Hereditary Transthyretin-Mediated Amyloid Polyneuropathy Clinical Trial
Official title:
A Phase 3 Global, Open-Label, Randomized Study to Evaluate the Efficacy and Safety of ION-682884 in Patients With Hereditary Transthyretin-Mediated Amyloid Polyneuropathy
| Verified date | March 2024 |
| Source | Ionis Pharmaceuticals, Inc. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
To evaluate the efficacy and safety of eplontersen after administration for 65 weeks to patients with hereditary transthyretin-mediated amyloid polyneuropathy (hATTR-PN), as compared to the NEURO-TTR trial (NCT01737398). For more information, please visit http://www.neuro-ttransform.com/.
| Status | Completed |
| Enrollment | 168 |
| Est. completion date | July 12, 2023 |
| Est. primary completion date | April 11, 2023 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 82 Years |
| Eligibility | Inclusion Criteria: 1. Aged 18 to 82 years at the time of informed consent 2. Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal or abstinent 3. Males must be surgically sterile or, abstinent or, if engaged in sexual relations with a woman of child-bearing potential, the subject or the subject's non-pregnant female partner must be using a highly effective contraceptive method 4. Diagnosis of hereditary transthyretin-mediated polyneuropathy as defined by meeting all 3 of the following: - Stage 1 or Stage 2 Familial Amyloid Polyneuropathy (FAP) or Coutinho Stage - Documented genetic mutation in the TTR gene - Symptoms and signs consistent with neuropathy associated with transthyretin amyloidosis, including NIS = 10 and = 130 Exclusion Criteria: 1. Clinically-significant (CS) abnormalities in medical history, screening laboratory results, physical or physical examination that would render a subject unsuitable for inclusion, including but not limited to abnormal safety labs 2. Karnofsky performance status = 50 3. Other causes of sensorimotor or autonomic neuropathy (e.g., autoimmune disease), including uncontrolled diabetes 4. Prior liver transplant or anticipated liver transplant within 1-yr of Screening 5. New York Heart Association (NYHA) functional classification of = 3 6. Acute coronary syndrome within 6 months of screening or major surgery within 3 months of Screening 7. Other types of amyloidosis 8. Have any other conditions, which, in the opinion of the Investigator or Sponsor would make the subject unsuitable for inclusion, or could interfere with the subject participating in or completing the Study 9. Current treatment with any approved drug for hereditary TTR amyloidosis such as Vyndaqel® / Vyndamax™ (tafamidis), Tegsedi™ (inotersen), Onpattro™ (patisiran), off-label use of diflunisal or doxycycline, and tauroursodeoxycholic acid (TUDCA). If previously treated with Vyndaqel® / Vyndamax™, diflunisal or doxycycline, and TUDCA, must have discontinued treatment for at least 2 weeks prior to Study Day 1 10. Previous treatment with Tegsedi™ (Inotersen) or Onpattro™ (patisiran), or other oligonucleotide or RNA therapeutic (including siRNA) |
| Country | Name | City | State |
|---|---|---|---|
| Argentina | Instituto Fleni | Buenos Aires | |
| Argentina | STAT Research | Buenos Aires | |
| Argentina | Hospital Italiano de Buenos Aires | Ciudad Autónoma De Buenos Aires | Buenos Aires |
| Argentina | Hospital El Cruce | Florencio Varela | Buenos Aires |
| Australia | Perron Institute for Neurological and Translational Science | Nedlands | Western Australia |
| Brazil | Universidade Estadual de Campinas | Campinas | |
| Brazil | Instituto de Neurologia de Curitiba | Curitiba | Parana |
| Brazil | Instituto de Neurologia de Curitiba | Curitiba | Paraná |
| Brazil | Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto | Ribeirão Preto | |
| Brazil | Hospital Universitário Clementino Fraga Filho | Rio De Janeiro | |
| Brazil | Associação de Assistência à Criança Deficiente - Unidade Lar Escola | São Paulo | |
| Canada | Toronto General Hospital | Toronto | Ontario |
| Cyprus | The Cyprus Institute of Neurology and Genetics | Egkomi | |
| France | Hôpital Bicêtre | Le Kremlin-Bicêtre | Ile-De-France |
| France | Hôpital de la Timone | Marseille | |
| France | Centre Hospitalier Universitaire de Toulouse | Toulouse | Haute-Garonne |
| Germany | Universitätsklinikum Heidelberg | Heidelberg | |
| Germany | Universitätsklinikum Würzburg | Würzburg | Bayern |
| Greece | University General Hospital of Heraklion (PAGNI) | Heraklion | Crete |
| Italy | Azienda Ospedaliera Universitaria Policlinico Gaetano Martino | Messina | |
| Italy | Fondazione IRCCS Istituto Neurologico Carlo Besta | Milano | |
| Italy | Fondazione IRCCS Policlinico San Matteo | Pavia | |
| Italy | Fondazione Policlinico Universitario Agostino Gemelli | Roma | |
| New Zealand | Auckland City Hospital | Grafton | Auckland |
| Portugal | Centro Hospitalar Universitário Lisboa Norte - Hospital De Santa Maria | Lisbon | |
| Portugal | Centro Hospitalar Universitário do Porto - Hospital Geral de Santo Antonio | Porto | |
| Spain | Hospital Clínico San Carlos | Madrid | |
| Spain | Hospital Son Llàtzer | Palma | Illes Balears |
| Spain | Hospital Son Llàtzer | Palma De Mallorca | Illes Balears |
| Sweden | Norrlands Universitetssjukhus | Umeå | |
| Taiwan | China Medical University Hospital | Taichung City | Taichung |
| Taiwan | National Taiwan University Hospital | Taipei | |
| Taiwan | Taipei Veterans General Hospital | Taipei City | Taipei |
| Taiwan | Chang Gung Memorial Hospital - Linkou Branch | Taoyuan City | Guishan District |
| Turkey | Istanbul Üniversitesi - Istanbul Tip Fakültesi | Istanbul | |
| United States | Johns Hopkins University Neurology Research Office | Baltimore | Maryland |
| United States | Boston University School of Medicine | Boston | Massachusetts |
| United States | University of North Carolina Hospitals - Neurology Clinic | Chapel Hill | North Carolina |
| United States | Indiana University School of Medicine - Indianapolis | Indianapolis | Indiana |
| United States | Mayo Clinic - Jacksonville | Jacksonville | Florida |
| United States | University of Kansas Medical Center | Kansas City | Kansas |
| United States | The Neurological Institute of New York | New York | New York |
| United States | Penn Presbyterian Medical Center | Philadelphia | Pennsylvania |
| United States | Oregon Health and Science University | Portland | Oregon |
| United States | Mayo Clinic - Rochester | Rochester | Minnesota |
| United States | Mayo Clinic - Arizona | Scottsdale | Arizona |
| United States | University of Washington Medical Center | Seattle | Washington |
| Lead Sponsor | Collaborator |
|---|---|
| Ionis Pharmaceuticals, Inc. |
United States, Argentina, Australia, Brazil, Canada, Cyprus, France, Germany, Greece, Italy, New Zealand, Portugal, Spain, Sweden, Taiwan, Turkey,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Change from baseline in mNIS+7 at Week 66 | The mNIS+7 composite score is a measure of neurologic impairment that evaluates muscle weakness, sensation, reflexes, nerve conduction, and autonomic function. The mNIS+7 composite score has a range of -22.32 to 346.32, and a higher score indicates lower function. | Baseline, Week 66 | |
| Primary | Change from baseline in the Norfolk Quality of Life Diabetic Neuropathy (QoL-DN) Questionnaire at Week 66 | The Norfolk QoL-DN score is a measure of physical function/large fiber neuropathy, symptoms, activities of daily living, small fiber neuropathy, and autonomic neuropathy. The Norfolk QoL-DN total score has a range of -4 to 136, and a higher score indicates poorer quality of life. | Baseline, Week 66 | |
| Primary | Percent change from baseline in serum TTR concentration at Week 66 | Baseline, Week 66 | ||
| Primary | Percent change from baseline in serum transthyretin (TTR) concentration at Week 35 | Baseline, Week 35 | ||
| Primary | Change from baseline in modified neuropathy impairment score plus 7 (mNIS+7) at Week 35 | The mNIS+7 composite score is a measure of neurologic impairment that evaluates muscle weakness, sensation, reflexes, nerve conduction, and autonomic function. The mNIS+7 Composite Score has a range of -22.32 to 346.32, and a higher score indicates lower function. | Baseline, Week 35 | |
| Secondary | Change from baseline in Norfolk QOL-DN at Week 35 | The Norfolk QoL-DN score is a measure of physical function/large fiber neuropathy, symptoms, activities of daily living, small fiber neuropathy, and autonomic neuropathy. The Norfolk QoL-DN total score has a range of -4 to 136, and a higher score indicates poorer quality of life. | Baseline, Week 35 | |
| Secondary | Change from baseline in Neuropathy Symptom and Change (NSC) score at Weeks 35 and 66 | NSC score is a questionnaire composed of 38 questions that assess the presence and severity of these neuropathy symptoms (including weakness, loss of temperature and pain sensation, and manifestations associated with autonomic nervous system dysfunction). | Baseline, Week 35, Week 66 | |
| Secondary | Change from baseline in the Physical Component Summary (PCS) score of the 36-Item Short Form Survey (SF-36) at Week 65 | The SF-36 is composed of 8 multi-item scales (35 items) assessing physical function (10 items), role limitations due to physical health problems (4 items), bodily pain (2 items), general health (5 items), vitality (4 items), social functioning (2 items), role limitations due to emotional problems (3 items) and emotional well-being (5 items). Each of the 8 scales is scored from 0 to 100 with higher scores indicating better health. The 8 scales can be aggregated into a PCS score, which is also scaled from 0 to 100 with higher scores indicating better health. | Baseline, Week 65 | |
| Secondary | Change from baseline in Polyneuropathy Disability (PND) score at Week 65 | The PND is a 6-stage scoring system: Stage 0: no impairment; Stage 1: sensory disturbances but preserved walking capabilities; Stage 2: impaired walking capacity, but ability to walk without a stick or crutches; Stage 3A/B: walking with help of 1 or 2 sticks or crutches; Stage 4: confined to wheel chair or bedridden. | Baseline, Week 65 | |
| Secondary | Change from baseline in modified body mass index (mBMI) at Week 65 | mBMI is defined as body mass index in kilograms per square meter (kg/m^2) multiplied by serum albumin in grams per liter (g/L). | Baseline, Week 65 |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT05071300 -
A Study to Assess the Long-Term Safety and Efficacy of Eplontersen (Formerly Known as ION-682884, IONIS-TTR-LRx and AKCEA-TTR-LRx) in Patients With Hereditary Transthyretin-Mediated Amyloid Polyneuropathy
|
Phase 3 |