Clinical trial NCT05937581: First-In-Human Study To Evaluate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Escalating Single And Multiple Doses Of CSL040 In Healthy Subjects
Official 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Disease Driven by Complement Activation
Keywords: Complement
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2023-07-10
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria:

1. Male or female 18 to 64 years of age, inclusive, at Screening
2. Body weight in the range of greater than or equal to (≥) 50 kg and less than or equal to (≤) 100 kilogram (kg) , with a body mass index of ≥ 18 kilogram per meter square (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 adequate vaccination (as determined by the Investigator) against meningococcal disease, including vaccination against meningococcal serogroup B and meningococcal serogroups A, C, W, and Y OR be willing to receive additional vaccinations against these serogroups with the first dose 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
8. Able to provide proof of adequate vaccination (as determined by the Investigator) against Haemophilus influenzae type b, Pneumococcus OR be willing to receive additional vaccinations against these pathogens with the first dose at least 21 days before the first dose of CSL040
9. Able to provide proof of adequate vaccination (as determined by the Investigator) against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS_CoV-2) OR be willing to receive additional vaccination(s) to achieve adequate vaccination status at least 14 days before the first dose of CSL040. If there is proof of a recent SARS-CoV-2 infection (as determined by the Investigator) within 90 days of the first dose of CSL040, the requirement for a vaccination will follow the current local clinical practice

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. Vaccination with any live replication-competent vaccine 90 days before Day 1 or planned vaccination with the same within 90 days after the last administration of CSL040
3. A positive test result for any of the following: hepatitis B screening, 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, as well as to potential backup medications including azithromycin, ciprofloxacin, and ceftriaxone
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 infection, or any infection which makes participation in this study 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 CSL040 or any excipients including polysorbate 80, monoclonal antibodies, or any documented history of a severe allergic reaction (in the opinion of the Investigator), angioedema, or anaphylaxis to food or any other drugs.
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) and cotinine 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 any vaccinations or other medications required/permitted as per protocol) within the 21 days before first 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 milliLiter (mL) of blood within 3 months, or donation of plasma within 7 days, before admission to the unit or plans to donate blood or plasma and for 5 half-lives of the last dose of CSL040 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
22. Prior dosing with CSL040

Primary outcomes:
measure: Number of participants with treatment emergent adverse events (TEAEs), adverse events of special interests (AESIs), and serious adverse events (SAEs)
timeFrame: Part A (SAD): Up to 105 days; Part B (MAD): Up to 118 days
measure: Percentages of participants with TEAEs, AESIs, and SAEs
timeFrame: Part A (SAD): Up to 105 days; Part B (MAD): Up to 118 days
measure: The Number of Clinically Significant Changes from Baseline in Clinical Laboratory Tests Reported as AE
timeFrame: Baseline and up to 69 days
measure: Number of participants with vital signs out of normal range
timeFrame: Baseline and up to 69 days
measure: Change from Baseline in corrected QT interval using Fridericia's formula (QTcF) values of triplicate electrocardiograms
timeFrame: Baseline and up to 69 days
measure: Absolute values of QTcF on electrocardiograms
timeFrame: Baseline and up to 69 days
measure: Number of participants with abnormal electrocardiogram findings
timeFrame: Baseline and up to 69 days
Secondary outcomes:
measure: Part A (SAD): Maximum concentration (Cmax)
timeFrame: Up to 56 days
measure: Part A (SAD): Time to reach maximum concentration (Tmax)
timeFrame: Up to 56 days
measure: Part A (SAD): Time to Area under the concentration-time curve from time 0 to the last measurable concentration (AUC0-last)
timeFrame: Up to 56 days
measure: Part A (SAD): Area under the concentration-time curve from time 0 to infinity (AUC0-infinity)
timeFrame: Up to 56 days
measure: Part A (SAD): Total systemic clearance (CL)
timeFrame: Up to 56 days
measure: Part A (SAD): Volume of distribution (V)
timeFrame: Up to 56 days
measure: Part A (SAD): Terminal elimination half-life (T1/2)
timeFrame: Up to 56 days
measure: Part B (MAD): Maximum concentration (Cmax)
timeFrame: Up to 69 days
measure: Part B (MAD): Time to reach maximum concentration (Tmax)
timeFrame: Up to 69 days
measure: Part B (MAD): Time to Area under the concentration-time curve in 1 dosing interval (AUCtau)
timeFrame: Up to 69 days
measure: Part B (MAD): Accumulation index (accumulation ratio determined by the ratio of steady state AUCtau to single dose AUCtau)
timeFrame: Up to 69 days
measure: Part B (MAD): Lowest concentration prior to dosing (Ctrough)
timeFrame: Up to 69 days
measure: Part B (MAD): Total systemic clearance (CL)
timeFrame: Up to 69 days
measure: Part B (MAD): Volume of distribution at steady state (Vss)
timeFrame: Up to 69 days
measure: Part A (SAD) and Part B (MAD): Percent change from Baseline in pharmacodynamic (PD) parameters
timeFrame: Up to 56 days (Part A) and up to 69 days (Part B)
measure: Part A (SAD) and Part B (MAD): Maximum percent change from Baseline (Emax) in PD parameters
timeFrame: Up to 56 days (Part A) and up to 69 days (Part B)
measure: Part A (SAD) and Part B (MAD): Time to maximum percent change from Baseline (TEmax) in PD parameters
timeFrame: Up to 56 days (Part A) and up to 69 days (Part B)
measure: Part A (SAD) and Part B (MAD): Time below Baseline in PD parameters
timeFrame: Up to 56 days (Part A) and up to 69 days (Part B)
measure: Part A (SAD) and Part B (MAD): AUC below Baseline in PD parameters
timeFrame: Up to 56 days (Part A) and up to 69 days (Part B)
measure: Part A (SAD) and Part B (MAD): Number of serum samples with Positive antidrug antibodies (ADAs) binding to CSL040
timeFrame: Up to 56 days (Part A) and up to 69 days (Part B)
measure: Part A (SAD) and Part B (MAD): Number of participants with presence of treatment-emergent ADAs
timeFrame: Up to 56 days (Part A) and up to 69 days (Part B)
Other outcomes:
Locations:
city: Herston
country: Australia
facility: Nucleus Network Pty Ltd
state: Queensland
Study officials:
affiliation: CSLBehring LLC
name: Study Director
role: STUDY_DIRECTOR
References: