March 20, 2026
Welcome to the fifth 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, your Medpace regulatory submissions coordinator, or the study team.
Below you will see an overview of current enrollment status and recognition of our highest enrolling sites to date. Thank you for your patience during the clinical hold. We look forward to resuming screening soon!
Brazil 07606 / PSEG Centro de Pesquisa Clínica S.A. |Paulo Sgobbi de Souza: 6 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 80
Randomized 47
Screen Failed 22
In Screening 11
We are closely tracking participant demographics and baseline characteristics. Please see below for a high-level summary of enrolled participants’ characteristics:
Median Age (Range) 59 (22-76)
Gender 2:1 (M:F)
Mutation Type A97S: 14 (30%) V30M: 22 (47%) V30M early onset: 13 (28%) Others: 11 (23%)
* Please screen failure the participants in screening at your site as they will be reassigned a new ID upon rescreening.
Medpace regulatory teams are working with sites to obtain the regulatory approvals needed to restart the study in a timely manner.
• Per Protocol Amendment V5.0, participants should be provided with corticosteroids at the Week 1 or Crossover Week 1 visit to ensure they have access to corticosteroid therapy in cases of transaminase elevations; see Appendix 5 (PV5.0, dated 29-Jan-2026) for specific guidance. Sites are expected to provide an initial supply of corticosteroids (Dexamethasone 10 mg) to each participant along with clear instructions of use only upon instruction by their study doctor, in accordance with the guidance provided in the protocol Appendix 5 (PV5.0, dated 29-Jan-2026).
• Sites will be expected to place a study-provided sticker on the distributed steroid medication, reminding participants not to take the medication unless instructed.
• The document “Participant Reminders for Risk Mitigation” with key reminders for liver elevations should also be shared with the participants at the time of corticosteroids distribution. This document will be available after PV5.0approval at your site.
• The lab kits, Requisition Forms, and labels will be updated to reflect the visit changes implemented by PV5.0.
• New PV5.0 kits and bulk extra supply kits will be shipped to all sites to ensure that proper supplies are delivered in time for any additional participant visits.
• Please contact your CRA if your site is reactivated for screening or crossover and you have not received the updated/extra MRL kits
• PV5.0 increases the number of site visits in the first 6 weeks after dosing to allow for rapid identification and mitigation of potential hepatoxicity. Intellia and Medpace will work with your site to reduce participant and caregiver burden. Please inform your CRA if your site would like to use Patient Concierge Services (PCS) for upcoming participant visits.
• For sites already using PCS, long-stay accommodation can be offered to patients. Please contact PCS and request their support.
• For sites managing patient travel and reimbursements, please contact your CRA/CTM to request prior approval when long-stay accommodation is needed.
• To reduce participant burden and results’ turnaround time, PV5.0 now allows for most chemistry and coagulation sample collection at a laboratory local to the participant. This may occur at your clinical site or a lab closer to the participants’ homes.
• Please ensure that all lab reports are accessible for review in a timely manner. The results must be added to the patient source documents and reported in EDC immediately (including normal ranges).
• Please notify the Medical Monitors and your CRA as soon as you are aware of any out-of-range labs.
• Costs associated with local lab testing will be reimbursed by Intellia. Supporting documents may be requested for reimbursement.
Kindly inform your CRA of potential participants and send the Screening Authorization Form to Intellia for IRT slot allocation.
A kind reminder to enter data within 5 business days of the subject visit and to resolve any queries within 5 business days of issuance. If you have any questions or concerns, please contact your CRA.
• Please remember to review the normal control consent process with your CRA at next monitoring visit. An example Consent Form is forthcoming if new assessors need to be re-trained.
• Please inform your CRA of the mNIS+7 assessments scheduled at your site. This is particularly important for Month 12 visits when rapid progression will be assessed for early crossover. This will also help shorten the review turnaround time.
• Please remember to properly redact any PHI that may be on NCS waveforms when printed from your EMG machine.
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