The purpose of this study is to measure the safety, tolerability, PK, and PD of AZD5492 administered subcutaneously in adult participants with SLE or IIM or RA Study details include: • The study duration will be a minimum of 180 days in addition to the screening period. Additional follow-up visits may be required up to 12 months from study start. * Depending on the study part they are assigned to, participants will be administered AZD5492 once (Part 1) or twice (Part 2). * Study visits will occur at: Screening, Days 1-4, 8, 15, 22, 30, 60, 90, 120, 150, and 180 in Part 1, Screening, Days 1-4, 8-11, 15, 22, 29, 43, 60, 90, 120, 150, and 180 in Part 2.
This is an open-label, multi-centre Phase I study to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of AZD5492 in adult participants with either SLE or IIM or RA. The study consists of 2 parts: Part 1 - Single ascending dose (SAD) Part 1 will be a sequential SAD design in adult participants with SLE. Up to 5 dose levels of AZD5492 are planned to be investigated. Depending on emerging data, up to 4 additional dose levels may be added at the discretion of the Sponsor. The decision to open Part 2 will be made by the Safety Review Committee (SRC) based on the evaluation of all available data including safety, tolerability, PK, and PD from Part 1 and pertinent data arising from other ongoing studies with AZD5492 will also be considered, and the dose levels and dosing strategy for Part 2 will be confirmed. After a screening period of up to 42 days, participants will receive 1 dose of AZD5492 and be followed up for at least 179 days post-dose. Part 2 - Step-up dosing (SUD) Part 2 will be a SUD design in adult participants who have SLE (and did not participate in Part 1), as well as adult participants with IIM or RA. In Part 2, participants will receive 2 dose administrations, 7 days apart. The first (priming) dose of the step-up regimen will be agreed by the SRC. The second (target) dose will be escalated, and a minimum of 3 target dose levels are planned to be investigated in Part 2.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
72
IMP: subcutaneous.
Research Site
Anniston, Alabama, United States
RECRUITINGResearch Site
Birmingham, Alabama, United States
NOT_YET_RECRUITINGResearch Site
Iowa City, Iowa, United States
RECRUITINGResearch Site
Hamilton, Ontario, Canada
NOT_YET_RECRUITINGResearch Site
Sherbrooke, Quebec, Canada
NOT_YET_RECRUITINGResearch Site
Beijing, China
RECRUITINGResearch Site
Shanghai, China
RECRUITINGResearch Site
Wuhan, China
RECRUITINGResearch Site
Bordeaux, France
RECRUITINGResearch Site
Montpellier, France
RECRUITING...and 21 more locations
Safety evaluation of AZD5492: Number of participants with treatment-emergent adverse events.
Number and percentage of participants with AEs, AESIs, and SAEs
Time frame: Day 1 to end of the study (up to 52 weeks)
Safety evaluation of AZD5492: Number of participants with related treatment-emergent adverse events.
Number and percentage of participants with AEs related to IMP as assessed by the investigator
Time frame: Day 1 to end of the study (up to 52 weeks)
Safety evaluation of AZD5492: Frequency of dose limiting toxicities (DLTs).
Number and percentage of participants with DLTs (dose-limiting toxicities) as defined in the study protocol.
Time frame: Day 1 to end of the study (up to 52 weeks)
Safety evaluation of AZD5492: Number of SAEs leading to death
Number and percentage of participants with SAEs leading to death.
Time frame: Day 1 to end of the study (up to 52 weeks)
Safety evaluation of AZD5492: Number of participants with treatment-emergent adverse events by grade.
Number and percentage of participants with AEs according ASTCT, IEC-HS, and CTCAE grades.
Time frame: Day 1 to end of the study (up to 52 weeks)
Tolerability evaluation of AZD5492: Number of participants with treatment-emergent vital signs abnormalities.
Number and percentage of participants with treatment-related vital signs abnormalities.
Time frame: Day 1 to end of the study (up to 52 weeks)
Tolerability evaluation of AZD5492: Number of participants with treatment-emergent clinical laboratory abnormalities.
Number and percentage of participants with treatment-related clinical laboratory abnormalities.
Time frame: Day 1 to end of the study (up to 52 weeks)
Tolerability evaluation of AZD5492: Number of participants with abnormal ECG.
Number and percentage of participants with abnormal ECG.
Time frame: From Day 1 up to Day 180
Serum Pharmacokinetics (PK) parameters of AZD5492 (Cmax)
Maximum observed serum drug concentration (Cmax) (μg/mL)
Time frame: From Day 1 through Day 60
Serum Pharmacokinetics (PK) parameters of AZD5492 (AUC)
Area under the serum concentration-time curve (AUC) (μg/mL\*h)
Time frame: From Day 1 through Day 60
Serum Pharmacokinetics (PK) parameters of AZD5492 (t1/2λz)
Terminal elimination half-life (t1/2λz) (In hours)
Time frame: From Day 1 through Day 60
Serum Pharmacokinetics (PK) parameters of AZD5492 (AUClast)
Area under the serum concentration time curve from time zero to the time of last quantifiable analyte concentration (AUClast) (nmol\*h/L)
Time frame: From Day 1 through Day 60
Incidence of ADAs to AZD5492 measured in serum.
Incidence of ADAs to AZD5492 measured in serum.
Time frame: From Day 1 through Day 180
Absolute counts at Day 180 in blood CD19+ B-cells.
Absolute counts at Day 180 in blood CD19+ B-cells.
Time frame: Day 180
AstraZeneca Clinical Study Information Center
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