Study to Evaluate Plozasiran in Adults with Severe Hypertriglyceridemia (SHASTA-4 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

4 Nov 2024 → ongoing

Decision date (initial)

2024-09-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Arrowhead Pharmaceuticals Inc.

External identifiers

EU CT number

2023-509301-80-00

ClinicalTrials.gov

NCT06347016

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacodynamic, Pharmacokinetic

To demonstrate the efficacy of plozasiran on reducing fasting serum TG levels

Secondary objectives 3

1. To demonstrate the proportion of subjects who achieve the attainment goal of reduction in TG levels
2. To demonstrate the efficacy of plozasiran on reducing remnant cholesterol (very low-density lipoprotein cholesterol [VLDL-C]) and non-high-density lipoprotein cholesterol (non HDL C).
3. To evaluate the efficacy of plozasiran on the adjudicated AP event 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 7

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 ≥500 mg/dL (≥5.65 mmol/L)
3. 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
4. Fasting LDL-C ≤130 mg/dL (≤3.37 mmol/L) at screening
5. Screening HbA1c ≤9.0%
6. Willing to follow diet counseling and maintain a stable low-fat diet
7. Subjects must be on standard of care lipid-and TG-lowering medications per local guidelines (unless documented as intolerant as determined by the Investigator including an inability to safely administer or re-administer a specific drug because of fear, preference, genetic, clinical, or metabolic considerations, or a previous adverse reaction associated with, attributed to, or caused by specific drug) prior to collection of qualifying TG levels.)

Exclusion criteria 5

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. Known diagnosis of familial chylomicronemia syndrome (FCS) (type 1 hyperlipoproteinemia) by documentation of confirmed homozygote, compound heterozygote or double heterozygote for loss-of-function mutations in type 1-causing genes
4. Acute pancreatitis within 4 weeks prior to screening (S1).
5. Body mass index >45 kg/m2

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percent change in fasting serum TG levels from baseline to Month 12 (V10 and V11) compared to placebo

Secondary endpoints 6

1. Percent change in fasting serum TG levels from baseline to Month 10 (V8 and V9) compared to placebo
2. Proportion of subjects who achieve fasting TG levels of <500 mg/dL (<5.65 mmol/L) at Month 12 (V10 and V11) compared to placebo
3. Proportion of subjects who achieve fasting TG levels of <150 mg/dL (<1.69 mmol/L) at Month 12 (V10 and V11) compared to placebo
4. Percent change in remnant cholesterol (VLDL-C) from baseline to Month 12 (V11) compared to placebo
5. Percent change in non-HDL-C from baseline to Month 12 (V11) compared to placebo
6. Adjudicated AP event rate during the treatment period compared to placebo from day 1 to Month 12 (V11)

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

Jennifer Hellawell

Public contact point

Organisation

Arrowhead Pharmaceuticals Inc.

Contact name

SUMMIT Study team

Third parties 11

Locations

10 EU/EEA countries · 70 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 248 files

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

Application history

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