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

Sponsor

Alnylam Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04561518

Collaborator

(none)

1,500

Enrollment

Locations

117.3

Anticipated Duration (Months)

62.5

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

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 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) mutation

Condition or Disease	Intervention/Treatment	Phase
Transthyretin-Mediated Amyloidosis ATTR Amyloidosis

Study Design

Study Type:

Observational

Anticipated Enrollment :

1500 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Nov 23, 2020

Anticipated Primary Completion Date :

Sep 1, 2030

Anticipated Study Completion Date :

Sep 1, 2030

Arms and Interventions

Arm	Intervention/Treatment
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 mutation will be eligible for the study and will follow routine clinical care.

Outcome Measures

Primary Outcome Measures

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) [From 1 year prior to enrollment for up to 10 years]
Selected events of interest are defined as hepatic events, cardiovascular events, renal events, ocular events and infusion-related reactions in patients diagnosed with ATTRv amyloidosis.
Health Care Provider (HCP)-Assessed Polyneuropathy (PND) Disability Score [Up to 11 years]
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.
HCP-Assessed Familial Amyloidotic Polyneuropathy (FAP) Score [Up to 11 years]
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.
HCP-Assessed Neuropathy Impairment Score of the Lower Limb (NIS-LL) Score [Up to 11 years]
The NIS-LL assesses muscle weakness, reflexes and sensation, scored separately for the left and right limbs. Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) are scored on 0 to 4 scale (0=normal, 4=paralysis). Components of reflexes (quadriceps femoris, triceps surae) and sensation (touch pressure, pin-prick, vibration, joint position) are scored 0=normal, 1=decreased, or 2=absent. Total possible NIS-LL score ranges 0-88 with higher score=greater impairment.
HCP-Assessed Cardiomyopathy [Up to 11 years]
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.
Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Total Score [Up to 11 years]
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).
Kansas City Cardiomyopathy Questionnaire (KCCQ) [Up to 11 years]
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).
Rasch-built Overall Disability Scale (R-ODS) [Up to 11 years]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of ATTR amyloidosis or documented known disease-causing TTR mutation 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

Exclusion Criteria:

Current enrollment in a clinical trial for any investigational agent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Trial Site	La Jolla	California	United States	92037
2	Clinical Trial Site	Los Angeles	California	United States	90095
3	Clinical Trial Site	Jacksonville	Florida	United States	32224
4	Clinical Trial Site	Iowa City	Iowa	United States	52242
5	Clinical Trial Site	Kansas City	Kansas	United States	66160
6	Clinical Trial Site	Baltimore	Maryland	United States	21224
7	Clinical Trial Site	Boston	Massachusetts	United States	02127
8	Clinical Trial Site	New York	New York	United States	10034
9	Clinical Trial Site	Durham	North Carolina	United States	27710
10	Clinical Trial Site	Columbus	Ohio	United States	43210
11	Clinical Trial Site	Philadelphia	Pennsylvania	United States	19104
12	Clinical Trial Site	Austin	Texas	United States	78756
13	Clinical Trial Site	Copenhagen		Denmark
14	Clinical Trial Site	Bordeaux		France
15	Clinical Trial Site	Bron		France
16	Clinical Trial Site	Hanover		Germany
17	Clinical Trial Site	Jerusalem		Israel
18	Clinical Trial Site	Ramat Gan		Israel
19	Clinical Trial Site	Milan		Italy
20	Clinical Trial Site	Roma		Italy
21	Clinical Trial Site	Groningen		Netherlands
22	Clinical Trial Site	Lisbon		Portugal
23	Clinical Trial Site	Barcelona		Spain
24	Clinical Trial Site	Palma		Spain