Study to Evaluate Plozasiran in Adults with Hypertriglyceridemia (SHASTA-10 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

8 Dec 2025 → ongoing

Decision date (initial)

2025-06-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Arrowhead Pharmaceuticals, Inc.

External identifiers

EU CT number

2024-519712-13-00

ClinicalTrials.gov

NCT06822790

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To demonstrate the long-term safety of plozasiran in subjects with HTG and SHTG.

Secondary objectives 5

1. To evaluate the efficacy of plozasiran on the reduction of fasting TG levels over time.
2. To demonstrate the effects of plozasiran on fasting APOC3, remnant cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C), HDL-C, apolipoprotein B (Apo B), and low-density lipoprotein cholesterol (LDL-C) over time.
3. To evaluate adjudicated major adverse cardiovascular event (MACE) rate.
4. To evaluate immunogenicity (anti-drug antibodies [ADAs]) of the investigational medicinal product (IMP).
5. To evaluate the efficacy of plozasiran on the adjudicated AP event rate.

Conditions and MedDRA coding

Hypertriglyceridemia (HTG)

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 3

1. Adult males, or nonpregnant (who do not plan to become pregnant), nonlactating adult females, who are able and willing to provide written informed consent prior to the performance of any study-specific procedures
2. Completed all required study visits per protocol in the parent study (i.e. AROAPOC3-3001 [Canada and Japan only], AROAPOC3-3003, AROAPOC3-3004, or AROAPOC3-3009).
3. Female subjects of childbearing potential must agree to use a highly effective method of contraception during the study and for at least 90 days after the EOS or the last dose of IMP, whichever is later. Male subjects must agree to use a condom during the study and for at least 90 days after the EOS or the last dose of IMP, whichever is later. Subjects must not donate sperm or eggs during the study and for at least 90 days after the EOS or last dose of IMP, whichever is later. Female subjects of childbearing potential on hormonal contraceptives must be stable on the medication for >1 menstrual cycle prior to Day 1 (V1).

Exclusion criteria 5

1. Subject was permanently discontinued from receiving IMP in the parent study due to elevated AST or ALT or due to HbA1c elevation that did not respond to antidiabetic regimen.
2. Subject withdrew consent for continued study treatment in the parent study
3. Known hypersensitivity to the active substance or to any of the excipients of plozasiran
4. Any new condition or worsening of existing condition (eg, renal, hematologic, gastrointestinal, endocrine, cardiovascular, pulmonary, immunologic, psychiatric) or any other situation that, in the Investigator’s judgment, would make the subject unsuitable for enrollment, could interfere with the subject participating in or completing the study, would make it difficult to comply with protocol requirements, or put the subject at an additional safety risk.
5. Unwilling to limit alcohol consumption to within moderate limits for the duration of the study. Moderate limits are defined as follows: no more than 14 units per week (1 unit approximately corresponds to 80 mL of wine, 200 mL of beer, or 25 mL of 40% alcohol).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Subject incidence of treatment-emergent adverse events (TEAEs)

Secondary endpoints 12

1. Change and percent change from baseline over time in fasting TG levels
2. Change and percent change from baseline over time in APOC3
3. Change and percent change from baseline over time in remnant cholesterol
4. Change and percent change from baseline over time in fasting non-HDL-C
5. Change and percent change from baseline over time in fasting HDL-C
6. Change and percent change from baseline over time in fasting total Apo B
7. Change and percent change from baseline over time in fasting LDL-C using ultracentrifugation
8. Change from baseline over time in hemoglobin A1c (HbA1c)
9. Subject incidence of emergent apheresis
10. Adjudicated MACE event rates during the treatment period
11. Incidence and titers of ADA to plozasiran in those receiving plozasiran over time
12. Adjudicated AP event rate during the treatment period.

Investigational products

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

Test 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

Jennifer Hellawell

Public contact point

Organisation

Arrowhead Pharmaceuticals Inc.

Contact name

SUMMIT Study team

Third parties 9

Locations

14 EU/EEA countries · 112 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 124 files

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

Application history

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