April 10, 2025
Welcome to the second 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.
• Congratulations to Dr. Sgobbi and the study team at site 07606 for dosing the first patient on the MAGNITUDE-2 study!
• Congratulations to all our sites who have screened patients! We appreciate all your hard work!
55401/Gane 4 Patients Screened
07606/Sgobbi de Souza 3 Patients Screened
03602/Silsby 1 Patient Screened
15804/Ro 1 Patient Screened
15803/Chao 1 Patient Screened
Consider leveraging available clinical data to select patients who are likely to meet eligibility criteria. Common reasons for observed screen failure in MAGNITUDE-2 have been related to either low NIS score < 10, or lack of abnormalities on nerve conductions studies as defined in the Protocol’s inclusion criteria 2D. Findings of neurologic abnormalities on exam (e.g., reduced sensation in lower extremities, loss of reflexes, or foot drop), and abnormalities on the nerve conduction studies may minimize the risk of screen failure.
If you have any questions or concerns, please contact your unblinded CRA.
Password: Mag2IP2025
Please remember to review the e-Blast regarding the CASE IV QST laptop login details and the examiner ID codes while completing your Normal Controls and your patients’ assessments.
An e-Blast with the mNIS+7 “Frequently Asked Questions” was shared with your teams. Please read carefully and provide feedback on additional topics that assessors may find helpful. The last mNIS+7 training will be held on 25–26 April.
1. Question: How long after infusion were abnormal liver function tests such as Alanine transaminase (ALT) and Aspartate transferase (AST) noted?
Answer: Most elevations in liver enzymes were Grade 1, and occurred within 24-hours of infusion, were rapidly normalized, and were not clinically significant. Grade 3 elevation were infrequent, noted around four weeks following NTLA-2001 infusion, not associated with change in prothrombin time or serum bilirubin, and resolved spontaneously without any interventions or sequala.
2. Question: Is thyroxine replacement therapy required?
Answer: Thyroid function will be monitored, but no replacement is required unless deemed clinically indicated per the treating physician.
3. Question: When is the appropriate time to approach patients for screening?
Answer: Three-to-six months prior to screening would be appropriate to reach out to patients.
4. Question: What are some tips to be effectively prepared on a dosing day?
Answer: Ensure your study team is well trained, appropriate delegation is documented, and that there is good coordination among investigators, nurses, study coordinators, and pharmacists help to effectively manage Day 1. It is important to consider the distance between pharmacy and dosing location and work accordingly. Sites have found success in having a group meeting ahead of Day 1 to ensure all is in place. Your site’s unblinded CRA will be available to support with any technical issues during infusion.
5. Question: Can the neurologists responsible for mNIS+7 assessment do physical examinations?
Answer: Neurologists should only be involved in conduction of mNIS+7 assessments. Other examinations should be conducted by the other study team members as delegated.
6. Question: What potential information should be added to the prescreening portal?
Answer: Information about the screening date, mutation type, neurologic abnormalities, abnormalities on nerve conduction studies (if available), and intended dosing date can be added to comments
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