A Single and Multiple Doses Safety, Tolerability, Pharmacokinetics and Food Effect Study of KVD824 in Healthy Volunteers

NCT05178355 | Completed Phase 1 DMC

• 1 other identifier: KVD824-101
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

This is a 3 part phase 1, randomized, double-blind, placebo-controlled, study of the safety, tolerability, and pharmacokinetics of KVD824 following administration of single and multiple ascending oral doses; followed by a crossover food effect sub-study in healthy male volunteers.

Conditions

Hereditary Angioedema

Outcome Measures

Primary Outcomes (4)

• Safety - Treatment Emergent Adverse Events

  Number of Subjects with Treatment Emergent Adverse Events

  Part A Days 0-10; Part B Days 0-12

• Safety - Vital signs

  Number of participants with clinically significant changes in vital signs

  Part A: Days (-1)-10;Part B: Days (-1)-12

• Safety - Laboratory Parameters

  Number of participants with clinically significant changes in laboratory assessments

  Part A: Days (-1)-10;Part B: Days (-1)-12

• Safety - ECG change in QTcF

  Number of subjects who had any increase in QTcF parameters.

  Part A: Days (-1)-10; Part B: Days (-1)-12

Secondary Outcomes (16)

• Pharmacokinetic - Maximum Concentration (Cmax)

  Part A: Predose and up to 18 samples over a 48 hour period post dose; Part B: Pre-dose and up to 11 samples over a 24 hour period post morning dose, day 1 and 5; Part C: Predose and up to 16 samples over a 24 hour period post dose per treatment period.

• Pharmacokinetic - Time to maximum concentration (Tmax)

  Part A: Predose and up to 18 samples over a 48 hour period post dose; Part B: Pre-dose and up to 11 samples over a 24 hour period post morning dose, day 1 and 5; Part C: Predose and up to 16 samples over a 24 hour period post dose per treatment period.

• Pharmacokinetic - Terminal Elimination Rate Constant (Kel)

  Part A: Predose and up to 18 samples over a 48 hour period post dose; Part B: Pre-dose and up to 11 samples over a 24 hour period post morning dose, day 1 and 5; Part C: Predose and up to 16 samples over a 24 hour period post dose per treatment period.

• Pharmacokinetic - Terminal elimination half-life (t1/2)

  Part A: Predose and up to 18 samples over a 48 hour period post dose; Part B: Pre-dose and up to 11 samples over a 24 hour period post morning dose, day 1 and 5; Part C: Predose and up to 16 samples over a 24 hour period post dose per treatment period.

• Pharmacokinetic - Area under the concentration-time curve from time 0 to 24 hour post dose (AUC0-24)

  Part A: Predose and up to 18 samples over a 48 hour period post dose; Part B: Pre-dose and up to 11 samples over a 24 hour period post morning dose, day 1 and 5; Part C: Predose and up to 16 samples over a 24 hour period post dose per treatment period.

Study Arms (14)

Part A - KVD824 - 10 mg

EXPERIMENTAL

6 participants were administered10 mg of KVD824 in capsule form (1 x 10 mg capsule) on one occasion on Day 1. 2 participants received matching placebo.

Drug: KVD824; Drug: Placebo to KVD824

Part A - KVD824 - 20 mg

EXPERIMENTAL

6 participants were administered 20mg of KVD824 in capsule form ( 2 x 10 mg capsules) on one occasion on Day 1. 2 participants received matching placebo.

Drug: KVD824; Drug: Placebo to KVD824

Part A - KVD824 - 40 mg

EXPERIMENTAL

6 participants were administered 40mg of KVD824 in capsule form (1 x 40 mg capsule) on one occasion on Day 1. 2 participants received matching placebo.

Drug: KVD824; Drug: Placebo to KVD824

Part A - KVD824 - 80 mg

EXPERIMENTAL

6 participants were administered 80mg of KVD824 in capsule form (2 x 40 mg capsules) on one occasion on Day 1. 2 participants received matching placebo.

Drug: KVD824; Drug: Placebo to KVD824

Part A - KVD824 - 160mg

EXPERIMENTAL

6 participants were administered 160mg of KVD824 in capsule form (1 x 160 mg capsule) on one occasion on Day 1. 2 participants received matching placebo.

Drug: KVD824; Drug: Placebo to KVD824

Part A - KVD824 - 320 mg

EXPERIMENTAL

6 participants were administered 320mg of KVD824 in capsule form (1 x 320 mg capsule) on one occasion on Day 1. 2 participants received matching placebo.

Drug: KVD824; Drug: Placebo to KVD824

Part A - KVD824 - 640 mg

EXPERIMENTAL

6 participants were administered 640 mg of KVD824 in capsule form (2 x 320 mg capsule) on one occasion on Day 1. 2 participants received matching placebo.

Drug: KVD824; Drug: Placebo to KVD824

Part A - KVD824 - 1280 mg

EXPERIMENTAL

6 participants were administered 1280 mg of KVD824 in capsule form (4 x 320 mg capsule) on one occasion on Day 1. 2 participants received matching placebo.

Drug: KVD824; Drug: Placebo to KVD824

Part B - KVD824 - 80 mg Multi-Dose

EXPERIMENTAL

6 participants were administered 80 mg of KVD824 in capsule form (2 x 40 mg capsules) in multiple doses over a period of 5 days (twice a day on Days 1-4 and once in morning of Day 5; the first dose on each day was administered fasted). 2 participants received matching placebo.

Drug: KVD824; Drug: Placebo to KVD824

Part B - KVD824 - 160 mg Multi-Dose

EXPERIMENTAL

6 participants were administered 160mg of KVD824 in capsule form (1 x 160 mg capsule) in multiple doses over a period of 5 days (twice a day on Days 1-4 and once in morning of Day 5; the first dose on each day was administered fasted). 2 participants received matching placebo.

Drug: KVD824; Drug: Placebo to KVD824

Part B - KVD824 - 320 mg Multi-Dose

EXPERIMENTAL

6 participants were administered 320mg of KVD824 in capsule form (1 x 320 mg capsule) in multiple doses over a period of 5 days (twice a day on Days 1-4 and once in morning of Day 5; the first dose on each day was administered fasted). 2 participants received matching placebo.

Drug: KVD824; Drug: Placebo to KVD824

Part B - KVD824 - 640 mg Multi-Dose

EXPERIMENTAL

6 participants were administered 640mg of KVD824 in capsule form (2 x 320 mg capsules) in multiple doses over a period of 5 days (twice a day on Days 1-4 and once in morning of Day 5; the first dose on each day was administered fasted). 2 participants received matching placebo.

Drug: KVD824; Drug: Placebo to KVD824

Part C - KVD824 - 320 mg Fasted

EXPERIMENTAL

12 participants were administered 320 mg of KVD824 in capsule form (1 x 320 mg capsule) on one occasion on Day 1 in a fasted state.

Drug: KVD824

Part C - KVD824 - 320 mg High fat breakfast

EXPERIMENTAL

12 participants were administered 320 mg of KVD824 in capsule form (1 x 320 mg capsule) on one occasion on Day 1 following consumption of a high fat breakfast.

Drug: KVD824

Interventions

KVD824 DRUG

Active

Part A - KVD824 - 10 mg; Part A - KVD824 - 1280 mg; Part A - KVD824 - 160mg; Part A - KVD824 - 20 mg; Part A - KVD824 - 320 mg; Part A - KVD824 - 40 mg; Part A - KVD824 - 640 mg; Part A - KVD824 - 80 mg; Part B - KVD824 - 160 mg Multi-Dose; Part B - KVD824 - 320 mg Multi-Dose; Part B - KVD824 - 640 mg Multi-Dose; Part B - KVD824 - 80 mg Multi-Dose; Part C - KVD824 - 320 mg Fasted; Part C - KVD824 - 320 mg High fat breakfast

Placebo to KVD824 DRUG

Placebo

Part A - KVD824 - 10 mg; Part A - KVD824 - 1280 mg; Part A - KVD824 - 160mg; Part A - KVD824 - 20 mg; Part A - KVD824 - 320 mg; Part A - KVD824 - 40 mg; Part A - KVD824 - 640 mg; Part A - KVD824 - 80 mg; Part B - KVD824 - 160 mg Multi-Dose; Part B - KVD824 - 320 mg Multi-Dose; Part B - KVD824 - 640 mg Multi-Dose; Part B - KVD824 - 80 mg Multi-Dose

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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 / deputy.
• Male subject willing to wear a condom and whose partner of child bearing potential uses a highly effective method of contraception (e.g. partner use of intrauterine device (IUD)) or an effective method of contraception, i.e., established method of contraception + condom, if applicable (unless anatomically sterile or where abstaining from sexual intercourse is in line with the preferred and usual lifestyle of the subject) from first dose until 3 months after last dose of IMP. Men whose partners are already pregnant must continue to use a condom during the trial and for three months thereafter.
• Subject with a body mass index (BMI) of 18-32 kg/m2.
• Subject with no clinically significant history of previous allergy / sensitivity to KVD824 or any of the excipients contained within the Investigational Medicinal Product.
• Subject with no clinically significant abnormal serum biochemistry, haematology, clotting profiles, and urine examination values within 28 days before the first dose of Investigational Medicinal Product.
• Subject with a negative urinary drugs of abuse screen, determined within 28 days before the first dose of Investigational Medicinal Product (N.B. a positive result may be repeated at the Chief Investigator's discretion).
• 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 (QTcF ≤ 430 ms and PR interval 120-220 ms) determined within 28 days before first dose of Investigational Medicinal Product.
• Subject with no clinically significant abnormalities in vital signs (supine systolic (≤140 mmHg) and diastolic blood pressure (≤ 90 mmHg), pulse (≤ 100 bpm), oral temperature (≤ 37.5°C)) determined within 28 days before first dose of Investigational Medicinal Product.
• Subjects must not donate sperm from first dose until at least 3 months after last dose of Investigational Medicinal Product.
• Subjects without any special food restrictions that would hinder ability to consume gelatin (Part A and Part B placebo), or the high fat breakfast provided during study Part C; such as vegetarian, lactose intolerance, vegan, low-fat, low sodium, etc.
• Subjects with no known allergy or sensitivity to lactose and/or any additional excipients contained in Investigational Medicinal Product.
• Subject must be available to complete the study (including all follow up visits).
• Subject must satisfy the Chief Investigator / deputy about their fitness to participate in the study.

You may not qualify if:

• A clinically significant history of gastrointestinal disorder likely to influence Investigational Medicinal Product absorption.
• Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 28 days or 5 half-lives (which ever is longer) prior to the first dose of Investigational Medicinal Product, unless in the opinion of the Chief Investigator the medication will not interfere with the study procedures or compromise subject safety.
• Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular 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 (e.g., e-cigarettes, nicotine patches or gums).
• Inability to communicate well with Investigators (i.e., language problem, poor mental development or impaired cerebral function).
• 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 Investigational Medicinal Product. (Washout period between studies is defined as the period of time elapsed between the last dose of the previous study and the first dose of the next study).
• Donation of 450 mL or more blood within the 3 months before the first dose of Investigational Medicinal Product.

Sponsors & Collaborators

• KalVista Pharmaceuticals, Ltd.: lead

Study Sites (1)

KalVista Investigative Site

Merthyr Tydfil, United Kingdom

Location

MeSH Terms

Conditions

Angioedemas, Hereditary

Condition Hierarchy (Ancestors)

Angioedema; Vascular Diseases; Cardiovascular Diseases; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Immunologic Deficiency Syndromes

Study Officials

• Study Director

  KalVista Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2021
• First Posted: January 5, 2022
• Study Start: February 12, 2019
• Primary Completion: June 21, 2019
• Study Completion: June 21, 2019
• Last Updated: February 17, 2022

Record last verified: 2022-02

Locations

GB (1)