TTR-mediated AmyloidosisPhase 3NCT01960348
APOLLO: The Study of an Investigational Drug, Patisiran (ALN-TTR02), for the Treatment of Transthyretin (TTR)-Mediated Amyloidosis
A Phase 3 study testing patisiran (ALN-TTR02) and Sterile Normal Saline (0.9% NaCl) in people with TTR-mediated Amyloidosis and Amyloidosis, Hereditary, run by Alnylam Pharmaceuticals at 52 sites in 21 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- TTR-mediated Amyloidosis, Amyloidosis, Hereditary, Amyloid Neuropathies, Familial
- What is being tested?
- patisiran (ALN-TTR02) and Sterile Normal Saline (0.9% NaCl)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 225 participants
- Where
- 52 sitesin 21 countries
- Study dates
- Nov 2013to Aug 2017
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
52 sites in 21 countries.
52 sites in 21 countries
United States13 sites
Clinical Trial Site
Baltimore, Maryland
Clinical Trial Site
Boston, Massachusetts
Clinical Trial Site
Chicago, Illinois
Clinical Trial Site
Denver, Colorado
Clinical Trial Site
Detroit, Michigan
Clinical Trial Site
Durham, North Carolina
Clinical Trial Site
La Mesa, California
Clinical Trial Site
New York, New York, 10029
Clinical Trial Site
New York, New York, 10032
Clinical Trial Site
Orange, California
Clinical Trial Site
Portland, Oregon
Clinical Trial Site
Rochester, Minnesota
Clinical Trial Site
St Louis, Missouri
France5 sites
Clinical Trial Site
Bourdeaux
Clinical Trial Site
Créteil
Clinical Trial Site
Le Kremlin-Bicêtre
Clinical Trial Site
Lille
Clinical Trial Site
Marseille
Spain4 sites
Clinical Trial Site
Barcelona
Clinical Trial Site
Huelva
Clinical Trial Site
Madrid
Clinical Trial Site
Palma de Mallorca
Brazil3 sites
Clinical Trial Site
Ribeirão Preto
Clinical Trial Site
Rio de Janeiro
Clinical Trial Site
São Paulo
Germany3 sites
Clinical Trial Site
Heidelberg
Clinical Trial Site
Münster
Clinical Trial Site
Regensburg
Italy3 sites
Clinical Trial Site
Pavia
Clinical Trial Site
Rome
Clinical Trial Site
Sicily
Japan3 sites
Clinical Trial Site
Aichi
Clinical Trial Site
Kumamoto
Clinical Trial Site
Matsumoto, Nagano
South Korea2 sites
Clinical Trial Site
Seoul, 135-710
Clinical Trial Site
Seoul, 143-729
Taiwan2 sites
Clinical Trial Site
Taipai, 11217
Clinical Trial Site
Taipei, 10002
United Kingdom2 sites
Clinical Trial Site
London, NW32PF
Clinical Trial Site
London, SW17 0RE
About this study
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)
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.
- Conditions
- TTR-mediated Amyloidosis, Amyloidosis, Hereditary, Amyloid Neuropathies, Familial, Familial Amyloid Polyneuropathies, Amyloid Neuropathies, Amyloidosis, Hereditary, Transthyretin-Related
- Being tested
- patisiran (ALN-TTR02), Sterile Normal Saline (0.9% NaCl)
- Keywords
- RNAi therapeutic, FAP, Familial Amyloid Polyneuropathy, TTR, Transthyretin, Amyloidosis
- Medical subject headings
- Amyloidosis, Familial, Amyloid Neuropathies, Familial, Amyloid Neuropathies, Amyloidosis, Hereditary, Transthyretin-Related, Amyloidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
patisiran (ALN-TTR02)Drug
administered by intravenous (IV) infusion
Sterile Normal Saline (0.9% NaCl)Drug
administered by intravenous (IV) infusion
| Study group | Role | What they receive |
|---|---|---|
| patisiran (ALN-TTR02) | Active comparator | Not described Receives: Drug: patisiran (ALN-TTR02) |
| Sterile Normal Saline (0.9% NaCl) | Placebo comparator | Not described Receives: Drug: Sterile Normal Saline (0.9% NaCl) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Modified Neuropathy Impairment Score +7 (mNIS+7)
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.
Measured: 18mo
Secondary outcomes (6)
Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Questionnaire
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.
Measured: 18mo
Neurological Impairment Score-Weakness (NIS-W) Score
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.
Measured: 18mo
Rasch-built Overall Disability Scale (R-ODS) Score
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.
Measured: 18mo
Timed 10-meter Walk Test (10-MWT, Gait Speed)
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.
Measured: 18mo
Modified Body Mass Index (mBMI)
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).
Measured: 18mo
Autonomic Symptoms Questionnaire (Composite Autonomic Symptom Score [COMPASS 31])
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.
Measured: 18mo
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2013 (estimated)
- Study startNov 2013
- Primary completionAug 2017
- Study completionAug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for TTR-mediated AmyloidosisStudies of the same condition, open and under way.
- More trials run by Alnylam PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 225 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alnylam Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jared Gollob, Study director, Alnylam Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01960348
- Sponsor's protocol ID
- ALN-TTR02-004
- Other IDs
- 2013-002987-17
- Status last verified
- Nov 2018
- First submitted
- 9 Oct 2013
- Last updated
- 22 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Access to Anonymized individual participant data that support these results is made available 12 months after study completion and not less than 12 months after the product and indication have been approved in the US and/or the EU. Data will be provided contingent upon the approval of a research proposal and the execution of a data sharing agreement. Requests for access to data can be submitted via the website www.vivli.org.
- Expanded access
- Available
Publications
Lin KP, Yang CC, Lee YC, Lee MJ, Vest J, Sweetser MT, White MT, Badri P, Hsieh ST, Chao CC. Patisiran, an RNAi therapeutic for hereditary transthyretin-mediated amyloidosis: Sub-analysis in Taiwanese patients from the APOLLO study. J Formos Med Assoc. 2024 Sep;123(9):975-984. doi: 10.1016/j.jfma.2024.03.008. Epub 2024 Mar 27.
PubMed 38548524Quan D, Obici L, Berk JL, Ando Y, Aldinc E, White MT, Adams D. Impact of baseline polyneuropathy severity on patisiran treatment outcomes in the APOLLO trial. Amyloid. 2023 Mar;30(1):49-58. doi: 10.1080/13506129.2022.2118043. Epub 2022 Sep 18.
PubMed 36120830Zhang X, Goel V, Attarwala H, Sweetser MT, Clausen VA, Robbie GJ. Patisiran Pharmacokinetics, Pharmacodynamics, and Exposure-Response Analyses in the Phase 3 APOLLO Trial in Patients With Hereditary Transthyretin-Mediated (hATTR) Amyloidosis. J Clin Pharmacol. 2020 Jan;60(1):37-49. doi: 10.1002/jcph.1480. Epub 2019 Jul 19.
PubMed 31322739Minamisawa M, Claggett B, Adams D, Kristen AV, Merlini G, Slama MS, Dispenzieri A, Shah AM, Falk RH, Karsten V, Sweetser MT, Chen J, Riese R, Vest J, Solomon SD. Association of Patisiran, an RNA Interference Therapeutic, With Regional Left Ventricular Myocardial Strain in Hereditary Transthyretin Amyloidosis: The APOLLO Study. JAMA Cardiol. 2019 May 1;4(5):466-472. doi: 10.1001/jamacardio.2019.0849.
PubMed 30878017Solomon SD, Adams D, Kristen A, Grogan M, Gonzalez-Duarte A, Maurer MS, Merlini G, Damy T, Slama MS, Brannagan TH 3rd, Dispenzieri A, Berk JL, Shah AM, Garg P, Vaishnaw A, Karsten V, Chen J, Gollob J, Vest J, Suhr O. Effects of Patisiran, an RNA Interference Therapeutic, on Cardiac Parameters in Patients With Hereditary Transthyretin-Mediated Amyloidosis. Circulation. 2019 Jan 22;139(4):431-443. doi: 10.1161/CIRCULATIONAHA.118.035831.
PubMed 30586695Adams D, Gonzalez-Duarte A, O'Riordan WD, Yang CC, Ueda M, Kristen AV, Tournev I, Schmidt HH, Coelho T, Berk JL, Lin KP, Vita G, Attarian S, Plante-Bordeneuve V, Mezei MM, Campistol JM, Buades J, Brannagan TH 3rd, Kim BJ, Oh J, Parman Y, Sekijima Y, Hawkins PN, Solomon SD, Polydefkis M, Dyck PJ, Gandhi PJ, Goyal S, Chen J, Strahs AL, Nochur SV, Sweetser MT, Garg PP, Vaishnaw AK, Gollob JA, Suhr OB. Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis. N Engl J Med. 2018 Jul 5;379(1):11-21. doi: 10.1056/NEJMoa1716153.
PubMed 29972753Adams D, Suhr OB, Dyck PJ, Litchy WJ, Leahy RG, Chen J, Gollob J, Coelho T. Trial design and rationale for APOLLO, a Phase 3, placebo-controlled study of patisiran in patients with hereditary ATTR amyloidosis with polyneuropathy. BMC Neurol. 2017 Sep 11;17(1):181. doi: 10.1186/s12883-017-0948-5.
PubMed 28893208