A Trial to Evaluate the Efficacy and Safety of Different Doses of KVD824 for Prophylactic Treatment of HAE Type I or II

NCT ID: NCT05055258

Last Updated: 2023-10-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

33 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-09-27

Study Completion Date

2022-10-27

Brief Summary

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A study to assess whether different doses of KVD824 are effective in preventing attacks of Hereditary Angiodedema Type I or Type II.

Detailed Description

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Conditions

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Angioedema, Hereditary, Types I and II

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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300 mg KVD824

300 mg KVD824 twice a day for 12 weeks

Group Type EXPERIMENTAL

KVD824

Intervention Type DRUG

KVD824 300 mg Modified-Release Tablets

600 mg KVD824

Two 300 mg KVD824 tablets twice a day for 12 weeks

Group Type EXPERIMENTAL

KVD824

Intervention Type DRUG

KVD824 300 mg Modified-Release Tablets

900 mg KVD824

Three 300 mg KVD824 tablets twice a day for 12 weeks

Group Type EXPERIMENTAL

KVD824

Intervention Type DRUG

KVD824 300 mg Modified-Release Tablets

Placebo to KVD824

One, two or three placebo tablets to be taken twice a day for 12 weeks

Group Type PLACEBO_COMPARATOR

Placebo to KVD824

Intervention Type DRUG

Placebo to KVD824 300 mg Modified-Release Tablets

Interventions

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KVD824

KVD824 300 mg Modified-Release Tablets

Intervention Type DRUG

Placebo to KVD824

Placebo to KVD824 300 mg Modified-Release Tablets

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Male or female subjects 18 years of age and older.
2. Confirmed diagnosis of HAE type I or II at any time in the medical history:

1. Documented clinical history consistent with HAE (subcutaneous or mucosal, nonpruritic swelling episodes without accompanying urticaria) AND EITHER
2. Diagnostic testing results obtained prior to randomization that confirm HAE Type I or II: C1-INH functional level \<40% of the normal level. Subjects with functional C1-INH level 40-50% of the normal level may be enrolled if they also have a C4 level below the normal range. Testing may be obtained from central or local laboratories or obtained from documented historical testing results. Subjects may be restested at anytime prior to randomization if results are incongruent with clinical history or believed by the Investigator to be confounded by recent prophylactic or therapeutic C1 INH use, OR
3. Documented genetic results that confirm known mutations for HAE Type I or II.
3. Subject has access to and ability to use conventional treatment for HAE attacks.
4. Subject is willing to cease any current medications being taken for HAE prophylaxis and Investigator determines that doing so would not place the subject at any undue safety risk.
5. Subject's last dose of attenuated androgens was at least 28 days prior to first dose of IMP.
6. During the Run-in Period subject meets one of the following criteria:

1. Two Investigator-confirmed attacks in the first 4-week period.
2. Three Investigator-confirmed attacks in ≤8 weeks.
7. Subjects who are fertile and heterosexually active must adhere to contraception requirements throughout the trial as follows:

a) Female subjects must agree to use at least one highly effective contraception method from the Screening Visit until the end of the trial. Highly effective methods of contraception include: i) Progestogen-only hormonal contraception associated with inhibition of ovulation: oral/injectable/implantable (hormonal contraception that contains estrogen including ethinylestradiol is excluded per Exclusion 4).

ii) Intrauterine device (IUD). iii) Intrauterine hormone-releasing system (IUS). iv) Bilateral tubal occlusion. v) Vasectomized partner (provided that the partner is the sole sexual partner of the female subject of childbearing potential and that the vasectomized partner has received medical assessment of surgical success).

b) Male subjects with a female partner of childbearing potential must agree to use condoms for the entire Treatment Period AND for 90 days following the final dose of investigational medicinal product (IMP). Female partners are encouraged to use contraception as outlined in Inclusion 7a) from the Screening Visit until the end of the trial. Hormonal contraception that contains estrogen including ethinylestradiol is acceptable for the female partner.
8. Subjects who are not fertile or not sexually active, as defined below, do not require contraception.

1. Subjects who refrain from heterosexual intercourse during the trial if the reliability of the heterosexual abstinence has been evaluated in relation to the duration of the clinical trial and is the preferred and usual lifestyle of the subject.
2. Male subjects who are surgically sterile (e.g. vasectomized with medical assessment of surgical success).
3. Female subjects who are surgically sterile (e.g. status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or post menopausal for at least 12 months.
9. Subjects must be able to swallow trial tablets whole.
10. Subjects assessed by the Investigator must be able to appropriately receive and store IMP, and be able to read, understand, and complete the eDiary.
11. Investigator believes that the subject is willing and able to adhere to all protocol requirements.
12. Subject provides signed informed consent and is willing and capable of complying with trial requirements and procedures.

Exclusion Criteria

1. 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.
2. A clinically significant history of poor response to C1-INH therapy or plasma kallikrein inhibitor therapy for the management of HAE, in the opinion of the Investigator.
3. Use of angiotensin converting enzyme (ACE) inhibitors after the Screening Visit or within 7 days prior to randomization.
4. Any estrogen containing medications with systemic absorption (such as oral contraceptives including ethinylestradiol or hormonal replacement therapy) after the Screening Visit or within 7 days prior to randomization.
5. Use of narrow therapeutic index drugs metabolized by CYP3A4 or CYP2C9 or transported by OAT1, OCT2, and OATP1B1, starting at screening, as determined by the Investigator.
6. Use of strong CYP3A4 inhibitors and inducers during participation in the trial, starting at the Screening Visit.

Note: These medications include but are not limited to the following:

Inhibitors: boceprevir, clarithromycin, cobicistat, dasabuvir, denoprevir, elvitegravir, idelalisib, indinavir, itraconazole, ketoconazole, lopinavir, nefazodone, nelfinavir ombitasvir, paritaprevir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, tipranavir, troleandomycin, and voriconazole.

Inducers: apalutamide, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John's Wort.
7. 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.
6. Estimated glomerular filtration rate (eGFR) \<60 mL/min.
8. Any clinically significant comorbidity or systemic dysfunction that in the opinion of the Investigator would jeopardize the safety of the subject by participating in the trial.
9. History of substance abuse or dependence that would interfere with the completion of the trial, as determined by the Investigator.
10. Known hypersensitivity to KVD824 or placebo or to any of the excipients.
11. Any prior use of any gene therapy treatment for HAE.
12. 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 screening.
13. Any pregnant or breastfeeding subject.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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KalVista Pharmaceuticals, Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Study Director

Role: STUDY_DIRECTOR

KalVista Pharmaceuticals

Locations

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KalVista Investigative Site

Birmingham, Alabama, United States

Site Status

KalVista Investigative Site

Scottsdale, Arizona, United States

Site Status

KalVista Investigative Site

La Jolla, California, United States

Site Status

KalVista Investigative Site

Santa Monica, California, United States

Site Status

KalVista Investigative Site

Centennial, Colorado, United States

Site Status

KalVista Investigative Site

Tampa, Florida, United States

Site Status

KalVista Investigative Site

Chevy Chase, Maryland, United States

Site Status

KalVista Investigative Site

Boston, Massachusetts, United States

Site Status

KalVista Investigative Site

St Louis, Missouri, United States

Site Status

KalVista Investigative Site

Cincinnati, Ohio, United States

Site Status

KalVista Investigative Site

Hershey, Pennsylvania, United States

Site Status

KalVista Investigative Site

Dallas, Texas, United States

Site Status

KalVista Investigative Site

Spokane, Washington, United States

Site Status

KalVista Investigative Site

Campbelltown, New South Wales, Australia

Site Status

KalVista Investigative Site

Sofia, , Bulgaria

Site Status

KalVista Investigative Site

North York, Ontario, Canada

Site Status

KalVista Investigative Site

Brno, , Czechia

Site Status

KalVista Investigative Site

Prague, , Czechia

Site Status

KalVista Investigative Site

Grenoble, , France

Site Status

KalVista Investigative Site

Paris, , France

Site Status

KalVista Investigative Site

Mainz, Rhineland-Palatinate, Germany

Site Status

KalVista Investigative Site

Berlin, , Germany

Site Status

KalVista Investigative Site

Frankfurt am Main, , Germany

Site Status

KalVista Investigative Site

Budapest, , Hungary

Site Status

KalVista Investigative Site

Milan, , Italy

Site Status

KalVista Investigative Site

Padua, , Italy

Site Status

KalVista Investigative Site

Grafton, Auckland, New Zealand

Site Status

KalVista Investigative Site

Skopje, , North Macedonia

Site Status

KalVista Investigative Site

San Juan, , Puerto Rico

Site Status

KalVista Investigative Site

Birmingham, , United Kingdom

Site Status

KalVista Investigative Site

Leeds, , United Kingdom

Site Status

KalVista Investigative Site

London, , United Kingdom

Site Status

KalVista Investigative Site

Newcastle upon Tyne, , United Kingdom

Site Status

Countries

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United States Australia Bulgaria Canada Czechia France Germany Hungary Italy New Zealand North Macedonia Puerto Rico United Kingdom

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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KVD824-201

Identifier Type: -

Identifier Source: org_study_id

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