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A Phase III, Crossover Trial Evaluating the Efficacy and Safety of KVD900 for On-Demand Treatment of Angioedema Attacks in Adolescent and Adult Patients With Hereditary Angioedema (HAE)

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ClinicalTrials.gov Identifier: NCT05259917
Recruitment Status : Completed
First Posted : March 2, 2022
Last Update Posted : January 31, 2024
Sponsor:
Information provided by (Responsible Party):
KalVista Pharmaceuticals, Ltd.

Tracking Information
First Submitted Date  ICMJE February 4, 2022
First Posted Date  ICMJE March 2, 2022
Last Update Posted Date January 31, 2024
Actual Study Start Date  ICMJE February 23, 2022
Actual Primary Completion Date December 31, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 28, 2022)
Time to beginning of symptom relief Patient Global Impression of Change (PGI-C) [ Time Frame: within 12 hours of the first investigational medicinal product (IMP) administration. ]
Time to beginning of symptom relief defined as at least "a little better" (2 time points in a row)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 3, 2023)
  • Time to first incidence of decrease from baseline Patient Global Impression of Severity (PGI-S) (2 time points in a row) [ Time Frame: within 12 hours of the first IMP administration. ]
  • Time to HAE attack resolution (PGI-S) [ Time Frame: within 24 hours of the first IMP administration. ]
    Time to HAE attack resolution defined as "none"
  • Proportion of attacks with beginning of symptom relief (PGI-C) [ Time Frame: within 4 hours and within 12 hours of the first IMP administration. ]
    Proportion of attacks with beginning of symptom relief defined as at least "a little better" (2 time points in a row)
  • Time to at least "better" (2 time points in a row) (PGI-C) [ Time Frame: within 12 hours of the first IMP administration. ]
  • Time to first incidence of decrease from baseline (2 time points in a row) (PGI-S) [ Time Frame: within 24 hours of the first IMP administration. ]
  • Time to at least a 50% decrease from baseline (3 time points in a row) Composite Visual Analogue Scale (VAS) [ Time Frame: within 12 hours and within 24 hours of the first IMP administration ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 28, 2022)
  • Time to first incidence of decrease from baseline Patient Global Impression of Severity (PGI-S) [ Time Frame: within 12 hours of the first IMP administration. ]
  • Time to HAE attack resolution (PGI-S) [ Time Frame: within 24 hours of the first IMP administration. ]
    Time to HAE attack resolution defined as "none"
  • Proportion of attacks with beginning of symptom relief (PGI-C) [ Time Frame: within 4 hours and within 12 hours of the first IMP administration. ]
    Proportion of attacks with beginning of symptom relief defined as at least "a little better" (2 time points in a row)
  • Time to at least "better" (PGI-C) [ Time Frame: within 12 hours of the first IMP administration. ]
  • Time to first incidence of decrease from baseline (PGI-S) [ Time Frame: within 24 hours of the first IMP administration. ]
  • Time to at least a 50% decrease from baseline (3 time points in a row) Composite Visual Analogue Scale (VAS) [ Time Frame: within 12 hours and within 24 hours of the first IMP administration ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase III, Crossover Trial Evaluating the Efficacy and Safety of KVD900 for On-Demand Treatment of Angioedema Attacks in Adolescent and Adult Patients With Hereditary Angioedema (HAE)
Official Title  ICMJE A Randomized, Double-Blind, Placebo-Controlled, Phase 3, Three-way Crossover Trial to Evaluate the Efficacy and Safety of Two Dose Levels of KVD900, an Oral Plasma Kallikrein Inhibitor, for On-Demand Treatment of Angioedema Attacks in Adolescent and Adult Patients With Hereditary Angioedema Type I or II
Brief Summary This study is a randomized, double-blind, placebo-controlled, phase III, three-way crossover clinical trial evaluating the efficacy and safety of KVD900, in the treatment of hereditary angioedema attacks in adolescent and adult Patients
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Hereditary Angioedema
Intervention  ICMJE
  • Drug: Placebo
    Placebo to KVD900 Tablet
  • Drug: KVD900 600 mg
    KVD900 Tablet 600 mg (2 x 300 mg)
  • Drug: KVD900 300 mg
    KVD900 Tablet 300 mg (1 x 300 mg)
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
  • Experimental: KVD900 600 mg
    Intervention: Drug: KVD900 600 mg
  • Experimental: KVD900 300 mg
    Intervention: Drug: KVD900 300 mg
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 15, 2023)
136
Original Estimated Enrollment  ICMJE
 (submitted: February 28, 2022)
114
Actual Study Completion Date  ICMJE December 31, 2023
Actual Primary Completion Date December 31, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male or female patients 12 years of age and older.
  • Confirmed diagnosis of HAE type I or II at any time in the medical history.
  • Patient has access to and ability to use conventional on-demand treatment for HAE attacks.
  • If a patient is receiving long-term prophylactic treatment with one of the protocol-allowed therapies, they must be on a stable dose and regimen for at least 3 months prior to the Screening Visit (except for danazol, which requires a stable dose and regimen for 6 months prior to the Screening Visit). Patient must be willing to remain on a stable dose and regimen for the duration of the trial.
  • Patient's last dose of attenuated androgens other than danazol was at least 28 days prior to randomization.
  • Patient:

    1. has had at least 2 documented HAE attacks within 3 months prior to screening or randomization; or
    2. is a completer of the KVD824-201 trial within 3 months prior to randomization and meets all other entry criteria to enroll in KVD900-301
  • Patients must meet the contraception requirements.
  • Patients must be able to swallow trial tablets whole.
  • Patients, as assessed by the Investigator, must be able to appropriately receive and store IMP, and be able to read, understand, and complete the electronic diary (eDiary).
  • Investigator believes that the patient is willing and able to adhere to all protocol requirements.
  • Patient provides signed informed consent or assent (when applicable). A parent or legally authorized representative (LAR) must also provide signed informed consent when required.

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 bradykinin receptor 2 (BR2) blocker, 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) within 7 days prior to the Screening Visit.
  • Patients who require sustained use of strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers.
  • 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
  • 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.
  • History of substance abuse or dependence that would interfere with the completion of the trial, as determined by the Investigator.
  • Known hypersensitivity to KVD900 or placebo or to any of the excipients.
  • Prior participation in trial KVD900-201.
  • Participation in any gene therapy treatment or trial for HAE.
  • Participation in any interventional investigational clinical trial (with the exception of KVD824-201), including an investigational COVID-19 vaccine trial, within 4 weeks of the last dosing of investigational drug prior to screening.
  • Any pregnant or breastfeeding patient.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Bulgaria,   Canada,   France,   Germany,   Greece,   Hungary,   Israel,   Italy,   Japan,   Netherlands,   New Zealand,   North Macedonia,   Poland,   Portugal,   Puerto Rico,   Romania,   Slovakia,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05259917
Other Study ID Numbers  ICMJE KVD900-301
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: Data will not be shared until all global regulatory filings are complete
Current Responsible Party KalVista Pharmaceuticals, Ltd.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE KalVista Pharmaceuticals, Ltd.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Study Director KalVista Pharmaceuticals, Ltd.
PRS Account KalVista Pharmaceuticals, Ltd.
Verification Date January 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP