ConTTRibute: A Global Observational Study of Patients With Transthyretin (TTR)-Mediated Amyloidosis (ATTR Amyloidosis)

NCT04561518 | Recruiting

• 1 other identifier: ALN-TTR02-013
• Study Type: observational
• Target: 1,500
• Locations: 12 countries
• Sites: 40

Brief Summary

The purpose of this study is to:

• Describe epidemiological and clinical characteristics, natural history and real-world clinical management of ATTR amyloidosis patients
• Characterize the safety and effectiveness of patisiran and vutrisiran as part of routine clinical practice in the real-world clinical setting
• Describe disease emergence/progression in pre-symptomatic carriers of a known disease-causing transthyretin (TTR) variant

Conditions

Transthyretin-Mediated Amyloidosis; ATTR Amyloidosis

Keywords

RNAi therapeutic; Transthyretin; TTR; Amyloidosis; Hereditary Transthyretin-mediated (hATTR) Amyloidosis; hATTR amyloidosis; Hereditary ATTR amyloidosis; Wild-type amyloidosis; wtATTR amyloidosis; ATTRv amyloidosis; ATTRwt amyloidosis; Polyneuropathy; Familial amyloid polyneuropathies; ATTR; Transthyretin amyloidosis; TTR-mediated amyloidosis; Polyneuropathies; Amyloid neuropathies; Amyloid neuropathies, familial; Amyloidosis, familial

Outcome Measures

Primary Outcomes (10)

• Incidence of Adverse Events

  From time of enrollment for up to 10 years

• Selected Events of Interest in Patients with Hereditary Transthyretin-mediated (hATTR) Amyloidosis (ATTRv Amyloidosis)

  Selected events of interest are defined as hepatic events, cardiovascular events, renal events, ocular events and infusion-related reactions, hypersensitivity, and other events in patients diagnosed with hATTR amyloidosis.

  From 1 year prior to enrollment for up to 10 years

• Health Care Provider (HCP)-Assessed Polyneuropathy (PND) Disability Score

  PND Scores: Stage 0=No symptoms; Stage I=Sensory disturbances but preserved walking capabilities; Stage II=Impaired walking capacity, but ability to walk without a stick or crutches; Stage IIIA=Walking with help of 1 stick or crutch; Stage IIIB=Walking with the help of 2 sticks or crutches; Stage IV=confined to wheel chair or bedridden.

  Up to 11 years

• HCP-Assessed Familial Amyloidotic Polyneuropathy (FAP) Score

  FAP Scores: Stage 0=No symptoms; Stage I=Unimpaired ambulation; mostly mild sensory, motor and autonomic neuropathy in the lower limbs; Stage II=Assistance with ambulation required, mostly moderate impairment progression to the lower limbs, upper limbs, and trunk; Stage III=Wheelchair-bound or bedridden; severe sensory, motor, and autonomic involvement of all limbs.

  Up to 11 years

• HCP-Assessed Neuropathy Impairment Score (NIS)

  NIS : 74 items, assess muscle weakness, reflexes and sensation; scored separately for left, right limbs (37 items for each side). Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) scored on scale 0 (normal) to 4 (paralysis), higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae) and sensation (touch pressure, pin-prick, vibration, joint position) scored 0 = normal, 1= decreased, or 2 = absent. Total possible NIS score range 0-244, higher score=greater impairment.

  Up to 11 years

• HCP-Assessed Cardiomyopathy

  Cardiomyopathy will be assessed using New York Heart Association (NYHA) Class: I=No symptoms; II=Symptoms with ordinary physical activity; III=Symptoms with less than ordinary physical activity; IV=Symptoms at rest.

  Up to 11 years

• HCP- Assessed Cardiopulmonary Exercise Testing (CPET) Performance

  Up to 11 years

• Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Total Score

  Norfolk-QoL-DN: The Norfolk QOL-DN questionnaire is a standardized 35-item patient-reported outcomes measure that assesses 6 domains: physical function, large-fiber neuropathy, activities of daily living, symptoms, small-fiber neuropathy, and autonomic neuropathy. The total score ranges from -4 points (best possible quality of life) to 136 points (worst possible quality of life).

  Up to 11 years

• Kansas City Cardiomyopathy Questionnaire (KCCQ)

  The KCCQ is a 23-item self-administered questionnaire developed to independently measure the patient's perception of health status, which includes heart failure symptoms, impact on physical and social function, and how their heart failure impacts their quality of life within a 2-week recall period. The KCCQ quantifies 6 domains (symptoms, physical function, quality of life, social limitation, self-efficacy, and symptom stability) and 2 summary scores (clinical and overall summary \[OS\] scores).

  Up to 11 years

• Rasch-built Overall Disability Scale (R-ODS)

  The R-ODS is a 24-item self-administered questionnaire for assessment of the disability a patient experiences. It uses a linearly weighted categorical rating scale that specifically captures domains of activity and social participation limitations in patients.

  Up to 11 years

Study Arms (2)

Patients with ATTR amyloidosis

Patients with a diagnosis of ATTR amyloidosis, hereditary or wild type, will be eligible for the study and will follow routine clinical care.

Pre-symptomatic Carriers

Pre-symptomatic carriers with a known disease-causing TTR variant will be eligible for the study and will follow routine clinical care.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with a diagnosis of ATTR amyloidosis, hereditary or wild type, and pre-symptomatic carriers with a known disease-causing TTR variant will be eligible for the study.

You may qualify if:

• Diagnosis of ATTR amyloidosis or documented known disease-causing TTR variant for the cohort of pre-symptomatic carriers
• Germany Only: Patients must be treated per the summary of product characteristics (SmPC) for any approved treatment for ATTR amyloidosis

You may not qualify if:

• Current enrollment in a clinical trial for any investigational agent

Sponsors & Collaborators

• Alnylam Pharmaceuticals: lead

Study Sites (40)

Clinical Trial Site

La Jolla, California, 92037, United States

RECRUITING

Clinical Trial Site

Los Angeles, California, 90095, United States

RECRUITING

Clinical Trial Site

Jacksonville, Florida, 32224, United States

RECRUITING

Clinical Trial Site

Iowa City, Iowa, 52242, United States

RECRUITING

Clinical Trial Site

Kansas City, Kansas, 66160, United States

RECRUITING

Clinical Trial Site

Baltimore, Maryland, 21224, United States

RECRUITING

Clinical Trial Site

Boston, Massachusetts, 02127, United States

COMPLETED

Clinical Trial Site

New York, New York, 10034, United States

RECRUITING

Clinical Trial Site

Durham, North Carolina, 27710, United States

RECRUITING

Clinical Trial Site

Columbus, Ohio, 43210, United States

RECRUITING

Clinical Trial Site

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Clinical Trial Site

Austin, Texas, 78756, United States

RECRUITING

Clinical Trial Site

Houston, Texas, 77030, United States

RECRUITING

Clinical Trial Site

Salvador, Brazil

RECRUITING

Clinical Trial Site

São Paulo, Brazil

RECRUITING

Clinical Trial Site

Sofia, Bulgaria

RECRUITING

Clinical Trial Site

Aarhus, Denmark

RECRUITING

Clinical Trial Site

Copenhagen, Denmark

COMPLETED

Clinical Trial Site

Bordeaux, France

RECRUITING

Clinical Trial Site

Bron, France

RECRUITING

Clinical Trial Site

Créteil, France

RECRUITING

Clinical Trial Site

Le Kremlin-Bicêtre, France

RECRUITING

Clinical Trial Site

Marseille, France

RECRUITING

Clinical Trial Site

Berlin, Germany

RECRUITING

Clinical Trial Site

Giessen, Germany

RECRUITING

Clinical Trial Site

Hanover, Germany

RECRUITING

Clinical Trial Site

Jerusalem, Israel

RECRUITING

Clinical Trial Site

Ramat Gan, Israel

RECRUITING

Clinical Trial Site

Milan, Italy

RECRUITING

Clinical Trial Site

Naples, Italy

RECRUITING

Clinical Trial Site

Palermo, Italy

RECRUITING

Clinical Trial Site

Roma, Italy

RECRUITING

Clinical Trial Site

Groningen, Netherlands

RECRUITING

Clinical Trial Site

Lisbon, Portugal

RECRUITING

Clinical Trial Site

Porto, Portugal

RECRUITING

Clinical Trial Site

Barcelona, Spain

RECRUITING

Clinical Trial Site

Madrid, Spain

RECRUITING

Clinical Trial Site

Palma, Spain

RECRUITING

Clinical Trial Site

New Taipei City, Taiwan

RECRUITING

Clinical Trial Site

Taipei, Taiwan

RECRUITING

MeSH Terms

Conditions

Amyloidosis; Amyloid Neuropathies, Familial; Polyneuropathies; Amyloidosis, Hereditary, Transthyretin-Related; Amyloid Neuropathies; Amyloidosis, Familial

Condition Hierarchy (Ancestors)

Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors

Study Officials

• Medical Director

  Alnylam Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Alnylam Clinical Trial Information Line

CONTACT

1-877-ALNYLAM; clinicaltrials@alnylam.com

Alnylam Clinical Trial Information Line

CONTACT

1-877-256-9526; clinicaltrials@alnylam.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2020
• First Posted: September 23, 2020
• Study Start: November 23, 2020
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): September 1, 2030
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (5); NL (1); IL (2); US (13); BU (1); DE (3); BR (2); DK (2); ES (3); TW (2); PT (2); IT (4)