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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 16 May 2022
Main ID:  EUCTR2021-000136-59-DE
Date of registration: 22/07/2021
Prospective Registration: Yes
Primary sponsor: Kalvista Pharmaceuticals Ltd
Public title: A study to assess whether different doses of KVD824 are effective in preventing attacks of Hereditary Angiodedema Type I or Type II.
Scientific title: 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
Date of first enrolment: 20/09/2021
Target sample size: 48
Recruitment status: Authorised-recruitment may be ongoing or finished
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-000136-59
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 4  
Phase:  Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no
Countries of recruitment
Australia Bulgaria Canada Czech Republic Czechia France Germany Hungary
Italy New Zealand North Macedonia Romania United Kingdom United States
Contacts
Contact type: Scientific
Name: KalVista Clinical   
Address:  Porton Down Science Park, Bybrook Road SP4 0BF Porton Down, Salisbury United Kingdom
Telephone: +441980619368
Email: clinical@kalvista.com
Affiliation:  KalVista Pharmaceuticals Ltd
Contact type: Public
Name: KalVista Clinical   
Address:  Porton Down Science Park, Bybrook Road SP4 0BF Porton Down, Salisbury United Kingdom
Telephone: +441980619368
Email: clinical@kalvista.com
Affiliation:  KalVista Pharmaceuticals Ltd
Key inclusion & exclusion 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:
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

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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Hereditary Angioedema Type I or II
MedDRA version: 21.0 Level: LLT Classification code 10080956 Term: Hereditary angioedema type I System Organ Class: 100000004850
MedDRA version: 24.0 Level: LLT Classification code 10080960 Term: Hereditary angioedema type II System Organ Class: 100000004850
Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
Intervention(s)

Product Name: KVD824 300 mg Modified Release Tablets
Pharmaceutical Form: Modified-release tablet
INN or Proposed INN: To be confirmed
Current Sponsor code: KVD824.HCl
Other descriptive name: KVD824 hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Modified-release tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)
Main Objective: To demonstrate the clinical efficacy of prophylactic treatment with KVD824 compared with placebo in preventing hereditary angioedema (HAE) attacks.
Timepoint(s) of evaluation of this end point: 12 Weeks
Primary end point(s): The primary endpoint of this trial is the rate of Investigator-confirmed HAE attacks during the Treatment Period.
Secondary Objective: To further characterize the clinical efficacy of KVD824.
To investigate the safety and tolerability of KVD824.
Secondary Outcome(s)
Secondary 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.
Timepoint(s) of evaluation of this end point: 12 Weeks
Secondary ID(s)
KVD824-201
2021-000136-59-HU
Source(s) of Monetary Support
Kalvista Pharmaceuticals Ltd
Secondary Sponsor(s)
Ethics review
Status: Approved
Approval date: 08/09/2021
Contact name:
Contact address:
Contact telephone:
Contact email:
Results
Results available:
URL:
URL of the protocol:
Date Posted:
Date of completion:
Date of first publication:
Results summary:
Baseline characteristics: No results available
Adverse events: No results available
Outcome measures: No results available
IPD sharing plan:
IPD sharing description:
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