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

• ClinicalTrials.gov Identifier: NCT04349800
• Recruitment Status: Completed
• First Posted: April 16, 2020
• Last Update Posted: April 16, 2020
• Sponsor: KalVista Pharmaceuticals, Ltd.
• Information provided by (Responsible Party): KalVista Pharmaceuticals, Ltd.

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Hereditary Angioedema	Drug: KVD900; Drug: Placebo to KVD900	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 84 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: January 4, 2018
• Actual Primary Completion Date: September 10, 2018
• Actual Study Completion Date: September 10, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

United Kingdom

KalVista Investigative Site

Wales, United Kingdom

Sponsors and Collaborators

KalVista Pharmaceuticals, Ltd.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: KalVista Pharmaceuticals, Ltd.
• ClinicalTrials.gov Identifier: NCT04349800
• Other Study ID Numbers: KVD900-101
• First Posted: April 16, 2020
• Last Update Posted: April 16, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Angioedema; Angioedemas, Hereditary; Vascular Diseases; Cardiovascular Diseases; Urticaria; Skin Diseases, Vascular; Skin Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Immunologic Deficiency Syndromes