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

A Randomised, Parallel, Double-Blind, Placebo-Controlled Phase 2b Study to Assess the Safety, Tolerability and Efficacy of AZD8233 Treatment in Participants With Hyperlipidaemia

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.

Study Overview

• Status: Completed
• Conditions: Hyperlipidaemia
• Intervention / Treatment: Drug: Placebo; Drug: AZD8233

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.

• Study Type: Interventional
• Enrollment (Actual): 411
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czechia
  • Benesov, Czechia, 256 01
    • Research Site
  • Brandys nad Labem, Czechia, 250 01
    • Research Site
  • Brno, Czechia, 603 00
    • Research Site
  • Jaromer, Czechia, 551 01
    • Research Site
  • Liberec 2, Czechia, 460 01
    • Research Site
  • Louny, Czechia, 440 01
    • Research Site
  • Ostrava-Dubina, Czechia, 700 30
    • Research Site
  • Pribram, Czechia, 261 01
    • Research Site
  • Teplice, Czechia, 415 01
    • Research Site
  • Uherske Hradiste, Czechia, 686 01
    • Research Site
• Denmark
  • Aarhus N, Denmark, 8200
    • Research Site
  • Herlev, Denmark, 2730
    • Research Site
  • Herning, Denmark, 7400
    • Research Site
  • Hvidovre, Denmark, 2650
    • Research Site
  • København NV, Denmark, 2400
    • Research Site
  • Roskilde, Denmark, 4000
    • Research Site
  • Svendborg, Denmark, 5700
    • Research Site
  • Viborg, Denmark, 8800
    • Research Site
• Hungary
  • Balatonfüred, Hungary, 8230
    • Research Site
  • Békéscsaba, Hungary, 5600
    • Research Site
  • Debrecen, Hungary, 4032
    • Research Site
  • Orosháza, Hungary, 5900
    • Research Site
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Research Site
  • Doetinchem, Netherlands, 7009 BL
    • Research Site
  • Ede, Netherlands, 6716 RP
    • Research Site
  • Gouda, Netherlands, 2803 HH
    • Research Site
  • Harderwijk, Netherlands, 3844 DG
    • Research Site
  • Rotterdam, Netherlands, 3045 PM
    • Research Site
• Poland
  • Bydgoszcz, Poland, 85-079
    • Research Site
  • Chrzanów, Poland, 32-500
    • Research Site
  • Kraków, Poland, 30-082
    • Research Site
  • Puławy, Poland, 24-100
    • Research Site
  • Ruda Śląska, Poland, 41-710
    • Research Site
  • Tychy, Poland, 43-100
    • Research Site
  • Wierzchosławice, Poland, 33-122
    • Research Site
  • Łódź, Poland, 91-002
    • Research Site
• Slovakia
  • Bratislava, Slovakia, 831 03
    • Research Site
  • Brezno, Slovakia, 977 01
    • Research Site
  • Lucenec, Slovakia, 984 01
    • Research Site
  • Presov, Slovakia, 080 01
    • Research Site
  • Roznava, Slovakia, 048 01
    • Research Site
  • Svidnik, Slovakia, 08901
    • Research Site
  • Trebišov, Slovakia, 7501
    • Research Site
• Spain
  • Ferrol, Spain, 15405
    • Research Site
  • L'Hospitalet de Llobregat, Spain, 08907
    • Research Site
  • La Coruña, Spain, 15006
    • Research Site
  • Santiago de Compostela, Spain, 15706
    • Research Site
  • Sevilla, Spain, 41009
    • Research Site
  • Sevilla, Spain, 41014
    • Research Site
  • Zaragoza, Spain, 50009
    • Research Site
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Research Site
  • California
    • Canoga Park, California, United States, 91303
      • Research Site
    • Lincoln, California, United States, 95648
      • Research Site
  • Florida
    • Inverness, Florida, United States, 34452
      • Research Site
    • Jacksonville, Florida, United States, 32216
      • Research Site
    • Pembroke Pines, Florida, United States, 33024
      • Research Site
  • Idaho
    • Meridian, Idaho, United States, 83646
      • Research Site
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Research Site
  • New York
    • New Windsor, New York, United States, 12553
      • Research Site
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
      • Research Site
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Research Site
    • Cincinnati, Ohio, United States, 45246
      • Research Site
    • Stow, Ohio, United States, 44224
      • Research Site
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Research Site
  • Virginia
    • Suffolk, Virginia, United States, 23435
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change From Baseline on Serum LDL-C	Percentage change in Low-density Lipoprotein Cholesterol (LDL-C) from baseline to Day 197.	From baseline to Day 197
Number of Subjects With Adverse Events (AEs)	Please refer to the adverse event module for specifics.	On-study includes adverse events with an onset date on or after the date of first dose of IP through study competition, planned visit date Day 281.
Vital Signs - Temperature	Mean and standard deviation of Temperature at each scheduled visit by treatment.	Baseline, Days 15, 29, 57, 85, 113, 141, 169, 197, 225, and 281.
Vital Sign - Weight	Mean and standard deviation of Weight at each scheduled visit by treatment.	Baseline and Day 281.
Number of Participants With an ECG Determined to be Abnormal and Clinically Significant	Number of participants With an ECG Determined to be Abnormal and Clinically Significant at each scheduled visit by treatment	Baseline, Days 85, 169, 225, and 281.
Vital Sign - Systolic Blood Pressure	Mean and standard deviation of Systolic Blood Pressure at each scheduled visit by treatment.	Baseline, Days 15, 29, 57, 85, 113, 141, 169, 197, 225, and 281.
Vital Sign - Diastolic Blood Pressure	Mean and standard deviation of Diastolic Blood Pressure at each scheduled visit by treatment.	Baseline, Days 15, 29, 57, 85, 113, 141, 169, 197, 225, and 281.
Vital Sign - Pulse Rate	Mean and standard deviation of Pulse rate at each scheduled visit by treatment.	Baseline, Days 15, 29, 57, 85, 113, 141, 169, 197, 225, and 281.
Treatment Emergent Platelet Count Abnormalities	Treatment emergent platelet count abnormalities by pre-specified criteria by treatment.	Treatment emergent includes results after the first dose of IP through study competition, planned visit date Day 281.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change From Baseline on Serum PCSK9	Percentage change in Proprotein convertase subtilisin/kexin type-9 (PCSK9) from baseline to Day 197.	From baseline to Day 197
Plasma Concentration of AZD8233	AZD8233 full length ASO concentrations in plasma were summarised by descriptive statistics by sampling time point and listed on individual level based on the PK analysis set.	Pre-dose of Day 29, Day 85, Day 141, Day 183, Day 197
Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period	Number of ADA positive subjects at each time point during the treatment period and follow-up period.	Pre-dose of Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 197, Day 281

Other Outcome Measures

Outcome Measure	Time Frame
Number of subjects with adverse events (AEs)	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
Number of subjects with an ECG determined to be abnormal and clinically significant	Day 1, Day 85, Day 169, Day 225, Day 281
Vital sign: Pulse rate	Day 1, Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 197, Day 225, Day 281
Vital sign: Blood pressure	Day 1, Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 197, Day 225, Day 281
Vital sign: Temperature	Day 1, Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 197, Day 225, Day 281
Number of subjects with clinically significant hematology and/or clinical chemistry parameters as defined by AEs	Day 1, Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 197, Day 225, Day 281

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

Helpful Links

• CSRsynopsis_redacted
• CSP_redacted
• SAP_redacted

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2021
• Primary Completion (Actual): July 15, 2022
• Study Completion (Actual): July 15, 2022

Study Registration Dates

• First Submitted: June 15, 2021
• First Submitted That Met QC Criteria: July 6, 2021
• First Posted (Actual): July 16, 2021

Study Record Updates

• Last Update Posted (Estimated): December 15, 2023
• Last Update Submitted That Met QC Criteria: November 20, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Safety; Efficacy; PK; Tolerability; PD; AZD8233
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias; Hyperlipidemias; Hyperlipoproteinemias
• Other Study ID Numbers: D7990C00004; 2020-005845-18 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD 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.

• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No