Clinical trial NCT05490017: To Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Escalating Single and Multiple Doses of KP104
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Paroxysmal Nocturnal Hemoglobinuria
Keywords: KP104
Paroxysmal Nocturnal Hemoglobinuria
Single ascending Dose
Multiple Ascending Dose
First in Human
Complement Inhibitor
Healthy participants
Lead sponsor: Kira Pharmacenticals (US), LLC.
Sponsor class: INDUSTRY
First posted: 2022-08-05
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants reporting Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to Day 85
measure: Number of participants reporting Treatment Emergent Serious Adverse Events (TESAEs)
timeFrame: Up to Day 85
measure: Number of participants with Dose-limiting toxicities (DLT)
timeFrame: Up to Day 85
measure: Number of participants reporting AEs of Special interests (AESIs)
timeFrame: Up to Day 85
Secondary outcomes:
measure: Maximum concentration (Cmax) of KP104
timeFrame: Up to Day 29
measure: Area under the concentration-time profile (AUC) of KP104
timeFrame: Up to Day 29
measure: Change from baseline in total and free serum C5 levels
timeFrame: Baseline and up to Day 29
measure: Change from baseline in rabbit red blood cell (RBC) assay
timeFrame: Baseline and up to Day 29
Other outcomes:
measure: Changes in serum free C5 levels to Minimum concentration (Cmin) correlation
timeFrame: Baseline and up to Day 29
measure: Changes in serum free C5 levels to AUC correlation
timeFrame: Baseline and up to Day 29
measure: Changes in C3b activity to Cmax correlation
timeFrame: Baseline and up to Day 29
measure: Changes in C3b activity to Cmin correlation
timeFrame: Baseline and up to Day 29
measure: Changes in C3b activity to AUC correlation
timeFrame: Baseline and up to Day 29
measure: Changes in rabbit RBC lysis to Cmax correlation
timeFrame: Baseline and up to Day 29
measure: Changes in rabbit RBC lysis to Cmin correlation
timeFrame: Baseline and up to Day 29
measure: Changes in rabbit RBC lysis to AUC correlation
timeFrame: Baseline and up to Day 29
measure: Immunogenicity of KP104
timeFrame: Up to Day 29
measure: Maximum tolerated dose (MTD) of KP104
timeFrame: Up to Day 29
measure: Optimal biologic dose (OBD) of KP104
timeFrame: Up to Day 29
measure: Number of participants with clinically significant changes in laboratory values, electrocardiograms (ECGs), physical examinations, and vital signs
timeFrame: Up to Day 29
measure: Changes in serum free complement component C5 levels to Cmax correlation
timeFrame: Baseline and up to Day 29
measure: Dose optimization of KP104
timeFrame: Up to Day 29
measure: Systemic clearance (Cl) of KP104
timeFrame: Up to Day 29
measure: Elimination half-life (t½) of KP104
timeFrame: Up to Day 29
measure: Change from baseline in complement component of C3b activity assay
timeFrame: Baseline and up to Day 29
measure: Absolute bioavailability of KP104 administered SC (F)
timeFrame: Up to Day 29
measure: Change from baseline in Factor H (FH) serum levels
timeFrame: Baseline and up to Day 29
Locations:
city: Adelaide
country: Australia
facility: CMAX Clinical Research
Study officials:
References: