Clinical trial NCT06834932: A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of AZD0780 in Participants With Dyslipidaemia
Official title: A Randomised, Double-blind, Placebo-controlled, Multi-centre, Sequential Phase II, and Phase III Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of AZD0780 Administered for up to 52 Weeks in Participants With Dyslipidaemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Dyslipidaemia
Keywords: AZD0780
Dyslipidaemia
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2025-02-19
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomised, double-blind, placebo-controlled, multi-centre, sequential Phase II and Phase III study that will evaluate the efficacy, safety, and PK of AZD0780 administered orally for up to 52 weeks in participants with elevated LDL-C. The study consist of 2 separate parts (Part A and Part B) approximately 60 participants will be randomised in Part A. There will be 2 cohorts in Part B (approximately 220 participants in Cohort 1 and 100 participants in Cohort 2).

Detailed description: The planned study includes 2 parts. Part A will be the Phase II study and aims to evaluate the PK, PD, safety, and tolerability of AZD0780. Part B will be the Phase III study and aims to evaluate the reduction of LDL-C as well as the safety and tolerability after oral administration of AZD0780 on background lipid-lowing therapy including moderate to high-intensity statins.

For Part A, approximately 60 participants who meet the eligibility criteria will be randomised. Part A will comprise 4 periods totalling up to 80 days.

For Part B, approximately 220 participants who meet the eligibility criteria will be randomised in Cohort 1, and approximately 100 participants who meet the eligibility criteria will be randomised in Cohort 2. Cohort 1: participants are on a stable dose of LLTs, including moderate to high-intensity statins for≥ 28 days Cohort 2: participants could be with moderate-intensity or without statins therapy (not due to statin intolerance) in background LLTs or not on any LLTs .

Eligibility criteria: Inclusion Criteria:

PART A

1. Males, and females of non-childbearing potential, 18 to 55 years of age, at the time of signing the informed consent.
2. Diagnosis of dyslipidaemia: and with fasting LDL-C ≥ 100 mg/dL (2.6 mmol/L) and \< 190 mg/dL (4.9 mmol/L) at screening (Visit 1).
3. Fasting triglycerides \< 400 mg/dL (\< 4.52 mmol/L) at screening (Visit 1).
4. Not on any LLTs for ≥ 8 weeks prior to screening (Visit 1), except for a heart-healthy lifestyle.
5. No planned LLTs using during study participation.
6. Body mass index ≥ 18 and ≤35 kg/m\^2 , weigh ≥50 kg and ≤120 kg.

PART B

1. Males, and females, ≥ 18 years of age, at the time of signing the informed consent.
2. Meets one of the ASCVD status/risk categories and has a corresponding fasted LDL-C value at screening (Visit 1) .

(1) LDL ≥ 55 mg/dl if ASCVD present OR LDL ≥ 100 mg/dl if there is no history of clinical ASCVD.

(2) Subject without clinical ASCVD are eligible if they have either, ASCVD risk equivalents \[diabetes mellitus,LDL-C ≥ 4.9 mmol/L or TC ≥ 7.2 mmol/L, HeFH, CKD (stage 3-5)\]. OR a 10 year moderate to high risk for ASCVD.

3. Fasting triglycerides \< 400 mg/dL (\< 4.52 mmol/L). 4. Background LLTs: For Cohort 1: on a stable dose of LLTs including medications and supplements ≥ 28 days before screening (Visit 1).

For Cohort 2: Meet one of the following before screening (Visit 1):

1. On a stable dose of LLTs.
2. On a stable dose of LLTs without any statins.
3. Not received treatment with any LLTs.

Exclusion Criteria:

PART A

1. 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.
2. Recipient of any major organ transplant, eg, lung, liver, heart, bone marrow, renal.
3. Homozygous familial hypercholesterolaemia, Know diagnosis of HeFH, LDL apheresis or plasma apheresis within 12 months prior to screening (Visit 1).
4. QTcF \> 450 ms; high degree atrioventricular-block grade II-III and sinus node dysfunction with significant sinus pause untreated with pacemaker; and cardiac tachyarrhythmias.
5. A LDL-C reduction that is \< 30% post rosuvastatin run-in period (Day -8).

PART B

1. Acute ischaemic cardiovascular event within 7 days prior to screening (Visit 1).
2. Coronary revascularisation procedure planned within 6 months after the screening procedures (Visit 1).
3. eGFR \< 45 mL/min/1.73m2 using the CKD-EPI 2021 (age, sex) equation at screening (Visit 1).
4. Poorly controlled type 2 diabetes mellitus, defined as HbA1c \> 10% at screening (Visit 1).
5. Heart failure with New York Heart Association Class IV.
6. Malignancy (except non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal carcinoma in-situ, or Stage 1 prostate carcinoma) within 5 years prior to screening (Visit 1).
7. Severe concomitant non-CVD with risk of life expectancy \< 2 years.
8. Recipient of any major organ transplant, eg, lung, liver, heart, bone marrow, renal.
9. Homozygous familial hypercholesterolaemia, LDL apheresis, or plasma apheresis within 12 months prior to screening or any other underlying known disease or condition that may interfere with interpretation of the clinical study results as judged by the Investigator.
10. Uncontrolled hypertension defined as average sitting SBP \> 160 mmHg or DBP \> 90 mmHg at screening (Visit 1).
11. Participants with one or more of these findings (shortened QTcF \< 340 ms; family history of long QT syndrome; PR interval shortening \< 120 ms; PR interval prolongation \>220 ms; persistent or intermittent complete bundle branch block, incomplete bundle branch, or interventricular conduction delay with QRS \> 110 ms) should be excluded only if they are judged to be clinically important by the Investigator.
12. QTcF \> 450 ms; high degree atrioventricular-block grade II-III and sinus node dysfunction with significant sinus pause untreated with pacemaker; and cardiac tachyarrhythmias.

Primary outcomes:
measure: AZD0780 Concentrations in plasma (PART A)
timeFrame: Day 1 and Day 8: Pre-dose, 0.25,0.5,1,1.5,2,3,4,6,8,12,16 hours post-dose. Day 2, Day 9, Day 11, Day 15, Day 22, Day 29: Pre-dose (PART A)
measure: AZD0780 PK Parameter: AUC0-t (PART A, intensive PK subgroup).
timeFrame: Day 1 and Day 8: Pre-dose, 0.25,0.5,1,1.5,2,3,4,6,8,12,16 hours post-dose. Day 2, Day 9, Day 11, Day 15, Day 22, Day 29: Pre-dose (PART A)
measure: AZD0780 PK parameter: Cmax (PART A, intensive PK subgroup)
timeFrame: Day 1 and Day 8: Pre-dose, 0.25,0.5,1,1.5,2,3,4,6,8,12,16 hours post-dose. Day 2, Day 9, Day 11, Day 15, Day 22, Day 29: Pre-dose (PART A)
measure: AZD0780 PK parameter: AUCtau (PART A, intensive PK sub group)
timeFrame: Day 1 and Day 8: Pre-dose, 0.25,0.5,1,1.5,2,3,4,6,8,12,16 hours post-dose. Day 2, Day 9, Day 11, Day 15, Day 22, Day 29: Pre-dose (PART A)
measure: Relative change in LDL-C from baseline to Week 12 (PART B)
timeFrame: From baseline to Week 12 (PART B)
Secondary outcomes:
measure: Relative change from baseline of LDL-C at week 4 (PART A)
timeFrame: From baseline to Week 4 (PART A)
measure: Absolute change in LDL-C from baseline to Week 12 (PART B)
timeFrame: From baseline to Week 12 (PART B)
measure: Relative change in LDL-C from baseline to Week 12 (PART B cohort 2)
timeFrame: From baseline to Week 12 (PART B cohort 2)
measure: Absolute change in LDL-C from baseline to Week 12 (PART B cohort 2)
timeFrame: From baseline to Week 12 (PART B cohort 2)
measure: Proportion of participants have died prior to or at Week 12 or LDL-C ≥ 55 mg/dL (≥ 1.4 mmol/L) at Week 12 (PART B)
timeFrame: From baseline to Week 12 (PART B)
measure: Proportion of participants have died prior to or at Week 12 or LDL-C ≥ 70 mg/dL (≥ 1.8 mmol/L) at Week 12 (PART B)
timeFrame: From baseline to Week 12 (PART B)
measure: Proportion of participants with LDL-C ≥ 50% reduction from baseline at Week 12 (PART B cohort 2)
timeFrame: From baseline to Week 12 (PART B cohort 2)
measure: Relative change in lipid parameters from baseline to Week 12 (PART B cohort 2)
timeFrame: From baseline to Week 12 (PART B cohort 2)
Other outcomes:
measure: Number of participants with adverse events (PART A)
timeFrame: From baseline up to Day 39 (PART A)
measure: Number of participants with adverse events (PART B)
timeFrame: Cohort 1: From baseline up to Day 375 (PART B) Cohort 2: From baseline up to Day 95 (PART B)
Locations:
city: Baotou
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Changde
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Deyang
country: China
facility: Research Site
city: Hengyang
country: China
facility: Research Site
city: Nanchang
country: China
facility: Research Site
city: Nanchong
country: China
facility: Research Site
city: Pingxiang
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Taiyuan
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Xi'an
country: China
facility: Research Site
city: Xianyang
country: China
facility: Research Site
city: Yinchuan
country: China
facility: Research Site
city: Zigong
country: China
facility: Research Site
city: Hong Kong
country: Hong Kong
facility: Research Site
city: Hong Kong
country: Hong Kong
facility: Research Site
Study officials:
References: