Single Ascending Dose of FXI-GalNAc-siRNA in Healthy Subjects

NCT05844293 | Recruiting Phase 1 FDA Drug

• 1 other identifier: SRN-122-001
• Study Type: interventional
• Target: 40
• Locations: 2 countries
• Sites: 2

Brief Summary

The purpose of this study is to evaluate safety, tolerability, PK, and PD of SAD of FXI-GalNAc-siRNA administered SC to healthy subjects.

Conditions

FXI

Outcome Measures

Primary Outcomes (6)

• Maximum peak concentration

  Individual plasma concentration data of FXI-GalNAc-siRNA will be used to determine Maximum peak concentration.

  145 days

• Time to maximum concentration.

  Individual plasma concentration data of FXI-GalNAc-siRNA will be used to determine time to maximum concentration.

  145 days

• Apparent terminal elimination rate constant.

  Individual plasma concentration data of FXI-GalNAc-siRNA will be used to determine apparent terminal elimination rate constant.

  145 days

• Half life

  Individual plasma concentration data of FXI-GalNAc-siRNA will be used to determine half life.

  145 days

• Area under the curve

  Individual plasma concentration data of FXI-GalNAc-siRNA will be used to determine area under the plasma concentration-time curve from 0 to the last quantifiable plasma concentration.

  145 days

• Area under the curve from 0-infinity

  Individual plasma concentration data of FXI-GalNAc-siRNA will be used to determine area under the curve from time 0 to infinity.

  145 days

Study Arms (5)

Cohort 1

OTHER

6 subjects injected with 25 mg dose of FXI-GalNAc-siRNA 2 subjects with Saline

Drug: FXI-GalNAc-siRNA; Other: Placebo

Cohort 2

OTHER

6 subjects injected with 50 mg dose of FXI-GalNAc-siRNA 2 subjects with Saline

Drug: FXI-GalNAc-siRNA; Other: Placebo

Cohort 3

OTHER

6 subjects injected with 100 mg dose of FXI-GalNAc-siRNA 2 subjects with Saline

Drug: FXI-GalNAc-siRNA; Other: Placebo

Cohort 4

OTHER

6 subjects injected with 200 mg dose of FXI-GalNAc-siRNA 2 subjects with Saline

Drug: FXI-GalNAc-siRNA; Other: Placebo

Cohort 5

OTHER

6 subjects injected with 400 mg dose of FXI-GalNAc-siRNA 2 subjects with Saline

Drug: FXI-GalNAc-siRNA; Other: Placebo

Interventions

FXI-GalNAc-siRNA DRUG

FXI-GalNAc-siRNA solution for injection

Also known as: FXI-GalNAc-siRNA Solution for Injection

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5

Placebo OTHER

Saline

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects who meet all the following criteria will be eligible to participate in the study:
• Male or female subjects 18 to 55 years of age, inclusive, at the time of signing the informed consent form (ICF).
• Subjects must be in generally reasonable health with clinically insignificant screening and admission results (medical history, 12-lead electrocardiogram (ECG), physical examination, and laboratory tests), as determined by the Investigator.
• Subjects must have a body mass index (BMI) ≥ 18 kg/m2 or ≤ 32 kg/m2 at Screening and Day -1 (Admission).
• Subjects must have aspartate transaminase (AST), alanine transaminase (ALT), total bilirubin (TBIL), alkaline phosphatase (ALP), and glucose within upper limit of normal (ULN) range per reference laboratory reference ranges at Screening and Day -1 (Admission); one repeat laboratory analysis allowed per Investigator discretion.
• Subjects must have baseline Factor XI plasma levels within normal range as per testing laboratory requirements.
• Subjects must have prothrombin time (PT) and partial thromboplastin time (PTT) within the ULN range per reference laboratory reference ranges at Screening and Day -1 (Admission); one repeat laboratory analysis allowed per Investigator discretion.
• Women of childbearing potential must have a negative serum pregnancy test at Screening and negative urine pregnancy test at Day -1 (Admission), must not be actively breastfeeding, or planning to become pregnant during the study, and if not practicing abstinence from heterosexual activity that could result in conception (if this is the preferred and usual lifestyle of the subject), must agree to use 2 approved methods of birth control, during the study and for at least 140 days after study drug administration from the list below:
• Condom plus diaphragm with spermicide started at least 28 days prior to dosing.
• Condom plus cervical cap or female condom with spermicide started at least 28 days prior to dosing.
• Hormonal contraceptives (stable dose for 28 days \[4 weeks\] prior to Screening) plus condom.
• Intrauterine device (in place for 28 days \[4 weeks\] prior to Screening) plus condom.
• Condom plus spermicide.
• Partner vasectomy and use of barrier contraception methods (eg, male condom, diaphragm, or sponge with spermicide).
• Women of nonchildbearing potential must be either surgically sterile (partial/total hysterectomy, bilateral oophorectomy) for at least 6 months confirmed by medical/operative report, or if medical/operative report is not available, confirmed by follicle stimulating hormone \[FSH\] and 17β-estradiol tests) or \> 1 year in the postmenopausal women confirmed by FSH and 17β-estradiol tests.

You may not qualify if:

• Subjects who meet any of the following criteria will be excluded from participation in the study:
• Patients with known diagnosis of Hemophilia C, Factor XI deficiency or another known bleeding disorder.
• Current or previous cancer except superficial forms of non-melanoma skin cancers that have been resolved with clear histology reporting; diabetes or known diagnosis of prediabetes; or any clinically significant cardiovascular (including ECG disturbances or history of rhythm disturbance/abnormality), endocrine, renal, hepatic, gastrointestinal, hematologic, respiratory, dermatological, neurological, psychiatric disorder that could be deemed by the investigator to interfere with study participation, or other disorders that the investigator deems could interfere with study participation.
• Hypertension, defined as blood pressure \> 140/90 mmHg (2 separate readings at least 15 minutes apart if first reading is not within normal range) at Screening and Day -1 (Admission).
• Hyperlipidemia, defined as:
• Cholesterol \> 300 mg/dL.
• Low-density lipoprotein cholesterol \> 190 mg/dL.
• And/or triglycerides \>500 mg/dL.
• Hemoglobin A1c (HbA1c) \> 6.0% at Screening. Note: Abnormal laboratory values may be repeated once at Investigator discretion
• Hemoglobin less than 12 g/dL for females and less than 13 g/dL for males or hematocrit outside upper or lower limits of normal range per reference laboratory range at both Screening and Day -1 (Admission).
• Serum creatinine above ULN per reference laboratory range at both Screening and Day -1 (Admission).
• Unwillingness to abstain from alcohol for 72 hours prior to dosing through the EOS Visit (or ET).
• Use of prescription or nonprescription drugs (excluding hormonal contraceptives), if clinically applicable, including vitamins, supplements, herbal preparations, and medicines that prolong Q wave interval (QT)/ Q wave interval corrected (QTc) within 7 days or 5 times longer than the half-life (whichever is longer) prior to the study drug administration through the EOS Visit (approximately 140 days) or at ET.
• Blood donation within 56 days or plasma donation within 10 days prior to dosing.
• Use of live or non-live vaccine (except SARS-CoV-2 and influenza) within 30 days prior to the first dose of study drug or an intention to receive such a vaccine at any time during the study.

Sponsors & Collaborators

• Sirnaomics: lead

Study Sites (2)

BioPharma

Creve Coeur, Missouri, 63141, United States

COMPLETED

BioPharma

Toronto, Ontario, M9L 3A2, Canada

RECRUITING

MeSH Terms

Interventions

Injections

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Francois Lebel, MD

  Chief Medical Officer

  STUDY DIRECTOR

Central Study Contacts

Mamta Jha

CONTACT

(301) 740-1730; ClinicalOps@sirnaomics.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2023
• First Posted: May 6, 2023
• Study Start: May 16, 2023
• Primary Completion: May 1, 2024
• Study Completion: June 1, 2024
• Last Updated: March 18, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (1)