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A Study to Assess the Safety, Efficacy and Tolerability of AZD8233 Treatment in Participants With Hyperlipidaemia (SOLANO)

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: NCT04964557
Recruitment Status : Recruiting
First Posted : July 16, 2021
Last Update Posted : September 16, 2021
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
AZD8233 is a PCSK9-targeted ASO for the reduction of circulating levels of LDL-C. This study aims to evaluate safety, efficacy and tolerability of AZD8233.

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

Detailed Description:

This is a randomized parallel, double-blind, placebo-controlled Phase 2b study in approximately 376 participants with hyperlipidaemia. The primary objective of the study is to assess the safety and tolerability of AZD8233 as compared with placebo, and the effect of AZD8233 versus placebo on relative change in LDL-C. The study will be conducted at up to 100 sites in up to 8 countries.

The screening period starts up to 28 days before the randomization visit and ends on Day -1. Eligible participants will attend 1 enrollment visit and 15 visits during the treatment period and 2 additional visits during the safety follow up period.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 376 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomised, Parallel, Double-Blind, Placebo-Controlled Phase 2b Study to Assess the Safety, Tolerability and Efficacy of AZD8233 Treatment in Participants With Hyperlipidaemia
Actual Study Start Date : July 7, 2021
Estimated Primary Completion Date : July 8, 2022
Estimated Study Completion Date : July 8, 2022

Arm Intervention/treatment
Experimental: AZD8233
AZD8233 for subcutaneous use
Drug: AZD8233
PCSK9-targeted ASO for the reduction of circulating levels of LDL-C.

Placebo Comparator: Placebo
Placebo solution for subcutaneous injection
Drug: Placebo
Placebo solution




Primary Outcome Measures :
  1. Percentage change from baseline on serum LDL-C [ Time Frame: From baseline to Day 197 ]

Secondary Outcome Measures :
  1. Percentage change from baseline in PCSK9 [ Time Frame: From baseline to Day197 ]
  2. Plasma concentration of AZD8233 [ Time Frame: Day 29, Day 85, Day 99, Day 141, Day 197 ]
  3. Anti-drug antibodies (ADAs) during the treatment period and follow-up period [ Time Frame: Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 197, Day 281 ]

Other Outcome Measures:
  1. Number of subjects with adverse events (AEs) [ Time Frame: Day 1, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85, Day 99, Day 113, Day 127, Day 141, Day 155, Day 169, Day 183, Day 197, Day 225, Day 281 ]
  2. Number of subjects with an ECG determined to be abnormal and clinically significant [ Time Frame: Day 1, Day 85, Day 169, Day 225, Day 281 ]
  3. Vital sign: Pulse rate [ Time Frame: Day 1, Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 197, Day 225, Day 281 ]
  4. Vital sign: Blood pressure [ Time Frame: Day 1, Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 197, Day 225, Day 281 ]
  5. Vital sign: Temperature [ Time Frame: Day 1, Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 197, Day 225, Day 281 ]
  6. Number of subjects with clinically significant hematology and/or clinical chemistry parameters as defined by AEs [ Time Frame: Day 1, Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 197, Day 225, Day 281 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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

Inclusion Criteria:

  • Participant must be 18 to 75 years of age, inclusive, at the time of signing the informed consent
  • Participants who have a fasting LDL-C ≥ 70 mg/dL (1.8 mmol/L) but < 190 mg/dL (4.9 mmol/L) at screening
  • Participants who have fasting triglycerides < 400 mg/dL (< 4.52 mmol/L) at screening
  • Participants are receiving a stable dose (≥ 3 months) of maximally tolerated statin and/or ezetimibe therapy
  • Male or female of non-childbearing potential
  • Signed and dated written informed consent prior to any mandatory study specific procedures, sampling, and analyses

Exclusion Criteria:

  • eGFR < 40 mL/min/1.73m2 using the CKD-EPI
  • History or presence of gastrointestinal, hepatic or renal disease or any other conditions known to interfere with absorption, distribution, metabolism or excretion of drugs
  • Any uncontrolled or serious disease, or any medical (eg,. known major active infection or major haematological, renal, metabolic, gastrointestinal or endocrine 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 (according to the investigator's judgment) if he/she participates in the clinical study
  • Poorly controlled T2DM, defined as HbA1c > 10%
  • Acute ischaemic cardiovascular events including stroke within 30 days, or heart failure with New York Heart Association (NYHA) Class III to IV
  • Blood dyscrasias with increased risk of bleeding including idiopathic thrombocytopenic purpura and thrombotic thrombocytopenic purpura or symptoms of increased risk of bleeding (frequent bleeding gums or nose bleeds)
  • High-risk of bleeding diathesis or anti-platelet therapy other than low dose aspirin (≤100mg/day).
  • Malignancy within the last 10 years
  • Recipient of any major organ transplant
  • LDL or plasma apheresis within 12 months prior to randomisation
  • Uncontrolled hypertension defined as average supine SBP > 160 mmHg or DBP > 90 mmHg
  • Heart rate after 10 minutes supine rest < 50 or > 100 bpm
  • Any laboratory values with the following deviations at the Screening Visit; test may be repeated at the discretion of the investigator if abnormal:

    • Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV)
    • ALT > 1.5 × ULN
    • AST > 1.5 × ULN
    • TBL > ULN
    • ALP > 1.5 × ULN
    • WBC < lower limit of normal (LLN).
    • Haemoglobin < 12 g/dL in males or < 11 g/dL in females
    • Platelet count ≤ LLN
    • aPTT > ULN or Prothrombin Time > ULN
    • UACR > 11 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
  • QTcF > 470 ms; high degree atrioventricular (AV)-block grade II-III and sinus node dysfunction with significant sinus pause untreated with pacemaker; and cardiac tachyarrhythmias
  • History of drug and/or alcohol abuse or a positive screen for drugs of abuse
  • Use of warfarin, direct or indirect thrombin inhibitors or factor Xa inhibitors
  • Mipomersen, or lomitapide within 12 months prior to randomisation
  • Any fibrate therapy other than fenofibrate; if the participant is on fenofibrate therapy, the dose should be stable for at least 6 weeks prior to randomisation
  • Previous administration of AZD8233/AZD6615) or inclisiran (LEQVIO ® Novartis)
  • Use of evolocumab (REPATHA® Amgen) and alirocumab (PRALUENT® Regeneron) within 3 months of screening

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): NCT04964557


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

Locations
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Sponsors and Collaborators
AstraZeneca
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04964557    
Other Study ID Numbers: D7990C00004
First Posted: July 16, 2021    Key Record Dates
Last Update Posted: September 16, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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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:
AZD8233
Efficacy
PK
PD
Safety
Tolerability
Additional relevant MeSH terms:
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Hyperlipidemias
Hyperlipoproteinemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases