A Single Dose Safety, Tolerability, Pharmacokinetic and Food Effect Study of KVD900 in Healthy Volunteers

A Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study of the Safety, Tolerability, and Pharmacokinetics of KVD900 Followed by Crossover Sub-studies of KVD900 Formulations, and Food Effect in Healthy Male Volunteers

A safety, tolerability, pharmacokinetic and food effect study of KVD900 in healthy volunteers.

Study Overview

• Status: Completed
• Conditions: Hereditary Angioedema
• Intervention / Treatment: Drug: KVD900; Drug: Placebo to KVD900

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Wales, United Kingdom
    • KalVista Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male subjects between 18 and 55 years of age.
• Healthy subjects as determined by past medical history and as judged by the Chief Investigator or designee.
• Male subject willing to use a highly effective method of contraception.
• Subject with a body mass index (BMI) of 18-32 kg/m2.
• Subject with no clinically significant history of previous allergy or sensitivity to KVD900 or any of the excipients contained within the investigational medicinal product (IMP).
• Subject with no clinically significant abnormal serum biochemistry, haematology, clotting profiles, and urine examination values within 28 days before the first dose of IMP.
• Subject with a negative urinary drugs of abuse screen, determined within 28 days before the first dose of IMP
• Subject with negative human immunodeficiency virus (HIV) and hepatitis B surface antigen (Hep B) and hepatitis C virus antibody (Hep C) results.
• Subject with no clinically significant abnormalities in 12-lead electrocardiogram
• Subjects must not donate sperm from first dose until at least 3 months after last dose of IMP.
• Subjects without any special food restrictions that would hinder ability to consume the high fat breakfast provided during study Part C; such as lactose intolerance , vegan, low-fat, low sodium, etc.
• Subjects with no known allergy or sensitivity to lactose and/or any additional excipients contained in IMP.
• Subject must be available to complete the study (including all follow up visits).
• Subject must satisfy the Chief Investigator or designee about their fitness to participate in the study.
• Subject must provide written informed consent to participate in the study.

Exclusion Criteria:

• A clinically significant history of gastrointestinal disorder likely to influence IMP absorption.
• Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements .
• Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular (no history of syncope or vasovagal events), or metabolic dysfunction.
• Subjects with a history of clotting abnormalities.
• A clinically significant history of drug or alcohol abuse in the last 5 years.
• Users of nicotine products i.e., current smokers or ex-smokers who have smoked within the 6 months prior to dosing with the study medication or users of cigarette replacements.
• Inability to communicate well with Investigators.
• Participation in a New Chemical Entity clinical study within the previous 3 months or a marketed drug clinical study within the 30 days before the first dose of IMP.
• Donation of 450 mL or more blood within the 3 months before the first dose of IMP.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Ascending Dose - 5 mg	Drug: KVD900; Active; Drug: Placebo to KVD900; Placebo
Experimental: Single Ascending Dose - 10 mg	Drug: KVD900; Active; Drug: Placebo to KVD900; Placebo
Experimental: Single Ascending Dose - 20 mg	Drug: KVD900; Active; Drug: Placebo to KVD900; Placebo
Experimental: Single Ascending Dose - 40 mg	Drug: KVD900; Active; Drug: Placebo to KVD900; Placebo
Experimental: Single Ascending Dose - 80 mg	Drug: KVD900; Active; Drug: Placebo to KVD900; Placebo
Experimental: Single Ascending Dose - 160 mg	Drug: KVD900; Active; Drug: Placebo to KVD900; Placebo
Experimental: Single Ascending Dose - 300 mg	Drug: KVD900; Active; Drug: Placebo to KVD900; Placebo
Experimental: Single Ascending Dose - 600 mg	Drug: KVD900; Active; Drug: Placebo to KVD900; Placebo
Experimental: Formulation Screen	Drug: KVD900; Active
Experimental: Food Effect	Drug: KVD900; Active

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Subjects with Adverse Events	Change from pre-dose to last visit, 5-7 days post dose.
Number of Subjects with Serious Adverse Events	Change from pre-dose to last visit, 5-7 days post dose.
Number of participants with clinically significant changes in laboratory assessments	Throughout study until last visit, 5-7 days post dose.
Number of participants with clinically significant changes in vital signs	Throughout study until last visit, 5-7 days post dose.
Number of participants with clinically significant changes in electrocardiogram (ECG) measurements	Throughout study until last visit, 5-7 days post dose.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics - Cmax	Derived from time-concentration plasma levels of KVD900	Up to 48 hours post dose
Pharmacokinetics - AUC0-t	Derived from time-concentration plasma levels of KVD900	Up to 48 hours post dose
Pharmacokinetics - AUC0-24	Derived from time-concentration plasma levels of KVD900	Up to 24 hours post dose
Pharmacokinetics - AUC0-inf	Derived from time-concentration plasma levels of KVD900	Up to 48 hours post dose
Pharmacokinetics - food effect (Part C only)	90% confidence intervals of the ratios for AUC0-t and Cmax with and without food lie in the range 80-125	Up to 24 hours post dose
Pharmacokinetics - formulation bridge - relative bioavailability (Part B only)	90% confidence intervals of the ratios for AUC0-t and Cmax between the two dosages lie in the range 80-125	Up to 24 hours post dose

Collaborators and Investigators

• Sponsor: KalVista Pharmaceuticals, Ltd.

Publications and helpful links

General Publications

• Maetzel A, Smith MD, Duckworth EJ, Hampton SL, De Donatis GM, Murugesan N, Rushbrooke LJ, Li L, Francombe D, Feener EP, Yea CM. KVD900, an oral on-demand treatment for hereditary angioedema: Phase 1 study results. J Allergy Clin Immunol. 2022 Jun;149(6):2034-2042. doi: 10.1016/j.jaci.2021.10.038. Epub 2022 Jan 24.

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2018
• Primary Completion (Actual): September 10, 2018
• Study Completion (Actual): September 10, 2018

Study Registration Dates

• First Submitted: March 9, 2020
• First Submitted That Met QC Criteria: April 14, 2020
• First Posted (Actual): April 16, 2020

Study Record Updates

• Last Update Posted (Actual): April 16, 2020
• Last Update Submitted That Met QC Criteria: April 14, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Angioedema; Angioedemas, Hereditary
• Other Study ID Numbers: KVD900-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No