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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)

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ClinicalTrials.gov Identifier: NCT05055258
Recruitment Status : Recruiting
First Posted : September 24, 2021
Last Update Posted : January 19, 2022
Sponsor:
Information provided by (Responsible Party):
KalVista Pharmaceuticals, Ltd.

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

Condition or disease Intervention/treatment Phase
Angioedema, Hereditary, Types I and II Drug: KVD824 Drug: Placebo to KVD824 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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
Actual Study Start Date : September 27, 2021
Estimated Primary Completion Date : July 31, 2023
Estimated Study Completion Date : July 31, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 300 mg KVD824
300 mg KVD824 twice a day for 12 weeks
Drug: KVD824
KVD824 300 mg Modified-Release Tablets

Experimental: 600 mg KVD824
Two 300 mg KVD824 tablets twice a day for 12 weeks
Drug: KVD824
KVD824 300 mg Modified-Release Tablets

Experimental: 900 mg KVD824
Three 300 mg KVD824 tablets twice a day for 12 weeks
Drug: KVD824
KVD824 300 mg Modified-Release Tablets

Placebo Comparator: Placebo to KVD824
One, two or three placebo tablets to be taken twice a day for 12 weeks
Drug: Placebo to KVD824
Placebo to KVD824 300 mg Modified-Release Tablets




Primary Outcome Measures :
  1. The Rate of Investigator-confirmed HAE attacks during the Treatment Period [ Time Frame: 12 weeks ]
    To examine the number of investigator-confirmed attacks whilst on treatment compared to placebo


Secondary Outcome Measures :
  1. Proportion of subjects without Investigator-confirmed HAE attacks during the Treatment Period. [ Time Frame: 12 weeks ]
  2. Rate of Investigator-confirmed HAE attacks that require conventional treatment during the Treatment Period. [ Time Frame: 12 weeks ]
  3. Angioedema Quality of Life Questionnaire (AE-QoL) total score and domain scores during the Treatment Period. [ Time Frame: 12 weeks ]
    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.

  4. Angioedema Control Test (AECT) score and domain scores during the Treatment Period. [ Time Frame: 12 weeks ]
    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.

  5. Proportion of subjects with an AECT score ≥12 at the end of the Treatment Period. [ Time Frame: 12 weeks ]
    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 during the Screening Period 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. Subjects may be retested during the Screening Period 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 randomization.
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05055258


Contacts
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Contact: KalVista Pharmaceuticals 1 (857) 999-0075 clinicalstudies@kalvista.com

Locations
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United States, Alabama
KalVista Investigative Site Recruiting
Birmingham, Alabama, United States, 35294
United States, Arizona
KalVista Investigative Site Recruiting
Scottsdale, Arizona, United States, 85251
United States, California
KalVista Investigative Site Recruiting
La Jolla, California, United States, 92093
KalVista Investigative Site Recruiting
Santa Monica, California, United States, 90404
KalVista Investigative Site Recruiting
Walnut Creek, California, United States, 94598
United States, Colorado
KalVista Investigative Site Recruiting
Centennial, Colorado, United States, 80112
United States, Florida
KalVista Investigative Site Recruiting
Tampa, Florida, United States, 33620
United States, Maryland
KalVista Investigative Site Recruiting
Chevy Chase, Maryland, United States, 20815
United States, Massachusetts
KalVista Investigative Site Not yet recruiting
Boston, Massachusetts, United States, 02114
United States, Missouri
KalVista Investigative Site Recruiting
Saint Louis, Missouri, United States, 63110
United States, Ohio
KalVista Investigative Site Recruiting
Cincinnati, Ohio, United States, 45231
United States, Pennsylvania
KalVista Investigative Site Not yet recruiting
Hershey, Pennsylvania, United States, 17033
United States, Texas
KalVista Investigative Site Recruiting
Dallas, Texas, United States, 75390
United States, Washington
KalVista Investigative Site Recruiting
Spokane, Washington, United States, 99204
Australia, New South Wales
KalVista Investigative Site Not yet recruiting
Campbelltown, New South Wales, Australia
Australia, South Australia
KalVista Investigative Site Not yet recruiting
Adelaide, South Australia, Australia
Canada, Alberta
KalVista Investigative Site Not yet recruiting
Edmonton, Alberta, Canada
Canada, Ontario
KalVista Investigative Site Recruiting
North York, Ontario, Canada
Czechia
KalVista Investigative Site Not yet recruiting
Brno, Czechia
KalVista Investigative Site Not yet recruiting
Praha, Czechia
France
KalVista Investigative Site Recruiting
Grenoble, France
KalVista Investigative Site Recruiting
Paris, France
Germany
KalVista Investigative Site Not yet recruiting
Mainz, Rheinland-Pfalz, Germany
KalVista Investigative Site Not yet recruiting
Berlin, Germany
KalVista Investigative Site Recruiting
Frankfurt am main, Germany
Hungary
KalVista Investigative Site Recruiting
Budapest, Hungary
Italy
KalVista Investigative Site Not yet recruiting
Milan, Italy
KalVista Investigative Site Not yet recruiting
Padova, Italy
New Zealand
KalVista Investigative Site Not yet recruiting
Grafton, Auckland, New Zealand
Puerto Rico
KalVista Investigative Site Recruiting
San Juan, Puerto Rico
United Kingdom
KalVista Investigative Site Not yet recruiting
Birmingham, United Kingdom
KalVista Investigative Site Recruiting
Leeds, United Kingdom
KalVista Investigative Site Recruiting
London, United Kingdom
KalVista Investigative Site Not yet recruiting
Newcastle Upon Tyne, United Kingdom
Sponsors and Collaborators
KalVista Pharmaceuticals, Ltd.
Investigators
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Study Director: Study Director KalVista Pharmaceuticals
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Responsible Party: KalVista Pharmaceuticals, Ltd.
ClinicalTrials.gov Identifier: NCT05055258    
Other Study ID Numbers: KVD824-201
First Posted: September 24, 2021    Key Record Dates
Last Update Posted: January 19, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by KalVista Pharmaceuticals, Ltd.:
KVD824
KOMPLETE
Additional relevant MeSH terms:
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Angioedema
Angioedemas, Hereditary
Hereditary Angioedema Types I and II
Vascular Diseases
Cardiovascular Diseases
Urticaria
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Hereditary Complement Deficiency Diseases
Primary Immunodeficiency Diseases
Genetic Diseases, Inborn
Immunologic Deficiency Syndromes