Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

A Phase 1, Single- and Multi-Dose, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered ALN-TTRSC (Revusiran) in Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Alnylam Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01814839
First received: March 18, 2013
Last updated: February 4, 2016
Last verified: February 2016
  Purpose
The purpose of this study is to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of ALN-TTRSC (revusiran) in healthy volunteer subjects.

Condition Intervention Phase
TTR-mediated Amyloidosis
Drug: ALN-TTRSC (revusiran)
Drug: Sterile Normal Saline (0.9% NaCl)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 1, Randomized, Double-blind, Placebo-controlled, Single- and Multi-Dose, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered ALN-TTRSC in Healthy Volunteers

Further study details as provided by Alnylam Pharmaceuticals:

Primary Outcome Measures:
  • The proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs) and study drug discontinuation. [ Time Frame: Up to 63 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics (PK) of ALN-TTRSC (revusiran) (Cmax, tmax, t1/2, AUC0-last, CL). [ Time Frame: Up to 90 days ] [ Designated as safety issue: No ]
  • Effect of ALN-TTRSC (revusiran) on transthyretin (TTR) (Determination of % Lowering of TTR to pretreatment/Baseline Levels). [ Time Frame: Up to 90 days ] [ Designated as safety issue: No ]
  • Effect of ALN-TTRSC (revusiran) on vitamin A (Determination of % Lowering of vitamin A to pretreatment/Baseline Levels). [ Time Frame: Up to 90 days ] [ Designated as safety issue: No ]
  • Effect of ALN-TTRSC (revusiran) on retinol binding protein (RBP) (Determination of % Lowering of RBP to pretreatment/Baseline Levels). [ Time Frame: Up to 90 days ] [ Designated as safety issue: No ]

Enrollment: 85
Study Start Date: March 2013
Study Completion Date: May 2015
Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: ALN-TTRSC (revusiran) Drug: ALN-TTRSC (revusiran)
Ascending doses of ALN-TTRSC (revusiran) by subcutaneous (SC) injection
Placebo Comparator: Sterile Normal Saline (0.9% NaCl) Drug: Sterile Normal Saline (0.9% NaCl)
Calculated volume to match active comparator

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Body mass index (BMI) must be ≥ 16.5 kg/m2 and ≤ 35.0 kg/m2;
  • Female subjects must be of non-childbearing potential; e.g., postmenopausal or pre-menopausal with surgical sterilization;
  • Male subjects agree to use appropriate contraception;
  • Adequate blood counts, liver and renal function;
  • Non-smokers for at least 3 months;
  • Willing to give written informed consent and are willing to comply with the study requirements;
  • Subject was born in Japan and has lived outside of Japan for <10 years, and subject's biological parents and grandparents are fully Japanese and were born in Japan (cohorts 19 and 20).

Exclusion Criteria:

  • Known human immunodeficiency virus (HIV) positive status or known or suspected systemic bacterial, viral, parasitic, or fungal infection;
  • Subjects with a history of multiple drug allergies or intolerance to SC injection;
  • History of drug abuse and/or alcohol abuse;
  • Receiving an investigational agent within 3 months prior to study drug administration;
  • Considered unfit for the study by the Principal Investigator.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01814839

Locations
United Kingdom
Clinical Site
Leeds, United Kingdom, LS2 9LH
Clinical Site
London, United Kingdom, NW10 7EW
Sponsors and Collaborators
Alnylam Pharmaceuticals
Investigators
Study Director: Jared Gollob, MD Alnylam Pharmaceuticals
  More Information

Responsible Party: Alnylam Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01814839     History of Changes
Other Study ID Numbers: ALN-TTRSC-001 
Study First Received: March 18, 2013
Last Updated: February 4, 2016
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Alnylam Pharmaceuticals:
RNAi therapeutic

Additional relevant MeSH terms:
Amyloidosis
Proteostasis Deficiencies
Metabolic Diseases

ClinicalTrials.gov processed this record on September 30, 2016