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

NCT05490017 | Completed Phase 1 DMC

• 1 other identifier: KP104-101
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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).

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Keywords

KP104; Paroxysmal Nocturnal Hemoglobinuria; Single ascending Dose; Multiple Ascending Dose; First in Human; Complement Inhibitor; Healthy participants

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (4)

• 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 Outcomes (19)

• 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

Study Arms (12)

Part 1: Single Ascending Dose Cohort 1

EXPERIMENTAL

Drug: KP104

Part 1: Single Ascending Dose Cohort 2

EXPERIMENTAL

Drug: KP104

Part 1: Single Ascending Dose Cohort 3

EXPERIMENTAL

Drug: KP104

Part 1: Single Ascending Dose Cohort 4

EXPERIMENTAL

Drug: KP104

Part 1: Single Ascending Dose Cohort 5

EXPERIMENTAL

Drug: KP104

Part 1: Single Ascending Dose Cohort 6

EXPERIMENTAL

Drug: KP104

Part 1: Single Ascending Dose Cohort 7

EXPERIMENTAL

Drug: KP104

Part 2: Multiple Ascending Dose Cohort 1

EXPERIMENTAL

Drug: KP104

Part 2: Multiple Ascending Dose Cohort 2

EXPERIMENTAL

Drug: KP104

Part 2: Multiple Ascending Dose Cohort 3

EXPERIMENTAL

Drug: KP104

Part 1: Placebo

PLACEBO COMPARATOR

Drug: Placebo

Part 2: Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

KP104 DRUG

Participants will receive KP104 intravenous (IV) dose approximately for 1 hour or subcutaneous (SC) dose.

Part 1: Single Ascending Dose Cohort 1; Part 1: Single Ascending Dose Cohort 2; Part 1: Single Ascending Dose Cohort 3; Part 1: Single Ascending Dose Cohort 4; Part 1: Single Ascending Dose Cohort 5; Part 1: Single Ascending Dose Cohort 6; Part 1: Single Ascending Dose Cohort 7; Part 2: Multiple Ascending Dose Cohort 1; Part 2: Multiple Ascending Dose Cohort 2; Part 2: Multiple Ascending Dose Cohort 3

Placebo DRUG

Participants will receive matching placebo which is KP104 vehicle containing sodium phosphate, sodium chloride, and L-Lysine Hydrochloride (L-Lys-HCL).

Part 1: Placebo; Part 2: Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Kira Pharmacenticals (US), LLC.: lead

Study Sites (1)

CMAX Clinical Research

Adelaide, Australia

Location

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases

Study Design

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

Study Record Dates

• First Submitted: August 4, 2022
• First Posted: August 5, 2022
• Study Start: December 30, 2020
• Primary Completion: May 4, 2022
• Study Completion: September 2, 2022
• Last Updated: March 1, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share

Locations

AU (1)