A Phase 3 Study of NTLA 2001 in participants with amyloidosis with cardiac muscle disease.

Temporary halt TH-104348

Halt date

2025-10-25

Member states concerned

Germany

Publication date

2025-10-30

Reason

Sponsor decision

Explanation

Effective 25 October 2025, dosing and screening in the MAGNITUDE trial is temporarily paused until further notification. Systems necessary to screen and randomize participants have been temporarily disabled to prevent inadvertent screening or dosing. Further, as a precautionary measure another study related to NTLA-2001, Study ITL-2001-CL-311 (MAGNITUDE-2 Phase 3 study for ATTR-PN) is also temporarily paused. In addition, all investigational sites and Data Monitoring Committee (DMC) members for MAGNITUDE and MAGNITUDE-2 have been notified of the temporary pause.

Follow-up measures

Effective 25 October 2025, chemistry and coagulation samples are collected at Weeks 3, 5, and 6 for patients that have already dosed but have not passed those timepoints yet.

Benefit-risk balance changed

Yes

Treatment stopped

Yes

Temporary halt TH-104358

Halt date

2025-10-25

Member states concerned

Netherlands

Publication date

2025-10-30

Reason

Sponsor decision

Explanation

Effective 25 October 2025, dosing and screening in the MAGNITUDE trial is temporarily paused until further notification. Systems necessary to screen and randomize participants have been temporarily disabled to prevent inadvertent screening or dosing. Further, as a precautionary measure another study related to NTLA-2001, Study ITL-2001-CL-311 (MAGNITUDE-2 Phase 3 study for ATTR-PN) is also temporarily paused. In addition, all investigational sites and Data Monitoring Committee (DMC) members for MAGNITUDE and MAGNITUDE-2 have been notified of the temporary pause.

Follow-up measures

Effective 25 October 2025, chemistry and coagulation samples are collected at Weeks 3, 5, and 6 for patients that have already dosed but have not passed those timepoints yet.

Benefit-risk balance changed

Yes

Treatment stopped

Yes

Temporary halt TH-104368

Halt date

2025-10-25

Member states concerned

Norway

Publication date

2025-10-30

Reason

Sponsor decision

Explanation

Effective 25 October 2025, dosing and screening in the MAGNITUDE trial is temporarily paused until further notification. Systems necessary to screen and randomize participants have been temporarily disabled to prevent inadvertent screening or dosing. Further, as a precautionary measure another study related to NTLA-2001, Study ITL-2001-CL-311 (MAGNITUDE-2 Phase 3 study for ATTR-PN) is also temporarily paused. In addition, all investigational sites and Data Monitoring Committee (DMC) members for MAGNITUDE and MAGNITUDE-2 have been notified of the temporary pause.

Follow-up measures

Effective 25 October 2025, chemistry and coagulation samples are collected at Weeks 3, 5, and 6 for patients that have already dosed but have not passed those timepoints yet.

Benefit-risk balance changed

Yes

Treatment stopped

Yes

Temporary halt TH-104346

Halt date

2025-10-25

Member states concerned

France

Publication date

2025-10-30

Reason

Sponsor decision

Explanation

Effective 25 October 2025, dosing and screening in the MAGNITUDE trial is temporarily paused until further notification. Systems necessary to screen and randomize participants have been temporarily disabled to prevent inadvertent screening or dosing. Further, as a precautionary measure another study related to NTLA-2001, Study ITL-2001-CL-311 (MAGNITUDE-2 Phase 3 study for ATTR-PN) is also temporarily paused. In addition, all investigational sites and Data Monitoring Committee (DMC) members for MAGNITUDE and MAGNITUDE-2 have been notified of the temporary pause.

Follow-up measures

Effective 25 October 2025, chemistry and coagulation samples are collected at Weeks 3, 5, and 6 for patients that have already dosed but have not passed those timepoints yet.

Benefit-risk balance changed

Yes

Treatment stopped

Yes

Temporary halt TH-104356

Halt date

2025-10-25

Member states concerned

Portugal

Publication date

2025-10-30

Reason

Sponsor decision

Explanation

Effective 25 October 2025, dosing and screening in the MAGNITUDE trial is temporarily paused until further notification. Systems necessary to screen and randomize participants have been temporarily disabled to prevent inadvertent screening or dosing. Further, as a precautionary measure another study related to NTLA-2001, Study ITL-2001-CL-311 (MAGNITUDE-2 Phase 3 study for ATTR-PN) is also temporarily paused. In addition, all investigational sites and Data Monitoring Committee (DMC) members for MAGNITUDE and MAGNITUDE-2 have been notified of the temporary pause.

Follow-up measures

Effective 25 October 2025, chemistry and coagulation samples are collected at Weeks 3, 5, and 6 for patients that have already dosed but have not passed those timepoints yet.

Benefit-risk balance changed

Yes

Treatment stopped

Yes

Temporary halt TH-104362

Halt date

2025-10-25

Member states concerned

Hungary

Publication date

2025-10-30

Reason

Sponsor decision

Explanation

Effective 25 October 2025, dosing and screening in the MAGNITUDE trial is temporarily paused until further notification. Systems necessary to screen and randomize participants have been temporarily disabled to prevent inadvertent screening or dosing. Further, as a precautionary measure another study related to NTLA-2001, Study ITL-2001-CL-311 (MAGNITUDE-2 Phase 3 study for ATTR-PN) is also temporarily paused. In addition, all investigational sites and Data Monitoring Committee (DMC) members for MAGNITUDE and MAGNITUDE-2 have been notified of the temporary pause.

Follow-up measures

Effective 25 October 2025, chemistry and coagulation samples are collected at Weeks 3, 5, and 6 for patients that have already dosed but have not passed those timepoints yet.

Benefit-risk balance changed

Yes

Treatment stopped

Yes

Temporary halt TH-104350

Halt date

2025-10-25

Member states concerned

Italy

Publication date

2025-10-30

Reason

Sponsor decision

Explanation

Effective 25 October 2025, dosing and screening in the MAGNITUDE trial is temporarily paused until further notification. Systems necessary to screen and randomize participants have been temporarily disabled to prevent inadvertent screening or dosing. Further, as a precautionary measure another study related to NTLA-2001, Study ITL-2001-CL-311 (MAGNITUDE-2 Phase 3 study for ATTR-PN) is also temporarily paused. In addition, all investigational sites and Data Monitoring Committee (DMC) members for MAGNITUDE and MAGNITUDE-2 have been notified of the temporary pause.

Follow-up measures

Effective 25 October 2025, chemistry and coagulation samples are collected at Weeks 3, 5, and 6 for patients that have already dosed but have not passed those timepoints yet.

Benefit-risk balance changed

Yes

Treatment stopped

Yes

Temporary halt TH-104360

Halt date

2025-10-25

Member states concerned

Belgium

Publication date

2025-10-30

Reason

Sponsor decision

Explanation

Effective 25 October 2025, dosing and screening in the MAGNITUDE trial is temporarily paused until further notification. Systems necessary to screen and randomize participants have been temporarily disabled to prevent inadvertent screening or dosing. Further, as a precautionary measure another study related to NTLA-2001, Study ITL-2001-CL-311 (MAGNITUDE-2 Phase 3 study for ATTR-PN) is also temporarily paused. In addition, all investigational sites and Data Monitoring Committee (DMC) members for MAGNITUDE and MAGNITUDE-2 have been notified of the temporary pause.

Follow-up measures

Effective 25 October 2025, chemistry and coagulation samples are collected at Weeks 3, 5, and 6 for patients that have already dosed but have not passed those timepoints yet.

Benefit-risk balance changed

Yes

Treatment stopped

Yes

Temporary halt TH-104370

Halt date

2025-10-25

Member states concerned

Czechia

Publication date

2025-10-30

Reason

Sponsor decision

Explanation

Effective 25 October 2025, dosing and screening in the MAGNITUDE trial is temporarily paused until further notification. Systems necessary to screen and randomize participants have been temporarily disabled to prevent inadvertent screening or dosing. Further, as a precautionary measure another study related to NTLA-2001, Study ITL-2001-CL-311 (MAGNITUDE-2 Phase 3 study for ATTR-PN) is also temporarily paused. In addition, all investigational sites and Data Monitoring Committee (DMC) members for MAGNITUDE and MAGNITUDE-2 have been notified of the temporary pause.

Follow-up measures

Effective 25 October 2025, chemistry and coagulation samples are collected at Weeks 3, 5, and 6 for patients that have already dosed but have not passed those timepoints yet.

Benefit-risk balance changed

Yes

Treatment stopped

Yes

Temporary halt TH-104366

Halt date

2025-10-25

Member states concerned

Poland

Publication date

2025-10-30

Reason

Sponsor decision

Explanation

Effective 25 October 2025, dosing and screening in the MAGNITUDE trial is temporarily paused until further notification. Systems necessary to screen and randomize participants have been temporarily disabled to prevent inadvertent screening or dosing. Further, as a precautionary measure another study related to NTLA-2001, Study ITL-2001-CL-311 (MAGNITUDE-2 Phase 3 study for ATTR-PN) is also temporarily paused. In addition, all investigational sites and Data Monitoring Committee (DMC) members for MAGNITUDE and MAGNITUDE-2 have been notified of the temporary pause.

Follow-up measures

Effective 25 October 2025, chemistry and coagulation samples are collected at Weeks 3, 5, and 6 for patients that have already dosed but have not passed those timepoints yet.

Benefit-risk balance changed

Yes

Treatment stopped

Yes

Temporary halt TH-104344

Halt date

2025-10-25

Member states concerned

Denmark

Publication date

2025-10-30

Reason

Sponsor decision

Explanation

Effective 25 October 2025, dosing and screening in the MAGNITUDE trial is temporarily paused until further notification. Systems necessary to screen and randomize participants have been temporarily disabled to prevent inadvertent screening or dosing. Further, as a precautionary measure another study related to NTLA-2001, Study ITL-2001-CL-311 (MAGNITUDE-2 Phase 3 study for ATTR-PN) is also temporarily paused. In addition, all investigational sites and Data Monitoring Committee (DMC) members for MAGNITUDE and MAGNITUDE-2 have been notified of the temporary pause.

Follow-up measures

Effective 25 October 2025, chemistry and coagulation samples are collected at Weeks 3, 5, and 6 for patients that have already dosed but have not passed those timepoints yet.

Benefit-risk balance changed

Yes

Treatment stopped

Yes

Temporary halt TH-104354

Halt date

2025-10-25

Member states concerned

Sweden

Publication date

2025-10-30

Reason

Sponsor decision

Explanation

Effective 25 October 2025, dosing and screening in the MAGNITUDE trial is temporarily paused until further notification. Systems necessary to screen and randomize participants have been temporarily disabled to prevent inadvertent screening or dosing. Further, as a precautionary measure another study related to NTLA-2001, Study ITL-2001-CL-311 (MAGNITUDE-2 Phase 3 study for ATTR-PN) is also temporarily paused. In addition, all investigational sites and Data Monitoring Committee (DMC) members for MAGNITUDE and MAGNITUDE-2 have been notified of the temporary pause.

Follow-up measures

Effective 25 October 2025, chemistry and coagulation samples are collected at Weeks 3, 5, and 6 for patients that have already dosed but have not passed those timepoints yet.

Benefit-risk balance changed

Yes

Treatment stopped

Yes

Temporary halt TH-104364

Halt date

2025-10-25

Member states concerned

Austria

Publication date

2025-10-30

Reason

Sponsor decision

Explanation

Effective 25 October 2025, dosing and screening in the MAGNITUDE trial is temporarily paused until further notification. Systems necessary to screen and randomize participants have been temporarily disabled to prevent inadvertent screening or dosing. Further, as a precautionary measure another study related to NTLA-2001, Study ITL-2001-CL-311 (MAGNITUDE-2 Phase 3 study for ATTR-PN) is also temporarily paused. In addition, all investigational sites and Data Monitoring Committee (DMC) members for MAGNITUDE and MAGNITUDE-2 have been notified of the temporary pause.

Follow-up measures

Effective 25 October 2025, chemistry and coagulation samples are collected at Weeks 3, 5, and 6 for patients that have already dosed but have not passed those timepoints yet.

Benefit-risk balance changed

Yes

Treatment stopped

Yes

Temporary halt TH-104352

Halt date

2025-10-25

Member states concerned

Spain

Publication date

2025-10-30

Reason

Sponsor decision

Explanation

Effective 25 October 2025, dosing and screening in the MAGNITUDE trial is temporarily paused until further notification. Systems necessary to screen and randomize participants have been temporarily disabled to prevent inadvertent screening or dosing. Further, as a precautionary measure another study related to NTLA-2001, Study ITL-2001-CL-311 (MAGNITUDE-2 Phase 3 study for ATTR-PN) is also temporarily paused. In addition, all investigational sites and Data Monitoring Committee (DMC) members for MAGNITUDE and MAGNITUDE-2 have been notified of the temporary pause.

Follow-up measures

Effective 25 October 2025, chemistry and coagulation samples are collected at Weeks 3, 5, and 6 for patients that have already dosed but have not passed those timepoints yet.

Benefit-risk balance changed

Yes

Treatment stopped

Yes

Corrective measure CM-IT-0001

Member state

Italy

Publication date

2025-07-28

Type

1

Reason

6

Reverted date

2025-07-28

Immediate action required

Yes

Notes

Reverted (2025-07-28)

Justification

Dear Applicant,
Considering the expiration of the three-year mandate of the members of the National Ethics Committee (CEN) for clinical trials relating to advanced therapies (“ATMP”) and of the National Ethics Committee (CEN) for clinical trials in the pediatric field, appointed by Decree of the Minister of Health - 2 March 2022;
Considering the fact that, due to the expiration of the mandate of the members of the aforementioned National Ethics Committee (CEN), for the procedure in subject the assessment of the aspects relating to Part II of the evaluation report pursuant to art. 7 of the aforementioned Regulation (EU) No. 536/2014 has not been carried out, and as a result there is no conclusion of Part II for the EU CT 2023-507220-23-00 procedure (AIFA authorization provision n° 0062315-22/05/2025-AIFA-AIFA_USC-P);
In compliance with CHAPTER XIII (SUPERVISION BY MEMBER STATES, UNION INSPECTIONS AND CONTROLS) of Regulation 536/2014 with specific reference to Article 77 (Corrective measures to be taken by Member States):
1. Where a Member State concerned has justified grounds for considering that the requirements set out in this Regulation are no longer met, it may take the following measures on its territory:
(a) revoke the authorisation of a clinical trial;
(b) suspend a clinical trial;
(c) require the sponsor to modify any aspect of the clinical trial.
A corrective measure is applied suspending the trial. This corrective measure is only applicable to Italy.