Hereditary AngioedemaPhase 2NCT04208412
A Phase II, Cross-over Clinical Trial Evaluating the Efficacy and Safety of KVD900 (Sebetralstat) in the On-demand Treatment of Angioedema Attacks in Adult Subjects With Hereditary Angioedema Type I or II
A Phase 2 study testing KVD900 in people with Hereditary Angioedema, run by KalVista Pharmaceuticals, Ltd. at 25 sites in 10 countries.
Trial summary
This study is a randomized, double-blind, placebo-controlled, phase II, cross-over clinical trial evaluating the efficacy and safety of KVD900, in the treatment of hereditary angioedema attacks in adult subjects. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hereditary Angioedema
- What is being tested?
- KVD900
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 84 participants
- Where
- 25 sitesin 10 countries
- Study dates
- 2 Jul 2019to 8 Dec 2020
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female adult subjects 18 years of age and older.
- Confirmed diagnosis of HAE type I or II at anytime in the medical history
- At least 3 documented HAE attacks in the past 93 days, as supported by medical history.
- Access to and ability to use conventional attack treatment for attacks of HAE
- Adequate organ functions
- Females of childbearing potential must agree to use highly effective birth control from the Screening visit until the end of the trial follow-up procedures.
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- Females of non-childbearing potential, defined as surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or post-menopausal for at least 12 months, do not require contraception during the study
- Males with female partners of childbearing potential must agree to be abstinent or else use a highly effective method of birth control as defined in inclusion 6 from the Screening visit until the end of the trial follow-up procedures
- Provide signed informed consent and are willing and capable of complying with study requirements and procedures
Who cannot join
- Any concomitant diagnosis of another form of chronic angioedema, such as acquired C1 inhibitor (C1-INH) deficiency, HAE with normal C1-INH (also known as HAE type III), idiopathic angioedema, or angioedema associated with urticaria
- Current use of C1INH, androgens, or tranexamic acid for HAE prophylaxis
- Use of angiotensin-converting enzyme (ACE) inhibitors or any estrogen-containing medications with systemic absorption (such as oral contraceptives or hormonal replacement therapy) within 93 days prior to initial study treatment.
- Use of androgens (e.g. stanozolol, danazol, oxandrolone, methyltestosterone, testosterone) or antifibrinolytics within 30 days prior to initial study treatment.
- Use of lanadelumab within 10 weeks prior to initial study treatment.
- Use of strong CYP3A4/CYP2C9 inhibitors and inducers during participation in the trial
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- Clinically significant abnormal ECG at Visit 1 and pre-dose at Visit 2. This includes, but is not limited to, a QT interval by Fredericia, QTcF > 470 msec (for women) or > 450 msec (for men), a PR > 220 msec or ventricular and/or atrial premature contractions that are more frequent than occasional and/or occur as couplets or higher in grouping
- Any clinically significant history of angina, myocardial infarction, syncope, clinically significant cardiac arrhythmias, left ventricular hypertrophy, cardiomyopathy, or any other cardiovascular abnormality
- Any other systemic dysfunction (e.g., gastrointestinal, renal, respiratory, cardiovascular) or significant disease or disorder which, in the opinion of the Investigator, would jeopardize the safety of the subject by taking part in the trial
- History of substance abuse or dependence that would interfere with the completion of the study, as determined by the Investigator
- Known lactose allergy or intolerance
- Known hypersensitivity to KVD900 or placebo or to any of the excipients
- Participation in an interventional investigational clinical study within 93 days or within 5 half-lives of the last dosing of investigational drug (whichever is longer) prior to initial study treatment
- Any pregnant or breast-feeding subject
Trial locations and contacts
25 sites in 10 countries.
25 sites in 10 countries
United States6 sites
KalVista Investigative Site
Centennial, Colorado, 80112
KalVista Investigative Site
Chevy Chase, Maryland, 20815
KalVista Investigative Site
Cincinnati, Ohio, 45231
KalVista Investigative Site
Dallas, Texas, 75231
KalVista Investigative Site
Scottsdale, Arizona, 85251
KalVista Investigative Site
Spokane, Washington, 99204
United Kingdom4 sites
KalVista Investigative Site
Camberley
KalVista Investigative Site
Cambridge
KalVista Investigative Site
London
KalVista Investigative Site
Newcastle
Czechia3 sites
KalVista Investigative Site
Brno
KalVista Investigative Site
Hradec Králové
KalVista Investigative Site
Pilsen
Germany3 sites
KalVista Investigative Site
Berlin
KalVista Investigative Site
Frankfurt
KalVista Investigative Site
Mörfelden-Walldorf
Italy3 sites
KalVista Investigative Site
Milan, 1
KalVista Investigative Site
Milano-2
KalVista Investigative Site
Padova
Poland2 sites
KalVista Investigative Site
Krakow
KalVista Investigative Site
Warsaw
About this study
Official title: A Randomized, Double-blind, Placebo-controlled, Phase II, Cross-over Clinical Trial Evaluating the Efficacy and Safety of KVD900, an Oral Plasma Kallikrein Inhibitor, in the On-demand Treatment of Angioedema Attacks in Adult Subjects With Hereditary Angioedema Type I or II
This study is a randomized, double-blind, placebo-controlled, phase II, cross-over clinical trial evaluating the efficacy and safety of KVD900, in the treatment of hereditary angioedema attacks in adult subjects.
- Conditions
- Hereditary Angioedema
- Being tested
- KVD900, Placebo
- Keywords
- Sebetralstat
- Medical subject headings
- Angioedemas, Hereditary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KVD900Drug
KVD900 tablet 600 mg
PlaceboOther
KVD900-matched Placebo Tablet
| Study group | Role | What they receive |
|---|---|---|
| Part 1 | Experimental | Subjects received a single dose of 600 mg KVD900. Receives: Drug: KVD900 |
| Part 2 - Sequence 1: 600 mg KVD900, Then Placebo | Experimental | Subjects received a single dose of 600 mg KVD900 to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of placebo to treat the second eligible HAE attack. Receives: Drug: KVD900; Other: Placebo |
| Part 2 - Sequence 2: Placebo, Then 600 mg KVD900 | Experimental | Subjects received a single dose of placebo to treat the first eligible HAE attack. Following resolution of this attack, subjects received a second single dose of 600 mg KVD900 to treat the second eligible HAE attack. Receives: Drug: KVD900; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Conventional Attack Treatment Use Within 12 Hours of Study Drug (Full Analysis Set)
The primary variable for statistical comparison between treatments in Part 2 of the study was time to use of conventional attack treatment (pdC1INH or rhC1INH intravenous [iv] or icatibant) within 12 hours of study drug.
Censoring occurs where a subject did not use conventional attack treatment within 12h post-study drug dosing.
When an endpoint result was non-calculable (NC) within 12 hours, if the event did occur, the event must have occurred >12 hours following study drug.
Measured: 12 hours
Secondary outcomes (4)
Proportion of HAE Attacks That Worsen in Severity by One Level or More on the PGI-S or Require Conventional Attack Treatment Within 12 Hours of Study Drug (Full Analysis Set)
The proportion of participant's HAE attacks to either worsen in attack severity on the PGI-S by one level or more or conventional attack treatment (pdC1INH or rhC1INH intravenous [iv] or icatibant) use are listed with censored observations flagged. Frequencies (n, %) of subjects experiencing a worsening on the PGI-S by one level or more or using conventional attack treatment and the number censored are presented. "Y" Row indicates "participants who experienced a worsening in severity, and the "N" Row indicates participants who did not.
Measured: 12 hours
Time to Either Worsening in HAE Attack Severity by One Level or More on the PGI-S or to Conventional Attack Treatment Use Within 12 Hours of Study Drug (Full Analysis Set)
HAE attack severity assessed using the Patient Global Impression of Severity scale (PGI-S).
Censoring occurs where a subject did not worsen in severity or use conventional attack treatment (pdC1INH or rhC1INH intravenous [iv] or icatibant) within 12h post-study drug dosing.
When an endpoint result was non-calculable (NC) within 12 hours, if the event did occur, the event must have occurred >12 hours following study drug.
Measured: 12 hours
Time to Symptom Relief Defined as HAE Attack Rated as "A Little Better" or Higher on the PGI-C for Two Consecutive Time Points Within 12 Hours of Study Drug (Full Analysis Set)
Change in HAE attack severity assessed using the Patient Global Impression of Change 7-point transition question (PGI-C).
Censoring occurs where an attack rating of "a little better" or higher for two consecutive time points does not occur or conventional attack treatment is used within 12h post-study drug dosing.
When an endpoint result was non-calculable (NC) within 12 hours, if the event did occur, the event must have occurred >12 hours following study drug.
Measured: 12 hours
Time to Symptom Relief Defined as 50% Reduction in Composite VAS Score for Three Consecutive Time Points Within 12 Hours of Study Drug (Full Analysis Set)
The HAE attack symptoms were assessed on a 100 mm visual analogue scale (VAS) ranging from 0 (none) to 100 (very severe).
The Composite VAS score is defined as the mean score across all symptoms. Censoring occurs where a ≥50% reduction in Composite VAS Score for three consecutive time points does not occur or conventional attack treatment is used within 12h post-study drug dosing.
When an endpoint result was non-calculable (NC) within 12 hours, if the event did occur the event must have occurred >12 hours following study drug.
Measured: 12 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2019
- Study start2 Jul 2019
- Primary completion8 Dec 2020
- Study completion8 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hereditary AngioedemaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 84 participants (actual)
Sponsor and investigators
- Lead sponsor
- KalVista Pharmaceuticals, Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, KalVista Pharmaceuticals, Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04208412
- Sponsor's protocol ID
- KVD900-201
- Status last verified
- Apr 2025
- First submitted
- 20 Dec 2019
- Last updated
- 2 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Aygoren-Pursun E, Cohn DM, Agmon-Levin N, Banerji A, Bernstein JA, Busse P, Cancian M, de Castro ED, Farkas H, Grivcheva-Panovska V, Hagin D, Hakl R, Honda D, Kessel A, Kinaciyan T, Ifaad, Kurowski M, Li HH, Lleonart R, Longhurst HJ, Lumry WR, Magerl M, Martinez-Saguer I, Melamed I, Psarros F, Savic S, Soteres DF, Staevska M, Stobiecki M, Wedner HJ, Zanichelli A, Hao J, Patil K, Iverson M, Owiredu-Yeboa S, Smith MD, Yea CM, Audhya PK, Riedl MA, Kiani-Alikhan S, Maurer M. Sebetralstat for on-demand treatment of hereditary angioedema: A pooled analysis of placebo-controlled clinical trials. World Allergy Organ J. 2026 Jun 9;19(7):101401. doi: 10.1016/j.waojou.2026.101401. eCollection 2026 Jul.
PubMed 42318595Aygoren-Pursun E, Zanichelli A, Cohn DM, Cancian M, Hakl R, Kinaciyan T, Magerl M, Martinez-Saguer I, Stobiecki M, Farkas H, Kiani-Alikhan S, Grivcheva-Panovska V, Bernstein JA, Li HH, Longhurst HJ, Audhya PK, Smith MD, Yea CM, Maetzel A, Lee DK, Feener EP, Gower R, Lumry WR, Banerji A, Riedl MA, Maurer M. An investigational oral plasma kallikrein inhibitor for on-demand treatment of hereditary angioedema: a two-part, randomised, double-blind, placebo-controlled, crossover phase 2 trial. Lancet. 2023 Feb 11;401(10375):458-469. doi: 10.1016/S0140-6736(22)02406-0.
PubMed 36774155