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    Summary
    EudraCT Number:2021-000136-59
    Sponsor's Protocol Code Number:KVD824-201
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2021-07-22
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedGermany - BfArM
    A.2EudraCT number2021-000136-59
    A.3Full title of the trial
    A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial to Evaluate the Efficacy and Safety of Three Dose Levels of KVD824, an Oral Plasma Kallikrein Inhibitor, for Long-Term Prophylactic Treatment of Hereditary Angioedema Type I or II
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to assess whether different doses of KVD824 are effective in preventing attacks of Hereditary Angiodedema Type I or Type II.
    A.4.1Sponsor's protocol code numberKVD824-201
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorKalvista Pharmaceuticals Ltd
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportKalvista Pharmaceuticals Ltd
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationKalVista Pharmaceuticals Ltd
    B.5.2Functional name of contact pointKalVista Clinical
    B.5.3 Address:
    B.5.3.1Street AddressPorton Down Science Park, Bybrook Road
    B.5.3.2Town/ cityPorton Down, Salisbury
    B.5.3.3Post codeSP4 0BF
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+441980619368
    B.5.6E-mailclinical@kalvista.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameKVD824 300 mg Modified Release Tablets
    D.3.4Pharmaceutical form Modified-release tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTo be confirmed
    D.3.9.2Current sponsor codeKVD824.HCl
    D.3.9.3Other descriptive nameKVD824 hydrochloride
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number300
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboModified-release tablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Hereditary Angioedema Type I or II
    E.1.1.1Medical condition in easily understood language
    Hereditary Angioedema is a genetic condition characterised by swelling of tissues. These swellings can occur on any part of the body.
    E.1.1.2Therapeutic area Diseases [C] - Blood and lymphatic diseases [C15]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10080956
    E.1.2Term Hereditary angioedema type I
    E.1.2System Organ Class 100000004850
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 24.0
    E.1.2Level LLT
    E.1.2Classification code 10080960
    E.1.2Term Hereditary angioedema type II
    E.1.2System Organ Class 100000004850
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To demonstrate the clinical efficacy of prophylactic treatment with KVD824 compared with placebo in preventing hereditary angioedema (HAE) attacks.
    E.2.2Secondary objectives of the trial
    To further characterize the clinical efficacy of KVD824.
    To investigate the safety and tolerability of KVD824.
    E.2.3Trial contains a sub-study No
    E.3Principal 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:
    a) Documented clinical history consistent with HAE (subcutaneous or mucosal, nonpruritic swelling episodes without accompanying urticaria) AND EITHER
    b) 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 retested at any time prior to randomization if results are incongruent with clinical history or believed by the Investigator to be confounded by therapeutic C1-INH use, OR
    c) 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. NOT APPLICABLE FOR GERMANY
    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:
    a) Two Investigator-confirmed attacks in the first 4-week period.
    b) 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.
    a) 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.
    b) Male subjects who are surgically sterile (e.g. vasectomized with medical assessment of surgical success).
    c) 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.
    13) Subject has received a full COVID-19 vaccination series prior to Screening.
    E.4Principal 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:
    a) Alanine aminotransferase (ALT) > 2x ULN.
    b) Aspartate aminotransferase (AST) > 2x ULN.
    c) Bilirubin direct > 1.25x ULN.
    d) International normalized ratio (INR) > 1.2.
    e) Clinically significant hepatic impairment defined as a Child-Pugh B or C.
    f) 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 within 4 weeks of the last dosing of investigational drug prior to screening.
    13) Any pregnant or breastfeeding subject.
    14) Any subject who is currently stabilized under an indicated licensed HAE
    prophylactic therapy.
    15) Any subject who has previously had HAE attacks that were life threatening.
    16) Any subject who is committed to an institution by virtue of an order issued by the judicial or the administrative authorities.
    17) Any subject who is an employee of the study Sponsor or Investigator or who is a dependent of a Sponsor employee or an Investigator.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint of this trial is the rate of Investigator-confirmed HAE attacks during the Treatment Period.
    E.5.1.1Timepoint(s) of evaluation of this end point
    12 Weeks
    E.5.2Secondary end point(s)
    • 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.
    • Angioedema Control Test (AECT) score and domain scores during the Treatment Period.
    • Proportion of subjects with an AECT score ≥12 at the end of the Treatment Period.
    E.5.2.1Timepoint(s) of evaluation of this end point
    12 Weeks
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis Yes
    E.6.3Therapy No
    E.6.4Safety No
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial4
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Canada
    New Zealand
    United States
    France
    Bulgaria
    Romania
    Czechia
    Germany
    Italy
    Hungary
    North Macedonia
    United Kingdom
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months3
    E.8.9.1In the Member State concerned days10
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months3
    E.8.9.2In all countries concerned by the trial days10
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 46
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 2
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 25
    F.4.2.2In the whole clinical trial 48
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Once the Week 12/ET Visit has occurred the subject, in consultation with their treating physician, will determine their treatment regimen. KVD824 will not be supplied after the conclusion of the subject’s participation in the trial.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2021-09-20
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-09-08
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2022-09-30
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