Study to Evaluate Plozasiran in Adults with Severe Hypertriglyceridemia at high risk of Acute Pancreatitis (SHASTA-5 Study)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Arrowhead Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

3 Nov 2025 → ongoing

Decision date (initial)

2025-09-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Arrowhead Pharmaceuticals Inc.

External identifiers

EU CT number

2024-518206-40-00

ClinicalTrials.gov

NCT06880770

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the efficacy of plozasiran on adjudicated Acute Pancreatitis (AP) events during double-blind treatment period

Secondary objectives 6

1. To demonstrate the efficacy of plozasiran on reducing fasting serum triglyceride (TG) levels
2. To demonstrate the proportion of participants receiving plozasiran who achieve the attainment goal of reduction in TG levels
3. To evaluate the efficacy of plozasiran on major abdominal pain events
4. To evaluate the effect of plozasiran on patient-reported outcomes
5. To evaluate the safety and tolerability of plozasiran administered subcutaneously (SC) every 3 months
6. To evaluate adjudicated major adverse cardiovascular event (MACE) rate

Conditions and MedDRA coding

Severe hypertriglyceridemia (SHTG)

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Males, or nonpregnant (who do not plan to become pregnant) nonlactating females, who are ≥18 years of age at screening
2. Established diagnosis of SHTG and prior documented evidence (medical history) of fasting TG levels of ≥880 mg/dL (≥10 mmol/L)
3. Fasting TG level ≥500 mg/dL (≥5.65 mmol/L) collected during the screening period
4. Documented evidence of at least 1 prior AP event (according to the clinical diagnosis per medical records) not attributed to other etiologies (eg, gallstones, alcohol), occurring within the last 5 years (60 months) prior to screening
5. Fasting LDL-C ≤130 mg/dL (≤3.37 mmol/L) at screening
6. Screening HbA1c ≤9.5%
7. Willing to follow diet counseling and maintain a stable low-fat diet
8. Participants must be on standard of care lipid- and TG-lowering medications per local guidelines (unless documented as intolerant as determined by the Investigator)

Exclusion criteria 4

1. Use of any hepatocyte-targeted 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.
2. 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 PK, whichever is longer.
3. Acute pancreatitis ≤ 4 weeks prior to Randomization/Day 1.
4. Body mass index >45 kg/m2

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to first occurrence of positively adjudicated AP event (event occurring more than 10 days after the first dose of study drug) compared with placebo during the double-blind treatment period

Secondary endpoints 8

1. Percent change in fasting serum TG levels from baseline to Month 12 (V9) compared with placebo
2. Proportion of participants who achieve average fasting TG levels of <880 mg/dL (10 mmol/L) from Month 3 to the end of the double-blind treatment period
3. Proportion of participants who achieve average fasting TG levels of <500 mg/dL (5.65 mmol/L) from Month 3 to the end of the double-blind treatment period
4. Time to first occurrence of major abdominal pain event* (event occurring more than 10 days after the first dose of study drug) compared with placebo * Major abdominal pain event defined as any of the following: 1) positively adjudicated AP, or 2) positively adjudicated presentation to emergency room and/or hospitalization with abdominal pain for which no other etiology has been identified, or 3) need to initiate apheresis to decrease TG levels
5. Change from baseline in patient-reported productivity and activity impairment as assessed by the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI SHP) score
6. Change from baseline in patient-reported health status as assessed by the EuroQol 5-dimension instrument (EQ 5D 5L) score
7. The frequency and severity of treatment-emergent adverse events (TEAEs) from baseline to end of study (EOS) of each treatment period
8. Adjudicated MACE event rates

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Arrowhead Pharmaceuticals Inc.

Sponsor organisation

Arrowhead Pharmaceuticals Inc.

Address

177 East Colorado Boulevard Suite 700

City

Pasadena

Postcode

91105-1976

Country

United States

Scientific contact point

Organisation

Arrowhead Pharmaceuticals Inc.

Contact name

Joe Thakuria

Public contact point

Organisation

Arrowhead Pharmaceuticals Inc.

Contact name

SUMMIT Study Team

Third parties 7

Locations

5 EU/EEA countries · 23 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 73 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications