July 10, 2026
Welcome to the sixth issue of the MAGNITUDE-2 newsletter, containing important study-related information, updates, and data. Please file it in your Investigator Site File (ISF) binder because it is a study correspondence. If you have any comments or suggestions, contact your CRA.
• We would like to especially thank all regulatory personnel at sites for their incredible help these past few months while submitting Protocol Amendment V5.0! It is expected that study enrollment will be completed in the next 6 weeks. We appreciate all of the effort that you have put towards enrolling efficiently.
• Please your CRA know if you are unable to attend the study site call which is scheduled for 05Aug2026. An individual call can be arranged as needed.
General Reminders
• Please inform your CRA if a subject is expected to miss a safety blood collection during weeks 2-6 after dosing.
• Complete forms accurately and completely
• Follow GCP guidelines for all corrections.
Heat as Pain
Perform heat spot test one week prior and on the day of testing.
Nerve Conduction Studies (NCS)
• Submit waveforms, tables, and worksheets in one PDF file.
Norfolk Assessment
• Please make every effort to ensure that all participants respond to questionnaires accurately and fully.
• A few cases have been identified where a participant skipped questions or responded with multiple conflicting answers to the same question.
• All questionnaires should be reviewed for completeness and accuracy before the participant departs from the clinic.
• Month 12 visits are underway for participants who enrolled early in the trial. The first crossover occurred 05Jun2025 at Dr Chao’s site 15803 / National Taiwan University Hospital.
• As participants are evaluated for early crossover eligibility at Month 12, please remember that site staff are blinded to the mNIS+7 composite scores to minimize potential bias in the study. However, Intellia’s Medical Monitors are available if you would like to discuss the clinical status of any of your participants.
• Mayo Clinic will upload Rapid Progression Eligibility Forms within business 5 days of Month 12 # 2 mNIS+7 approval. We are here to support you and your team throughout this process.
The study team would like to remind site staff that there are a few key differences between the Schedule of Activities for the Primary Period and Crossover Period. Please refer to the PV5.0 for full details.
• For WOCBP, serum pregnancy and FSH are not collected during crossover. Urine pregnancy testing locally is still expected.
• Medical eye examinations are not conducted during the crossover period unless there is an early termination visit.
• Pre-crossover mNIS+7 visits do not need to be conducted within 7 days of crossover dosing.
Lab kits, requisition forms, and labels have been updated to reflect the visit changes implemented by PV5.0. Please note a discrepancy was identified on the Medpace Reference Laboratories (MRL) Requisition Forms stating crossover Month 9, crossover Month 15, and crossover Month 21 have samples collected. These visits do not have any samples collected nor samples sent to MRL per PV5.0. QRC was corrected and new version available at MRL portal. Updated forms are being shipped to all sites and will be delivered as soon as cleared from customs. Please escalate any issues with your samples to your CRA (up until week 6 especially).
Please see the updated patient/site materials for PV5.0 listed below.
• Pre-Eligibility Checklist (V2.0, 02Apr2026)
• Pre-Day 1 Checklist (V3.0, 02Apr2026)
• Pre-Crossover Eligibility Checklist (V1.0, 03Apr2026)
• Pre-Crossover Day 1 Checklist (V1.0, 06Apr2026)
• Dosing Order of Procedures (V3.0, 02Apr2026)
• Key Talking Points (V2.0, 28Apr2026)
• Liver Function Test (LFT) Reference List
• Participant Emergency Contact Card (V2.0, 26Feb2026)
• Key Study Reminders (V1.0, 09Feb2026)
• Dear Participant/Family Member Letter (V2, 02Feb2026)
• Participant Medication Sticker (V1.0, 09Feb2026)
• Please reference V5.0 of the CRF Completion Guidelinesdated 22May2026 when entering data moving forward.
• If you have any questions or concerns, please contact your CRA.
The DMC met on 18May2026 and 06Jul2026. They determined the study may continue as planned according to the current protocol and related amendments. An update to the ICF is expected in the coming months. Please work with your CRA and your local Medpace team to have the recommendation letter submitted, if needed. If you have any questions or concerns, please contact your CRA.
Intellia is working on building a new system to facilitate easier mNIS+7 submission, review, and evaluation. We will keep you updated about the changes, timelines, and upcoming trainings. Sites should expect further information in the coming weeks.
Intellia and Medpace are working on building a new system to assemble important study references in one site-facing website. This Hub is meant to assist site staff in understanding the latest available study materials, important contact information, and relevant study links. Please stay tuned for more information and let us know of any recommendations you’d find helpful
Thank you for your efforts as many sites have resumed enrollment activities under PV5.0! As we are resuming enrollment and initiating cross-over please do not hesitate to give a quick update on the participant status on the day post dosing to your CRA or the Intellia team! It will be much appreciated!
As of 10Jul2026, we have nearly reached the enrollment cap for early onset V30M. If you have any patients with early onset V30M who express interest in participating, you may continue to submit a Screening Authorization Form, and they will be placed on a waiting list for our consideration.
Brazil 07606 / PSEG Centro de Pesquisa Clínica S.A. | Paulo Sgobbi de Souza: 9 Randomizations
Brazil 07607 / Hospital das Clinicas da Universidade Estadual de Campinas (UNICAMP) | Marcondes Cavalcante França Jr.: 6 Randomizations
Taiwan 15803 / National Taiwan University Hospital | Chi-Chao Chao: 5 Randomizations
Brazil 07601 / HCFMRP - Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto | Wilson Marques Jr: 5 Randomizations
Taiwan 15804 / Chang Gung Medical Foundation - Linkou Branch | Long-Sun Ro: 4 Randomizations
Brazil 07609 / Instituto de Educação, Pesquisa e Gestão em Saúde | Marcia Waddington Cruz: 4 Randomizations
Singapore 70203 / National University Hospital - National University Health System | Kay Wei Ping Ng: 4 Randomizations
Argentina 03205 / Hospital El Cruce |Cristian Calandra 3 Randomizations
Taiwan 15802 / Taipei Veterans General Hospital | Yi-Chung Lee: 3 Randomizations
Thailand 76401 / Siriraj Hospital | Pannathat Soontrapa: 3 Randomizations
Argentina 03206 / Hospital Británico de Buenos Aires |Ricardo Reisin: 2 Randomizations
Singapore 70204 / Singapore General Hospital | Kaavya Narasimhalu: 1 Randomization
Argentina 03203 / Hospital Italiano de Buenos Aires |Marcelo Rugiero 1 Randomization
Screened 95
Randomized 50
Screen Failed 35
In Screening 10
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