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A Study of AZD8233 in Participants With Dyslipidemia

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 evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04641299
Recruitment Status : Recruiting
First Posted : November 23, 2020
Last Update Posted : November 23, 2020
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Description
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Brief Summary:
AZD8233 is a PCSK9-targeted ASO for the reduction of circulating levels of LDL-C. This study aims to evaluate the dose-dependent reduction in LDL-C after SC administration of multiple doses of AZD8233 as well as the associated adverse effects profile. The data generated will be used to guide choice of doses, dosing regimens, and sample sizes, as well as safety and PD monitoring in the further clinical development program.

Condition or disease Intervention/treatment Phase
Dyslipidaemia Drug: AZD8233 Drug: Placebo Phase 2

Detailed Description:

This is a randomized parallel, double-blind, placebo-controlled, dose-ranging Phase 2b study in approximately 108 participants with dyslipidemia. The primary objective of the study is to investigate the effect of AZD8233 on LDL-C across different dose levels. The study will be conducted at up to 25 sites in up to 4 countries.

The screening period starts up to 42 days before the randomization visit and ends on Day -1. Eligible participants will attend 7 visits during the treatment period and 7 additional visits during the safety follow up period. Eligible participants are randomized across four different treatment arms in a 1:1:1:1 ratio for a 12-week treatment period. The planned treatment arms are AZD8233 low dose, AZD8233 medium dose, AZD8233 high dose, and Placebo. Participants will be dosed SC on Days 1, 8, 29, and 57.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 108 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Parallel, Double-blind, Placebo-controlled, Dose-ranging, Phase 2b Study to Evaluate the Efficacy, Safety and Tolerability of AZD8233 Treatment in Participants With Dyslipidemia
Actual Study Start Date : October 28, 2020
Estimated Primary Completion Date : September 20, 2021
Estimated Study Completion Date : September 20, 2021
Arms and Interventions
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Arm Intervention/treatment
Placebo Comparator: Placebo
Placebo solution for subcutaneous injection.
 Drug: Placebo
Placebo solution
Experimental: AZD8233 high dose
AZD8233 high dose for subcutaneous injection.
 Drug: AZD8233
PCSK9-targeted ASO for the reduction of circulating levels of LDL-C.
Experimental: AZD8233 medium dose
AZD8233 medium dose for subcutaneous injection.
 Drug: AZD8233
PCSK9-targeted ASO for the reduction of circulating levels of LDL-C.
Experimental: AZD8233 low dose
AZD8233 low does for subcutaneous injection.
 Drug: AZD8233
PCSK9-targeted ASO for the reduction of circulating levels of LDL-C.


Outcome Measures
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Primary Outcome Measures :
  1. Percentage change from baseline in geometric mean of LDL-C concentration in plasma at week 12. [ Time Frame: Measurement at week 12 ]

Secondary Outcome Measures :
  1. Percentage change from baseline in geometric mean of PCSK9 concentration in plasma at weeks 1, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22 and 24. [ Time Frame: Measurement at screening, week 0, week 1, week 3, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18, week 20, week 22, week 24 ]
  2. Percentage change from baseline in concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants cholesterol [ Time Frame: Measurement at screening, week 0, week 1, week 3, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18, week 20, week 22, week 24 ]
  3. Plasma concentration of AZD8233 [ Time Frame: Measurement at week 1, week 4, week 6, week 8, week 10, week 12, week 16, week 20, week 24 ]
  4. Anti-drug antibodies (ADAs) during the treatment period and follow-up period [ Time Frame: Measurement at week 0, week 1, week 4, week 8, week 12, week 16, week 20, week 24 ]
  5. Percentage change from baseline in levels of LDL-C in plasma [ Time Frame: Measurement at screening, week 0, week 1, week 3, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18, week 20, week 22, week 24 ]

Other Outcome Measures:
  1. Number of subjects with adverse events (AEs) [ Time Frame: Measurement at week 0, week 1, week 3, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18, week 20, week 22, week 24 ]
  2. Vital sign: Systolic blood pressure (SBP) [ Time Frame: Measurement at week 0, week 1, week 3, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18, week 20, week 22, week 24 ]
  3. Vital sign: Diastolic blood pressure (DBP) [ Time Frame: Measurement at week 0, week 1, week 3, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18, week 20, week 22, week 24 ]
  4. Vital sign: Pulse rate [ Time Frame: Measurement at week 0, week 1, week 3, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18, week 20, week 22, week 24 ]
  5. Vital sign: Oral body temperature [ Time Frame: Measurement at week 0, week 1, week 3, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18, week 20, week 22, week 24 ]
  6. Number of subjects with an ECG determined to be abnormal and clinically significant [ Time Frame: Measurement at week 0, week 1, week 3, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18, week 20, week 22, week 24 ]
  7. Number of subjects with clinically significant changes in haematology and or clinical chemistry parameters [ Time Frame: Measurement at week 0, week 1, week 3, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18, week 20, week 22, week 24 ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Male or female.
  • Participant must be 18 to 75 years of age.
  • Body mass index between 19 and 40 kg/m2.
  • Participants who have a fasting LDL-C ≥ 70 mg/dL but < 190 mg/dL.
  • Have fasting triglycerides < 400 mg/dL.
  • Should be receiving moderate- or high-intensity statin therapy.

Key Exclusion Criteria:

  • Estimated glomerular filtration rate < 40 mL/min/1.73m2 CKD-EPI.
  • Any uncontrolled or serious disease, or any medical dysfunction or surgical condition that, in the opinion of the Investigator, may either interfere with participation in the clinical study and/or put the participant at significant risk.
  • Poorly controlled type 2 diabetes mellitus, defined as HbA1c > 10% at Visit 1.
  • Acute ischaemic cardiovascular event in the last 12 months prior to randomization.
  • Heart failure with New York Heart Association (NYHA) Class III-IV.
  • High-risk of bleeding as judged by the Investigator.
  • Malignancy (except non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal
  • Carcinoma in-situ, or Stage 1 prostate carcinoma) within the last 10 years.
  • LDL or plasma apheresis within 12 months prior to randomization.
  • Uncontrolled hypertension defined as average sitting SBP > 160 mmHg or DBP > 90 mmHg.
  • Heart rate after 10 minutes supine rest < 50 bpm or > 100 bpm.

  • Any laboratory values with the following deviations at Screening:

    • Positive result on screening for hepatitis B, hepatitis C or HIV.
    • ALT > 1.5 × ULN.
    • AST > 1.5 × ULN.
    • TBL > ULN.
    • ALP > 1.5 × ULN.
    • WBC < LLN.
    • Haemoglobin < 12 g/dL in men or < 11 g/dL in women.
    • Platelet count ≤ LLN.
    • aPTT > ULN and PT > ULN.
    • UACR > 11.3 mg/mmol (100 mg/g).
    • UPCR > 300 mg/g.
  • Any clinically important abnormalities in rhythm, conduction or morphology of the resting ECG and any clinically important abnormalities in the 12-lead ECG as judged by the Investigator.
  • Mipomersen, or lomitapide within 12 months prior to randomization.
  • Previous administration of AZD8233/AZD6615.
  • Previous administration of PCSK9 inhibition treatment.
  • Participation in another clinical study with a study intervention administered in the last 3 months prior to randomization or 5 half-lives from last dose to first administration of study intervention, whichever is the longest.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04641299


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

Locations
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United States, California
Research Site Recruiting
Roseville, California, United States, 95661
United States, Florida
Research Site Not yet recruiting
Inverness, Florida, United States, 34452
Research Site Recruiting
Jacksonville, Florida, United States, 32216
Research Site Recruiting
Pembroke Pines, Florida, United States, 33024
United States, Idaho
Research Site Recruiting
Meridian, Idaho, United States, 83646
United States, Indiana
Research Site Recruiting
Indianapolis, Indiana, United States, 46260
United States, New York
Research Site Recruiting
New Windsor, New York, United States, 12553
United States, North Carolina
Research Site Recruiting
Greensboro, North Carolina, United States, 27408
United States, North Dakota
Research Site Recruiting
Fargo, North Dakota, United States, 58104
United States, Ohio
Research Site Recruiting
Cincinnati, Ohio, United States, 45219
Canada, New Brunswick
Research Site Not yet recruiting
Moncton, New Brunswick, Canada, E1G 1A7
Canada, Ontario
Research Site Not yet recruiting
Toronto, Ontario, Canada, M4G 3E8
Research Site Not yet recruiting
Toronto, Ontario, Canada, M9W 4L6
Canada, Quebec
Research Site Not yet recruiting
Chicoutimi, Quebec, Canada, G7H 7K9
Research Site Not yet recruiting
Saint-Marc-des-Carrieres, Quebec, Canada, G0A 4B0
Denmark
Research Site Not yet recruiting
Aarhus N, Denmark, 8200
Research Site Not yet recruiting
Herlev, Denmark, 2730
Research Site Not yet recruiting
København NV, Denmark, 2400
Research Site Not yet recruiting
Roskilde, Denmark, 4000
Research Site Not yet recruiting
Viborg, Denmark, 8800
Slovakia
Research Site Recruiting
Bratislava, Slovakia, 831 03
Research Site Not yet recruiting
Bratislava, Slovakia, 85101
Research Site Recruiting
Rožňava, Slovakia, 048 01
Research Site Not yet recruiting
Svidnik, Slovakia, 08901
Research Site Recruiting
Trebišov, Slovakia, 7501
Sponsors and Collaborators
AstraZeneca
More Information
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04641299    
Other Study ID Numbers: D7990C00003
First Posted: November 23, 2020    Key Record Dates
Last Update Posted: November 23, 2020
Last Verified: November 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Dose Range Finding
AZD8233
Efficacy
PK
 PD
Immunogenicity
Safety
Tolerability
Additional relevant MeSH terms:
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Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases