To Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Escalating Single and Multiple Doses of KP104

SYNERGY-1: A Phase 1 First-in-human, Randomized, Double Blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Escalating Single and Multiple Doses of KP104 in Healthy Subjects

The purpose of this study is to evaluate safety, tolerability, immunogenicity, pharmacokinetics, pharmacodynamics, and efficacy of KP104 in healthy volunteers. The study will be conducted in 2 parts: Part 1, the single ascending dose (SAD) is the first in human (FIH) study of KP104 and Part 2, multiple ascending dose (MAD).

Study Overview

• Status: Completed
• Conditions: Paroxysmal Nocturnal Hemoglobinuria
• Intervention / Treatment: Drug: KP104; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia
    • CMAX Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Weight of > 40 kilograms (kg) and < 120 kg at Screening.
• In good general health, determined by no clinically significant findings in the opinion of the Investigator from medical history, physical examination, 12-lead ECG, clinical laboratory findings, and vital signs at Screening and Check-in.
• Hemoglobin, hematocrit, white blood cell count, absolute neutrophil count, and platelet count results within the normal range at the Screening Visit; participants with Gilbert's disease with associated abnormalities of liver function tests are eligible for enrollment. Tests may be repeated at the discretion of the Investigator to confirm abnormalities.
• Creatinine clearance based on the Cockcroft-Gault equation of >= 80 milliliters per minute (ml/min).
• Females of childbearing potential and males must practice effective contraception from Screening until 28 days after the end of study (EOS) visit.
• Females of childbearing potential must have a negative pregnancy test at Screening and within 24 hours prior to dosing of study drug; for post-menopausal subjects, a blood sample will also be tested for follicle stimulating hormone to confirm post-menopausal status.

Exclusion Criteria:

• Any clinically significant underlying illness in the opinion of the Investigator.
• Any history or sign of significant chronic active or recurrent infection, or screening laboratory evidence consistent with a significant chronic active or recurrent infection requiring treatment with antibacterials, antivirals, or antifungals.
• Treatment of any infection with IV (within 30 days of Screening) or oral (within 14 days of Screening) antibacterials, antivirals, or antifungals.
• History of clinically significant hematologic or bone marrow disease or blood dyscrasias.
• History of meningococcal infection.
• History of tuberculosis.
• History of asplenia (functional or anatomical).
• Prior exposure to KP104.
• Known allergy to penicillin antibiotics or history of allergy or contraindication to required prophylactic antibiotic therapy to be used during the study.
• Known or suspected complement deficiency during screening.
• Positive serology for Hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV) at Screening.
• History of drug or alcohol abuse within 1 year of Screening in the opinion of the investigator, or a positive test for drugs of abuse or alcohol at Screening or Check-in.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

12

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Single Ascending Dose Cohort 1	Drug: KP104; Participants will receive KP104 intravenous (IV) dose approximately for 1 hour or subcutaneous (SC) dose.
Experimental: Part 1: Single Ascending Dose Cohort 2	Drug: KP104; Participants will receive KP104 intravenous (IV) dose approximately for 1 hour or subcutaneous (SC) dose.
Experimental: Part 1: Single Ascending Dose Cohort 3	Drug: KP104; Participants will receive KP104 intravenous (IV) dose approximately for 1 hour or subcutaneous (SC) dose.
Experimental: Part 1: Single Ascending Dose Cohort 4	Drug: KP104; Participants will receive KP104 intravenous (IV) dose approximately for 1 hour or subcutaneous (SC) dose.
Experimental: Part 1: Single Ascending Dose Cohort 5	Drug: KP104; Participants will receive KP104 intravenous (IV) dose approximately for 1 hour or subcutaneous (SC) dose.
Experimental: Part 1: Single Ascending Dose Cohort 6	Drug: KP104; Participants will receive KP104 intravenous (IV) dose approximately for 1 hour or subcutaneous (SC) dose.
Experimental: Part 1: Single Ascending Dose Cohort 7	Drug: KP104; Participants will receive KP104 intravenous (IV) dose approximately for 1 hour or subcutaneous (SC) dose.
Experimental: Part 2: Multiple Ascending Dose Cohort 1	Drug: KP104; Participants will receive KP104 intravenous (IV) dose approximately for 1 hour or subcutaneous (SC) dose.
Experimental: Part 2: Multiple Ascending Dose Cohort 2	Drug: KP104; Participants will receive KP104 intravenous (IV) dose approximately for 1 hour or subcutaneous (SC) dose.
Experimental: Part 2: Multiple Ascending Dose Cohort 3	Drug: KP104; Participants will receive KP104 intravenous (IV) dose approximately for 1 hour or subcutaneous (SC) dose.
Placebo Comparator: Part 1: Placebo	Drug: Placebo; Participants will receive matching placebo which is KP104 vehicle containing sodium phosphate, sodium chloride, and L-Lysine Hydrochloride (L-Lys-HCL).
Placebo Comparator: Part 2: Placebo	Drug: Placebo; Participants will receive matching placebo which is KP104 vehicle containing sodium phosphate, sodium chloride, and L-Lysine Hydrochloride (L-Lys-HCL).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants reporting Treatment Emergent Adverse Events (TEAEs)	An Adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding), symptom, or disease or any worsening of a pre-existing condition temporally associated with the use of a study drug, whether or not related to study drug. A TEAE is defined as any AE that started or worsened in severity on or after the first dose of study treatment.	Up to Day 85
Number of participants reporting Treatment Emergent Serious Adverse Events (TESAEs)	A TESAE is defined as any AE that started or worsened in severity on or after the first dose of study treatment.	Up to Day 85
Number of participants with Dose-limiting toxicities (DLT)	A DLT is defined as any adverse event considered by the investigator to be KP104-related with a severity greater than or equal to (>=) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grade 3 which also represents a shift from baseline clinical status of > 1 NCI CTCAE grade. A hypersensitivity/administration reaction occurring with a severity of Grade 2 despite the use of pre-medications will also be designated as a DLT.	Up to Day 85
Number of participants reporting AEs of Special interests (AESIs)	An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease or any worsening of a pre-existing condition temporally associated with the use of a study drug, whether or not related to study drug. Number of participants with AESIs including infections and local or systemic administration reactions will be assessed.	Up to Day 85

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum concentration (Cmax) of KP104	Up to Day 29
Area under the concentration-time profile (AUC) of KP104	Up to Day 29
Change from baseline in total and free serum C5 levels	Baseline and up to Day 29
Change from baseline in rabbit red blood cell (RBC) assay	Baseline and up to Day 29

Other Outcome Measures

Outcome Measure	Time Frame
Changes in serum free C5 levels to Minimum concentration (Cmin) correlation	Baseline and up to Day 29
Changes in serum free C5 levels to AUC correlation	Baseline and up to Day 29
Changes in C3b activity to Cmax correlation	Baseline and up to Day 29
Changes in C3b activity to Cmin correlation	Baseline and up to Day 29
Changes in C3b activity to AUC correlation	Baseline and up to Day 29
Changes in rabbit RBC lysis to Cmax correlation	Baseline and up to Day 29
Changes in rabbit RBC lysis to Cmin correlation	Baseline and up to Day 29
Changes in rabbit RBC lysis to AUC correlation	Baseline and up to Day 29
Immunogenicity of KP104	Up to Day 29
Maximum tolerated dose (MTD) of KP104	Up to Day 29
Optimal biologic dose (OBD) of KP104	Up to Day 29
Number of participants with clinically significant changes in laboratory values, electrocardiograms (ECGs), physical examinations, and vital signs	Up to Day 29
Changes in serum free complement component C5 levels to Cmax correlation	Baseline and up to Day 29
Dose optimization of KP104	Up to Day 29
Systemic clearance (Cl) of KP104	Up to Day 29
Elimination half-life (t½) of KP104	Up to Day 29
Change from baseline in complement component of C3b activity assay	Baseline and up to Day 29
Absolute bioavailability of KP104 administered SC (F)	Up to Day 29
Change from baseline in Factor H (FH) serum levels	Baseline and up to Day 29

Collaborators and Investigators

• Sponsor: Kira Pharmacenticals (US), LLC.

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2020
• Primary Completion (Actual): May 4, 2022
• Study Completion (Actual): September 2, 2022

Study Registration Dates

• First Submitted: August 4, 2022
• First Submitted That Met QC Criteria: August 4, 2022
• First Posted (Actual): August 5, 2022

Study Record Updates

• Last Update Posted (Actual): March 1, 2023
• Last Update Submitted That Met QC Criteria: February 28, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Healthy participants; First in Human; Paroxysmal Nocturnal Hemoglobinuria; Multiple Ascending Dose; KP104; Single ascending Dose; Complement Inhibitor
• Additional Relevant MeSH Terms: Urologic Diseases; Urological Manifestations; Bone Marrow Diseases; Hematologic Diseases; Urination Disorders; Anemia; Proteinuria; Anemia, Hemolytic; Myelodysplastic Syndromes; Hemoglobinuria; Hemoglobinuria, Paroxysmal
• Other Study ID Numbers: KP104-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

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