ANZCTR - Registration

Technical difficulties have been reported by some users of the search function and is being investigated by technical staff. Thank you for your patience and apologies for any inconvenience caused.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05937581

Registration number

NCT05937581

Ethics application status

Date submitted

18/05/2023

Date registered

10/07/2023

Date last updated

28/06/2024

Titles & IDs

Public title

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

Scientific title

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

Secondary ID [1]

CSL040_1001

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Complement Deficiencies

Condition category

Condition code

Human Genetics and Inherited Disorders

Other human genetics and inherited disorders

Inflammatory and Immune System

Other inflammatory or immune system disorders

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Treatment: Drugs - CSL040
Treatment: Drugs - Placebo

Experimental: Part A (SAD): CSL040 (minimum dose) - Single Intravenous (IV) administration

Experimental: Part A (SAD): CSL040 (lower dose) - Single IV Administration

Experimental: Part A (SAD): CSL040 (low dose) - Single IV Administration

Experimental: Part A (SAD): CSL040 (medium dose) - Single IV Administration

Experimental: Part A (SAD): CSL040 (medium-high dose) - Single IV Administration

Experimental: Part A (SAD): CSL040 (maximum dose) - Single IV Administration

Placebo comparator: Part A (SAD): Placebo - Single IV Administration

Experimental: Part B (MAD): CSL040 (minimum dose) - IV Administration not to exceed 5 doses over 14 days)

Experimental: Part B (MAD): CSL040 (medium dose) - IV Administration not to exceed 5 doses over 14 days

Experimental: Part B (MAD): CSL040 (high dose) - IV Administration not to exceed 5 doses over 14 days

Placebo comparator: Part B (MAD): Placebo - IV Administration not go exceed 5 doses over 14 days

Treatment: Drugs: CSL040
IV Administration

Treatment: Drugs: Placebo
0.9% w/v NaCI, IV Administration

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Frequency counts for subjects with treatment emergent adverse events (TEAEs) leading to withdrawal or discontinuation of investigational product

Timepoint [1]

Up to 10 weeks

Primary outcome [2]

Percentages for subjects with treatment emergent TEAEs leading to withdrawal or discontinuation of investigational product

Timepoint [2]

Up to 10 weeks

Primary outcome [3]

Change from Baseline in tympanic temperature

Timepoint [3]

Up to 10 weeks

Primary outcome [4]

Change from Baseline in pulse rate

Timepoint [4]

Up to 10 weeks

Primary outcome [5]

Change from Baseline in blood pressure

Timepoint [5]

Up to 10 weeks

Primary outcome [6]

Change from Baseline in leukocytes (white blood cell count)

Timepoint [6]

Up to 10 weeks

Primary outcome [7]

Change from Baseline of hemoglobin values

Timepoint [7]

Up to 10 weeks

Primary outcome [8]

Change from Baseline of C-reactive protein (CRP)

Timepoint [8]

Up to 10 weeks

Primary outcome [9]

Change from Baseline in Creatinine levels

Timepoint [9]

Up to 10 weeks

Primary outcome [10]

Change from Baseline above the upper limit of normal (ULN) for alanine aminotransaminase (ALT)

Timepoint [10]

Up to 10 weeks

Primary outcome [11]

Change from Baseline above the upper limit of normal (ULN) for aspartate aminotransaminase (AST)

Timepoint [11]

Up to 10 weeks

Primary outcome [12]

Change from Baseline in corrected QT interval using Fridericia's formula (QTcF) values of triplicate electrocardiograms

Timepoint [12]

Up to 10 weeks

Secondary outcome [1]

Part A (Single Ascending Dose [SAD]): Maximum concentration (Cmax)

Timepoint [1]

Up to 56 Days

Secondary outcome [2]

Part A (SAD): Time to reach maximum concentration (Tmax)

Timepoint [2]

Up to 56 Days

Secondary outcome [3]

Part A (SAD): Time to Area under the concentration-time curve from time 0 to the last measurable concentration (AUC0-last)

Timepoint [3]

Up to 56 Days

Secondary outcome [4]

Part A (SAD): Area under the concentration-time curve from time 0 to infinity (AUC0-infinity)

Timepoint [4]

Up to 56 Days

Secondary outcome [5]

Part A (SAD): Total systemic clearance (CL)

Timepoint [5]

Up to 56 Days

Secondary outcome [6]

Part A (SAD): Volume of distribution (V)

Timepoint [6]

Up to 56 Days

Secondary outcome [7]

Part A (SAD): Terminal elimination half-life (T1/2)

Timepoint [7]

Up to 56 Days

Secondary outcome [8]

Part B (Multiple Ascending Dose [MAD]): Maximum concentration (Cmax)

Timepoint [8]

Up to 70 Days

Secondary outcome [9]

Part B (MAD): Time to reach maximum concentration (Tmax)

Timepoint [9]

Up to 70 Days

Secondary outcome [10]

Part B (MAD): Time to Area under the concentration-time curve in 1 dosing interval (AUCtau)

Timepoint [10]

Up to 70 Days

Secondary outcome [11]

Part B (MAD): Accumulation index (accumulation ratio determined by the ratio of steady state AUCtau to single dose AUCtau

Timepoint [11]

Up to 70 Days

Secondary outcome [12]

Part B (MAD): Lowest concentration prior to dosing (Ctrough)

Timepoint [12]

Up to 70 Days

Secondary outcome [13]

Part B (MAD): Total systemic clearance (CL)

Timepoint [13]

Up to 70 Days

Secondary outcome [14]

Part B (MAD): Volume of distribution at steady state (Vss)

Timepoint [14]

Up to 70 Days

Secondary outcome [15]

Part A (SAD) and Part B (MAD): Maximum percent change from Baseline (Emax)

Timepoint [15]

Up to 56 Days (Part A) and up to 70 days (Part B)

Secondary outcome [16]

Part A (SAD) and Part B (MAD): Time to maximum percent change from Baseline (TEmax)

Timepoint [16]

Up to 56 Days (Part A) and up to 70 days (Part B)

Secondary outcome [17]

Part A (SAD) and Part B (MAD): Time to return to baseline

Timepoint [17]

Up to 56 Days (Part A) and up to 70 days (Part B)

Secondary outcome [18]

Part A (SAD) and Part B (MAD): Presence of treatment-emergent antidrug antibodies after administration of CSL040

Timepoint [18]

Up to 56 Days (Part A) and up to 70 days (Part B)

Eligibility

Key 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

Minimum age

18 Years

Maximum age

64 Years

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key 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 design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Other

Other design features

Phase

Phase 1

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Recruiting

Data analysis

Reason for early stopping/withdrawal

Other reasons

Date of first participant enrolment

Anticipated

Actual

28/09/2023

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

1/03/2025

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

QLD

Recruitment hospital [1]

Nucleus Network Pty Ltd - Herston

Recruitment postcode(s) [1]

4006 - Herston

Funding & Sponsors

Primary sponsor type

Commercial sector/industry

Name

CSL Behring

Address

Country

Ethics approval

Ethics application status

Summary

Brief summary

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

Trial website

https://clinicaltrials.gov/study/NCT05937581

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Study Director

Address

CSLBehring LLC

Country

Phone

Fax

Contact person for public queries

Name

Trial Registration Coordinator

Address

Country

Phone

1-610-878-4000

Fax

clinicaltrials@cslbehring.com

Contact person for scientific queries

Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05937581

Trial Review

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05937581