Phase 2
N=47
Evaluate the Safety and Tolerability, as Well as the Pharmacokinetic and Pharmacodynamic Profiles of Single and Multiple Doses of Eplontersen Administered Subcutaneously to Healthy Volunteers and Patients With Hereditary Transthyretin-Mediated Amyloidosis (hATTR ).
Healthy Volunteers · hATTR Amyloidosis
Bottom Line
View on ClinicalTrials.gov: NCT03728634 ↗Enrolled (actual)
47
Serious AEs
0.0%
Results posted
Dec 2022
Primary outcome: Primary: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) — 3; 1; 3; 7 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- ION-682884 (Drug); Placebo (Drug); Vitamin A (Dietary_supplement)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Ionis Pharmaceuticals, Inc.
- Primary completion
- Feb 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) |
3; 1; 3; 7; 1; 4 | — |
| PRIMARY Percentage of Participants Using Concomitant Medications |
0.0; 0.0; 30.0; 0.0; 0.0; 22.2 | — |
| PRIMARY Number of Participants With Clinically Significant Laboratory Values |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Clinically Significant Physical Examination Findings |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Clinically Significant Electrocardiogram (ECG) Values |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Cmax: Maximum Observed Plasma Drug Concentration of ION-TTR-LRx |
0.143; 0.239; 0.332; 0.542; 0.215; 0.282 | — |
| SECONDARY Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of ION-TTR-LRx |
2.01; 6.00; 2.25; 4.00; 3.00; 1.00 | — |
| SECONDARY AUCt: Area Under the Plasma Concentration-Time Curve From Time Zero to Time t for ION-TTR-LRx |
6.78; 1.81; 2.73; 4.35 | — |
| SECONDARY CL/F: Apparent Total Clearance of ION-TTR-LRx |
17.7; 24.8; 22.0; 20.7 | — |
| SECONDARY t1/2λz: Termination Half-Life of ION-TTR-LRx |
17.9; 22.3; 30.3; 24.8 | — |
| SECONDARY Ae0-24h: Amount of Administered Dose of ION-TTR-LRx Excreted in Urine Over a 24-Hour Period |
17.0; 23.5; 29.9; 87.4; 40.6; 68.3 | — |
| SECONDARY Change From Baseline in Plasma Transthyretin (TTR) Levels Following Single and Multiple-dose Administration of ION-TTR-LRx |
-0.225; -13.40; -18.63; -19.42; 0.725; -20.06 | <0.001 sig |
| SECONDARY Change From Baseline in Plasma Retinol Binding Protein 4 (RBP4) Levels Following Single and Multiple-Dose Administration of ION-TTR-LRx |
69; -19317; -16383; -21961; 1786; -24765 | <0.001 sig |
| SECONDARY Percent Abundance of ION-682884 Antisense Oligonucleotide (ASO) Species (Metabolite) Following Administration of ION-682884 90 mg |
99.1 | — |
Summary
To evaluate the safety and tolerability, as well as the pharmacokinetic and pharmacodynamic profiles of single and multiple doses of Eplontersen administered subcutaneously to healthy volunteers and patients with Hereditary Transthyretin-Mediated Amyloidosis (hATTR ).
Eligibility Criteria
Inclusion Criteria for Healthy Volunteers (Cohorts A, B, C, and E)
- Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal
- Males must be surgically sterile or, abstinent or, if engaged in sexual relations with a woman of child-bearing potential, the subject or the subject's non-pregnant female partner must be using a highly effective contraceptive method
- Weight ≥ 50 kg and BMI 16 kg/m2
Exclusion Criteria for hATTR Patients (Cohort D)
- Clinically-significant (CS) abnormalities in medical history, screening laboratory results, physical or physical examination that would render a subject unsuitable for inclusion, including but not limited to abnormal safety labs
- Karnofsky performance status ≤ 50
- Other causes of sensorimotor or autonomic neuropathy (e.g., autoimmune disease), including uncontrolled diabetes
- Prior liver transplant or anticipated liver transplant within 1-yr of Screening
- New York Heart Association (NYHA) functional classification of ≥ 3
- Acute coronary syndrome or major surgery within 3 months of Screening
- Other types of amyloidosis
- Have any other conditions, which, in the opinion of the Investigator or Sponsor would make the subject unsuitable for inclusion, or could interfere with the subject participating in or completing the Study
Data sourced from ClinicalTrials.gov (NCT03728634). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.