Purpose

The purpose of this study is to evaluate the safety and pharmacokinetics (PK) of AZD7760 when given as an intravenous infusion to healthy participants (Phase I) or participants with end-stage kidney disease receiving hemodialysis through a central venous catheter (Phase IIa).

Condition

Eligibility

Eligible Ages
Between 18 Years and 55 Years
Eligible Sex
All
Accepts Healthy Volunteers
Yes

Inclusion Criteria

Phase I: - Participant must be 18 to 55 years of age (inclusive), at the time of signing the informed consent. - Body weight ≥ 45 kilograms (kg) and ≤ 110 kg and Body Mass Index (BMI) within the range ≥ 18.0 to ≤ 30.0 kilograms per square meter (kg/m2) (inclusive) at screening. - Healthy participants with no clinically significant concomitant diseases or medications (except for those specifically permitted by the protocol) according to medical history, physical examination, screening safety laboratory tests, and screening parameters, as perthe judgement of the investigator. Phase IIa: - Participant must be ≥ 18 years of age at the time of signing the informed consent. - Participants who meet all of the following disease status requirements: 1. Diagnosed with End-stage kidney disease (ESKD). 2. Requiring hemodialysis through a tunneled central venous catheter as the primary vascular access for hemodialysis. 3. Receiving hemodialysis for treatment of ESKD for at least 90 days before randomization. 4. At least 3 previous dialysis sessions using current dialyzer. 5. Receiving adequate hemodialysis based on a single-pool Kt/V measurement > 1.2 within the last 30 days. 6. No new medications have been added to the participant's regimen in the last 2 weeks prior to dosing. 'New medication' is defined as any medication that has not been prescribed or used by the participant previously (including formulation changes). Medication previously prescribed or used by the participant with dose adjustments is allowed and not considered as new medication for the purpose of this study. 7. Not taking long-term systemic antibiotics with activity against S aureus.

Exclusion Criteria

Phase I: - Known hypersensitivity to any component of the study intervention - Previous hypersensitivity, infusion-related reaction, or severe adverse reaction following administration of monoclonal antibodies (mAbs). - Clinically significant bleeding disorder (eg, factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following intramuscular injections or venipuncture. - Aspartate Aminotransferase (AST) or alanine Aminotransferase (ALT) above 1.5 × upper limit of normal (ULN) at screening. Testing may be repeated once at the investigator's discretion. - Estimated glomerular filtration rate < 90 mL/min/1.73 m2 calculated using the Chronic Kidney Disease Epidemiology Collaboration equation at screening. - Hemoglobin or platelet count below the lower limit of normal at screening. Testing may be repeated once at the investigator's discretion. - White blood cell counts outside normal reference ranges unless judged by the investigator to be out of range given the known variation in white blood cell count reference interval by ethnicity. Testing may be repeated once at the investigator's discretion. - History of malignancy other than treated non-melanoma skin cancers or locally treated cervical cancer in the previous 5 years. - Any laboratory value in the screening panel that, in the opinion of the investigator, is clinically significant or might confound analysis of study results. Testing may be repeated once at the investigator's discretion. - Any clinically significant abnormalities on 12-lead electrocardiogram (ECG) at screening, as judged by the investigator. - Acute (time-limited) illness, including fever ≥ 38 °C (100.4 °F), one day prior to or on day of planned dosing; participants excluded for transient acute illness may be dosed if illness resolves within the 28-day Screening Period or may be rescreened once. - Known or suspected congenital or acquired immunodeficiency, or receipt of immunosuppressive therapy, including any course of glucocorticoid therapy exceeding 2 weeks of prednisone or equivalent at a dose of 20 mg daily or every other day within 6 months prior to screening. - Any condition that has the potential to increase clearance of the study intervention (eg, protein loss conditions such as severe enteropathies, or plasmapheresis). - Blood drawn in excess of a total of 450 milliliters (mL) (1 unit) for any reason within 2 months prior to screening. - Absence of suitable veins for blood sampling and administration of study intervention. - Any other condition that would compromise safety of the participants. - Any condition that, in the opinion of the investigator, might interfere with evaluation of the study intervention or interpretation of participant safety or study results. Phase IIa: - Known hypersensitivity to any component of the study intervention. - History of allergic disease or reactions likely to be exacerbated by any component of the study intervention as listed in dose formulation section. - Previous hypersensitivity, infusion-related reaction, or severe adverse reaction following administration of mAbs. - Hemoglobin < 9 g/dL at screening considered by the investigator to be due to acute condition(s). Testing may be repeated once at the investigator's discretion. - Serum albumin of < 3 g/dL at screening considered by the investigator to be due to acute condition(s). Testing may be repeated once at the investigator's discretion. - Myocardial infarction, acute coronary syndrome, stroke, seizure, or a thrombotic/thromboembolic event (eg, deep vein thrombosis or pulmonary embolism, but excluding vascular access thrombosis) within 90 days prior to randomization. - Known S aureus infection within 90 days of study entry. - Known acute viral or bacterial infection or symptoms/signs consistent with such an infection within the 21 days prior to infusion or study intervention. Mild intercurrent viral illness with a temperature of 38.1 °C (100.6 °F) or less does not require exclusion, if in the judgement of the investigator this illness will not interfere with the evaluation of the mAb. - Participants with malignancy undergoing chemotherapy. - Scheduled date for living donor kidney transplant. - Plans to switch to peritoneal dialysis within the primary endpoint time period (181 days). - Participants with a scheduled calendar date for transition to arteriovenous graft or arteriovenous graft in place and maturing. - Participants with a scheduled calendar date for transition to arteriovenous fistula, or arteriovenous fistula in place and maturing, with anticipated use of fistula within 90 days.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Prevention
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Phase I: AZD7760 Dose A
Participants will receive a single dose of AZD7760 Dose A intravenously on Day 1.
  • Drug: AZD7760
    Participants will receive AZD7760 as a single intravenous infusion.
Experimental
Phase I: AZD7760 Dose B
Participants will receive a single dose of AZD7760 Dose B intravenously on Day 1.
  • Drug: AZD7760
    Participants will receive AZD7760 as a single intravenous infusion.
Experimental
Phase I: AZD7760 Dose C
Participants will receive a single dose of AZD7760 Dose C intravenously on Day 1.
  • Drug: AZD7760
    Participants will receive AZD7760 as a single intravenous infusion.
Placebo Comparator
Phase I: Placebo
Participants will receive a single dose of placebo on Day 1.
  • Other: Placebo
    Participants will be administered placebo through intravenous infusion.
Experimental
Phase IIa: AZD7760 Dose D and Placebo
Participants will receive AZD7760 Dose D and placebo on Day 1 on Day 91.
  • Drug: AZD7760
    Participants will receive AZD7760 as a single intravenous infusion.
  • Other: Placebo
    Participants will be administered placebo through intravenous infusion.
Experimental
Phase IIa: AZD7760 Dose E
Participants will receive AZD7760 Dose E on Day 1 and Day 91.
  • Drug: AZD7760
    Participants will receive AZD7760 as a single intravenous infusion.
Placebo Comparator
Phase IIa: Placebo
Participants will receive placebo on Day 1 and on Day 91.
  • Other: Placebo
    Participants will be administered placebo through intravenous infusion.

Recruiting Locations

Research Site
Huntsville, Alabama 35805

Research Site
Chula Vista, California 91910

Research Site
Glendale, California 91206

Research Site
Granada Hills, California 91344

Research Site
Los Angeles, California 90027

Research Site
Northridge, California 91324

Research Site
Northridge, California 91325

Research Site
Oxnard, California 93036

Research Site
Riverside, California 92503

Research Site
San Dimas, California 91773

Research Site
Tarzana, California 91356

Research Site
Valencia, California 91355

Research Site
Victorville, California 92392

Research Site
Englewood, Colorado 80110

Research Site
Bradenton, Florida 34209

Research Site
Coral Springs, Florida 33071

Research Site
Hollywood, Florida 33024

Research Site
Orlando, Florida 32806

Research Site
Tampa, Florida 33603

Research Site
Chicago, Illinois 60640

Research Site
Baltimore, Maryland 21225

Research Site
Detroit, Michigan 48202

Research Site
Pontiac, Michigan 48341

Research Site
Tupelo, Mississippi 38801

Research Site
Kansas City, Missouri 64111

Research Site
Lincoln, Nebraska 68510

Research Site
Jersey City, New Jersey 07305

Research Site
Albuquerque, New Mexico 87109

Research Site
Ridgewood, New York 11385

Research Site
Winston-Salem, North Carolina 27103

Research Site
Bethlehem, Pennsylvania 18017

Research Site
Beaumont, Texas 77706

Research Site
Dallas, Texas 75246

Research Site
Houston, Texas 77074

Research Site
McAllen, Texas 78503

More Details

Status
Recruiting
Sponsor
AstraZeneca

Study Contact

AstraZeneca Clinical Study Information Center
1-877-240-9479
information.center@astrazeneca.com

Detailed Description

In the Phase I portion of the study, participants will be randomized to receive one of 3 dosages of AZD7760 or placebo as a single intravenous infusion. Study details include: - A 28-day Screening Period. - A Dosing Period of 3 days in which a single intravenous infusion will be given on Day 1. - A Follow-up Period of 12 months from the time of administration of the study intervention. In the Phase IIa portion of the study, participants will be randomized to receive either AZD7760 or placebo as 2 intravenous infusions given 3 months apart. Study details include: - A 28-day Screening Period. - A Dosing Period in which 2 intravenous infusions will be given 3 months apart (Day 1 and Day 91). - A Follow-up Period of 12 months after the last administration of the study intervention on Day 91.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.