Design and Rationale of the Global Phase 3 NEURO-TTRansform Study of Antisense Oligonucleotide AKCEA-TTR-LRx (ION-682884-CS3) in Hereditary Transthyretin-Mediated Amyloid Polyneuropathy
dc.contributor.author | Coelho, Teresa | |
dc.contributor.author | Ando, Yukio | |
dc.contributor.author | Benson, Merrill D. | |
dc.contributor.author | Berk, John L. | |
dc.contributor.author | Waddington-Cruz, Márcia | |
dc.contributor.author | Dyck, Peter J. | |
dc.contributor.author | Gillmore, Julian D. | |
dc.contributor.author | Khella, Sami L. | |
dc.contributor.author | Litchy, William J. | |
dc.contributor.author | Obici, Laura | |
dc.contributor.author | Monteiro, Cecilia | |
dc.contributor.author | Tai, Li-Jung | |
dc.contributor.author | Viney, Nicholas J. | |
dc.contributor.author | Buchele, Gustavo | |
dc.contributor.author | Brambatti, Michela | |
dc.contributor.author | Jung, Shiangtung W. | |
dc.contributor.author | O’Dea, Louis St. L. | |
dc.contributor.author | Tsimikas, Sotirios | |
dc.contributor.author | Schneider, Eugene | |
dc.contributor.author | Geary, Richard S. | |
dc.contributor.author | Monia, Brett P. | |
dc.contributor.author | Gertz, Morie | |
dc.contributor.department | Pathology and Laboratory Medicine, School of Medicine | en_US |
dc.date.accessioned | 2022-12-16T12:01:09Z | |
dc.date.available | 2022-12-16T12:01:09Z | |
dc.date.issued | 2021-06 | |
dc.description.abstract | Introduction: AKCEA-TTR-LRx is a ligand-conjugated antisense (LICA) drug in development for the treatment of hereditary transthyretin amyloidosis (hATTR), a fatal disease caused by mutations in the transthyretin (TTR) gene. AKCEA-TTR-LRx shares the same nucleotide sequence as inotersen, an antisense medicine approved for use in hATTR polyneuropathy (hATTR-PN). Unlike inotersen, AKCEA-TTR-LRx is conjugated to a triantennary N-acetylgalactosamine moiety that supports receptor-mediated uptake by hepatocytes, the primary source of circulating TTR. This advanced design increases drug potency to allow for lower and less frequent dosing. The NEURO-TTRansform study will investigate whether AKCEA-TTR-LRx is safe and efficacious, with the aim of improving neurologic function and quality of life in hATTR-PN patients. Methods/design: Approximately 140 adults with stage 1 (independent ambulation) or 2 (requires ambulatory support) hATTR-PN are anticipated to enroll in this multicenter, open-label, randomized, phase 3 study. Patients will be assigned 6:1 to AKCEA-TTR-LRx 45 mg subcutaneously every 4 weeks or inotersen 300 mg once weekly until the prespecified week 35 interim efficacy analysis, after which patients receiving inotersen will receive AKCEA-TTR-LRx 45 mg subcutaneously every 4 weeks. All patients will then receive AKCEA-TTR-LRx through the remainder of the study treatment period. The final efficacy analysis at week 66 will compare the AKCEA-TTR-LRx arm with the historical placebo arm from the phase 3 trial of inotersen (NEURO-TTR). The primary outcome measures are between-group differences in the change from baseline in serum TTR, modified Neuropathy Impairment Score + 7, and Norfolk Quality of Life-Diabetic Neuropathy questionnaire. Conclusion: NEURO-TTRansform is designed to determine whether targeted delivery of AKCEA-TTR-LRx to hepatocytes with lower and less frequent doses will translate into clinical and quality-of-life benefits for patients with hATTR-PN. | en_US |
dc.eprint.version | Final published version | en_US |
dc.identifier.citation | Coelho T, Ando Y, Benson MD, et al. Design and Rationale of the Global Phase 3 NEURO-TTRansform Study of Antisense Oligonucleotide AKCEA-TTR-LRx (ION-682884-CS3) in Hereditary Transthyretin-Mediated Amyloid Polyneuropathy. Neurol Ther. 2021;10(1):375-389. doi:10.1007/s40120-021-00235-6 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/30757 | |
dc.language.iso | en_US | en_US |
dc.publisher | SpringerLink | en_US |
dc.relation.isversionof | 10.1007/s40120-021-00235-6 | en_US |
dc.relation.journal | Neurology and Therapy | en_US |
dc.rights | Attribution-NonCommercial 4.0 International | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/4.0/ | * |
dc.source | PMC | en_US |
dc.subject | AKCEA-TTR-Lrx | en_US |
dc.subject | Antisense oligonucleotide | en_US |
dc.subject | Clinical trial design | en_US |
dc.subject | Hereditary transthyretin-mediated amyloid polyneuropathy | en_US |
dc.subject | Phase 3 clinical trial | en_US |
dc.title | Design and Rationale of the Global Phase 3 NEURO-TTRansform Study of Antisense Oligonucleotide AKCEA-TTR-LRx (ION-682884-CS3) in Hereditary Transthyretin-Mediated Amyloid Polyneuropathy | en_US |
dc.type | Article | en_US |