A Study to Evaluate AZD7760 Safety and Pharmacokinetics in Healthy Adults (Phase I) and Adults With End-stage Kidney Disease on Hemodialysis With a Central Venous Catheter (Phase IIa)
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
- Staphylococcus Aureus
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
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Phase I: AZD7760 Dose A |
Participants will receive a single dose of AZD7760 Dose A intravenously on Day 1. |
|
|
Experimental Phase I: AZD7760 Dose B |
Participants will receive a single dose of AZD7760 Dose B intravenously on Day 1. |
|
|
Experimental Phase I: AZD7760 Dose C |
Participants will receive a single dose of AZD7760 Dose C intravenously on Day 1. |
|
|
Placebo Comparator Phase I: Placebo |
Participants will receive a single dose of placebo on Day 1. |
|
|
Experimental Phase IIa: AZD7760 Dose D and Placebo |
Participants will receive AZD7760 Dose D and placebo on Day 1 on Day 91. |
|
|
Experimental Phase IIa: AZD7760 Dose E |
Participants will receive AZD7760 Dose E on Day 1 and Day 91. |
|
|
Placebo Comparator Phase IIa: Placebo |
Participants will receive placebo on Day 1 and on Day 91. |
|
Recruiting Locations
Huntsville 4068590, Alabama 4829764 35805
Chula Vista 5336899, California 5332921 91910
Glendale 5352423, California 5332921 91206
Los Angeles 5368361, California 5332921 90027
Northridge 5377985, California 5332921 91324
Northridge 5377985, California 5332921 91325
Oxnard 5380184, California 5332921 93036
Riverside 5387877, California 5332921 92503
San Dimas 5391891, California 5332921 91773
Tarzana 5401143, California 5332921 91356
Valencia 5405288, California 5332921 91355
Victorville 5406222, California 5332921 92392
Englewood 5421250, Colorado 5417618 80110
Bradenton 4148708, Florida 4155751 34209
Coral Springs 4151909, Florida 4155751 33071
Hollywood 4158928, Florida 4155751 33024
Orlando 4167147, Florida 4155751 32806
Tampa 4174757, Florida 4155751 33603
Chicago 4887398, Illinois 4896861 60640
Baltimore 4347778, Maryland 4361885 21225
Detroit 4990729, Michigan 5001836 48202
Pontiac 5006166, Michigan 5001836 48341
Tupelo 4448903, Mississippi 4436296 38801
Kansas City 4393217, Missouri 4398678 64111
Lincoln 5072006, Nebraska 5073708 68510
Jersey City 5099836, New Jersey 5101760 07305
Albuquerque 5454711, New Mexico 5481136 87109
Ridgewood 5133858, New York 5128638 11385
Winston-Salem 4499612, North Carolina 4482348 27103
Bethlehem 5180225, Pennsylvania 6254927 18017
Beaumont 4672989, Texas 4736286 77706
Dallas 4684888, Texas 4736286 75246
Houston 4699066, Texas 4736286 77074
McAllen 4709796, Texas 4736286 78503
More Details
- Status
- Recruiting
- Sponsor
- AstraZeneca
Study Contact
AstraZeneca Clinical Study Information Center1-877-240-9479
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.