A long-term study to evaluate if KVD900 is safe and effective in treating attacks in patients with Hereditary Angioedema.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Kalvista Pharmaceuticals Limited

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

17 Nov 2022 → 28 May 2026

Decision date (initial)

2024-02-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

KalVista Pharmaceuticals Ltd

External identifiers

EU CT number

2023-505904-41-00

EudraCT number

2021-001176-42

ClinicalTrials.gov

NCT05505916

ISRCTN

ISRCTN98539585

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Pharmacokinetic, Safety

To assess the safety of long-term administration of KVD900 in adolescent and adult patients with HAE type I or II.

Secondary objectives 2

1. To assess the long-term efficacy of KVD900 in the treatment of attacks in adolescent and adult patients with HAE type I or II
2. To assess the safety and efficacy of KVD900 when used as short-term prophylaxis in adolescent and adult patients with HAE types I or II.

Conditions and MedDRA coding

Hereditary Angioedema Type I or II

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002723-PIP01-19

Plan to share IPD

No

IPD plan description

Data will not be shared until all global regulatory filings are complete.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Patients may roll over from KVD900-301.
2. Confirmed diagnosis of HAE type I or II at any time in the medical history
3. Patient has had at least 2 documented HAE attacks within 3 months prior to the Enrollment Visit
4. If a patient is receiving long-term prophylactic treatment with one of the protocol-allowed therapies, they must have been on a stable dose and regimen for at least 3 months prior to the Enrollment Visit
5. Male or female patients 12 years of age and older.
6. Patients must meet the contraception requirements.
7. Patients must be able to swallow trial tablets whole.
8. Patients, as assessed by the Investigator, must be able to appropriately receive and store IMP, and be able to read, understand, and complete the eDiary.
9. Investigator believes that the patient is willing and able to adhere to all protocol requirements.
10. Patient provides signed informed consent or assent (when applicable). A parent or LAR must also provide signed informed consent when required.

Exclusion criteria 14

1. Discontinued from the KVD900-301 trial for reasons of non-compliance, withdrawal of consent, or safety.
2. Presence of any safety concerns that would preclude participation in the open-label trial as determined by the investigator.
3. 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.
4. 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.
5. Use of attenuated androgens (e.g., stanozolol, danazol, oxandrolone, methyltestosterone, testosterone), or anti-fibrinolytics (e.g., tranexamic acid) within 28 days prior to the Enrollment Visit.
6. Use of ACE inhibitors within 7 days prior to the Enrollment Visit.
7. Any estrogen-containing medications with systemic absorption (such as oral contraceptives including ethinylestradiol or hormonal replacement therapy) within 7 days prior to the Enrollment Visit.
8. Inadequate organ function, including but not limited to: a) Alanine aminotransferase (ALT) >2x ULN b) Aspartate aminotransferase (AST) >2x ULN c) Bilirubin direct >1.25x ULN d) INR >1.2 e) Clinically significant hepatic impairment defined as a Child-Pugh B or C
9. 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.
10. History of substance abuse or dependence that would interfere with the completion of the trial, as determined by the Investigator.
11. Known hypersensitivity to KVD900 or to any of the excipients.
12. Participation in any gene therapy treatment or trial for HAE.
13. Participation in any interventional investigational clinical trial, including an investigational COVID-19 vaccine trial, within 4 weeks of the last dosing of investigational drug prior to the Enrollment Visit.
14. Any pregnant or breastfeeding patient.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Frequencies and percentages of patients with AEs, AEs within 2 days of IMP administration, serious AEs, and AEs causing premature discontinuation
2. Number and percentage of patients with normal or abnormal laboratory results at each scheduled visit
3. Number and percentage of patients with normal or abnormal vital sign results at each scheduled visit

Secondary endpoints 3

1. PGI-C: time to beginning of symptom relief defined as at least '' a little better'' (2 time points in a row) within 12 hours of initial dose of IMP administration.
2. PGI-S: time to first incidence of 2 time points in a row decrease from baseline within 12 hours of initial dose of IMP administration.
3. PGI-S: time to HAE attack resolution defined as ''none'' within 24 hours of initial dose of IMP administration.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Kalvista Pharmaceuticals Limited

Sponsor organisation

Kalvista Pharmaceuticals Limited

Address

Porton Science Park, Bybrook Road, Porton Down Bybrook Road Porton Down

City

Salisbury

Postcode

SP4 0BF

Country

United Kingdom

Scientific contact point

Organisation

Kalvista Pharmaceuticals Limited

Contact name

KalVista Clinical

Public contact point

Organisation

Kalvista Pharmaceuticals Limited

Contact name

KalVista Clinical

Third parties 7

Locations

13 EU/EEA countries · 26 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 181 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications