First-In-Human Study To Evaluate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Escalating Single And Multiple Doses Of CSL040 In Healthy Subjects

A Phase 1, Double-Blind (Sponsor-Unblinded), Placebo-Controlled, Dose Escalation Study To Evaluate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Single And Multiple Doses Of CSL040 In Healthy Adult Subjects

First-In-Human Study To Evaluate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Escalating Single And Multiple Doses Of CSL040 In Healthy Subjects

Study Overview

• Status: Recruiting
• Conditions: Complement Deficiencies
• Intervention / Treatment: Drug: CSL040; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Trial Registration Coordinator; Phone Number: 1-610-878-4000; Email: clinicaltrials@cslbehring.com

Study Locations

• Australia
  • Queensland
    • Herston, Queensland, Australia, 4006
      • Recruiting
      • Nucleus Network Pty Ltd
      • Contact: Use Central Contact

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Male or female 18 to 64 years of age, inclusive, at Screening
2. Body weight in the range of ≥ 50 kg and ≤ 100 kg, with a body mass index of ≥ 18 kg/m2 and ≤ 30 kg/m2, at Screening
3. Judged as healthy by an Investigator after completion of a comprehensive clinical assessment
4. Capable of providing written informed consent and willing and able to adhere to all protocol requirements
5. Can understand the nature, scope, and possible consequences of the study and able to comply with study procedures, restrictions, and requirements
6. Able to provide proof of vaccination against meningococcal disease according to local requirements or willing to receive meningococcal vaccination aligned with local guidelines (vaccination with recombinant meningococcal B vaccine against B serogroup [Men B] and quadrivalent meningococcal conjugate vaccine against A, C, W, and Y serogroups [Men ACWY]), at least 21 days before the first dose of CSL040
7. Continuous nonsmoker who has not used nicotine- and tobacco-containing products for at least 30 days prior to the first dosing based on urine cotinine testing at Screening and Day-1

Exclusion Criteria:

1. Any individual at high risk of exposure to Neisseria meningitidis, including, but not limited to, health care workers, doctors, nurses, students working in a clinical setting, laboratory workers with exposure to N. meningitidis, individuals residing in a dormitory setting (eg, military workers), and childcare workers
2. Other than the required meningococcal vaccines, any live vaccinations within the last 90 days before and during the study and / or up to 90 days after the last administration of the investigational product
3. A positive test result for hepatitis B surface antigen (HBsAg), hepatitis B core antigen, hepatitis B surface antibody, hepatitis C virus antibody, or human immunodeficiency virus-1/2 antibody.
4. History concerning for a N. meningitidis infection
5. History of allergy or intolerance to Penicillin V
6. History of unexplained, recurrent infection, life-threatening infection, or history that suggests any immunodeficiency (functional immunodeficiency), including asplenia / functional asplenia
7. Infection requiring treatment with systemic antibiotics (IV and / or oral administration for more than 3 days) within the last 90 days prior to dosing
8. Clinical evidence of current active serious infection, including any localized infections, or any infection which makes the participation in this study of healthy subjects unacceptably high risk
9. Blood pressure or pulse rate measurements outside the normal range for the subject's age and assessed as clinically significant
10. Known history of severe hypersensitivity reactions or suspected hypersensitivity to the CSL040 or any of the excipients or other monoclonal antibodies
11. Subject has any condition that may compromise their safety or compliance, impede successful conduct of the study, interfere with interpretation of the results or would otherwise render the subject unsuitable for participation in the study
12. A positive test result for drugs of abuse (including alcohol) at Screening and / or Day -1.
13. Weekly alcohol intake of > 10 units for females and > 14 units for males during the 3 months before Day -1.
14. Any values above the upper limit of normal (ULN) for alanine aminotransaminase (ALT) or aspartate aminotransaminase (AST), or bilirubin test result
15. Use of prescription or over-the-counter medication, herbal and dietary supplements, and vitamins and minerals (except the vaccination as required per protocol) within the 21 days before administration of investigational product
16. Female subject of childbearing potential or fertile male subject who are neither using nor willing to use a highly effective method of contraception
17. Pregnant, lactating, or breastfeeding
18. Donation or loss of more than 500 mL of blood within 3 months, or donated plasma within 7 days, before admission to the unit and for 5 half-lives or until the end of the study, whichever is longer
19. Any planned surgical procedures during the study period
20. Participation in any other investigational product study in which receipt of an investigational product occurred within 5 half-lives or 28 days (whichever is longer) before dosing of investigational product, or participation in more than 4 clinical studies involving administration of an investigational product within the last 12 months before Screening
21. Subject who met all eligibility criteria but was not needed (ie, alternate subjects). Alternate subjects are eligible to participate in subsequent cohorts.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part B (MAD): CSL040 (minimum dose); IV Administration not to exceed 5 doses over 14 days)	Drug: CSL040; IV Administration
Experimental: Part B (MAD): CSL040 (medium dose); IV Administration not to exceed 5 doses over 14 days	Drug: CSL040; IV Administration
Experimental: Part B (MAD): CSL040 (high dose); IV Administration not to exceed 5 doses over 14 days	Drug: CSL040; IV Administration
Experimental: Part A (SAD): CSL040 (minimum dose); Single Intravenous (IV) administration	Drug: CSL040; IV Administration
Experimental: Part A (SAD): CSL040 (lower dose); Single IV Administration	Drug: CSL040; IV Administration
Experimental: Part A (SAD): CSL040 (low dose); Single IV Administration	Drug: CSL040; IV Administration
Experimental: Part A (SAD): CSL040 (medium dose); Single IV Administration	Drug: CSL040; IV Administration
Experimental: Part A (SAD): CSL040 (medium-high dose); Single IV Administration	Drug: CSL040; IV Administration
Experimental: Part A (SAD): CSL040 (maximum dose); Single IV Administration	Drug: CSL040; IV Administration
Placebo Comparator: Part A (SAD): Placebo; Single IV Administration	Drug: Placebo; 0.9% w/v NaCI, IV Administration
Placebo Comparator: Part B (MAD): Placebo; IV Administration not go exceed 5 doses over 14 days	Drug: Placebo; 0.9% w/v NaCI, IV Administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Frequency counts for subjects with treatment emergent adverse events (TEAEs) leading to withdrawal or discontinuation of investigational product	Up to 10 weeks
Percentages for subjects with treatment emergent TEAEs leading to withdrawal or discontinuation of investigational product	Up to 10 weeks
Change from Baseline in tympanic temperature	Up to 10 weeks
Change from Baseline in pulse rate	Up to 10 weeks
Change from Baseline in blood pressure	Up to 10 weeks
Change from Baseline in leukocytes (white blood cell count)	Up to 10 weeks
Change from Baseline of hemoglobin values	Up to 10 weeks
Change from Baseline of C-reactive protein (CRP)	Up to 10 weeks
Change from Baseline in Creatinine levels	Up to 10 weeks
Change from Baseline above the upper limit of normal (ULN) for alanine aminotransaminase (ALT)	Up to 10 weeks
Change from Baseline above the upper limit of normal (ULN) for aspartate aminotransaminase (AST)	Up to 10 weeks
Change from Baseline in corrected QT interval using Fridericia's formula (QTcF) values of triplicate electrocardiograms	Up to 10 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A (SAD): Time to reach maximum concentration (Tmax)		Up to 56 Days
Part A (SAD): Time to Area under the concentration-time curve from time 0 to the last measurable concentration (AUC0-last)		Up to 56 Days
Part A (SAD): Area under the concentration-time curve from time 0 to infinity (AUC0-infinity)		Up to 56 Days
Part A (SAD): Total systemic clearance (CL)		Up to 56 Days
Part A (SAD): Volume of distribution (V)		Up to 56 Days
Part A (SAD): Terminal elimination half-life (T1/2)		Up to 56 Days
Part A (Single Ascending Dose [SAD]): Maximum concentration (Cmax)		Up to 56 Days
Part B (Multiple Ascending Dose [MAD]): Maximum concentration (Cmax)		Up to 70 Days
Part B (MAD): Time to reach maximum concentration (Tmax)		Up to 70 Days
Part B (MAD): Time to Area under the concentration-time curve in 1 dosing interval (AUCtau)		Up to 70 Days
Part B (MAD): Accumulation index (accumulation ratio determined by the ratio of steady state AUCtau to single dose AUCtau		Up to 70 Days
Part B (MAD): Lowest concentration prior to dosing (Ctrough)		Up to 70 Days
Part B (MAD): Total systemic clearance (CL)		Up to 70 Days
Part B (MAD): Volume of distribution at steady state (Vss)		Up to 70 Days
Part A (SAD) and Part B (MAD): Maximum percent change from Baseline (Emax)	Using Percent change from Baseline versus time course profiles of complement activation components	Up to 56 Days (Part A) and up to 70 days (Part B)
Part A (SAD) and Part B (MAD): Time to maximum percent change from Baseline (TEmax)	Using Percent change from Baseline versus time course profiles of complement activation components	Up to 56 Days (Part A) and up to 70 days (Part B)
Part A (SAD) and Part B (MAD): Time to return to baseline	Using Percent change from Baseline versus time course profiles of complement activation components	Up to 56 Days (Part A) and up to 70 days (Part B)
Part A (SAD) and Part B (MAD): Presence of treatment-emergent antidrug antibodies after administration of CSL040		Up to 56 Days (Part A) and up to 70 days (Part B)

Collaborators and Investigators

• Sponsor: CSL Behring
• Investigators: Study Director: Study Director, CSLBehring LLC

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2023
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: May 18, 2023
• First Submitted That Met QC Criteria: July 6, 2023
• First Posted (Actual): July 10, 2023

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Complement
• Additional Relevant MeSH Terms: Immunologic Deficiency Syndromes; Immune System Diseases; Genetic Diseases, Inborn; Primary Immunodeficiency Diseases; Hereditary Complement Deficiency Diseases
• Other Study ID Numbers: CSL040_1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: CSL will consider on a case-by-case basis requests to share Individual Patient Data (IPD) with external bona-fide, qualified scientific and medical researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.
• IPD Sharing Time Frame: Requests for IPD will generally be considered once review by major regulatory authorities (ie FDA, EMA) is complete and/or the primary publication is available.

IPD Sharing Access Criteria

Proposed research should seek to answer a previously unanswered important medical or scientific question.

Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD.

If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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