A Study to Assess the Safety, Efficacy and Tolerability of AZD8233 Treatment in Participants With Hyperlipidaemia (SOLANO)
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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. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04964557 |
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Recruitment Status :
Completed
First Posted : July 16, 2021
Results First Posted : December 15, 2023
Last Update Posted : December 15, 2023
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Sponsor:
AstraZeneca
Information provided by (Responsible Party):
AstraZeneca
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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 safety, efficacy and tolerability of AZD8233.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Hyperlipidaemia | Drug: AZD8233 Drug: Placebo | Phase 2 |
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 (Clinical Trial) |
| Actual Enrollment : | 411 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 |
| Actual Primary Completion Date : | July 15, 2022 |
| Actual Study Completion Date : | July 15, 2022 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: AZD8233
AZD8233 for subcutaneous use
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Drug: AZD8233
PCSK9-targeted ASO for the reduction of circulating levels of LDL-C. |
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Placebo Comparator: Placebo
Placebo solution for subcutaneous injection
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Drug: Placebo
Placebo solution |
Primary Outcome Measures :
- Percentage Change From Baseline on Serum LDL-C [ Time Frame: From baseline to Day 197 ]Percentage change in Low-density Lipoprotein Cholesterol (LDL-C) from baseline to Day 197.
- Number of Subjects With Adverse Events (AEs) [ Time Frame: 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. ]Please refer to the adverse event module for specifics.
- Vital Signs - Temperature [ Time Frame: Baseline, Days 15, 29, 57, 85, 113, 141, 169, 197, 225, and 281. ]Mean and standard deviation of Temperature at each scheduled visit by treatment.
- Vital Sign - Weight [ Time Frame: Baseline and Day 281. ]Mean and standard deviation of Weight at each scheduled visit by treatment.
- Number of Participants With an ECG Determined to be Abnormal and Clinically Significant [ Time Frame: Baseline, Days 85, 169, 225, and 281. ]Number of participants With an ECG Determined to be Abnormal and Clinically Significant at each scheduled visit by treatment
- Vital Sign - Systolic Blood Pressure [ Time Frame: Baseline, Days 15, 29, 57, 85, 113, 141, 169, 197, 225, and 281. ]Mean and standard deviation of Systolic Blood Pressure at each scheduled visit by treatment.
- Vital Sign - Diastolic Blood Pressure [ Time Frame: Baseline, Days 15, 29, 57, 85, 113, 141, 169, 197, 225, and 281. ]Mean and standard deviation of Diastolic Blood Pressure at each scheduled visit by treatment.
- Vital Sign - Pulse Rate [ Time Frame: Baseline, Days 15, 29, 57, 85, 113, 141, 169, 197, 225, and 281. ]Mean and standard deviation of Pulse rate at each scheduled visit by treatment.
- Treatment Emergent Platelet Count Abnormalities [ Time Frame: Treatment emergent includes results after the first dose of IP through study competition, planned visit date Day 281. ]Treatment emergent platelet count abnormalities by pre-specified criteria by treatment.
Secondary Outcome Measures :
- Percentage Change From Baseline on Serum PCSK9 [ Time Frame: From baseline to Day 197 ]Percentage change in Proprotein convertase subtilisin/kexin type-9 (PCSK9) from baseline to Day 197.
- Plasma Concentration of AZD8233 [ Time Frame: Pre-dose of Day 29, Day 85, Day 141, Day 183, Day 197 ]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.
- Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period [ Time Frame: Pre-dose of Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 197, Day 281 ]Number of ADA positive subjects at each time point during the treatment period and follow-up period.
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.
| 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
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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
Locations
Show 66 study locations
Sponsors and Collaborators
AstraZeneca
Study Documents (Full-Text)
Documents provided by AstraZeneca:
Documents provided by AstraZeneca:
Study Protocol [PDF] February 8, 2022
Statistical Analysis Plan [PDF] July 8, 2022
Additional Information:
| Responsible Party: | AstraZeneca |
| ClinicalTrials.gov Identifier: | NCT04964557 |
| Other Study ID Numbers: |
D7990C00004 2020-005845-18 ( EudraCT Number ) |
| First Posted: | July 16, 2021 Key Record Dates |
| Results First Posted: | December 15, 2023 |
| Last Update Posted: | December 15, 2023 |
| Last Verified: | November 2023 |
| 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 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by AstraZeneca:
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AZD8233 Efficacy PK |
PD Safety Tolerability |
Additional relevant MeSH terms:
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Hyperlipidemias Hyperlipoproteinemias Dyslipidemias Lipid Metabolism Disorders Metabolic Diseases |