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A Trial to Evaluate the Efficacy and Safety of Different Doses of KVD824 for Prophylactic Treatment of HAE Type I or II (KVD824-201)

Primary Purpose

Angioedema, Hereditary, Types I and II

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
KVD824
Placebo to KVD824
Sponsored by
KalVista Pharmaceuticals, Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Angioedema, Hereditary, Types I and II focused on measuring KVD824, KOMPLETE

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • KalVista Investigative Site
  • KalVista Investigative Site
  • KalVista Investigative Site
  • KalVista Investigative Site
  • KalVista Investigative Site
  • KalVista Investigative Site
  • KalVista Investigative Site
  • KalVista Investigative Site
  • KalVista Investigative Site
  • KalVista Investigative Site
  • KalVista Investigative Site
  • KalVista Investigative Site
  • KalVista Investigative Site
  • KalVista Investigative Site
  • KalVista Investigative Site
  • KalVista Investigative Site
  • KalVista Investigative Site
  • KalVista Investigative Site
  • KalVista Investigative Site
  • KalVista Investigative Site
  • KalVista Investigative Site
  • KalVista Investigative Site
  • KalVista Investigative Site
  • KalVista Investigative Site
  • KalVista Investigative Site
  • KalVista Investigative Site
  • KalVista Investigative Site
  • KalVista Investigative Site
  • KalVista Investigative Site
  • KalVista Investigative Site
  • KalVista Investigative Site
  • KalVista Investigative Site
  • KalVista Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

300 mg KVD824

600 mg KVD824

900 mg KVD824

Placebo to KVD824

Arm Description

300 mg KVD824 twice a day for 12 weeks

Two 300 mg KVD824 tablets twice a day for 12 weeks

Three 300 mg KVD824 tablets twice a day for 12 weeks

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

Outcomes

Primary Outcome Measures

The Rate of Investigator-confirmed HAE attacks during the Treatment Period
To examine the number of investigator-confirmed attacks whilst on treatment compared to placebo

Secondary Outcome Measures

Proportion of subjects without Investigator-confirmed HAE attacks during the Treatment Period.
Rate of Investigator-confirmed HAE attacks that require conventional treatment during the Treatment Period.
Angioedema Quality of Life Questionnaire (AE-QoL) total score and domain scores during the Treatment Period.
AE-QoL is a quality of life questionnaire with a range of 0 (minimum) to 100 (maximum). A total score of 100 indicates worst possible impairment.
Angioedema Control Test (AECT) score and domain scores during the Treatment Period.
AECT is a 4-item patient-reported outcome measure. The total score is from 0 (minimum) to 16 (maximum). A higher score indicates a higher level of angioedema control.
Proportion of subjects with an AECT score ≥12 at the end of the Treatment Period.
AECT is a 4-item patient-reported outcome measure. The total score is from 0 (minimum) to 16 (maximum). A higher score indicates a higher level of angioedema control.

Full Information

First Posted
September 14, 2021
Last Updated
October 5, 2023
Sponsor
KalVista Pharmaceuticals, Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05055258
Brief Title
A Trial to Evaluate the Efficacy and Safety of Different Doses of KVD824 for Prophylactic Treatment of HAE Type I or II
Acronym
KVD824-201
Official Title
Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial to Evaluate the Efficacy and Safety of 3 Dose Levels of KVD824, an Oral Plasma Kallikrein Inhibitor, for Long-Term Prophylactic Treatment of Hereditary Angioedema Type I or II
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Terminated
Why Stopped
Terminated by Sponsor due to adverse events reported
Study Start Date
September 27, 2021 (Actual)
Primary Completion Date
October 27, 2022 (Actual)
Study Completion Date
October 27, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
KalVista Pharmaceuticals, Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Angioedema, Hereditary, Types I and II
Keywords
KVD824, KOMPLETE

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
33 (Actual)

8. Arms, Groups, and Interventions

Arm Title
300 mg KVD824
Arm Type
Experimental
Arm Description
300 mg KVD824 twice a day for 12 weeks
Arm Title
600 mg KVD824
Arm Type
Experimental
Arm Description
Two 300 mg KVD824 tablets twice a day for 12 weeks
Arm Title
900 mg KVD824
Arm Type
Experimental
Arm Description
Three 300 mg KVD824 tablets twice a day for 12 weeks
Arm Title
Placebo to KVD824
Arm Type
Placebo Comparator
Arm Description
One, two or three placebo tablets to be taken twice a day for 12 weeks
Intervention Type
Drug
Intervention Name(s)
KVD824
Intervention Description
KVD824 300 mg Modified-Release Tablets
Intervention Type
Drug
Intervention Name(s)
Placebo to KVD824
Intervention Description
Placebo to KVD824 300 mg Modified-Release Tablets
Primary Outcome Measure Information:
Title
The Rate of Investigator-confirmed HAE attacks during the Treatment Period
Description
To examine the number of investigator-confirmed attacks whilst on treatment compared to placebo
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Proportion of subjects without Investigator-confirmed HAE attacks during the Treatment Period.
Time Frame
12 weeks
Title
Rate of Investigator-confirmed HAE attacks that require conventional treatment during the Treatment Period.
Time Frame
12 weeks
Title
Angioedema Quality of Life Questionnaire (AE-QoL) total score and domain scores during the Treatment Period.
Description
AE-QoL is a quality of life questionnaire with a range of 0 (minimum) to 100 (maximum). A total score of 100 indicates worst possible impairment.
Time Frame
12 weeks
Title
Angioedema Control Test (AECT) score and domain scores during the Treatment Period.
Description
AECT is a 4-item patient-reported outcome measure. The total score is from 0 (minimum) to 16 (maximum). A higher score indicates a higher level of angioedema control.
Time Frame
12 weeks
Title
Proportion of subjects with an AECT score ≥12 at the end of the Treatment Period.
Description
AECT is a 4-item patient-reported outcome measure. The total score is from 0 (minimum) to 16 (maximum). A higher score indicates a higher level of angioedema control.
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female subjects 18 years of age and older. Confirmed diagnosis of HAE type I or II at any time in the medical history: Documented clinical history consistent with HAE (subcutaneous or mucosal, nonpruritic swelling episodes without accompanying urticaria) AND EITHER 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 Documented genetic results that confirm known mutations for HAE Type I or II. Subject has access to and ability to use conventional treatment for HAE attacks. 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. Subject's last dose of attenuated androgens was at least 28 days prior to first dose of IMP. During the Run-in Period subject meets one of the following criteria: Two Investigator-confirmed attacks in the first 4-week period. Three Investigator-confirmed attacks in ≤8 weeks. 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. Subjects who are not fertile or not sexually active, as defined below, do not require contraception. 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. Male subjects who are surgically sterile (e.g. vasectomized with medical assessment of surgical success). 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. Subjects must be able to swallow trial tablets whole. Subjects assessed by the Investigator must be able to appropriately receive and store IMP, and be able to read, understand, and complete the eDiary. Investigator believes that the subject is willing and able to adhere to all protocol requirements. Subject provides signed informed consent and is willing and capable of complying with trial requirements and procedures. 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 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) after the Screening Visit or within 7 days prior to randomization. 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. 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. Inadequate organ function, including but not limited to; Alanine aminotransferase (ALT) > 2x Upper limit of Normal (ULN). Aspartate aminotransferase (AST) > 2x ULN. Bilirubin direct > 1.25x ULN. International normalized ratio (INR) > 1.2. Clinically significant hepatic impairment defined as a Child-Pugh B or C. Estimated glomerular filtration rate (eGFR) <60 mL/min. 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. History of substance abuse or dependence that would interfere with the completion of the trial, as determined by the Investigator. Known hypersensitivity to KVD824 or placebo or to any of the excipients. Any prior use of any gene therapy treatment for HAE. 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. Any pregnant or breastfeeding subject.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
KalVista Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
KalVista Investigative Site
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
KalVista Investigative Site
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85251
Country
United States
Facility Name
KalVista Investigative Site
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
KalVista Investigative Site
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
KalVista Investigative Site
City
Centennial
State/Province
Colorado
ZIP/Postal Code
80112
Country
United States
Facility Name
KalVista Investigative Site
City
Tampa
State/Province
Florida
ZIP/Postal Code
33620
Country
United States
Facility Name
KalVista Investigative Site
City
Chevy Chase
State/Province
Maryland
ZIP/Postal Code
20815
Country
United States
Facility Name
KalVista Investigative Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
KalVista Investigative Site
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
KalVista Investigative Site
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45231
Country
United States
Facility Name
KalVista Investigative Site
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
KalVista Investigative Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
KalVista Investigative Site
City
Spokane
State/Province
Washington
ZIP/Postal Code
99204
Country
United States
Facility Name
KalVista Investigative Site
City
Campbelltown
State/Province
New South Wales
Country
Australia
Facility Name
KalVista Investigative Site
City
Sofia
Country
Bulgaria
Facility Name
KalVista Investigative Site
City
North York
State/Province
Ontario
Country
Canada
Facility Name
KalVista Investigative Site
City
Brno
Country
Czechia
Facility Name
KalVista Investigative Site
City
Praha
Country
Czechia
Facility Name
KalVista Investigative Site
City
Grenoble
Country
France
Facility Name
KalVista Investigative Site
City
Paris
Country
France
Facility Name
KalVista Investigative Site
City
Mainz
State/Province
Rheinland-Pfalz
Country
Germany
Facility Name
KalVista Investigative Site
City
Berlin
Country
Germany
Facility Name
KalVista Investigative Site
City
Frankfurt am main
Country
Germany
Facility Name
KalVista Investigative Site
City
Budapest
Country
Hungary
Facility Name
KalVista Investigative Site
City
Milan
Country
Italy
Facility Name
KalVista Investigative Site
City
Padova
Country
Italy
Facility Name
KalVista Investigative Site
City
Grafton
State/Province
Auckland
Country
New Zealand
Facility Name
KalVista Investigative Site
City
Skopje
Country
North Macedonia
Facility Name
KalVista Investigative Site
City
San Juan
Country
Puerto Rico
Facility Name
KalVista Investigative Site
City
Birmingham
Country
United Kingdom
Facility Name
KalVista Investigative Site
City
Leeds
Country
United Kingdom
Facility Name
KalVista Investigative Site
City
London
Country
United Kingdom
Facility Name
KalVista Investigative Site
City
Newcastle Upon Tyne
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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