetomipzomib, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. zetomipzomib: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Double-blind Treatment Period: Placebo + Standard-of-care (Glucocorticoids) n=8 Participants Participants received an initial 30 mg dose of placebo (sterile water for injection), followed by weekly 60 mg doses of placebo, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. placebo: Subcutaneous injection of placebo	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Zetomipzomib in DBTP) Participants, who received zetomipzomib in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received zetomipzomib during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Placebo in DBTP) Participants, who received placebo in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received placebo during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly
Disease Flare After CR	0 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: Week 24

Population: The Intent to Treat (ITT) Set included all randomized participants (N=24).

Proportion of participants who were considered treatment failures, defined as ALT or AST level worsened ≥2 times that of the Baseline value that is sustained for ≥1 week as verified via repeat laboratory assessments, despite compliance with standard of care (ie, with regard to inclusion criteria) or protocol-defined therapy or a glucocorticoid dose is increased above the Baseline dose, it may be considered a treatment failure unless attributed to an adverse event not relating to AIH, during the double-blind treatment period.

Outcome measures

Outcome measures
Measure	Double-blind Treatment Period: Zetomipzomib + Standard-of-care (Glucocorticoids) n=16 Participants Participants received an initial 30 mg dose of zetomipzomib, followed by weekly 60 mg doses of zetomipzomib, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. zetomipzomib: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Double-blind Treatment Period: Placebo + Standard-of-care (Glucocorticoids) n=8 Participants Participants received an initial 30 mg dose of placebo (sterile water for injection), followed by weekly 60 mg doses of placebo, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. placebo: Subcutaneous injection of placebo	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Zetomipzomib in DBTP) Participants, who received zetomipzomib in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received zetomipzomib during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Placebo in DBTP) Participants, who received placebo in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received placebo during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly
Treatment Failures	2 Participants	1 Participants	—	—

SECONDARY outcome

Timeframe: Weeks 12, 16, 20, and 24

Population: The Intent to Treat (ITT) Set included all randomized participants (N=24).

Percentage of participants who achieved complete response with successful glucocorticoid taper to ≤10 mg by Week 24 of the double-blind treatment period.

Outcome measures

Outcome measures
Measure	Double-blind Treatment Period: Zetomipzomib + Standard-of-care (Glucocorticoids) n=16 Participants Participants received an initial 30 mg dose of zetomipzomib, followed by weekly 60 mg doses of zetomipzomib, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. zetomipzomib: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Double-blind Treatment Period: Placebo + Standard-of-care (Glucocorticoids) n=8 Participants Participants received an initial 30 mg dose of placebo (sterile water for injection), followed by weekly 60 mg doses of placebo, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. placebo: Subcutaneous injection of placebo	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Zetomipzomib in DBTP) Participants, who received zetomipzomib in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received zetomipzomib during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Placebo in DBTP) Participants, who received placebo in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received placebo during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly
Complete Response With Glucocorticoid Taper to ≤10 mg By Week 12	18.8 percent of participants Interval 4.0 to 45.6	25.0 percent of participants Interval 3.2 to 65.1	—	—
Complete Response With Glucocorticoid Taper to ≤10 mg By Week 20	43.8 percent of participants Interval 19.8 to 70.1	25.0 percent of participants Interval 3.2 to 65.1	—	—
Complete Response With Glucocorticoid Taper to ≤10 mg By Week 24	43.8 percent of participants Interval 19.8 to 70.1	25.0 percent of participants Interval 3.2 to 65.1	—	—
Complete Response With Glucocorticoid Taper to ≤10 mg By Week 16	37.5 percent of participants Interval 15.2 to 64.6	25.0 percent of participants Interval 3.2 to 65.1	—	—

SECONDARY outcome

Timeframe: Weeks 12, 16, 20, and 24

Population: The Intent to Treat (ITT) Set included all randomized participants (N=24).

Percentage of participants who achieved complete response and glucocorticoid taper to ≤5 mg by Week 24 of the double-blind treatment period.

Outcome measures

Outcome measures
Measure	Double-blind Treatment Period: Zetomipzomib + Standard-of-care (Glucocorticoids) n=16 Participants Participants received an initial 30 mg dose of zetomipzomib, followed by weekly 60 mg doses of zetomipzomib, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. zetomipzomib: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Double-blind Treatment Period: Placebo + Standard-of-care (Glucocorticoids) n=8 Participants Participants received an initial 30 mg dose of placebo (sterile water for injection), followed by weekly 60 mg doses of placebo, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. placebo: Subcutaneous injection of placebo	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Zetomipzomib in DBTP) Participants, who received zetomipzomib in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received zetomipzomib during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Placebo in DBTP) Participants, who received placebo in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received placebo during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly
Complete Response With Glucocorticoid Taper to ≤5 mg By Week 12	12.5 percent of participants Interval 1.6 to 38.3	0 percent of participants Interval 0.0 to 36.9	—	—
Complete Response With Glucocorticoid Taper to ≤5 mg Be Week 16	25.0 percent of participants Interval 7.3 to 52.4	12.5 percent of participants Interval 0.3 to 52.7	—	—
Complete Response With Glucocorticoid Taper to ≤5 mg By Week 20	37.5 percent of participants Interval 15.2 to 64.6	12.5 percent of participants Interval 0.3 to 52.7	—	—
Complete Response With Glucocorticoid Taper to ≤5 mg By Week 24	37.5 percent of participants Interval 15.2 to 64.6	12.5 percent of participants Interval 0.3 to 52.7	—	—

SECONDARY outcome

Timeframe: Weeks 12, 16, 20, and 24

Population: The Intent to Treat (ITT) Set included all randomized participants (N=24).

Percentage of participants who achieved complete response with glucocorticoid taper to 0 mg by Week 24 of the double-blind treatment period.

Outcome measures

Outcome measures
Measure	Double-blind Treatment Period: Zetomipzomib + Standard-of-care (Glucocorticoids) n=16 Participants Participants received an initial 30 mg dose of zetomipzomib, followed by weekly 60 mg doses of zetomipzomib, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. zetomipzomib: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Double-blind Treatment Period: Placebo + Standard-of-care (Glucocorticoids) n=8 Participants Participants received an initial 30 mg dose of placebo (sterile water for injection), followed by weekly 60 mg doses of placebo, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. placebo: Subcutaneous injection of placebo	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Zetomipzomib in DBTP) Participants, who received zetomipzomib in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received zetomipzomib during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Placebo in DBTP) Participants, who received placebo in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received placebo during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly
Complete Response With Glucocorticoid Taper to 0 mg By Week 16	6.3 percent of participants Interval 0.2 to 30.2	0 percent of participants Interval 0.0 to 36.9	—	—
Complete Response With Glucocorticoid Taper to 0 mg By Week 12	6.3 percent of participants Interval 0.2 to 30.2	0 percent of participants Interval 0.0 to 36.9	—	—
Complete Response With Glucocorticoid Taper to 0 mg By Week 20	12.5 percent of participants Interval 1.6 to 38.3	0 percent of participants Interval 0.0 to 36.9	—	—
Complete Response With Glucocorticoid Taper to 0 mg By Week 24	25.0 percent of participants Interval 7.3 to 52.4	0 percent of participants Interval 0.0 to 36.9	—	—

SECONDARY outcome

Timeframe: Week 24

Population: The Intent to Treat (ITT) Set included all randomized participants (N=24).

Percentage of participants who achieved partial response with successful glucocorticoid taper to ≤10 mg by Week 24 of the double-blind treatment period.

Outcome measures

Outcome measures
Measure	Double-blind Treatment Period: Zetomipzomib + Standard-of-care (Glucocorticoids) n=16 Participants Participants received an initial 30 mg dose of zetomipzomib, followed by weekly 60 mg doses of zetomipzomib, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. zetomipzomib: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Double-blind Treatment Period: Placebo + Standard-of-care (Glucocorticoids) n=8 Participants Participants received an initial 30 mg dose of placebo (sterile water for injection), followed by weekly 60 mg doses of placebo, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. placebo: Subcutaneous injection of placebo	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Zetomipzomib in DBTP) Participants, who received zetomipzomib in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received zetomipzomib during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Placebo in DBTP) Participants, who received placebo in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received placebo during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly
Partial Response With Glucocorticoid Taper to ≤10 mg	31.3 percent of participants Interval 11.0 to 58.7	25.0 percent of participants Interval 3.2 to 65.1	—	—

SECONDARY outcome

Timeframe: Week 24

Population: The Intent to Treat (ITT) Set included all randomized participants (N=24).

Percentage of participants who achieved partial response and glucocorticoid taper to ≤5 mg by Week 24 of the double-blind treatment period.

Outcome measures

Outcome measures
Measure	Double-blind Treatment Period: Zetomipzomib + Standard-of-care (Glucocorticoids) n=16 Participants Participants received an initial 30 mg dose of zetomipzomib, followed by weekly 60 mg doses of zetomipzomib, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. zetomipzomib: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Double-blind Treatment Period: Placebo + Standard-of-care (Glucocorticoids) n=8 Participants Participants received an initial 30 mg dose of placebo (sterile water for injection), followed by weekly 60 mg doses of placebo, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. placebo: Subcutaneous injection of placebo	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Zetomipzomib in DBTP) Participants, who received zetomipzomib in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received zetomipzomib during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Placebo in DBTP) Participants, who received placebo in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received placebo during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly
Partial Response With Glucocorticoid Taper to ≤5 mg	12.5 percent of participants Interval 1.6 to 38.3	12.5 percent of participants Interval 0.3 to 52.7	—	—

SECONDARY outcome

Timeframe: Week 24

Population: The Intent to Treat (ITT) Set included all randomized participants (N=24).

Percentage of participants who achieved partial response with glucocorticoid taper to 0 mg by Week 24 of the double-blind treatment period.

Outcome measures

Outcome measures
Measure	Double-blind Treatment Period: Zetomipzomib + Standard-of-care (Glucocorticoids) n=16 Participants Participants received an initial 30 mg dose of zetomipzomib, followed by weekly 60 mg doses of zetomipzomib, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. zetomipzomib: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Double-blind Treatment Period: Placebo + Standard-of-care (Glucocorticoids) n=8 Participants Participants received an initial 30 mg dose of placebo (sterile water for injection), followed by weekly 60 mg doses of placebo, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. placebo: Subcutaneous injection of placebo	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Zetomipzomib in DBTP) Participants, who received zetomipzomib in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received zetomipzomib during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Placebo in DBTP) Participants, who received placebo in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received placebo during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly
Partial Response With Glucocorticoid Taper to 0 mg	12.5 percent of participants Interval 1.6 to 38.3	0 percent of participants Interval 0.0 to 36.9	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 12, 16, 20, and 24

Population: The Intent to Treat (ITT) Set included all randomized participants (N=24).

Mean change from Baseline in glucocorticoid dose for participants during the double-blind treatment period at Weeks 12, 16, 20 and 24

Outcome measures

Outcome measures
Measure	Double-blind Treatment Period: Zetomipzomib + Standard-of-care (Glucocorticoids) n=16 Participants Participants received an initial 30 mg dose of zetomipzomib, followed by weekly 60 mg doses of zetomipzomib, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. zetomipzomib: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Double-blind Treatment Period: Placebo + Standard-of-care (Glucocorticoids) n=8 Participants Participants received an initial 30 mg dose of placebo (sterile water for injection), followed by weekly 60 mg doses of placebo, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. placebo: Subcutaneous injection of placebo	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Zetomipzomib in DBTP) Participants, who received zetomipzomib in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received zetomipzomib during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Placebo in DBTP) Participants, who received placebo in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received placebo during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly
Change From Baseline in Glucocorticoid Dose Week 12	-6.2 mg/day Standard Deviation 9.44	-3.2 mg/day Standard Deviation 11.70	—	—
Change From Baseline in Glucocorticoid Dose Week 16	-8.3 mg/day Standard Deviation 10.59	-3.0 mg/day Standard Deviation 13.83	—	—
Change From Baseline in Glucocorticoid Dose Week 20	-10.0 mg/day Standard Deviation 11.35	-7.2 mg/day Standard Deviation 10.30	—	—
Change From Baseline in Glucocorticoid Dose Week 24	-12.5 mg/day Standard Deviation 9.79	-4.7 mg/day Standard Deviation 11.43	—	—

POST_HOC outcome

Timeframe: Weeks 12, 16, 20, and 24

Population: The subset of participants in the intent to treat population who were on glucocorticoids at Screening.

For the subset of the intent to treat population who were on glucocorticoid steroids at Screening, the percentage of participants who achieved complete response with successful glucocorticoid taper to ≤10 mg by Week 24 of the double-blind treatment period is presented.

Outcome measures

Outcome measures
Measure	Double-blind Treatment Period: Zetomipzomib + Standard-of-care (Glucocorticoids) n=14 Participants Participants received an initial 30 mg dose of zetomipzomib, followed by weekly 60 mg doses of zetomipzomib, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. zetomipzomib: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Double-blind Treatment Period: Placebo + Standard-of-care (Glucocorticoids) n=7 Participants Participants received an initial 30 mg dose of placebo (sterile water for injection), followed by weekly 60 mg doses of placebo, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. placebo: Subcutaneous injection of placebo	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Zetomipzomib in DBTP) Participants, who received zetomipzomib in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received zetomipzomib during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Placebo in DBTP) Participants, who received placebo in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received placebo during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly
Complete Response With Glucocorticoid Taper to ≤10 mg (Subset of Participants on Steroids at Screening) By Week 20	50.0 percent of participants Interval 23.0 to 77.0	14.3 percent of participants Interval 0.4 to 57.9	—	—
Complete Response With Glucocorticoid Taper to ≤10 mg (Subset of Participants on Steroids at Screening) By Week 12	21.4 percent of participants Interval 4.7 to 50.8	14.3 percent of participants Interval 0.4 to 57.9	—	—
Complete Response With Glucocorticoid Taper to ≤10 mg (Subset of Participants on Steroids at Screening) By Week 16	42.9 percent of participants Interval 17.7 to 71.1	14.3 percent of participants Interval 0.4 to 57.9	—	—
Complete Response With Glucocorticoid Taper to ≤10 mg (Subset of Participants on Steroids at Screening) By Week 24	50.0 percent of participants Interval 23.0 to 77.0	14.3 percent of participants Interval 0.4 to 57.9	—	—

POST_HOC outcome

Timeframe: Weeks 12, 16, 20, and 24

Population: The subset of participants in the intent to treat population who were on glucocorticoids at Screening. Of note, one participant met the SAP definition of CR with glucocorticoid taper to 0 mg at Week 4 with normalized ALT, AST, and IgG while taking no glucocorticoid steroids and is included in this dataset. After further review of the data, notes in the database stated the reason for the participant taking no glucocorticoids for 7 days was due to the glucocorticoid medication unavailability.

For the subset of the intent to treat population who were on glucocorticoid steroids at Screening, the percentage of participants who achieved complete response with successful glucocorticoid taper to ≤5 mg by Week 24 of the double-blind treatment period is presented.

Outcome measures

Outcome measures
Measure	Double-blind Treatment Period: Zetomipzomib + Standard-of-care (Glucocorticoids) n=14 Participants Participants received an initial 30 mg dose of zetomipzomib, followed by weekly 60 mg doses of zetomipzomib, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. zetomipzomib: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Double-blind Treatment Period: Placebo + Standard-of-care (Glucocorticoids) n=7 Participants Participants received an initial 30 mg dose of placebo (sterile water for injection), followed by weekly 60 mg doses of placebo, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. placebo: Subcutaneous injection of placebo	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Zetomipzomib in DBTP) Participants, who received zetomipzomib in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received zetomipzomib during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Placebo in DBTP) Participants, who received placebo in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received placebo during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly
Complete Response With Glucocorticoid Taper to ≤5 mg (Subset of Participants on Steroids at Screening) By Week 12	14.3 percent of participants Interval 1.8 to 42.8	0 percent of participants Interval 0.0 to 41.0	—	—
Complete Response With Glucocorticoid Taper to ≤5 mg (Subset of Participants on Steroids at Screening) By Week 16	28.6 percent of participants Interval 8.4 to 58.1	0 percent of participants Interval 0.0 to 41.0	—	—
Complete Response With Glucocorticoid Taper to ≤5 mg (Subset of Participants on Steroids at Screening) By Week 20	42.9 percent of participants Interval 17.7 to 71.1	0 percent of participants Interval 0.0 to 41.0	—	—
Complete Response With Glucocorticoid Taper to ≤5 mg (Subset of Participants on Steroids at Screening) By Week 24	42.9 percent of participants Interval 17.7 to 71.1	0 percent of participants Interval 0.0 to 41.0	—	—

POST_HOC outcome

Timeframe: Weeks 12, 16, 20, and 24

For the subset of the intent to treat population who were on glucocorticoid steroids at Screening, the percentage of participants who achieved complete response with successful glucocorticoid taper to 0 mg by Week 24 of the double-blind treatment period is presented.

Outcome measures

Outcome measures
Measure	Double-blind Treatment Period: Zetomipzomib + Standard-of-care (Glucocorticoids) n=14 Participants Participants received an initial 30 mg dose of zetomipzomib, followed by weekly 60 mg doses of zetomipzomib, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. zetomipzomib: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Double-blind Treatment Period: Placebo + Standard-of-care (Glucocorticoids) n=7 Participants Participants received an initial 30 mg dose of placebo (sterile water for injection), followed by weekly 60 mg doses of placebo, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. placebo: Subcutaneous injection of placebo	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Zetomipzomib in DBTP) Participants, who received zetomipzomib in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received zetomipzomib during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Placebo in DBTP) Participants, who received placebo in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received placebo during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly
Complete Response With Glucocorticoid Taper to 0 mg (Subset of Participants on Steroids at Screening) By Week 24	28.6 percent of participants Interval 8.4 to 58.1	0 percent of participants Interval 0.0 to 41.0	—	—
Complete Response With Glucocorticoid Taper to 0 mg (Subset of Participants on Steroids at Screening) By Week 12	7.1 percent of participants Interval 0.2 to 33.9	0 percent of participants Interval 0.0 to 41.0	—	—
Complete Response With Glucocorticoid Taper to 0 mg (Subset of Participants on Steroids at Screening) By Week 16	7.1 percent of participants Interval 0.2 to 33.9	0 percent of participants Interval 0.0 to 41.0	—	—
Complete Response With Glucocorticoid Taper to 0 mg (Subset of Participants on Steroids at Screening) By Week 20	14.3 percent of participants Interval 1.8 to 42.8	0 percent of participants Interval 0.0 to 41.0	—	—

POST_HOC outcome

Timeframe: Weeks 12, 16, 20, and 24

Population: The subset of participants in the intent to treat population who were on glucocorticoids at Screening.

For the subset of the intent to treat population who were on glucocorticoid steroids at Screening, the percentage of participants who achieved complete response by Week 24 of the double-blind treatment period is presented.

Outcome measures

Outcome measures
Measure	Double-blind Treatment Period: Zetomipzomib + Standard-of-care (Glucocorticoids) n=14 Participants Participants received an initial 30 mg dose of zetomipzomib, followed by weekly 60 mg doses of zetomipzomib, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. zetomipzomib: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Double-blind Treatment Period: Placebo + Standard-of-care (Glucocorticoids) n=7 Participants Participants received an initial 30 mg dose of placebo (sterile water for injection), followed by weekly 60 mg doses of placebo, for the remaining 23 weeks of the treatment period in addition to standard of care during the double-blind treatment period. placebo: Subcutaneous injection of placebo	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Zetomipzomib in DBTP) Participants, who received zetomipzomib in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received zetomipzomib during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Placebo in DBTP) Participants, who received placebo in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in open-label extension who received placebo during the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly
Complete Response (Subset of Participants on Steroids at Screening) Week 12	42.9 percent of participants Interval 17.7 to 71.1	28.6 percent of participants Interval 3.7 to 71.0	—	—
Complete Response (Subset of Participants on Steroids at Screening) Week 16	50.0 percent of participants Interval 23.0 to 77.0	28.6 percent of participants Interval 3.7 to 71.0	—	—
Complete Response (Subset of Participants on Steroids at Screening) Week 20	57.1 percent of participants Interval 28.9 to 82.3	28.6 percent of participants Interval 3.7 to 71.0	—	—
Complete Response (Subset of Participants on Steroids at Screening) Week 24	57.1 percent of participants Interval 28.9 to 82.3	28.6 percent of participants Interval 3.7 to 71.0	—	—

Adverse Events

Double-blind Treatment Period: Zetomipzomib + Standard-of-care (Glucocorticoids)

Serious events: 2 serious events

Other events: 16 other events

Deaths: 0 deaths

Double-blind Treatment Period: Placebo + Standard-of-care (Glucocorticoids)

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Zetomipzomib in DBTP)

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Placebo in DBTP)

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Double-blind Treatment Period: Zetomipzomib + Standard-of-care (Glucocorticoids) n=16 participants at risk Participants received an initial 30 mg dose of zetomipzomib, followed by weekly 60 mg doses of zetomipzomib, for the remaining 23 weeks of the double-blind treatment period in addition to standard of care. zetomipzomib in the double-blind treatment period: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Double-blind Treatment Period: Placebo + Standard-of-care (Glucocorticoids) n=7 participants at risk Participants received an initial 30 mg dose of placebo (sterile water for injection), followed by weekly 60 mg doses of placebo, for the remaining 23 weeks of the double-blind treatment period in addition to standard of care. placebo in the double-blind treatment period: Subcutaneous injection of placebo	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Zetomipzomib in DBTP) n=9 participants at risk Participants, who received zetomipzomib in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in OLE who received zetomipzomib during the DBTP: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly	Open-label Extension: Zetomipzomib + standard-of Care (Glucocorticoids) (Placebo in DBTP) n=5 participants at risk Participants, who received placebo in the double-blind treatment period (DBTP) and enrolled in the open-label extension period, received an initial 30 mg dose of zetomipzomib at the open-label extension (OLE) Week 1 visit, followed by weekly doses of 60 mg of zetomipzomib, for up to a total of 24 additional weeks of treatment in addition to standard of care. zetomipzomib in OLE who received placebo during the DBTP: Subcutaneous injection of zetomipzomib with a target dose of 60 mg weekly
Cardiac disorders Atrial fibrillation	0.00% 0/16 • 28 weeks during the double-blind treatment period and up to an additional 28 weeks for participants enrolled in the optional open label extension period	14.3% 1/7 • Number of events 1 • 28 weeks during the double-blind treatment period and up to an additional 28 weeks for participants enrolled in the optional open label extension period	0.00% 0/9 • 28 weeks during the double-blind treatment period and up to an additional 28 weeks for participants enrolled in the optional open label extension period	0.00% 0/5 • 28 weeks during the double-blind treatment period and up to an additional 28 weeks for participants enrolled in the optional open label extension period
Gastrointestinal disorders Haematemesis	0.00% 0/16 • 28 weeks during the double-blind treatment period and up to an additional 28 weeks for participants enrolled in the optional open label extension period	14.3% 1/7 • Number of events 1 • 28 weeks during the double-blind treatment period and up to an additional 28 weeks for participants enrolled in the optional open label extension period	0.00% 0/9 • 28 weeks during the double-blind treatment period and up to an additional 28 weeks for participants enrolled in the optional open label extension period	0.00% 0/5 • 28 weeks during the double-blind treatment period and up to an additional 28 weeks for participants enrolled in the optional open label extension period
Gastrointestinal disorders Oesophageal varices haemorrhage	0.00% 0/16 • 28 weeks during the double-blind treatment period and up to an additional 28 weeks for participants enrolled in the optional open label extension period	14.3% 1/7 • Number of events 2 • 28 weeks during the double-blind treatment period and up to an additional 28 weeks for participants enrolled in the optional open label extension period	0.00% 0/9 • 28 weeks during the double-blind treatment period and up to an additional 28 weeks for participants enrolled in the optional open label extension period	0.00% 0/5 • 28 weeks during the double-blind treatment period and up to an additional 28 weeks for participants enrolled in the optional open label extension period
Infections and infestations Influenza	6.2% 1/16 • Number of events 1 • 28 weeks during the double-blind treatment period and up to an additional 28 weeks for participants enrolled in the optional open label extension period	0.00% 0/7 • 28 weeks during the double-blind treatment period and up to an additional 28 weeks for participants enrolled in the optional open label extension period	0.00% 0/9 • 28 weeks during the double-blind treatment period and up to an additional 28 weeks for participants enrolled in the optional open label extension period	0.00% 0/5 • 28 weeks during the double-blind treatment period and up to an additional 28 weeks for participants enrolled in the optional open label extension period
Injury, poisoning and procedural complications Post procedural fever	6.2% 1/16 • Number of events 1 • 28 weeks during the double-blind treatment period and up to an additional 28 weeks for participants enrolled in the optional open label extension period	0.00% 0/7 • 28 weeks during the double-blind treatment period and up to an additional 28 weeks for participants enrolled in the optional open label extension period	0.00% 0/9 • 28 weeks during the double-blind treatment period and up to an additional 28 weeks for participants enrolled in the optional open label extension period	0.00% 0/5 • 28 weeks during the double-blind treatment period and up to an additional 28 weeks for participants enrolled in the optional open label extension period

Other adverse events

Additional Information

Regulatory Affairs

Kezar Life Sciences, Inc.

Phone: 650-822-5600

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place