A Study of Inclisiran in Participants With Renal Impairment Compared to Participants With Normal Renal Function (ORION-7)

NCT ID: NCT03159416

Last Updated: 2018-11-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-22
• Study Completion Date: 2018-03-24

Brief Summary

This study is a Phase I, single-dose, open-label trial to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of a single dose of inclisiran subcutaneous (SC) injection in participants with mild, moderate, and severe renal impairment compared to participants with normal renal function.

Conditions

Renal Impairment

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Inclisiran (moderate renal impairment)

Participants will receive a single dose of 300 mg inclisiran administered by SC injection on Day 1. Moderate renal impairment is defined as CrCl ranging from 30 to 59 mL/min.

Group Type: EXPERIMENTAL

Inclisiran

Intervention Type: DRUG

Inclisiran is a synthetic, chemically modified small interfering ribonucleic acid (siRNA) targeting proprotein convertase subtilisin kexin type 9 (PCSK9) messenger ribonucleic acid (mRNA) with a covalently attached triantennary N-acetylgalactosamine (GalNAc) ligand.

Inclisiran (severe renal impairment)

Participants will receive a single dose of 300 mg inclisiran administered by SC injection on Day 1. Severe renal impairment is defined as CrCl ranging from 15 to 29 mL/min.

Group Type: EXPERIMENTAL

Inclisiran

Intervention Type: DRUG

Inclisiran is a synthetic, chemically modified small interfering ribonucleic acid (siRNA) targeting proprotein convertase subtilisin kexin type 9 (PCSK9) messenger ribonucleic acid (mRNA) with a covalently attached triantennary N-acetylgalactosamine (GalNAc) ligand.

Inclisiran (normal renal function)

Participants will receive a single dose of 300 milligram (mg) inclisiran administered by SC injection on Day 1. Normal renal function is defined as estimated creatinine clearance (CrCl) of ≥90 milliliter (mL)/minute (min).

Group Type: EXPERIMENTAL

Inclisiran

Intervention Type: DRUG

Inclisiran is a synthetic, chemically modified small interfering ribonucleic acid (siRNA) targeting proprotein convertase subtilisin kexin type 9 (PCSK9) messenger ribonucleic acid (mRNA) with a covalently attached triantennary N-acetylgalactosamine (GalNAc) ligand.

Inclisiran (mild renal impairment)

Participants will receive a single dose of 300 mg inclisiran administered by SC injection on Day 1. Mild renal impairment is defined as CrCl ranging from 60 to 89 mL/min.

Group Type: EXPERIMENTAL

Inclisiran

Intervention Type: DRUG

Inclisiran is a synthetic, chemically modified small interfering ribonucleic acid (siRNA) targeting proprotein convertase subtilisin kexin type 9 (PCSK9) messenger ribonucleic acid (mRNA) with a covalently attached triantennary N-acetylgalactosamine (GalNAc) ligand.

Interventions

Inclisiran

Inclisiran is a synthetic, chemically modified small interfering ribonucleic acid (siRNA) targeting proprotein convertase subtilisin kexin type 9 (PCSK9) messenger ribonucleic acid (mRNA) with a covalently attached triantennary N-acetylgalactosamine (GalNAc) ligand.

Intervention Type: DRUG

Other Intervention Names

ALN-PCSSC

Eligibility Criteria

Inclusion Criteria

• Male and female participants 18 to 80 years of age
• Participants should be qualified for inclusion based upon estimated CrCl ranges for normal renal function group and mild, moderate, and severe renal impairment groups

Exclusion Criteria

• Participants with acute renal disease and/or history of renal transplant
• Urinary incontinence without catheterization
• Participants requiring hemodialysis
• Participants with LDL-C <60 mg/deciliter (dL) (or less than 1.55 millimoles/liter [mmol/L])
• Participants with Amyloid Kidney (if known by pathology)
• Participants with any significant hepatic, cardiac, or pulmonary disease or participants who are clinically nephritic

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

The Medicines Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Richard Robson, PhD

Role: PRINCIPAL_INVESTIGATOR

Christchurch Clinical Studies Trust

Locations

Auckland Clinical Studies Limited

Auckland, , New Zealand

Christchurch Clinical Studies Trust

Christchurch, , New Zealand

Countries

New Zealand

References

Wright RS, Collins MG, Stoekenbroek RM, Robson R, Wijngaard PLJ, Landmesser U, Leiter LA, Kastelein JJP, Ray KK, Kallend D. Effects of Renal Impairment on the Pharmacokinetics, Efficacy, and Safety of Inclisiran: An Analysis of the ORION-7 and ORION-1 Studies. Mayo Clin Proc. 2020 Jan;95(1):77-89. doi: 10.1016/j.mayocp.2019.08.021. Epub 2019 Oct 17.

Reference Type: DERIVED

PMID: 31630870 (View on PubMed)

Other Identifiers

MDCO-PCS-16-03

Identifier Type: -

Identifier Source: org_study_id