Hereditary Angioedema
Conditions
Keywords
KONFIDENT-KID
Brief summary
KVD900-303 is an open-label, multicenter clinical trial in patients aged 2 to 11 years old with HAE Type I or II.
Interventions
DRUGKVD900 150 mg
KVD900 Tablet 150 mg (2 x 75 mg)
DRUGKVD900 300 mg
KVD900 Tablet 300 mg (1 x 300 mg)
DRUGKVD900 600 mg
KVD900 Tablet 600 mg (2 x 300 mg)
Sponsors
KalVista Pharmaceuticals, Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female patients 2 to 11 years of age. 2. Confirmed diagnosis of HAE Type I or II. 3. For patients ≥20 kg at screening, patient has had at least 1 documented HAE attack in the last year prior to screening. 4. Caregiver, as assessed by the Investigator, must be able to appropriately store and administer IMP and be able to read, understand, and complete the diary. 5. Investigator believes that the patient and caregiver are willing and able to adhere to all protocol requirements. 6. Parent or Legally Authorized Representative (LAR) provides signed informed consent and patient provides assent (when applicable).
Exclusion criteria
1. Any concomitant diagnosis of another form of chronic angioedema, such as acquired C1 inhibitor deficiency, HAE with normal C1-INH, idiopathic angioedema, or angioedema associated with urticaria. 2. A clinically significant history of poor response to bradykinin receptor 2 blocker, C1-INH therapy, or plasma kallikrein inhibitor therapy for the management of HAE, in the opinion of the Investigator. 3. Patient weighs \<9.5 kg. 4. Use of angiotensin-converting enzyme inhibitors after the Screening Visit. 5. 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. 6. Patients who require sustained use of strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers or moderate CYP3A4 inducers. 7. 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. 8. Known hypersensitivity to sebetralstat or to any of the excipients. 9. Participation in any interventional investigational clinical trial within 4 weeks of the last dosing of investigational drug prior to the Screening Visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | From first dose of IMP until the Final/Early Termination (ET) Visit, up to a maximum of 54 weeks. | A TEAE was defined as an adverse event (AE) that met any of the following conditions: (1) began on or after the first dose of IMP, (2) began before the first dose of IMP and increased in severity on or after first dose, (3) was completely missing a start date and the stop date, (4) was completely missing a start date and the stop date was on or after the first dose of IMP. An on-treatment TEAE was defined as any TEAE occurring within 3 days of IMP administration. A treatment-related TEAE was an AE considered related to the IMP by the investigator. A serious AE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required in-patient hospitalization or prolongation, resulted in significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event (based upon medical and scientific judgment). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Concentrations of Sebetralstat | At 0.5 hours (±5 min), 2 hours (±15 min), and 4 hours (±15 min) post-dose. PK assessments for sebetralstat 300 mg ED were conducted at the Enrollment Visit, and for 600 mg ED at the Dose Increase Visit (up to 12.6 months after Enrollment Visit). | During the Enrollment Visit, participants were dosed with IMP (sebetralstat 300 mg ED) and monitored for tolerability. Pharmacokinetic (PK) samples were collected via venous access or capillary collection (eg, finger prick) at specified timepoints. For participants enrolled under protocol v3.4 who received sebetralstat 600 mg ED, a second PK assessment was performed at the Dose Increase Visit. The Dose Increase Visit occurred as soon as possible after implementation of the protocol amendment and could occur at any time during the participant's participation in the trial. |
Countries
Canada, France, Germany, Israel, Italy, Japan, United States
Contacts
STUDY_DIRECTORStudy Director
KalVista Pharmaceuticals, Ltd.
Participant flow
Recruitment details
Pediatric participants (aged 2 to 11 years) with hereditary angioedema (HAE) Type I or II were enrolled at trial sites in Canada, Germany, France, Israel, Italy, Japan, and the United States (US). Participants enrolled under protocol v1.0 to v3.3 received sebetralstat 300 mg equivalent dosing (ED). Following a US-specific protocol amendment, dose levels were increased; US-only participants who continued under protocol v3.4 had a Dose Increase Visit and received sebetralstat 600 mg ED thereafter.
Pre-assignment details
Dose levels for both sebetralstat 300 mg ED and 600 mg ED were selected by the investigator, based on the participant's weight. The screening visit occurred up to 8 weeks before enrolment. Participants were allowed to treat HAE attacks for up to 1 year following the first attack treated with sebetralstat, or until the participant reached 12 years of age, or the trial was completed.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 8.0 years |
| Age, Customized 2 - 5 years | 3 Participants |
| Age, Customized 6 - 11 years | 33 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants |
| Race American Indian or Alaska Native | 0 Participants |
| Race Asian | 1 Participants |
| Race Black | 1 Participants |
| Race Native Hawaiian or Pacific islander | 0 Participants |
| Race Not Reported | 5 Participants |
| Race Other | 1 Participants |
| Race White | 26 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 36 | 0 / 7 |
| other Total, other adverse events | 20 / 36 | 1 / 7 |
| serious Total, serious adverse events | 0 / 36 | 0 / 7 |
Outcome results
None listed