DyslipidaemiaPhase 2NCT04641299
A Study of AZD8233 in Participants With Dyslipidemia
A Phase 2 study testing AZD8233 in people with Dyslipidaemia, run by AstraZeneca at 19 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Dyslipidaemia
- What is being tested?
- AZD8233
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 119 participants
- Where
- 19 sitesin 3 countries
- Study dates
- 28 Oct 2020to 20 Jul 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- Should be on stable medication for ≥ 3 months prior to screening with no planned medication or dose change during study participation. The exception to this restriction is for fenofibrate; if the participant is receiving fenofibrate, the therapy must be stable for at least 6 weeks prior to randomization at a dose that is appropriate for the duration of the study in the judgement of the Investigator. Other fibrate therapy (and derivatives) are prohibited.
Who cannot join
- 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.
Show all 28Show fewer
- 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 supine SBP > 160 mmHg or DBP > 90 mmHg at Visit 1 or Visit 3.
- 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.
Trial locations and contacts
19 sites in 3 countries.
19 sites in 3 countries
United States10 sites
Research Site
Cincinnati, Ohio, 45219
Research Site
Fargo, North Dakota, 58104
Research Site
Greensboro, North Carolina, 27408
Research Site
Indianapolis, Indiana, 46260
Research Site
Inverness, Florida, 34452
Research Site
Jacksonville, Florida, 32216
Research Site
Meridian, Idaho, 83646
Research Site
New Windsor, New York, 12553
Research Site
Pembroke Pines, Florida, 33024
Research Site
Roseville, California, 95661
Denmark5 sites
Research Site
Aarhus N, 8200
Research Site
Frederiksberg, 2000
Research Site
Herlev, 2730
Research Site
Roskilde, 4000
Research Site
Viborg, 8800
Slovakia4 sites
Research Site
Bratislava, 831 03
Research Site
Bratislava, 85101
Research Site
Rožňava, 048 01
Research Site
Trebišov, 7501
About this study
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
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.
Read the 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.
- Conditions
- Dyslipidaemia
- Being tested
- AZD8233, Placebo
- Keywords
- Dose Range Finding, AZD8233, Efficacy, PK, PD, Immunogenicity, Safety, Tolerability
- Medical subject headings
- Dyslipidemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD8233Drug
PCSK9-targeted ASO for the reduction of circulating levels of LDL-C.
PlaceboDrug
Placebo solution
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo solution for subcutaneous injection. Receives: Drug: Placebo |
| AZD8233 high dose | Experimental | AZD8233 high dose for subcutaneous injection. Receives: Drug: AZD8233 |
| AZD8233 medium dose | Experimental | AZD8233 medium dose for subcutaneous injection. Receives: Drug: AZD8233 |
| AZD8233 low dose | Experimental | AZD8233 low does for subcutaneous injection. Receives: Drug: AZD8233 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12.
Change from baseline in low-density lipoprotein cholesterol (LDL-C) at week 12. Results are based on Mixed Model Repeated Measures (MMRM) analysis on the log-transformed change from baseline. Log-transformed change from baseline is calculated as the visit value in log minus the baseline value in log. The results from the model are then back transformed.
Measured: Baseline to week 12
Secondary outcomes (5)
Relative Change From Baseline in PCSK9 Concentration in Plasma at Week 12.
Relative change from baseline in PCSK9 concentration in plasma at week 12.
Measured: Baseline to week 12
Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol
Percentage change from baseline in concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants cholesterol at week 12
Measured: Baseline to week 12
Plasma Concentration of AZD8233
Plasma concentration of AZD8233 after first dose administration
Measured: Measurement at week 1, week 4, week 6, week 8, week 10, week 12, week 16, week 20, week 24 after first dose administration.
Anti-drug Antibodies (ADAs) During the Treatment Period and Follow-up Period
ADA titre results for subjects with positive ADA during the treatment period and follow-up period.
Measured: Measurement at week 0, week 1, week 4, week 8, week 12, week 16, week 20, week 24
Percentage Change From Baseline in Levels of LDL-C in Plasma
Percentage change from baseline in levels of LDL-C in plasma from baseline to week 12.
Measured: Baseline to week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2020
- Study start28 Oct 2020
- Primary completion20 Jul 2021
- Study completion20 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for DyslipidaemiaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 119 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04641299
- Sponsor's protocol ID
- D7990C00003
- Status last verified
- Oct 2022
- First submitted
- 28 Oct 2020
- Last updated
- 18 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Clewe O, Rekic D, Quartino AL, Carlsson B, Higashimori M, Wernevik L, Hofherr A, Ryden-Bergsten T, Nilsson C, Knochel J. Population pharmacokinetics of a novel PCSK9 antisense oligonucleotide. Br J Clin Pharmacol. 2024 Jun;90(6):1503-1513. doi: 10.1111/bcp.16046. Epub 2024 Mar 19.
PubMed 38504437
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04641299
- Acronym / sponsor ID
- D7990C00003
- Conditions
- Dyslipidaemia
- Keywords
- Dose Range Finding, AZD8233, Efficacy, PK, PD, Immunogenicity, Safety, Tolerability
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 119 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 28 Oct 2020 (actual)
- Primary completion
- 20 Jul 2021 (actual)
- Study completion
- 20 Jul 2021 (actual)
- First posted
- 23 Nov 2020 (actual)
- Results
- Posted 18 Nov 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboPlacebo solution for subcutaneous injection. |
| AZD8233 high dose | Experimental | Drug: AZD8233AZD8233 high dose for subcutaneous injection. |
| AZD8233 medium dose | Experimental | Drug: AZD8233AZD8233 medium dose for subcutaneous injection. |
| AZD8233 low dose | Experimental | Drug: AZD8233AZD8233 low does for subcutaneous injection. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (28 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD8233PCSK9-targeted ASO for the reduction of circulating levels of LDL-C. | Drug | AZD8233 high dose, AZD8233 low dose, AZD8233 medium dose |
| PlaceboPlacebo solution | Drug | Placebo |
Primary outcome
Change in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12.
Time frame: Baseline to week 12
Change from baseline in low-density lipoprotein cholesterol (LDL-C) at week 12. Results are based on Mixed Model Repeated Measures (MMRM) analysis on the log-transformed change from baseline. Log-transformed change from baseline is calculated as the visit value in log minus the baseline value in log. The results from the model are then back transformed.
5 secondary outcomes
Relative Change From Baseline in PCSK9 Concentration in Plasma at Week 12.
Time frame: Baseline to week 12
Percentage Change From Baseline in Concentration of TC, HDL-C, Non-HDL-C, VLDL-C, ApoA1, ApoB, Lp(a), Triglycerides, Remnants Cholesterol
Time frame: Baseline to week 12
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 after first dose administration.
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
Percentage Change From Baseline in Levels of LDL-C in Plasma
Time frame: Baseline to week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38504437Clewe O, Rekic D, Quartino AL, Carlsson B, Higashimori M, Wernevik L, Hofherr A, Ryden-Bergsten T, Nilsson C, Knochel J. Population pharmacokinetics of a novel PCSK9 antisense oligonucleotide. Br J Clin Pharmacol. 2024 Jun;90(6):1503-1513. doi: 10.1111/bcp.16046. Epub 2024 Mar 19.
- Redacted ProtocolLink provided by the sponsor.
- redacted Statistical Analysis PlanLink provided by the sponsor.
- Redacted Clinical Study Report SynopsisLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
19 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AZD8233 in people with Dyslipidaemia, run by AstraZeneca at 19 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in United States, Denmark, Slovakia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Nov 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12. (time frame: Baseline to week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04641299, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2022.