Trial Outcomes & Findings for Single Rising Dose Trial of Spesolimab (BI 655130) for Healthy Japanese Male Subjects (NCT NCT03123094)

Results Overview

The primary endpoint is to assess safety and tolerability of spesolimab as the number \[N\] of subjects with drug-related AEs.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

32 participants

Primary outcome timeframe

From first drug administration until the end of trial examination, up to 151 days.

Results posted on

2024-03-06

Participant Flow

This was a double-blind, randomised, and placebo-controlled trial of single rising intravenous (IV) doses and single subcutaneous (SC) doses of spesolimab (BI 655130) in healthy male Japanese subjects.

All subjects were screened for eligibility to participate in the trial. Subjects attended specialist sites which would then ensure that all subjects met all inclusion/exclusion criteria. Subjects were not to be randomised to trial treatment if any one of the specific entry criteria were not met. Dose level for each arm cannot be provided because the information is a combination of both commercially sensitive confidential information as well as proprietary information.

Participant milestones

Participant milestones
Measure	Spesolimab Low Dose Group (Intravenous) Subjects were administered intravenously a single dose of solution for infusion of spesolimab in the range of 300 -1200 milligrams (mg) as 90 minutes infusion on day 1 of visit 2.	Spesolimab Medium Dose Group (Intravenous) Subjects were administered intravenously a single dose of solution for infusion of spesolimab in the range of 300 -1200 milligrams (mg) as 90 minutes infusion on day 1 of visit 2.	Spesolimab High Dose Group (Intravenous) Subjects were administered intravenously a single dose of solution for infusion of spesolimab in the range of 300 -1200 milligrams (mg) as 90 minutes infusion on day 1 of visit 2.	Spesolimab Low Dose Group (Subcutaneous) Subjects were administered a single dose of solution for injection of spesolimab in the range of 300-1200 milligrams (mg) as subcutaneous injection on day 1 of visit 2.	Placebo Matching to Spesolimab Subjects administered placebo matching to spesolimab solution for infusion as intravenous as 90 min infusion or subcutaneous injection on day 1 of visit 2.
Overall Study STARTED	6	6	6	6	8
Overall Study COMPLETED	6	4	5	6	7
Overall Study NOT COMPLETED	0	2	1	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Spesolimab Low Dose Group (Intravenous) Subjects were administered intravenously a single dose of solution for infusion of spesolimab in the range of 300 -1200 milligrams (mg) as 90 minutes infusion on day 1 of visit 2.	Spesolimab Medium Dose Group (Intravenous) Subjects were administered intravenously a single dose of solution for infusion of spesolimab in the range of 300 -1200 milligrams (mg) as 90 minutes infusion on day 1 of visit 2.	Spesolimab High Dose Group (Intravenous) Subjects were administered intravenously a single dose of solution for infusion of spesolimab in the range of 300 -1200 milligrams (mg) as 90 minutes infusion on day 1 of visit 2.	Spesolimab Low Dose Group (Subcutaneous) Subjects were administered a single dose of solution for injection of spesolimab in the range of 300-1200 milligrams (mg) as subcutaneous injection on day 1 of visit 2.	Placebo Matching to Spesolimab Subjects administered placebo matching to spesolimab solution for infusion as intravenous as 90 min infusion or subcutaneous injection on day 1 of visit 2.
Overall Study Withdrawal by Subject	0	2	1	0	1

Baseline Characteristics

Single Rising Dose Trial of Spesolimab (BI 655130) for Healthy Japanese Male Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Spesolimab Low Dose Group (Intravenous) n=6 Participants Subjects were administered intravenously a single dose of solution for infusion of spesolimab in the range of 300 -1200 milligrams (mg) as 90 minutes infusion on day 1 of visit 2.	Spesolimab Medium Dose Group (Intravenous) n=6 Participants Subjects were administered intravenously a single dose of solution for infusion of spesolimab in the range of 300 -1200 milligrams (mg) as 90 minutes infusion on day 1 of visit 2.	Spesolimab High Dose Group (Intravenous) n=6 Participants Subjects were administered intravenously a single dose of solution for infusion of spesolimab in the range of 300 -1200 milligrams (mg) as 90 minutes infusion on day 1 of visit 2.	Spesolimab Low Dose Group (Subcutaneous) n=6 Participants Subjects were administered a single dose of solution for injection of spesolimab in the range of 300-1200 milligrams (mg) as subcutaneous injection on day 1 of visit 2.	Placebo Matching to Spesolimab n=8 Participants Subjects administered placebo matching to spesolimab solution for infusion as intravenous as 90 min infusion or subcutaneous injection on day 1 of visit 2.	Total n=32 Participants Total of all reporting groups
Age, Continuous	31.5 Years STANDARD_DEVIATION 4.51 • n=5 Participants	31.5 Years STANDARD_DEVIATION 4.85 • n=7 Participants	36.7 Years STANDARD_DEVIATION 3.56 • n=5 Participants	34.7 Years STANDARD_DEVIATION 5.24 • n=4 Participants	31.4 Years STANDARD_DEVIATION 7.65 • n=21 Participants	33.0 Years STANDARD_DEVIATION 5.61 • n=10 Participants
Sex: Female, Male Female	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	0 Participants n=10 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	8 Participants n=21 Participants	32 Participants n=10 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	0 Participants n=10 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	8 Participants n=21 Participants	32 Participants n=10 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	0 Participants n=10 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	0 Participants n=10 Participants
Race (NIH/OMB) White	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	0 Participants n=10 Participants
Race (NIH/OMB) More than one race	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	0 Participants n=10 Participants
Race (NIH/OMB) Unknown or Not Reported	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	0 Participants n=10 Participants

PRIMARY outcome

Timeframe: From first drug administration until the end of trial examination, up to 151 days.

Population: Treated set (TS): TS includes all subjects dispensed trial medication and documented to have taken at least one dose of investigational treatment.

The primary endpoint is to assess safety and tolerability of spesolimab as the number \[N\] of subjects with drug-related AEs.

Outcome measures

Outcome measures
Measure	Spesolimab Low Dose Group (Intravenous) n=6 Participants Subjects were administered intravenously a single dose of solution for infusion of spesolimab in the range of 300 -1200 milligrams (mg) as 90 minutes infusion on day 1 of visit 2.	Spesolimab Medium Dose Group (Intravenous) n=6 Participants Subjects were administered intravenously a single dose of solution for infusion of spesolimab in the range of 300 -1200 milligrams (mg) as 90 minutes infusion on day 1 of visit 2.	Spesolimab High Dose Group (Intravenous) n=6 Participants Subjects were administered intravenously a single dose of solution for infusion of spesolimab in the range of 300 -1200 milligrams (mg) as 90 minutes infusion on day 1 of visit 2.	Spesolimab Low Dose Group (Subcutaneous) n=6 Participants Subjects were administered a single dose of solution for injection of spesolimab in the range of 300-1200 milligrams (mg) as subcutaneous injection on day 1 of visit 2.	Placebo Matching to Spesolimab n=8 Participants Subjects administered placebo matching to spesolimab solution for infusion as intravenous as 90 min infusion or subcutaneous injection on day 1 of visit 2.
Number of Subjects With Drug-related Adverse Events (AEs)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 3528 hours after administration of spesolimab.

Population: Pharmacokinetic (PK) set (PKS): PKS includes all subjects in the treated set who provided at least one PK parameter not excluded due to a protocol violation relevant to the evaluation of PK. Only participants with evaluable results for this PK parameter are reported.

AUC0-∞, Area under the concentration-time curve of spesolimab in plasma over the time interval from 0 extrapolated to infinity is presented. Pharmacokinetic samples were collected within 2 hours pre-dose and at 1.5, 2, 3, 4, 8, 12, 24, 48, 72, 96, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2184, 2856 and 3528 hours after dosing of dose groups with intravenous administration of spesolimab. Pharmacokinetic samples were collected within 2 hours pre-dose and at 0.5, 1.5, 2, 3, 4, 8, 12, 24, 48, 72, 96, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2184, 2856 and 3528 hours after dosing of dose groups with subcutaneous administration of spesolimab.

Outcome measures

Outcome measures
Measure	Spesolimab Low Dose Group (Intravenous) n=6 Participants Subjects were administered intravenously a single dose of solution for infusion of spesolimab in the range of 300 -1200 milligrams (mg) as 90 minutes infusion on day 1 of visit 2.	Spesolimab Medium Dose Group (Intravenous) n=5 Participants Subjects were administered intravenously a single dose of solution for infusion of spesolimab in the range of 300 -1200 milligrams (mg) as 90 minutes infusion on day 1 of visit 2.	Spesolimab High Dose Group (Intravenous) n=5 Participants Subjects were administered intravenously a single dose of solution for infusion of spesolimab in the range of 300 -1200 milligrams (mg) as 90 minutes infusion on day 1 of visit 2.	Spesolimab Low Dose Group (Subcutaneous) n=6 Participants Subjects were administered a single dose of solution for injection of spesolimab in the range of 300-1200 milligrams (mg) as subcutaneous injection on day 1 of visit 2.	Placebo Matching to Spesolimab Subjects administered placebo matching to spesolimab solution for infusion as intravenous as 90 min infusion or subcutaneous injection on day 1 of visit 2.
Area Under the Concentration-time Curve of Spesolimab in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)	1890 Day*microgram/millilitre [day∙μg/mL] Geometric Coefficient of Variation 19.9	3930 Day*microgram/millilitre [day∙μg/mL] Geometric Coefficient of Variation 18.4	7060 Day*microgram/millilitre [day∙μg/mL] Geometric Coefficient of Variation 18.0	1390 Day*microgram/millilitre [day∙μg/mL] Geometric Coefficient of Variation 24.8	—

SECONDARY outcome

Timeframe: Up to 3528 hours after administration of spesolimab.

Population: Pharmacokinetic (PK) set (PKS): PKS includes all subjects in the treated set who provided at least one PK parameter not excluded due to a protocol violation relevant to the evaluation of PK.

Cmax, maximum measured concentration of spesolimab in plasma is presented. Pharmacokinetic samples were collected within 2 hours pre-dose and at 1.5, 2, 3, 4, 8, 12, 24, 48, 72, 96, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2184, 2856 and 3528 hours after dosing of dose groups with intravenous administration of Up to 3528 hours after administration of spesolimab. Pharmacokinetic samples were collected within 2 hours pre-dose and at 0.5, 1.5, 2, 3, 4, 8, 12, 24, 48, 72, 96, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2184, 2856 and 3528 hours after dosing of dose groups with subcutaneous administration of spesolimab.

Outcome measures

Outcome measures
Measure	Spesolimab Low Dose Group (Intravenous) n=6 Participants Subjects were administered intravenously a single dose of solution for infusion of spesolimab in the range of 300 -1200 milligrams (mg) as 90 minutes infusion on day 1 of visit 2.	Spesolimab Medium Dose Group (Intravenous) n=6 Participants Subjects were administered intravenously a single dose of solution for infusion of spesolimab in the range of 300 -1200 milligrams (mg) as 90 minutes infusion on day 1 of visit 2.	Spesolimab High Dose Group (Intravenous) n=6 Participants Subjects were administered intravenously a single dose of solution for infusion of spesolimab in the range of 300 -1200 milligrams (mg) as 90 minutes infusion on day 1 of visit 2.	Spesolimab Low Dose Group (Subcutaneous) n=6 Participants Subjects were administered a single dose of solution for injection of spesolimab in the range of 300-1200 milligrams (mg) as subcutaneous injection on day 1 of visit 2.	Placebo Matching to Spesolimab Subjects administered placebo matching to spesolimab solution for infusion as intravenous as 90 min infusion or subcutaneous injection on day 1 of visit 2.
Maximum Measured Concentration of Spesolimab in Plasma (Cmax)	99.7 Microgram/millilitre [μg/mL] Geometric Coefficient of Variation 10.4	193.0 Microgram/millilitre [μg/mL] Geometric Coefficient of Variation 17.9	400.0 Microgram/millilitre [μg/mL] Geometric Coefficient of Variation 12.9	32.2 Microgram/millilitre [μg/mL] Geometric Coefficient of Variation 21.8	—

SECONDARY outcome

Timeframe: Pharmacokinetic samples were collected within 2 hours (h) pre-dose and at 1.5, 2, 3, 4, 8, 12, 24, 48, 72, 96, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2184, 2856 and 3528 h after dosing of dose groups with intravenous administration of spesolimab.

Population: Pharmacokinetic (PK) set (PKS): PKS includes all subjects in the treated set who provided at least one PK parameter not excluded due to a protocol violation relevant to the evaluation of PK. Only participants with evaluable results for this PK parameter are reported.

CL, total clearance of spesolimab in plasma after intravenous administration is presented for intravenous dose groups.

Outcome measures

Outcome measures
Measure	Spesolimab Low Dose Group (Intravenous) n=6 Participants Subjects were administered intravenously a single dose of solution for infusion of spesolimab in the range of 300 -1200 milligrams (mg) as 90 minutes infusion on day 1 of visit 2.	Spesolimab Medium Dose Group (Intravenous) n=5 Participants Subjects were administered intravenously a single dose of solution for infusion of spesolimab in the range of 300 -1200 milligrams (mg) as 90 minutes infusion on day 1 of visit 2.	Spesolimab High Dose Group (Intravenous) n=5 Participants Subjects were administered intravenously a single dose of solution for infusion of spesolimab in the range of 300 -1200 milligrams (mg) as 90 minutes infusion on day 1 of visit 2.	Spesolimab Low Dose Group (Subcutaneous) Subjects were administered a single dose of solution for injection of spesolimab in the range of 300-1200 milligrams (mg) as subcutaneous injection on day 1 of visit 2.	Placebo Matching to Spesolimab Subjects administered placebo matching to spesolimab solution for infusion as intravenous as 90 min infusion or subcutaneous injection on day 1 of visit 2.
Total Clearance of Spesolimab in Plasma After Intravenous Administration (CL)	0.159 Litre/day [L/day] Geometric Coefficient of Variation 19.9	0.153 Litre/day [L/day] Geometric Coefficient of Variation 18.4	0.170 Litre/day [L/day] Geometric Coefficient of Variation 18.0	—	—

SECONDARY outcome

Timeframe: Pharmacokinetic samples were collected within 2 hours (h) pre-dose and at 1.5, 2, 3, 4, 8, 12, 24, 48, 72, 96, 168, 336, 504, 672, 840, 1008, 1344, 1680, 2184, 2856 and 3528 h after dosing of dose groups with intravenous administration of spesolimab.

Population: Pharmacokinetic (PK) set (PKS): PKS includes all subjects in the treated set who provided at least one PK parameter not excluded due to a protocol violation relevant to the evaluation of PK. Only participants with evaluable results for this PK parameter are reported.

Vss, volume of distribution at steady state after intravenous administration of spesolimab is presented for intravenous dose groups.