Healthy Volunteers Clinical Trial
Official title:
This Was a Phase 1/2, Double-blind, Randomized, Placebo-controlled, Dose-escalation Study Conducted at a Single Center for the Healthy Volunteer Cohorts in up to 56 Participants. It Consisted of 1 Single-dose Cohort and 3 Multiple-dose Cohorts (n = 12 Per Cohort, 10 Active:2 Placebo). The Open-label, hATTR Patient Cohort Portion of the Study Was Conducted at Multiple Centers.
Verified date | November 2022 |
Source | Ionis Pharmaceuticals, Inc. |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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 ).
Status | Completed |
Enrollment | 47 |
Est. completion date | February 20, 2020 |
Est. primary completion date | February 20, 2020 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years to 65 Years |
Eligibility | Inclusion Criteria for Healthy Volunteers (Cohorts A, B, C, and E) 1. Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal 2. 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 3. Weight = 50 kg and BMI < 32 kg/m^2 Exclusion Criteria for Healthy Volunteers (Cohorts A, B, C, and E) 1. Clinically-significant (CS) abnormalities in medical history, screening laboratory results, physical or physical examination that would render a subject unsuitable for inclusion including abnormal safety labs 2. Drug or alcohol dependency or abuse 3. Treatment with another investigational drug, biological agent, or device within 1 month of Screening, or 5 half-lives of investigational agent, whichever is longer 4. Blood donation within 28 days 5. 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 Inclusion Criteria for hATTR Patients (Cohort D) 1. Aged 18 to 82 years at the time of informed consent 2. Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal 3. 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 4. Diagnosis of hereditary transthyretin-mediated polyneuropathy 5. BMI > 16 kg/m2 Exclusion Criteria for hATTR Patients (Cohort D) 1. 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 2. Karnofsky performance status = 50 3. Other causes of sensorimotor or autonomic neuropathy (e.g., autoimmune disease), including uncontrolled diabetes 4. Prior liver transplant or anticipated liver transplant within 1-yr of Screening 5. New York Heart Association (NYHA) functional classification of = 3 6. Acute coronary syndrome or major surgery within 3 months of Screening 7. Other types of amyloidosis 8. 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 |
Country | Name | City | State |
---|---|---|---|
Canada | Bio Pharma Services, Inc. | Toronto | Ontario |
Lead Sponsor | Collaborator |
---|---|
Ionis Pharmaceuticals, Inc. |
Canada,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) | An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not the AE was considered related to the medicinal (investigational) product. An AE was to be regarded as a TEAE if it was present prior to receiving the first dose of study drug and subsequently worsened or was not present prior to receiving the first dose of study drug but subsequently appeared. | Up to Day 176 | |
Primary | Percentage of Participants Using Concomitant Medications | A concomitant therapy was any non-protocol-specified drug or substance (including over-the-counter [OTC] medications, herbal medications, and vitamin supplements) administered between signing of informed consent and the last study visit. | Up to Day 176 | |
Primary | Number of Participants With Clinically Significant Laboratory Values | Laboratory parameters included measurement of blood chemistry, hematology, coagulation, complement, or urinalysis parameters for the single-dose and multiple-dose cohorts. Number of participants with clinically significant values in laboratory based on Investigator's assessment are reported. Any value outside the normal range was to be flagged for the attention of the investigator was to assess whether or not a flagged value is of clinical significance. | Up to Day 176 | |
Primary | Number of Participants With Clinically Significant Physical Examination Findings | Physical examination included measurement of height and weight for body mass index (BMI) determination. Number of participants with clinically significant findings in physical examination based on Investigator's assessment are reported. Any value outside the normal range was to be flagged for the attention of the investigator was to assess whether or not a flagged value is of clinical significance. | Up to Day 176 | |
Primary | Number of Participants With Clinically Significant Electrocardiogram (ECG) Values | ECG measurements included assessment of ventricular rate (VR), PR interval, QR interval, QT interval, QT corrected using Fridericia's formula (QTcF), and QT corrected using Bazett's formula (QTcB). Number of participants with clinically significant values in electrocardiogram based on Investigator's assessment are reported. Any value outside the normal range was to be flagged for the attention of the investigator was to assess whether or not a flagged value is of clinical significance. | Up to Day 176 | |
Secondary | Cmax: Maximum Observed Plasma Drug Concentration of ION-TTR-LRx | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose on Days 1 and 85 | ||
Secondary | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of ION-TTR-LRx | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose on Days 1 and 85 | ||
Secondary | AUCt: Area Under the Plasma Concentration-Time Curve From Time Zero to Time t for ION-TTR-LRx | From 0 to 672 hours post-dose on Day 85 for Cohorts A, B, and E; 0 hours to extrapolation to infinity post-dose on Day 1 for Cohort C | ||
Secondary | CL/F: Apparent Total Clearance of ION-TTR-LRx | From 0 to 672 hours post-dose on Day 85 for Cohorts A, B, and E; 0 hours to extrapolation to infinity post-dose on Day 1 for Cohort C | ||
Secondary | t1/2?z: Termination Half-Life of ION-TTR-LRx | Up to 92 hours; post-dose on Day 85 for Cohorts A, B, and E, and on Day 1 for Cohort C | ||
Secondary | Ae0-24h: Amount of Administered Dose of ION-TTR-LRx Excreted in Urine Over a 24-Hour Period | From 0 to 24 hours post-dose on Days 1 and 85 | ||
Secondary | Change From Baseline in Plasma Transthyretin (TTR) Levels Following Single and Multiple-dose Administration of ION-TTR-LRx | Baseline, Days 29 and 99 | ||
Secondary | Change From Baseline in Plasma Retinol Binding Protein 4 (RBP4) Levels Following Single and Multiple-Dose Administration of ION-TTR-LRx | Baseline, Days 29 and 99 | ||
Secondary | Percent Abundance of ION-682884 Antisense Oligonucleotide (ASO) Species (Metabolite) Following Administration of ION-682884 90 mg | As prespecified in the protocol, this outcome measure was planned to be analyzed only in the Multiple Dose Cohort B: 90 mg ION-682884. | 2 hours post-dose on Day 85 |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT05001152 -
Taste Assessment of Ozanimod
|
Phase 1 | |
Completed |
NCT05029518 -
3-Way Crossover Study to Compare the PK (Pharmokinetics) and to Evaluate the Effect of Food on the Bioavailability
|
Phase 1 | |
Completed |
NCT04493255 -
A Study to Determine the Metabolism and Elimination of [14C]E7090 in Healthy Male Participants
|
Phase 1 | |
Completed |
NCT03457649 -
IV Dose Study to Assess the Safety, Tolerability, PK, PD and Immunogenicity of ARGX-113 in Healthy Volunteers
|
Phase 1 | |
Completed |
NCT00995891 -
Collection of Blood, Bone Marrow, and Buccal Mucosa Samples From Healthy Volunteers for Center for Human Immunology, Autoimmunity, and Inflammatory Diseases (CHI) Laboratory Research Studies
|
||
Completed |
NCT05043766 -
Evaluation of Oral PF614 Relative to OxyContin
|
Phase 1 | |
Completed |
NCT05050318 -
Annual Study for Collection of Serum Samples in Children and Older Adults Receiving the 2021-2022 Formulations of Fluzone Quadrivalent Vaccine and Fluzone High-Dose Quadrivalent Vaccine, Respectively
|
Phase 4 | |
Completed |
NCT04466748 -
A Multiple Ascending Dose Pharmacology Study of Anaprazole in Healthy Chinese Subjects
|
Phase 1 | |
Completed |
NCT00746733 -
Vyvanse and Adderall XR Given Alone and in Combination With Prilosec OTC
|
Phase 1 | |
Recruiting |
NCT05929651 -
Study of Immunogenicity and Safety of MenQuadfi® as a Booster Vaccine in Toddlers 12 to 23 Months, Regardless of the Quadrivalent Meningococcal Conjugate Vaccine Used for Priming in Infancy
|
Phase 4 | |
Completed |
NCT05954039 -
Evaluation of the Efficacy of a Dietary Supplement on Hair Loss and Hair Aspect
|
N/A | |
Completed |
NCT05045716 -
A Study of Subcutaneous Lecanemab in Healthy Participants
|
Phase 1 | |
Active, not recruiting |
NCT02747927 -
Efficacy, Safety and Immunogenicity of Takeda's Tetravalent Dengue Vaccine (TDV) in Healthy Children
|
Phase 3 | |
Completed |
NCT05533801 -
A Study to Demonstrate the Bioequivalence of Lecanemab Supplied in Vials and a Single-Use Auto-Injector (AI) in Healthy Participants
|
Phase 1 | |
Not yet recruiting |
NCT03931369 -
Adaptation of Thirst to a Single Administration of Tolvaptan (TOLVATHIRST)
|
Phase 2 | |
Completed |
NCT03279146 -
A Single Dose Study Evaluating PK of TXL Oral Formulations in Healthy Subjects
|
Phase 1 | |
Completed |
NCT06027437 -
A Study to Assess the Relative Biological Availability and the Effect of Food on the Drug Levels of Danicamtiv in Healthy Adult Participants
|
Phase 1 | |
Recruiting |
NCT05619874 -
Effects of Two Virtual HIFCT Programs in Adults With Abdominal Obesity
|
N/A | |
Completed |
NCT05553418 -
Investigational On-body Injector Clinical Study
|
N/A | |
Completed |
NCT04092712 -
Study Evaluating Pharmacokinetics and Mass Balance of [14C]-CTP-543 in Healthy Adult Male Volunteers
|
Phase 1 |