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APOLLO: The Study of an Investigational Drug, Patisiran (ALN-TTR02), for the Treatment of Transthyretin (TTR)-Mediated Amyloidosis

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ClinicalTrials.gov Identifier: NCT01960348
Recruitment Status : Completed
First Posted : October 10, 2013
Results First Posted : September 6, 2018
Last Update Posted : December 11, 2018
Sponsor:
Information provided by (Responsible Party):
Alnylam Pharmaceuticals

Brief Summary:
The purpose of this study is to evaluate the safety and efficacy of patisiran (ALN-TTR02) in patients with transthyretin (TTR) mediated amyloidosis. An open-label, single-arm, long-term follow-up extension study NCT02510261 (ALN-TTR02-006) was initiated to provide participants who completed this study with continued patisiran-LNP (lipid nanoparticle) treatment.

Condition or disease Intervention/treatment Phase
TTR-mediated Amyloidosis Amyloidosis, Hereditary Amyloid Neuropathies, Familial Familial Amyloid Polyneuropathies Amyloid Neuropathies Amyloidosis, Hereditary, Transthyretin-Related Drug: patisiran (ALN-TTR02) Drug: Sterile Normal Saline (0.9% NaCl) Phase 3

Expanded Access : An investigational treatment associated with this study has been approved for sale to the public.   More info ...

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 225 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: APOLLO: A Phase 3 Multicenter, Multinational, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Patisiran (ALN-TTR02) in Transthyretin (TTR)-Mediated Polyneuropathy (Familial Amyloidotic Polyneuropathy-FAP)
Study Start Date : November 2013
Actual Primary Completion Date : August 2017
Actual Study Completion Date : August 2017


Arm Intervention/treatment
Active Comparator: patisiran (ALN-TTR02) Drug: patisiran (ALN-TTR02)
administered by intravenous (IV) infusion

Placebo Comparator: Sterile Normal Saline (0.9% NaCl) Drug: Sterile Normal Saline (0.9% NaCl)
administered by intravenous (IV) infusion




Primary Outcome Measures :
  1. Modified Neuropathy Impairment Score +7 (mNIS+7) [ Time Frame: 18mo ]
    The difference between the patisiran (ALN-TTR02) and placebo groups in the change from baseline in mNIS+7 at 18 months. The mNIS+7 is a composite score that quantitates 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.


Secondary Outcome Measures :
  1. Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Questionnaire [ Time Frame: 18mo ]
    The difference between the patisiran (ALN-TTR02) and placebo groups in the change from baseline in Norfolk QoL-DN at 18 months. 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.

  2. Neurological Impairment Score-Weakness (NIS-W) Score [ Time Frame: 18mo ]
    The difference between the patisiran (ALN-TTR02) and placebo groups in the change from baseline in NIS-W at 18 months. NIS-W is a measure of motor strength, comprised of cranial nerve and both upper and lower limb motor assessments. The minimum and maximum values are 0 and 192, respectively. A higher score indicates a worse outcome.

  3. Rasch-built Overall Disability Scale (R-ODS) Score [ Time Frame: 18mo ]
    The difference between the patisiran (ALN-TTR02) and placebo groups in the change from baseline in R-ODS score at 18 months. The R-ODS is comprised of a 24-item linearly weighted scale that specifically captures activity and social participation limitations in patients. The minimum and maximum values are 0 and 48, respectively. A higher score indicates a better outcome.

  4. Timed 10-meter Walk Test (10-MWT, Gait Speed) [ Time Frame: 18mo ]
    The difference between the patisiran (ALN-TTR02) and placebo groups in the change from baseline in 10-MWT at 18 months. Ability to ambulate (gait speed) was assessed through the 10-meter walk test (10-MWT). The walk had to be completed without assistance from another person; ambulatory aids such as canes and walkers were permitted.

  5. Modified Body Mass Index (mBMI) [ Time Frame: 18mo ]
    The difference between the patisiran (ALN-TTR02) and placebo groups in the change from baseline in mBMI at 18 months. The nutritional status of patients was evaluated using the mBMI; calculated as the product of BMI (weight in kilograms divided by the square of height in meters) and serum albumin (g/L).

  6. Autonomic Symptoms Questionnaire (Composite Autonomic Symptom Score [COMPASS 31]) [ Time Frame: 18mo ]
    The difference between the patisiran (ALN-TTR02) and placebo groups in the change from baseline in COMPASS 31 at 18 months. The COMPASS 31 is a measure of autonomic neuropathy symptoms. The questions evaluated 6 autonomic domains (orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor). The minimum and maximum values are 0 and 100, respectively. A higher score indicates a worse outcome.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female of 18 to 85 years of age (inclusive);
  • Have a diagnosis of FAP
  • Neuropathy Impairment Score requirement of 5-130
  • Meet Karnofsky performance status requirements
  • Have adequate complete blood counts and liver function tests
  • Have adequate cardiac function
  • Have negative serology for hepatitis B virus (HBV) and hepatitis C virus (HCV)

Exclusion Criteria:

  • Had a prior liver transplant or is planned to undergo liver transplant during the study period;
  • Has untreated hypo- or hyperthyroidism;
  • Has known human immunodeficiency virus (HIV) infection;
  • Had a malignancy within 2 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated;
  • Recently received an investigational agent or device
  • Is currently taking diflunisal, tafamidis, doxycycline, or tauroursodeoxycholic acid

Information from the National Library of Medicine

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): NCT01960348


  Show 52 Study Locations
Sponsors and Collaborators
Alnylam Pharmaceuticals
Investigators
Study Director: Jared Gollob Alnylam Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Alnylam Pharmaceuticals:
Study Protocol  [PDF] September 8, 2015
Statistical Analysis Plan  [PDF] August 23, 2017


Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Alnylam Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01960348     History of Changes
Other Study ID Numbers: ALN-TTR02-004
2013-002987-17 ( EudraCT Number )
First Posted: October 10, 2013    Key Record Dates
Results First Posted: September 6, 2018
Last Update Posted: December 11, 2018
Last Verified: November 2018

Keywords provided by Alnylam Pharmaceuticals:
RNAi therapeutic
FAP
Familial Amyloid Polyneuropathy
TTR
Transthyretin
Amyloidosis

Additional relevant MeSH terms:
Amyloidosis
Polyneuropathies
Amyloid Neuropathies
Amyloid Neuropathies, Familial
Amyloidosis, Familial
Proteostasis Deficiencies
Metabolic Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Nervous System Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Metabolism, Inborn Errors