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Trial record 2 of 2 for:    NCT01960348

HELIOS-A: A Study of Vutrisiran (ALN-TTRSC02) in Patients With Hereditary Transthyretin Amyloidosis (hATTR Amyloidosis)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03759379
Recruitment Status : Active, not recruiting
First Posted : November 30, 2018
Last Update Posted : November 17, 2020
Sponsor:
Information provided by (Responsible Party):
Alnylam Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE November 28, 2018
First Posted Date  ICMJE November 30, 2018
Last Update Posted Date November 17, 2020
Actual Study Start Date  ICMJE February 14, 2019
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 2, 2020)
Change from Baseline in the Modified Neurologic Impairment Score +7 (mNIS+7) at Month 9 [ Time Frame: Baseline, Month 9 ]
The mNIS+7 is a composite score that quantifies motor, sensory, and autonomic neurologic impairment due to injury of large and small nerves. The minimum and maximum values are 0 and 304, respectively. A higher score indicates a worse outcome.
Original Primary Outcome Measures  ICMJE
 (submitted: November 28, 2018)
  • Change from Baseline in the Modified Neurologic Impairment Score +7 (mNIS+7) at Month 9 [ Time Frame: Baseline, Month 9 ]
    The mNIS+7 is a composite score that measures neurologic impairment which includes the following components: physical exam of lower limbs, upper limbs and cranial nerves to assess motor strength/weakness, electrophysiologic measurement of small and large nerve fiber function, sensory testing and postural blood pressure. The minimum and maximum values are 0 and 304, respectively. A higher score indicates a worse outcome. The change in mNIS+7 will be evaluated for ALN-TTRSC02 and compared to the placebo arm of the APOLLO study (NCT01960348).
  • Change from Baseline in Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Total Score at Month 9 [ Time Frame: Baseline, Month 9 ]
    The Norfolk QoL-DN is a standardized 35-item patient-rated questionnaire used to assess 5 domains: physical function, large fiber neuropathy, activities of daily living, symptoms, small fiber neuropathy, and autonomic neuropathy. The minimum and maximum values are -4 and 136, respectively. A higher score indicates a worse outcome. The change in Norfolk QoL-DN will be evaluated for ALN-TTRSC02 and compared to the placebo arm of the APOLLO study (NCT01960348).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 2, 2020)
  • Change from Baseline in Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Total Score at Month 9 [ Time Frame: Baseline, Month 9 ]
    The Norfolk QoL-DN questionnaire is a standardized 35-item patient-reported outcomes measure that is sensitive to the different features of diabetic neuropathy - small fiber, large fiber, and autonomic nerve function. The minimum and maximum values are -4 and 136, respectively. A higher score indicates a worse outcome.
  • Change from Baseline in the Timed 10-Meter Walk Test (10-MWT) at Month 9 [ Time Frame: Baseline, Month 9 ]
  • Change from Baseline in the Modified Neurologic Impairment Score +7 (mNIS+7) at Month 18 [ Time Frame: Baseline, Month 18 ]
    The mNIS+7 is a composite score that quantifies motor, sensory, and autonomic neurologic impairment due to injury of large and small nerves. The minimum and maximum values are 0 and 304, respectively. A higher score indicates a worse outcome.
  • Change from Baseline in Norfolk QoL-DN Total Score at Month 18 [ Time Frame: Baseline, Month 18 ]
    The Norfolk QoL-DN questionnaire is a standardized 35-item patient-reported outcomes measure that is sensitive to the different features of diabetic neuropathy - small fiber, large fiber, and autonomic nerve function. The minimum and maximum values are -4 and 136, respectively. A higher score indicates a worse outcome.
  • Change from Baseline in the 10-MWT at Month 18 [ Time Frame: Baseline, Month 18 ]
  • Change from Baseline in the Modified Body Mass Index (mBMI) at Month 18 [ Time Frame: Baseline, Month 18 ]
  • Change from Baseline in the Rasch-Built Overall Disability Scale (R-ODS) at Month 18 [ Time Frame: Baseline, Month 18 ]
    The R-ODS is comprised of a 24-item linearly weighted scale that specifically captures activity and social participation limitations. The minimum and maximum values are 0 and 48, respectively. A higher score indicates a better outcome.
  • Percentage Reduction in Serum Transthyretin (TTR) Levels Through Month 18 [ Time Frame: Up to Month 18 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 28, 2018)
  • Change from Baseline in the Timed 10-Meter Walk Test (10-MWT) at Months 9 and 18 [ Time Frame: Baseline, Months 9 and 18 ]
    The 10-MWT is the time a participant takes to walk 10 meters (gait speed) without assistance from another person; ambulatory aids such as canes and walkers are permitted. The change in 10-MWT will be evaluated for ALN-TTRSC02 and compared to the placebo arm of the APOLLO study (NCT01960348).
  • Change from Baseline in the Modified Body Mass Index (mBMI) at Months 9 and 18 [ Time Frame: Baseline, Months 9 and 18 ]
    The mBMI is calculated as the product of body mass index (BMI) (weight in kilograms divided by the square of height in meters) and serum albumin (g/L). The change in mBMI will be evaluated for ALN-TTRSC02 and compared to the placebo arm of the APOLLO study (NCT01960348).
  • Change from Baseline in the Rasch-Built Overall Disability Scale (R-ODS) at Months 9 and 18 [ Time Frame: Baseline, Months 9 and 18 ]
    The R-ODS is comprised of a 24-item linearly weighted scale that specifically captures activity and social participation limitations in participants. The minimum and maximum values are 0 and 48, respectively. A higher score indicates a better outcome. The change in R-ODS will be evaluated for ALN-TTRSC02 and compared to the placebo arm of the APOLLO study (NCT01960348).
  • Percentage Reduction in Serum Transthyretin (TTR) Levels at Months 9 and 18 [ Time Frame: Baseline, Months 9 and 18 ]
    The percentage reduction in TTR levels will be evaluated for ALN-TTRSC02 and and compared to that in the patisiran-LNP arm.
  • Frequency of All-Cause Deaths and/or All-Cause Hospitalizations Up to Month 18 [ Time Frame: Up to Month 18 ]
    The frequency of all-cause deaths and/or all-cause hospitalizations will be compared to the placebo arm of the APOLLO study (NCT01960348).
  • Frequency of All-Cause Deaths and/or All-Cause Hospitalizations in Participants with Cardiac Involvement Up to Month 18 [ Time Frame: Up to Month 18 ]
    The frequency of all-cause deaths and/or all-cause hospitalizations in participants with cardiac involvement will be compared to the placebo arm of the APOLLO study (NCT01960348).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE HELIOS-A: A Study of Vutrisiran (ALN-TTRSC02) in Patients With Hereditary Transthyretin Amyloidosis (hATTR Amyloidosis)
Official Title  ICMJE HELIOS-A: A Phase 3 Global, Randomized, Open-label Study to Evaluate the Efficacy and Safety of ALN-TTRSC02 in Patients With Hereditary Transthyretin Amyloidosis (hATTR Amyloidosis)
Brief Summary The purpose of this study is to evaluate the efficacy and safety of vutrisiran (ALN-TTRSC02) in patients with hereditary transthyretin amyloidosis (hATTR amyloidosis). Participants will receive vutrisiran or the reference comparator patisiran during the Treatment Period. The Treatment Period is followed by a Treatment Extension Period during which all participants in the patisiran group will switch to vutrisiran. This study will use the placebo arm of the APOLLO study (NCT01960348) as an external comparator for the primary and most other efficacy endpoints.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Amyloidosis, Hereditary
  • Transthyretin Amyloidosis
Intervention  ICMJE
  • Drug: Patisiran
    Patisiran will be administered by intravenous (IV) infusion.
  • Drug: Vutrisiran (ALN-TTRSC02)
    Vutrisiran will be administered by subcutaneous (SC) injection.
Study Arms  ICMJE
  • Experimental: Vutrisiran (ALN-TTRSC02)
    Participants will receive vutrisiran during the Treatment and Treatment Extension Periods.
    Intervention: Drug: Vutrisiran (ALN-TTRSC02)
  • Active Comparator: Patisiran
    Participants will receive patisiran during the Treatment Period and will switch to vutrisiran during the Treatment Extension Period.
    Interventions:
    • Drug: Patisiran
    • Drug: Vutrisiran (ALN-TTRSC02)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 16, 2020)
164
Original Estimated Enrollment  ICMJE
 (submitted: November 28, 2018)
160
Estimated Study Completion Date  ICMJE May 2024
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male or female of 18 to 85 years of age (inclusive);
  • Has a diagnosis of hATTR amyloidosis with transthyretin (TTR) mutation;
  • Has adequate neurologic impairment score (NIS);
  • Has adequate polyneuropathy disability (PND) score;
  • Has adequate Karnofsky Performance Status (KPS).

Exclusion Criteria:

  • Had a prior liver transplant or is likely to undergo liver transplantation during the study;
  • Has known other (non-hATTR) forms of amyloidosis or leptomeningeal amyloidosis;
  • Has New York Heart Association heart failure classification >2;
  • Clinically significant liver function test abnormalities;
  • Has known human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV) infection;
  • Received an experimental drug within 30 days of dosing;
  • Received prior TTR-lowering treatment;
  • Has other known causes of neuropathy.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Belgium,   Brazil,   Bulgaria,   Canada,   Cyprus,   France,   Germany,   Greece,   Italy,   Japan,   Korea, Republic of,   Malaysia,   Mexico,   Netherlands,   Portugal,   Spain,   Sweden,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03759379
Other Study ID Numbers  ICMJE ALN-TTRSC02-002
2018-002098-23 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Alnylam Pharmaceuticals
Study Sponsor  ICMJE Alnylam Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Alnylam Pharmaceuticals
PRS Account Alnylam Pharmaceuticals
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP