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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06347016




Registration number
NCT06347016
Ethics application status
Date submitted
29/03/2024
Date registered
4/04/2024

Titles & IDs
Public title
Study of Plozasiran in Adults With Severe Hypertriglyceridemia
Scientific title
Double-blind, Placebo-controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Plozsiran in Adults With Severe Hypertriglyceridemia
Secondary ID [1] 0 0
2023-509301-80
Secondary ID [2] 0 0
AROAPOC3-3004
Universal Trial Number (UTN)
Trial acronym
SHASTA-4
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 Subjects Who Achieve Fasting TG Levels of < 500 mg/dL (<5.65 mmol/L) at Month 10 and Month 12
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 Subjects Who Achieve Fasting TG Levels of <150mg/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 Subjects 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) and Other Glycemic Control Parameters 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
Change from Baseline in 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 Subjects 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 Subjects 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 (=5.65 mmol/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%
* 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 (except inclisiran, which is permitted)
* 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
* 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
23/07/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/10/2026
Actual
Sample size
Target
300
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
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
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Kansas
Country [7] 0 0
United States of America
State/province [7] 0 0
Louisiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Mississippi
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
New Jersey
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
Pennsylvania
Country [17] 0 0
United States of America
State/province [17] 0 0
South Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
United States of America
State/province [19] 0 0
Utah
Country [20] 0 0
United States of America
State/province [20] 0 0
Virginia
Country [21] 0 0
Bulgaria
State/province [21] 0 0
Byala
Country [22] 0 0
Bulgaria
State/province [22] 0 0
Sevlievo
Country [23] 0 0
Bulgaria
State/province [23] 0 0
Sofia
Country [24] 0 0
Canada
State/province [24] 0 0
British Columbia
Country [25] 0 0
Canada
State/province [25] 0 0
Quebec
Country [26] 0 0
Czechia
State/province [26] 0 0
Praha
Country [27] 0 0
Czechia
State/province [27] 0 0
Trutnov
Country [28] 0 0
France
State/province [28] 0 0
Gironde
Country [29] 0 0
France
State/province [29] 0 0
Pyrenees Atlantiques
Country [30] 0 0
France
State/province [30] 0 0
Paris
Country [31] 0 0
Germany
State/province [31] 0 0
Sachsen Anhalt
Country [32] 0 0
Hungary
State/province [32] 0 0
Békéscsaba
Country [33] 0 0
Latvia
State/province [33] 0 0
Kuldiga
Country [34] 0 0
Latvia
State/province [34] 0 0
Riga
Country [35] 0 0
Latvia
State/province [35] 0 0
Tukums
Country [36] 0 0
Lithuania
State/province [36] 0 0
Kaunas
Country [37] 0 0
Lithuania
State/province [37] 0 0
Šiauliai
Country [38] 0 0
New Zealand
State/province [38] 0 0
Christchurch
Country [39] 0 0
New Zealand
State/province [39] 0 0
New Plymouth
Country [40] 0 0
New Zealand
State/province [40] 0 0
Newtown
Country [41] 0 0
Poland
State/province [41] 0 0
Katowice
Country [42] 0 0
Poland
State/province [42] 0 0
Malbork
Country [43] 0 0
Poland
State/province [43] 0 0
Lódz
Country [44] 0 0
Slovakia
State/province [44] 0 0
Nové Zámky
Country [45] 0 0
Slovakia
State/province [45] 0 0
Prešov

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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
plozasiran@arrowheadpharma.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT06347016