Trial Outcomes & Findings for A Phase III, Crossover Trial Evaluating the Efficacy and Safety of KVD900 (Sebetralstat) for On-Demand Treatment of Angioedema Attacks in Adolescent and Adult Patients With Hereditary Angioedema (HAE) (NCT NCT05259917)

Last Updated: 2025-05-02

Results Overview

The analysis of time to the beginning of symptom relief defined as at least "a little better" (2 time points in a row) on the PGI-C within 12 hours of the first IMP administration using the Gehan score transformation test for Full Analysis Set (FAS). Attacks were treated as right-censored at 12 hours if they did not achieve beginning of symptom relief defined by PGI-C as at least "a little better" (2 time points in a row) or received conventional attack treatment prior to time-to-event within 12 hours of the first IMP administration. When an endpoint result was non-evaluable (NE) within 12 hours, if the event did occur, the event must have occurred \>12 hours following study drug.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

136 participants

Primary outcome timeframe

Within 12 hours of the first investigational medicinal product (IMP) administration.

Results posted on

2025-05-02

Participant Flow

A total of 158 patients were screened, of which 22 were screen failures. The majority of screen failures were due to inclusion criterion not met.

A total of 136 patients were randomized across the 6 treatment sequences in a 3-way crossover design, of which a total of 110 patients treated at least 1 attack with IMP and therefore were included in the Full Analysis Set (FAS).

Participant milestones

Participant milestones
Measure	Sequence A PLB/600 mg KVD900/300 mg KVD900	Sequence B PLB/ 300 mg KVD900/ 600 mg KVD900	Sequence C 300 mg KVD900/ 600 mg KVD900/PLB	Sequence D 300 mg KVD900/PLB/ 600 mg KVD900	Sequence E 600 mg KVD900/ 300 mg KVD900/PLB	Sequence F 600 mg KVD900/PLB/ 300 mg KVD900
Overall Study STARTED	18	18	15	17	20	22
Overall Study COMPLETED	10	14	8	12	8	16
Overall Study NOT COMPLETED	8	4	7	5	12	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Sequence A PLB/600 mg KVD900/300 mg KVD900	Sequence B PLB/ 300 mg KVD900/ 600 mg KVD900	Sequence C 300 mg KVD900/ 600 mg KVD900/PLB	Sequence D 300 mg KVD900/PLB/ 600 mg KVD900	Sequence E 600 mg KVD900/ 300 mg KVD900/PLB	Sequence F 600 mg KVD900/PLB/ 300 mg KVD900
Overall Study Protocol Violation	0	0	1	0	0	0
Overall Study Lost to Follow-up	0	0	1	0	0	1
Overall Study Physician Decision	0	1	0	0	0	0
Overall Study Withdrawal by Subject	0	1	0	0	1	1
Overall Study Trial Termination by Sponsor	7	2	3	5	11	4
Overall Study Other	1	0	2	0	0	0

Baseline Characteristics

A Phase III, Crossover Trial Evaluating the Efficacy and Safety of KVD900 (Sebetralstat) for On-Demand Treatment of Angioedema Attacks in Adolescent and Adult Patients With Hereditary Angioedema (HAE)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sequence A n=18 Participants PLB/600 mg KVD900/300 mg KVD900	Sequence B n=18 Participants PLB/ 300 mg KVD900/ 600 mg KVD900	Sequence C n=15 Participants 300 mg KVD900/ 600 mg KVD900/PLB	Sequence D n=17 Participants 300 mg KVD900/PLB/ 600 mg KVD900	Sequence E n=20 Participants 600 mg KVD900/ 300 mg KVD900/PLB	Sequence F n=22 Participants 600 mg KVD900/PLB/ 300 mg KVD900	Total n=110 Participants Total of all reporting groups
Age, Continuous	37.4 years STANDARD_DEVIATION 15.70 • n=5 Participants	35.8 years STANDARD_DEVIATION 16.90 • n=7 Participants	41.1 years STANDARD_DEVIATION 17.87 • n=5 Participants	31.8 years STANDARD_DEVIATION 11.42 • n=4 Participants	41.4 years STANDARD_DEVIATION 14.60 • n=21 Participants	38.2 years STANDARD_DEVIATION 13.14 • n=10 Participants	37.7 years STANDARD_DEVIATION 14.96 • n=115 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	14 Participants n=7 Participants	5 Participants n=5 Participants	12 Participants n=4 Participants	11 Participants n=21 Participants	11 Participants n=10 Participants	66 Participants n=115 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants	5 Participants n=4 Participants	9 Participants n=21 Participants	11 Participants n=10 Participants	44 Participants n=115 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants	0 Participants n=10 Participants	7 Participants n=115 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	15 Participants n=5 Participants	17 Participants n=7 Participants	10 Participants n=5 Participants	15 Participants n=4 Participants	17 Participants n=21 Participants	21 Participants n=10 Participants	95 Participants n=115 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	1 Participants n=10 Participants	8 Participants n=115 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	0 Participants n=115 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants	1 Participants n=21 Participants	1 Participants n=10 Participants	10 Participants n=115 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	0 Participants n=115 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants
Race (NIH/OMB) White	14 Participants n=5 Participants	18 Participants n=7 Participants	12 Participants n=5 Participants	11 Participants n=4 Participants	18 Participants n=21 Participants	19 Participants n=10 Participants	92 Participants n=115 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	0 Participants n=115 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	2 Participants n=10 Participants	7 Participants n=115 Participants
Height	1.646 meters STANDARD_DEVIATION 0.1216 • n=5 Participants	1.694 meters STANDARD_DEVIATION 0.1135 • n=7 Participants	1.715 meters STANDARD_DEVIATION 0.0877 • n=5 Participants	1.657 meters STANDARD_DEVIATION 0.1205 • n=4 Participants	1.686 meters STANDARD_DEVIATION 0.0884 • n=21 Participants	1.704 meters STANDARD_DEVIATION 0.1126 • n=10 Participants	1.684 meters STANDARD_DEVIATION 0.1088 • n=115 Participants
Weight	75.16 kilograms STANDARD_DEVIATION 16.109 • n=5 Participants	73.88 kilograms STANDARD_DEVIATION 16.603 • n=7 Participants	83.80 kilograms STANDARD_DEVIATION 18.157 • n=5 Participants	72.28 kilograms STANDARD_DEVIATION 23.735 • n=4 Participants	77.90 kilograms STANDARD_DEVIATION 16.321 • n=21 Participants	83.55 kilograms STANDARD_DEVIATION 21.949 • n=10 Participants	77.86 kilograms STANDARD_DEVIATION 19.179 • n=115 Participants
Body mass index	27.78 kg/m^2 STANDARD_DEVIATION 5.638 • n=5 Participants	25.62 kg/m^2 STANDARD_DEVIATION 4.743 • n=7 Participants	28.62 kg/m^2 STANDARD_DEVIATION 6.603 • n=5 Participants	26.15 kg/m^2 STANDARD_DEVIATION 7.701 • n=4 Participants	27.37 kg/m^2 STANDARD_DEVIATION 5.162 • n=21 Participants	28.90 kg/m^2 STANDARD_DEVIATION 7.329 • n=10 Participants	27.44 kg/m^2 STANDARD_DEVIATION 6.261 • n=115 Participants
Treatment Regimen Prophylaxis	3 Participants n=5 Participants	5 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	3 Participants n=21 Participants	7 Participants n=10 Participants	24 Participants n=115 Participants
Treatment Regimen On Demand Only	15 Participants n=5 Participants	13 Participants n=7 Participants	12 Participants n=5 Participants	14 Participants n=4 Participants	17 Participants n=21 Participants	15 Participants n=10 Participants	86 Participants n=115 Participants

PRIMARY outcome

Timeframe: Within 12 hours of the first investigational medicinal product (IMP) administration.

Population: The full analysis set (FAS) included all randomized patients who received trial medication from at least one period for the respective qualifying HAE attack and are presented according to the randomized treatment. The FAS was the population for efficacy analyses.

Outcome measures

Outcome measures
Measure	KVD900 300 mg n=87 Participants KVD900 300 mg: KVD900 Tablet 300 mg (1 x 300 mg)	KVD900 600 mg n=93 Participants KVD900 600 mg: Two KVD900 Tablets 300 mg (2 x 300 mg)	Placebo n=84 Participants Placebo: Placebo to KVD900 Tablet
Time to Beginning of Symptom Relief Patient Global Impression of Change (PGI-C)	1.61 Time (h) Interval 1.28 to 2.27	1.79 Time (h) Interval 1.33 to 2.27	6.72 Time (h) Interval 2.33 to NA represents non-evaluable (NE), defined as subjects not reaching at least "a little better" (2 time points in a row) on the PGI-C within 12 hours of the first IMP administration to complete descriptive statistics.

SECONDARY outcome

Timeframe: Within 12 hours of the first IMP administration.

First incidence of decrease in attack severity at two time points in a row (with possible missing values in between) within 12 hours of the first IMP administration. Attacks were treated as right-censored at 12 hours if they did not have a decrease in PGI-S score from baseline for 2 time points in a row or received conventional attack treatment prior to time-to-event within 12 hours of the first IMP administration. When an endpoint result was non-evaluable (NE) within 12 hours, if the event did occur, the event must have occurred \>12 hours following study drug.

Outcome measures

Outcome measures
Measure	KVD900 300 mg n=87 Participants KVD900 300 mg: KVD900 Tablet 300 mg (1 x 300 mg)	KVD900 600 mg n=93 Participants KVD900 600 mg: Two KVD900 Tablets 300 mg (2 x 300 mg)	Placebo n=84 Participants Placebo: Placebo to KVD900 Tablet
Time to First Incidence of Decrease From Baseline Patient Global Impression of Severity (PGI-S) (2 Time Points in a Row)	9.27 Time (h) Interval 4.08 to NA represents non-evaluable (NE), defined as subjects not reaching first incidence of decrease from baseline Patient Global Impression of Severity (PGI-S) within 12 hours of the first IMP administration to complete descriptive statistics.	7.75 Time (h) Interval 3.27 to NA represents non-evaluable (NE), defined as subjects not reaching first incidence of decrease from baseline Patient Global Impression of Severity (PGI-S) within 12 hours of the first IMP administration to complete descriptive statistics.	NA Time (h) NA represents non-evaluable (NE), defined as subjects not reaching first incidence of decrease from baseline Patient Global Impression of Severity (PGI-S) within 12 hours of the first IMP administration to complete descriptive statistics.

SECONDARY outcome

Timeframe: Within 24 hours of the first IMP administration.

Time to complete HAE attack resolution defined as "none". Attacks were treated as right-censored at 24 hours if they did reach complete HAE attack resolution or received conventional attack treatment prior to time-to-event within 24 hours of IMP administration. When an endpoint result was non-evaluable (NE) within 24 hours, if the event did occur, the event must have occurred \>24 hours following study drug.

Outcome measures

Outcome measures
Measure	KVD900 300 mg n=87 Participants KVD900 300 mg: KVD900 Tablet 300 mg (1 x 300 mg)	KVD900 600 mg n=93 Participants KVD900 600 mg: Two KVD900 Tablets 300 mg (2 x 300 mg)	Placebo n=84 Participants Placebo: Placebo to KVD900 Tablet
Time to Complete HAE Attack Resolution (PGI-S)	NA Time (h) Interval 16.6 to NA represents non-evaluable (NE), defined as not reaching complete HAE attack resolution defined as "none" within 24 hours of the first IMP administration to complete descriptive statistics.	24.00 Time (h) Interval 10.6 to NA represents non-evaluable (NE), defined as not reaching complete HAE attack resolution defined as "none" within 24 hours of the first IMP administration to complete descriptive statistics.	NA Time (h) NA represents non-evaluable (NE), defined as not reaching complete HAE attack resolution defined as "none" within 24 hours of the first IMP administration to complete descriptive statistics.

Adverse Events

KVD900 300 mg

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

KVD900 600 mg

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	KVD900 300 mg n=86 participants at risk KVD900 300 mg: KVD900 Tablet 300 mg (1 x 300 mg)	KVD900 600 mg n=93 participants at risk KVD900 600 mg: KVD900 Tablet 600 mg (2 x 300 mg)	Placebo n=83 participants at risk Placebo: Placebo to KVD900 Tablet
Congenital, familial and genetic disorders HEREDITARY ANGIOEDEMA	0.00% 0/86 • The period of observation for AEs extends from the time of the patient's first dose of IMP until the Final/ET Visit, an average of 18 weeks. Ongoing AEs at the Final/ET Visit will be followed up until the AE has resolved or is considered chronic or stable or the AE has been clearly shown to be unrelated to the IMP. The period of observation for SAEs extends from the time of signing the informed consent until the Final/ET Visit.	1.1% 1/93 • Number of events 1 • The period of observation for AEs extends from the time of the patient's first dose of IMP until the Final/ET Visit, an average of 18 weeks. Ongoing AEs at the Final/ET Visit will be followed up until the AE has resolved or is considered chronic or stable or the AE has been clearly shown to be unrelated to the IMP. The period of observation for SAEs extends from the time of signing the informed consent until the Final/ET Visit.	0.00% 0/83 • The period of observation for AEs extends from the time of the patient's first dose of IMP until the Final/ET Visit, an average of 18 weeks. Ongoing AEs at the Final/ET Visit will be followed up until the AE has resolved or is considered chronic or stable or the AE has been clearly shown to be unrelated to the IMP. The period of observation for SAEs extends from the time of signing the informed consent until the Final/ET Visit.
Eye disorders ANISOCORIA	0.00% 0/86 • The period of observation for AEs extends from the time of the patient's first dose of IMP until the Final/ET Visit, an average of 18 weeks. Ongoing AEs at the Final/ET Visit will be followed up until the AE has resolved or is considered chronic or stable or the AE has been clearly shown to be unrelated to the IMP. The period of observation for SAEs extends from the time of signing the informed consent until the Final/ET Visit.	1.1% 1/93 • Number of events 1 • The period of observation for AEs extends from the time of the patient's first dose of IMP until the Final/ET Visit, an average of 18 weeks. Ongoing AEs at the Final/ET Visit will be followed up until the AE has resolved or is considered chronic or stable or the AE has been clearly shown to be unrelated to the IMP. The period of observation for SAEs extends from the time of signing the informed consent until the Final/ET Visit.	0.00% 0/83 • The period of observation for AEs extends from the time of the patient's first dose of IMP until the Final/ET Visit, an average of 18 weeks. Ongoing AEs at the Final/ET Visit will be followed up until the AE has resolved or is considered chronic or stable or the AE has been clearly shown to be unrelated to the IMP. The period of observation for SAEs extends from the time of signing the informed consent until the Final/ET Visit.
Musculoskeletal and connective tissue disorders INTERVERTEBRAL DISC PROTRUSION	1.2% 1/86 • Number of events 1 • The period of observation for AEs extends from the time of the patient's first dose of IMP until the Final/ET Visit, an average of 18 weeks. Ongoing AEs at the Final/ET Visit will be followed up until the AE has resolved or is considered chronic or stable or the AE has been clearly shown to be unrelated to the IMP. The period of observation for SAEs extends from the time of signing the informed consent until the Final/ET Visit.	0.00% 0/93 • The period of observation for AEs extends from the time of the patient's first dose of IMP until the Final/ET Visit, an average of 18 weeks. Ongoing AEs at the Final/ET Visit will be followed up until the AE has resolved or is considered chronic or stable or the AE has been clearly shown to be unrelated to the IMP. The period of observation for SAEs extends from the time of signing the informed consent until the Final/ET Visit.	0.00% 0/83 • The period of observation for AEs extends from the time of the patient's first dose of IMP until the Final/ET Visit, an average of 18 weeks. Ongoing AEs at the Final/ET Visit will be followed up until the AE has resolved or is considered chronic or stable or the AE has been clearly shown to be unrelated to the IMP. The period of observation for SAEs extends from the time of signing the informed consent until the Final/ET Visit.

Other adverse events

Additional Information

Vice President Clinical

KalVista Pharmaceuticals Ltd.

Phone: 1 (857) 999-0075

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place