FindTrial
Sign In

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)

A Randomized, Double-Blind, Placebo-Controlled, Phase 3, Three-way Crossover Trial to Evaluate the Efficacy and Safety of Two Dose Levels of KVD900, an Oral Plasma Kallikrein Inhibitor, for On-Demand Treatment of Angioedema Attacks in Adolescent and Adult Patients With Hereditary Angioedema Type I or II

Status
Completed
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT05259917
Enrollment
136
Registered
2022-03-02
Start date
2022-02-22
Completion date
2023-12-31
Last updated
2025-05-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hereditary Angioedema

Keywords

KONFIDENT, Sebetralstat

Brief summary

This study is a randomized, double-blind, placebo-controlled, phase III, three-way crossover clinical trial evaluating the efficacy and safety of KVD900, in the treatment of hereditary angioedema attacks in adolescent and adult Patients

Interventions

DRUGPlacebo

Placebo to KVD900 Tablet

DRUGKVD900 600 mg

KVD900 Tablet 600 mg (2 x 300 mg)

DRUGKVD900 300 mg

KVD900 Tablet 300 mg (1 x 300 mg)

Sponsors

KalVista Pharmaceuticals, Ltd.
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No

Inclusion criteria

* Male or female patients 12 years of age and older. * Confirmed diagnosis of HAE type I or II at any time in the medical history. * Patient has access to and ability to use conventional on-demand treatment for HAE attacks. * If a patient is receiving long-term prophylactic treatment with one of the protocol-allowed therapies, they must be on a stable dose and regimen for at least 3 months prior to the Screening Visit (except for danazol, which requires a stable dose and regimen for 6 months prior to the Screening Visit). Patient must be willing to remain on a stable dose and regimen for the duration of the trial. * Patient's last dose of attenuated androgens other than danazol was at least 28 days prior to randomization. * Patient: 1. has had at least 2 documented HAE attacks within 3 months prior to screening or randomization; or 2. is a completer of the KVD824-201 trial within 3 months prior to randomization and meets all other entry criteria to enroll in KVD900-301 * Patients must meet the contraception requirements. * Patients must be able to swallow trial tablets whole. * Patients, as assessed by the Investigator, must be able to appropriately receive and store IMP, and be able to read, understand, and complete the electronic diary (eDiary). * Investigator believes that the patient is willing and able to adhere to all protocol requirements. * Patient provides signed informed consent or assent (when applicable). A parent or legally authorized representative (LAR) must also provide signed informed consent when required.

Exclusion criteria

* Any concomitant diagnosis of another form of chronic angioedema, such as acquired C1-inhibitor deficiency, HAE with normal C1-INH (previously known as HAE type III), idiopathic angioedema, or angioedema associated with urticaria. * A clinically significant history of poor response to bradykinin receptor 2 (BR2) blocker, C1-INH therapy or plasma kallikrein inhibitor therapy for the management of HAE, in the opinion of the Investigator. * Use of angiotensin-converting enzyme (ACE) inhibitors after the Screening Visit or within 7 days prior to randomization. * Any estrogen containing medications with systemic absorption (such as oral contraceptives including ethinylestradiol or hormonal replacement therapy) within 7 days prior to the Screening Visit. * Patients who require sustained use of strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers. * Inadequate organ function, including but not limited to: 1. Alanine aminotransferase (ALT) \>2x upper limit of normal (ULN) 2. Aspartate aminotransferase (AST) \>2x ULN 3. Bilirubin direct \>1.25x ULN 4. International normalized ratio (INR) \>1.2 5. Clinically significant hepatic impairment defined as a Child-Pugh B or C * Any clinically significant comorbidity or systemic dysfunction, which in the opinion of the Investigator, would jeopardize the safety of the patient by participating in the trial. * History of substance abuse or dependence that would interfere with the completion of the trial, as determined by the Investigator. * Known hypersensitivity to KVD900 or placebo or to any of the excipients. * Prior participation in trial KVD900-201. * Participation in any gene therapy treatment or trial for HAE. * Participation in any interventional investigational clinical trial (with the exception of KVD824-201), including an investigational COVID-19 vaccine trial, within 4 weeks of the last dosing of investigational drug prior to screening. * Any pregnant or breastfeeding patient.

Design outcomes

Primary

MeasureTime frameDescription
Time to Beginning of Symptom Relief Patient Global Impression of Change (PGI-C)Within 12 hours of the first investigational medicinal product (IMP) administration.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.

Secondary

MeasureTime frameDescription
Time to First Incidence of Decrease From Baseline Patient Global Impression of Severity (PGI-S) (2 Time Points in a Row)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.
Time to Complete HAE Attack Resolution (PGI-S)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.

Countries

Australia, Bulgaria, Canada, France, Germany, Greece, Hungary, Israel, Italy, Japan, Netherlands, New Zealand, North Macedonia, Poland, Portugal, Puerto Rico, Romania, Slovakia, Spain, United Kingdom, United States

Participant flow

Recruitment details

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.

Pre-assignment details

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).

Participants by arm

ArmCount
Sequence A
PLB/600 mg KVD900/300 mg KVD900
18
Sequence B
PLB/ 300 mg KVD900/ 600 mg KVD900
18
Sequence C
300 mg KVD900/ 600 mg KVD900/PLB
15
Sequence D
300 mg KVD900/PLB/ 600 mg KVD900
17
Sequence E
600 mg KVD900/ 300 mg KVD900/PLB
20
Sequence F
600 mg KVD900/PLB/ 300 mg KVD900
22
Total110

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003FG004FG005
Overall StudyLost to Follow-up001001
Overall StudyOther102000
Overall StudyPhysician Decision010000
Overall StudyProtocol Violation001000
Overall StudyTrial Termination by Sponsor7235114
Overall StudyWithdrawal by Subject010011

Baseline characteristics

CharacteristicSequence ATotalSequence FSequence ESequence DSequence CSequence B
Age, Continuous37.4 years
STANDARD_DEVIATION 15.7
37.7 years
STANDARD_DEVIATION 14.96
38.2 years
STANDARD_DEVIATION 13.14
41.4 years
STANDARD_DEVIATION 14.6
31.8 years
STANDARD_DEVIATION 11.42
41.1 years
STANDARD_DEVIATION 17.87
35.8 years
STANDARD_DEVIATION 16.9
Body mass index27.78 kg/m^2
STANDARD_DEVIATION 5.638
27.44 kg/m^2
STANDARD_DEVIATION 6.261
28.90 kg/m^2
STANDARD_DEVIATION 7.329
27.37 kg/m^2
STANDARD_DEVIATION 5.162
26.15 kg/m^2
STANDARD_DEVIATION 7.701
28.62 kg/m^2
STANDARD_DEVIATION 6.603
25.62 kg/m^2
STANDARD_DEVIATION 4.743
Ethnicity (NIH/OMB)
Hispanic or Latino
1 Participants7 Participants0 Participants2 Participants1 Participants3 Participants0 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
15 Participants95 Participants21 Participants17 Participants15 Participants10 Participants17 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
2 Participants8 Participants1 Participants1 Participants1 Participants2 Participants1 Participants
Height1.646 meters
STANDARD_DEVIATION 0.1216
1.684 meters
STANDARD_DEVIATION 0.1088
1.704 meters
STANDARD_DEVIATION 0.1126
1.686 meters
STANDARD_DEVIATION 0.0884
1.657 meters
STANDARD_DEVIATION 0.1205
1.715 meters
STANDARD_DEVIATION 0.0877
1.694 meters
STANDARD_DEVIATION 0.1135
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
2 Participants10 Participants1 Participants1 Participants5 Participants1 Participants0 Participants
Race (NIH/OMB)
Black or African American
0 Participants1 Participants0 Participants0 Participants0 Participants1 Participants0 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
2 Participants7 Participants2 Participants1 Participants1 Participants1 Participants0 Participants
Race (NIH/OMB)
White
14 Participants92 Participants19 Participants18 Participants11 Participants12 Participants18 Participants
Sex: Female, Male
Female
13 Participants66 Participants11 Participants11 Participants12 Participants5 Participants14 Participants
Sex: Female, Male
Male
5 Participants44 Participants11 Participants9 Participants5 Participants10 Participants4 Participants
Treatment Regimen
On Demand Only
15 Participants86 Participants15 Participants17 Participants14 Participants12 Participants13 Participants
Treatment Regimen
Prophylaxis
3 Participants24 Participants7 Participants3 Participants3 Participants3 Participants5 Participants
Weight75.16 kilograms
STANDARD_DEVIATION 16.109
77.86 kilograms
STANDARD_DEVIATION 19.179
83.55 kilograms
STANDARD_DEVIATION 21.949
77.90 kilograms
STANDARD_DEVIATION 16.321
72.28 kilograms
STANDARD_DEVIATION 23.735
83.80 kilograms
STANDARD_DEVIATION 18.157
73.88 kilograms
STANDARD_DEVIATION 16.603

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
0 / 860 / 930 / 83
other
Total, other adverse events
5 / 866 / 9313 / 83
serious
Total, serious adverse events
1 / 862 / 930 / 83

Outcome results

Primary

Time to Beginning of Symptom Relief Patient Global Impression of Change (PGI-C)

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.

Time frame: 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.

ArmMeasureValue (MEDIAN)
KVD900 300 mgTime to Beginning of Symptom Relief Patient Global Impression of Change (PGI-C)1.61 Time (h)
KVD900 600 mgTime to Beginning of Symptom Relief Patient Global Impression of Change (PGI-C)1.79 Time (h)
PlaceboTime to Beginning of Symptom Relief Patient Global Impression of Change (PGI-C)6.72 Time (h)
Comparison: Gehan score transformation test:~KVD900 300 mg vs Placebop-value: <0.0001Gehan score transformation test
Comparison: Gehan score transformation test:~KVD900 600 mg vs Placebop-value: 0.0013Gehan score transformation test
Secondary

Time to Complete HAE Attack Resolution (PGI-S)

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.

Time frame: Within 24 hours of the first 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.

ArmMeasureValue (MEDIAN)
KVD900 300 mgTime to Complete HAE Attack Resolution (PGI-S)NA Time (h)
KVD900 600 mgTime to Complete HAE Attack Resolution (PGI-S)24.00 Time (h)
PlaceboTime to Complete HAE Attack Resolution (PGI-S)NA Time (h)
Comparison: Gehan score transformation test:~KVD900 300 mg vs Placebop-value: 0.0022Gehan score transformation test
Comparison: Gehan score transformation test:~KVD900 600 mg vs Placebop-value: <0.0001Gehan score transformation test
Secondary

Time to First Incidence of Decrease From Baseline Patient Global Impression of Severity (PGI-S) (2 Time Points in a Row)

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.

Time frame: Within 12 hours of the first 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.

ArmMeasureValue (MEDIAN)
KVD900 300 mgTime to First Incidence of Decrease From Baseline Patient Global Impression of Severity (PGI-S) (2 Time Points in a Row)9.27 Time (h)
KVD900 600 mgTime to First Incidence of Decrease From Baseline Patient Global Impression of Severity (PGI-S) (2 Time Points in a Row)7.75 Time (h)
PlaceboTime to First Incidence of Decrease From Baseline Patient Global Impression of Severity (PGI-S) (2 Time Points in a Row)NA Time (h)
Comparison: Gehan score transformation test:~KVD900 300 mg vs Placebop-value: 0.0036Gehan score transformation test
Comparison: Gehan score transformation test:~KVD900 600 mg vs Placebop-value: 0.0032Gehan score transformation test

Source: ClinicalTrials.gov · Data processed: Mar 7, 2026