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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06347003




Registration number
NCT06347003
Ethics application status
Date submitted
29/03/2024
Date registered
4/04/2024
Date last updated
25/11/2024

Titles & IDs
Public title
Study of Plozasiran (ARO-APOC3) in Adults With Severe Hypertriglyceridemia
Scientific title
Double-blind, Placebo-controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Plozasiran in Adults With Severe Hypertriglyceridemia
Secondary ID [1] 0 0
2023-509300-14
Secondary ID [2] 0 0
AROAPOC3-3003
Universal Trial Number (UTN)
Trial acronym
SHASTA-3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Severe Hypertriglyceridemia 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Plozasiran Injection
Treatment: Drugs - Placebo

Experimental: Plozasiran Injection - 4 doses of plozasiran (ARO-APOC3) by subcutaneous (sc) injection

Placebo comparator: Placebo - calculated volume to match active treatment by sc injection


Treatment: Drugs: Plozasiran Injection
ARO-APOC3 Injection

Treatment: Drugs: Placebo
sterile normal saline (0.9% NaCl)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percent Change in Fasting Serum Triglyceride (TG) Levels from Baseline to Month 12 Compared to Placebo
Timepoint [1] 0 0
Baseline, Month 12
Secondary outcome [1] 0 0
Percent Change in Fasting Serum TG Levels from Baseline to Month 10 Compared to Placebo
Timepoint [1] 0 0
Baseline, Month 10
Secondary outcome [2] 0 0
Proportion of Participants Who Achieve Fasting TG Levels of <500 mg/dL (<5.65 mmol/L) at Month 10 and Month 12 Compared to Placebo
Timepoint [2] 0 0
Month 10, Month 12
Secondary outcome [3] 0 0
Adjudicated Abdominal Clinical Event Rate (Including Emergency Room Visits or Hospitalizations for Abdominal Pain Attributed to Hypertriglyceridemia and Events of Documented Pancreatitis) During the Treatment Period Compared to Placebo at Month 12
Timepoint [3] 0 0
Month 12
Secondary outcome [4] 0 0
Proportion of Participants Who Achieve Fasting TG Levels of <150 mg/dL (<1.69 mmol/L) at Month 10 and Month 12 Compared to Placebo
Timepoint [4] 0 0
Month 10, Month 12
Secondary outcome [5] 0 0
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) Over Time through Month 12 as Compared to Placebo
Timepoint [5] 0 0
From first dose of study drug through Month 12
Secondary outcome [6] 0 0
Incidence Rates of New-Onset Diabetes Mellitus (NODM) Throughout the Course of Treatment
Timepoint [6] 0 0
From first dose of study drug through Month 12
Secondary outcome [7] 0 0
Incidence Rates of Impaired Glucose Tolerance Throughout the Course of Treatment
Timepoint [7] 0 0
From first dose of study drug through Month 12
Secondary outcome [8] 0 0
Incidence Rates of Worsening of Existing Diabetes Throughout the Course of Treatment
Timepoint [8] 0 0
From first dose of study drug through Month 12
Secondary outcome [9] 0 0
Change from Baseline in Hemoglobin A1c (HbA1c) During the Treatment Period Compared to Placebo
Timepoint [9] 0 0
From first dose of study drug through Month 12
Secondary outcome [10] 0 0
Change from Baseline in Fasting Blood Glucose During the Treatment Period Compared to Placebo
Timepoint [10] 0 0
From first dose of study drug through Month 12
Secondary outcome [11] 0 0
Change from Baseline in C-peptide During the Treatment Period Compared to Placebo
Timepoint [11] 0 0
From first dose of study drug through Month 12
Secondary outcome [12] 0 0
Change from Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) During the Treatment Period Compared to Placebo
Timepoint [12] 0 0
From first dose of study drug through Month 12
Secondary outcome [13] 0 0
Incidence Rates of Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) Associated with Worsening Glycemic Control During the Treatment Period Compared to Placebo
Timepoint [13] 0 0
From first dose of study drug through Month 12
Secondary outcome [14] 0 0
Initiation of New Medication for Hyperglycemia Among Study Participants Not Known to Have Pre-existing Diabetes Mellitus During the Treatment Period Compared to Placebo
Timepoint [14] 0 0
From first dose of study drug through Month 12
Secondary outcome [15] 0 0
Adjudicated Major Adverse Cardiovascular Events (MACE) Rates During the Treatment Period Compared to Placebo
Timepoint [15] 0 0
From first dose of study drug through Month 12
Secondary outcome [16] 0 0
Incidence of Anti-drug Antibodies (ADA) to Plozasiran in Participants Receiving Plozasiran Over Time Through Month 12
Timepoint [16] 0 0
From first dose of study drug through Month 12
Secondary outcome [17] 0 0
Titers of Anti-drug Antibodies (ADA) to Plozasiran in Participants Receiving Plozasiran Over Time Through Month 12
Timepoint [17] 0 0
From first dose of study drug through Month 12

Eligibility
Key inclusion criteria
* Established diagnosis of severe hypertriglyceridemia (SHTG) and prior documented evidence (medical history) of fasting TG levels of = 500 mg/dL (=5.65mmol/L)
* Mean fasting TG level =500 mg/dL (=5.65 mmol/L) collected at 2 separate and consecutive visits at least 7 days apart and no more than 17 days apart during the screening period
* Fasting low density lipoprotein-cholesterol (LDL-C) =130 mg/dL (=3.37 mmol/L) at screening
* Screening HbA1C =8.5%
* Willing to follow diet counseling and maintain a stable low-fat diet
* Must be on standard of care lipid-lowering medications per local guidelines (unless documented as intolerant as determined by the Investigator)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Use of any hepatocyte-targeted small interfering ribonucleic acid (siRNA) that targets lipids and/or triglycerides within 365 days before Day 1 (except inclisiran, which is permitted). Administration of investigational drug and inclisiran must be separated by at least 4 weeks
* Use of any other hepatocyte-targeted siRNA or antisense oligonucleotide molecule within 60 days or within 5-half-lives before Day 1 based on plasma pharmacokinetics (PK), whichever is longer
* Known diagnosis of familial chylomicronemia syndrome (FCS) (type 1 Hyperlipoproteinemia) by documentation of confirmed homozygote or double heterozygote for loss-of-function mutations in type 1-causing genes
* Acute pancreatitis within 4 weeks prior to screening
* Body mass index >45kg/m^2

Note: Additional Inclusion/Exclusion criteria may apply per protocol

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/07/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/10/2026
Actual
Sample size
Target
405
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Paratus Clinical Research Western Sydney - Blacktown
Recruitment hospital [2] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [3] 0 0
Hunter Diabetes Centre and Aim Centre - Merewether
Recruitment hospital [4] 0 0
Eastern Clinical Research Unit - Endocrinology - Box Hill
Recruitment hospital [5] 0 0
Austin Health - Heidelberg
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
2139 - Concord
Recruitment postcode(s) [3] 0 0
2291 - Merewether
Recruitment postcode(s) [4] 0 0
3138 - Box Hill
Recruitment postcode(s) [5] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
Mississippi
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
Nebraska
Country [11] 0 0
United States of America
State/province [11] 0 0
Nevada
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
North Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
Country [15] 0 0
United States of America
State/province [15] 0 0
Oklahoma
Country [16] 0 0
United States of America
State/province [16] 0 0
Tennessee
Country [17] 0 0
United States of America
State/province [17] 0 0
Texas
Country [18] 0 0
Belgium
State/province [18] 0 0
Gozée
Country [19] 0 0
Belgium
State/province [19] 0 0
Mechelen
Country [20] 0 0
Belgium
State/province [20] 0 0
Namur
Country [21] 0 0
Belgium
State/province [21] 0 0
Wetteren
Country [22] 0 0
Bulgaria
State/province [22] 0 0
Pleven
Country [23] 0 0
Bulgaria
State/province [23] 0 0
Plovdiv
Country [24] 0 0
Bulgaria
State/province [24] 0 0
Sofia
Country [25] 0 0
Canada
State/province [25] 0 0
British Columbia
Country [26] 0 0
Canada
State/province [26] 0 0
Ontario
Country [27] 0 0
Canada
State/province [27] 0 0
Quebec
Country [28] 0 0
Canada
State/province [28] 0 0
Halifax
Country [29] 0 0
China
State/province [29] 0 0
Shanxi
Country [30] 0 0
China
State/province [30] 0 0
Xicheng
Country [31] 0 0
China
State/province [31] 0 0
Liaocheng
Country [32] 0 0
Croatia
State/province [32] 0 0
Krapinske Toplice
Country [33] 0 0
Croatia
State/province [33] 0 0
Zagreb
Country [34] 0 0
Czechia
State/province [34] 0 0
Ostrava
Country [35] 0 0
Czechia
State/province [35] 0 0
Uherské Hradište
Country [36] 0 0
Hungary
State/province [36] 0 0
Budapest
Country [37] 0 0
Poland
State/province [37] 0 0
Bydgoszcz
Country [38] 0 0
Poland
State/province [38] 0 0
Kraków
Country [39] 0 0
Romania
State/province [39] 0 0
Brasov
Country [40] 0 0
Romania
State/province [40] 0 0
Cluj
Country [41] 0 0
Romania
State/province [41] 0 0
Jud. Alba
Country [42] 0 0
Romania
State/province [42] 0 0
Jud. Prahova
Country [43] 0 0
Romania
State/province [43] 0 0
Timis
Country [44] 0 0
Romania
State/province [44] 0 0
Bucuresti
Country [45] 0 0
Slovakia
State/province [45] 0 0
Košice Region
Country [46] 0 0
Slovakia
State/province [46] 0 0
Banska Bystrica
Country [47] 0 0
Slovakia
State/province [47] 0 0
Žilina
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Cornwall
Country [49] 0 0
United Kingdom
State/province [49] 0 0
Devpn
Country [50] 0 0
United Kingdom
State/province [50] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Arrowhead Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This Phase 3 study will evaluate the safety and efficacy of plozasiran injection (ARO-APOC3) in adult participants with severe hypertriglyceridemia (SHTG). After providing informed consent eligible participants will be randomized to receive 4 doses (once every 3 months) of plozasiran or placebo, and be evaluated for efficacy and safety. After month 12, eligible participants will be offered an opportunity to continue in an optional open-label extension under a separate protocol.
Trial website
https://clinicaltrials.gov/study/NCT06347003
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Medical Monitor
Address 0 0
Country 0 0
Phone 0 0
626-304-3400
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06347003