A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ION-TTR-LRx in Healthy Volunteers and Patients With Hereditary Transthyretin-Mediated Amyloidosis
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ClinicalTrials.gov Identifier: NCT03728634 |
Recruitment Status :
Recruiting
First Posted : November 2, 2018
Last Update Posted : January 9, 2019
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Condition or disease | Intervention/treatment | Phase |
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Healthy Volunteers hATTR Amyloidosis | Drug: ION-TTR-LRx Drug: Placebo | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 56 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Double (Participant, Investigator) |
Primary Purpose: | Treatment |
Official Title: | A Phase 1/2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ION-682884, an Antisense Inhibitor of Transthyretin Production, in Healthy Volunteers and Patients With Hereditary Transthyretin-Mediated Amyloidosis |
Actual Study Start Date : | December 21, 2018 |
Estimated Primary Completion Date : | September 2019 |
Estimated Study Completion Date : | March 2020 |
Arm | Intervention/treatment |
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Experimental: ION-TTR-LRx
Single and multiple doses of ION-TTR-LRx administered subcutaneously
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Drug: ION-TTR-LRx
Single and multiple doses of ION-TTR-LRx administered subcutaneously
Other Name: ION-682884 |
Placebo Comparator: Placebo
Placebo comparator calculated volume to match active comparator administered subcutaneously
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Drug: Placebo
Placebo comparator calculated volume to match active comparator administered subcutaneously |
- Safety and Tolerability as Measured by the Number of Participants with at least one Treatment-Emergent Adverse Event [ Time Frame: Up to 176 Days ]
- Safety and Tolerability as Measured by the Number of Participants with clinically significant lab values [ Time Frame: Up to 176 Days ]
- Safety and Tolerability as Measured by the Number of Participants with clinically significant physical examination findings [ Time Frame: Up to 176 Days ]
- Safety and Tolerability as Measured by the Number of Participants with clinically significant ECG values [ Time Frame: Up to 176 Days ]
- Cmax: maximum observed drug concentration in plasma of ION-TTR-LRx [ Time Frame: Up to Day 176 ]
- Tmax: time taken to reach maximal concentration in plasma of ION-TTR-LRx [ Time Frame: Up to Day 176 ]
- AUCt: area under the plasma concentration-time curve from time zero to time t for ION-TTR-LRx [ Time Frame: Up to Day 176 ]
- CL/F: apparent total clearance of ION-TTR-LRx [ Time Frame: Up to Day 176 ]
- t1/2λz: termination half-life of ION-TTR-LRx [ Time Frame: Up to Day 176 ]
- The amount of administered dose of ION-TTR-LRx excreted in urine over a 24-hour period [ Time Frame: Up to Day 86 ]
- Change from Baseline in plasma TTR levels following single and multiple-dose administration of ION-TTR-LRx [ Time Frame: Day 29 (Cohort C); Day 99 (Cohorts A, B, and C) ]
- Change from Baseline in plasma RBP4 levels following single and multiple-dose administration of ION-TTR-LRx [ Time Frame: Day 29 (Cohort C); Day 99 (Cohorts A, B, and C) ]

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Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria for Healthy Volunteers (Cohorts A, B, and C)
- 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 < 32 kg/m2
Exclusion Criteria for Healthy Volunteers (Cohorts A, B, and C)
- 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
- Drug or alcohol dependency or abuse
- Treatment with another investigational drug, biological agent, or device within 1 month of Screening, or 5 half-lives of investigational agent, whichever is longer
- Blood donation within 28 days
- 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)
- Aged 18 to 82 years at the time of informed consent
- 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
- Diagnosis of hereditary transthyretin-mediated polyneuropathy
- 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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03728634
Contact: Ionis Pharmaceuticals | 800-679-4747 | patients@ionisph.com |
Canada, Ontario | |
Bio Pharma Services, Inc. | Recruiting |
Toronto, Ontario, Canada, M9L 3A2 | |
Contact +1 (416) 747-8484 info@biopharmaservices.com |
Responsible Party: | Ionis Pharmaceuticals, Inc. |
ClinicalTrials.gov Identifier: | NCT03728634 History of Changes |
Other Study ID Numbers: |
ION-682884-CS1 |
First Posted: | November 2, 2018 Key Record Dates |
Last Update Posted: | January 9, 2019 |
Last Verified: | January 2019 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes | |
Studies a U.S. FDA-regulated Device Product: | No | |
Product Manufactured in and Exported from the U.S.: | Yes |
Additional relevant MeSH terms:
Amyloidosis Proteostasis Deficiencies Metabolic Diseases |