A Phase 1/2 Study of VX-522 in Subjects with Cystic Fibrosis

Temporary halt TH-81061

Halt date

2025-04-25

Member states concerned

Netherlands

Publication date

2025-05-02

Reason

Sponsor decision

Explanation

Vertex has paused screening, enrollment, and dosing in Study VX21-522-001 (Study 001) as of 25 April 2025, due to signs and symptoms of fever and dyspnea, decline in percent predicted forced expiratory volume in 1 second (ppFEV1), and CT scan showing ground glass opacities, in 2 subjects recently dosed with VX-522 in multiple ascending dose (MAD) Cohort 1 Treatment Arm 2 (T2). One of these subjects (Subject 320-001) experienced a SUSAR (MedWatch #2025-004733), while the other subject (Subject 207-002) had non-serious adverse events (AEs) of moderate severity. The AEs in these subjects have either rapidly resolved or are improving following discontinuation of study drug and treatment with antibiotics and corticosteroids.
The study is paused while Vertex is evaluating potential additional risk mitigation measures to improve tolerability of study drug. Vertex will ensure agreement with the Independent Data Monitoring Committee (IDMC) and Health Authorities prior to study restart.
Vertex convened an IDMC meeting on 30 April 2025 to (1) review the data in these 2 subjects, (2) inform the IDMC of Vertex’s decision to pause screening, enrollment, and dosing in Study 001, and (3) propose to reconvene at a later date to discuss additional potential risk mitigation measures. The IDMC agreed with Vertex’s decision for Study 001 and agreed to reconvene at a later date.
No subjects are currently dosing with study drug and no subjects are in the Run-in Period or screening. We continue to follow the subjects in the Safety Follow-up Period, as required per protocol.

Please see the attached letter for more details.

Follow-up measures

Following this event, Vertex reviewed the safety data and made the following recommendations:
• Dosing with study drug in Subject 320-001 should not be resumed.
• Given the rapid resolution of AEs in Subject 320-001 after drug discontinuation, completion of dosing to Day 28 in the other 2 subjects in Cohort 1 T2, the fact that acute respiratory signs and symptoms can be clinically monitored and managed, and the high unmet medical need in patients who cannot be treated with CFTR modulators, Vertex recommended that dosing with VX-522 may proceed with the next subject in Cohort 1 T2.
This recommendation was discussed with the IDMC on 02 April 2025 and the IDMC agreed with Vertex’s recommendation. The IDMC stated that the study could continue without modification and considered it acceptable to initiate dosing of the next subject.
The next subject (Subject 207-002) was dosed with VX-522 in combination with IVA on 08 April 2025. On Day 5, Subject 207-002 had a non-serious, moderate AE of infective PEx of CF with symptoms of dyspnea, fever, and findings of decline in ppFEV1 and ground glass opacities which resulted in study drug discontinuation on Day 9. The events are improving rapidly following study drug discontinuation and initiation of antibiotics and corticosteroids.
Vertex assessed that these AEs likely represent a pulmonary inflammatory response to VX-522 and the current mitigation measures of inhaled steroids and bronchodilators are insufficient in mitigating the risk; therefore, Vertex paused screening, enrollment, and dosing in Study 001 on 25 April 2025. Vertex is evaluating potential additional risk mitigation measures to improve tolerability of study drug.
On 30 April 2025, an ad hoc IDMC meeting was held. The IDMC agreed with Vertex's decision to pause screening, enrollment and dosing in Study 001. The IDMC also agreed to reconvene at a later date to discuss additional potential risk mitigation measures.

Benefit-risk balance changed

No

Treatment stopped

Yes

Temporary halt TH-35182

Halt date

2024-07-01

Member states concerned

Germany

Publication date

2024-07-16

Reason

Sponsor decision

Explanation

Vertex has temporarily paused dosing in Study VX21-522-001 as of 01Jul2024 to amend the protocol with changes aimed at improving tolerability to VX-522 during the multiple ascending dose (MAD) portion of the study. The study will resume once the protocol changes are in place.

Follow-up measures

Vertex is also submitting a substantial amendment to update the protocol today on 16th July 2024. The trial will resume once the protocol has been approved.

Benefit-risk balance changed

No

Treatment stopped

Yes

Temporary halt TH-81053

Halt date

2025-04-25

Member states concerned

Belgium

Publication date

2025-05-02

Reason

Sponsor decision

Explanation

Vertex has paused screening, enrollment, and dosing in Study VX21-522-001 (Study 001) as of 25 April 2025, due to signs and symptoms of fever and dyspnea, decline in percent predicted forced expiratory volume in 1 second (ppFEV1), and CT scan showing ground glass opacities, in 2 subjects recently dosed with VX-522 in multiple ascending dose (MAD) Cohort 1 Treatment Arm 2 (T2). One of these subjects (Subject 320-001) experienced a SUSAR (MedWatch #2025-004733), while the other subject (Subject 207-002) had non-serious adverse events (AEs) of moderate severity. The AEs in these subjects have either rapidly resolved or are improving following discontinuation of study drug and treatment with antibiotics and corticosteroids.
The study is paused while Vertex is evaluating potential additional risk mitigation measures to improve tolerability of study drug. Vertex will ensure agreement with the Independent Data Monitoring Committee (IDMC) and Health Authorities prior to study restart.
Vertex convened an IDMC meeting on 30 April 2025 to (1) review the data in these 2 subjects, (2) inform the IDMC of Vertex’s decision to pause screening, enrollment, and dosing in Study 001, and (3) propose to reconvene at a later date to discuss additional potential risk mitigation measures. The IDMC agreed with Vertex’s decision for Study 001 and agreed to reconvene at a later date.
No subjects are currently dosing with study drug and no subjects are in the Run-in Period or screening. We continue to follow the subjects in the Safety Follow-up Period, as required per protocol.

Please see the attached letter for more details.

Follow-up measures

Following this event, Vertex reviewed the safety data and made the following recommendations:
• Dosing with study drug in Subject 320-001 should not be resumed.
• Given the rapid resolution of AEs in Subject 320-001 after drug discontinuation, completion of dosing to Day 28 in the other 2 subjects in Cohort 1 T2, the fact that acute respiratory signs and symptoms can be clinically monitored and managed, and the high unmet medical need in patients who cannot be treated with CFTR modulators, Vertex recommended that dosing with VX-522 may proceed with the next subject in Cohort 1 T2.
This recommendation was discussed with the IDMC on 02 April 2025 and the IDMC agreed with Vertex’s recommendation. The IDMC stated that the study could continue without modification and considered it acceptable to initiate dosing of the next subject.
The next subject (Subject 207-002) was dosed with VX-522 in combination with IVA on 08 April 2025. On Day 5, Subject 207-002 had a non-serious, moderate AE of infective PEx of CF with symptoms of dyspnea, fever, and findings of decline in ppFEV1 and ground glass opacities which resulted in study drug discontinuation on Day 9. The events are improving rapidly following study drug discontinuation and initiation of antibiotics and corticosteroids.
Vertex assessed that these AEs likely represent a pulmonary inflammatory response to VX-522 and the current mitigation measures of inhaled steroids and bronchodilators are insufficient in mitigating the risk; therefore, Vertex paused screening, enrollment, and dosing in Study 001 on 25 April 2025. Vertex is evaluating potential additional risk mitigation measures to improve tolerability of study drug.
On 30 April 2025, an ad hoc IDMC meeting was held. The IDMC agreed with Vertex's decision to pause screening, enrollment and dosing in Study 001. The IDMC also agreed to reconvene at a later date to discuss additional potential risk mitigation measures.

Benefit-risk balance changed

No

Treatment stopped

Yes

Temporary halt TH-35183

Halt date

2024-07-01

Member states concerned

Italy

Publication date

2024-07-16

Reason

Sponsor decision

Explanation

Vertex has temporarily paused dosing in Study VX21-522-001 as of 01Jul2024 to amend the protocol with changes aimed at improving tolerability to VX-522 during the multiple ascending dose (MAD) portion of the study. The study will resume once the protocol changes are in place.

Follow-up measures

Vertex is also submitting a substantial amendment to update the protocol today on 16th July 2024. The trial will resume once the protocol has been approved.

Benefit-risk balance changed

No

Treatment stopped

Yes

Temporary halt TH-35184

Halt date

2024-07-01

Member states concerned

Spain

Publication date

2024-07-16

Reason

Sponsor decision

Explanation

Vertex has temporarily paused dosing in Study VX21-522-001 as of 01Jul2024 to amend the protocol with changes aimed at improving tolerability to VX-522 during the multiple ascending dose (MAD) portion of the study. The study will resume once the protocol changes are in place.

Follow-up measures

Vertex is also submitting a substantial amendment to update the protocol today on 16th July 2024. The trial will resume once the protocol has been approved.

Benefit-risk balance changed

No

Treatment stopped

Yes

Temporary halt TH-81055

Halt date

2025-04-25

Member states concerned

Germany

Publication date

2025-05-02

Reason

Sponsor decision

Explanation

Vertex has paused screening, enrollment, and dosing in Study VX21-522-001 (Study 001) as of 25 April 2025, due to signs and symptoms of fever and dyspnea, decline in percent predicted forced expiratory volume in 1 second (ppFEV1), and CT scan showing ground glass opacities, in 2 subjects recently dosed with VX-522 in multiple ascending dose (MAD) Cohort 1 Treatment Arm 2 (T2). One of these subjects (Subject 320-001) experienced a SUSAR (MedWatch #2025-004733), while the other subject (Subject 207-002) had non-serious adverse events (AEs) of moderate severity. The AEs in these subjects have either rapidly resolved or are improving following discontinuation of study drug and treatment with antibiotics and corticosteroids.
The study is paused while Vertex is evaluating potential additional risk mitigation measures to improve tolerability of study drug. Vertex will ensure agreement with the Independent Data Monitoring Committee (IDMC) and Health Authorities prior to study restart.
Vertex convened an IDMC meeting on 30 April 2025 to (1) review the data in these 2 subjects, (2) inform the IDMC of Vertex’s decision to pause screening, enrollment, and dosing in Study 001, and (3) propose to reconvene at a later date to discuss additional potential risk mitigation measures. The IDMC agreed with Vertex’s decision for Study 001 and agreed to reconvene at a later date.
No subjects are currently dosing with study drug and no subjects are in the Run-in Period or screening. We continue to follow the subjects in the Safety Follow-up Period, as required per protocol.

Please see the attached letter for more details.

Follow-up measures

Following this event, Vertex reviewed the safety data and made the following recommendations:
• Dosing with study drug in Subject 320-001 should not be resumed.
• Given the rapid resolution of AEs in Subject 320-001 after drug discontinuation, completion of dosing to Day 28 in the other 2 subjects in Cohort 1 T2, the fact that acute respiratory signs and symptoms can be clinically monitored and managed, and the high unmet medical need in patients who cannot be treated with CFTR modulators, Vertex recommended that dosing with VX-522 may proceed with the next subject in Cohort 1 T2.
This recommendation was discussed with the IDMC on 02 April 2025 and the IDMC agreed with Vertex’s recommendation. The IDMC stated that the study could continue without modification and considered it acceptable to initiate dosing of the next subject.
The next subject (Subject 207-002) was dosed with VX-522 in combination with IVA on 08 April 2025. On Day 5, Subject 207-002 had a non-serious, moderate AE of infective PEx of CF with symptoms of dyspnea, fever, and findings of decline in ppFEV1 and ground glass opacities which resulted in study drug discontinuation on Day 9. The events are improving rapidly following study drug discontinuation and initiation of antibiotics and corticosteroids.
Vertex assessed that these AEs likely represent a pulmonary inflammatory response to VX-522 and the current mitigation measures of inhaled steroids and bronchodilators are insufficient in mitigating the risk; therefore, Vertex paused screening, enrollment, and dosing in Study 001 on 25 April 2025. Vertex is evaluating potential additional risk mitigation measures to improve tolerability of study drug.
On 30 April 2025, an ad hoc IDMC meeting was held. The IDMC agreed with Vertex's decision to pause screening, enrollment and dosing in Study 001. The IDMC also agreed to reconvene at a later date to discuss additional potential risk mitigation measures.

Benefit-risk balance changed

No

Treatment stopped

Yes

Temporary halt TH-35185

Halt date

2024-07-01

Member states concerned

Netherlands

Publication date

2024-07-16

Reason

Sponsor decision

Explanation

Vertex has temporarily paused dosing in Study VX21-522-001 as of 01Jul2024 to amend the protocol with changes aimed at improving tolerability to VX-522 during the multiple ascending dose (MAD) portion of the study. The study will resume once the protocol changes are in place.

Follow-up measures

Vertex is also submitting a substantial amendment to update the protocol today on 16th July 2024. The trial will resume once the protocol has been approved.

Benefit-risk balance changed

No

Treatment stopped

Yes

Temporary halt TH-81058

Halt date

2025-04-25

Member states concerned

Spain

Publication date

2025-05-02

Reason

Sponsor decision

Explanation

Vertex has paused screening, enrollment, and dosing in Study VX21-522-001 (Study 001) as of 25 April 2025, due to signs and symptoms of fever and dyspnea, decline in percent predicted forced expiratory volume in 1 second (ppFEV1), and CT scan showing ground glass opacities, in 2 subjects recently dosed with VX-522 in multiple ascending dose (MAD) Cohort 1 Treatment Arm 2 (T2). One of these subjects (Subject 320-001) experienced a SUSAR (MedWatch #2025-004733), while the other subject (Subject 207-002) had non-serious adverse events (AEs) of moderate severity. The AEs in these subjects have either rapidly resolved or are improving following discontinuation of study drug and treatment with antibiotics and corticosteroids.
The study is paused while Vertex is evaluating potential additional risk mitigation measures to improve tolerability of study drug. Vertex will ensure agreement with the Independent Data Monitoring Committee (IDMC) and Health Authorities prior to study restart.
Vertex convened an IDMC meeting on 30 April 2025 to (1) review the data in these 2 subjects, (2) inform the IDMC of Vertex’s decision to pause screening, enrollment, and dosing in Study 001, and (3) propose to reconvene at a later date to discuss additional potential risk mitigation measures. The IDMC agreed with Vertex’s decision for Study 001 and agreed to reconvene at a later date.
No subjects are currently dosing with study drug and no subjects are in the Run-in Period or screening. We continue to follow the subjects in the Safety Follow-up Period, as required per protocol.

Please see the attached letter for more details.

Follow-up measures

Following this event, Vertex reviewed the safety data and made the following recommendations:
• Dosing with study drug in Subject 320-001 should not be resumed.
• Given the rapid resolution of AEs in Subject 320-001 after drug discontinuation, completion of dosing to Day 28 in the other 2 subjects in Cohort 1 T2, the fact that acute respiratory signs and symptoms can be clinically monitored and managed, and the high unmet medical need in patients who cannot be treated with CFTR modulators, Vertex recommended that dosing with VX-522 may proceed with the next subject in Cohort 1 T2.
This recommendation was discussed with the IDMC on 02 April 2025 and the IDMC agreed with Vertex’s recommendation. The IDMC stated that the study could continue without modification and considered it acceptable to initiate dosing of the next subject.
The next subject (Subject 207-002) was dosed with VX-522 in combination with IVA on 08 April 2025. On Day 5, Subject 207-002 had a non-serious, moderate AE of infective PEx of CF with symptoms of dyspnea, fever, and findings of decline in ppFEV1 and ground glass opacities which resulted in study drug discontinuation on Day 9. The events are improving rapidly following study drug discontinuation and initiation of antibiotics and corticosteroids.
Vertex assessed that these AEs likely represent a pulmonary inflammatory response to VX-522 and the current mitigation measures of inhaled steroids and bronchodilators are insufficient in mitigating the risk; therefore, Vertex paused screening, enrollment, and dosing in Study 001 on 25 April 2025. Vertex is evaluating potential additional risk mitigation measures to improve tolerability of study drug.
On 30 April 2025, an ad hoc IDMC meeting was held. The IDMC agreed with Vertex's decision to pause screening, enrollment and dosing in Study 001. The IDMC also agreed to reconvene at a later date to discuss additional potential risk mitigation measures.

Benefit-risk balance changed

No

Treatment stopped

Yes

Temporary halt TH-81057

Halt date

2025-04-25

Member states concerned

Italy

Publication date

2025-05-02

Reason

Sponsor decision

Explanation

Vertex has paused screening, enrollment, and dosing in Study VX21-522-001 (Study 001) as of 25 April 2025, due to signs and symptoms of fever and dyspnea, decline in percent predicted forced expiratory volume in 1 second (ppFEV1), and CT scan showing ground glass opacities, in 2 subjects recently dosed with VX-522 in multiple ascending dose (MAD) Cohort 1 Treatment Arm 2 (T2). One of these subjects (Subject 320-001) experienced a SUSAR (MedWatch #2025-004733), while the other subject (Subject 207-002) had non-serious adverse events (AEs) of moderate severity. The AEs in these subjects have either rapidly resolved or are improving following discontinuation of study drug and treatment with antibiotics and corticosteroids.
The study is paused while Vertex is evaluating potential additional risk mitigation measures to improve tolerability of study drug. Vertex will ensure agreement with the Independent Data Monitoring Committee (IDMC) and Health Authorities prior to study restart.
Vertex convened an IDMC meeting on 30 April 2025 to (1) review the data in these 2 subjects, (2) inform the IDMC of Vertex’s decision to pause screening, enrollment, and dosing in Study 001, and (3) propose to reconvene at a later date to discuss additional potential risk mitigation measures. The IDMC agreed with Vertex’s decision for Study 001 and agreed to reconvene at a later date.
No subjects are currently dosing with study drug and no subjects are in the Run-in Period or screening. We continue to follow the subjects in the Safety Follow-up Period, as required per protocol.

Please see the attached letter for more details.

Follow-up measures

Following this event, Vertex reviewed the safety data and made the following recommendations:
• Dosing with study drug in Subject 320-001 should not be resumed.
• Given the rapid resolution of AEs in Subject 320-001 after drug discontinuation, completion of dosing to Day 28 in the other 2 subjects in Cohort 1 T2, the fact that acute respiratory signs and symptoms can be clinically monitored and managed, and the high unmet medical need in patients who cannot be treated with CFTR modulators, Vertex recommended that dosing with VX-522 may proceed with the next subject in Cohort 1 T2.
This recommendation was discussed with the IDMC on 02 April 2025 and the IDMC agreed with Vertex’s recommendation. The IDMC stated that the study could continue without modification and considered it acceptable to initiate dosing of the next subject.
The next subject (Subject 207-002) was dosed with VX-522 in combination with IVA on 08 April 2025. On Day 5, Subject 207-002 had a non-serious, moderate AE of infective PEx of CF with symptoms of dyspnea, fever, and findings of decline in ppFEV1 and ground glass opacities which resulted in study drug discontinuation on Day 9. The events are improving rapidly following study drug discontinuation and initiation of antibiotics and corticosteroids.
Vertex assessed that these AEs likely represent a pulmonary inflammatory response to VX-522 and the current mitigation measures of inhaled steroids and bronchodilators are insufficient in mitigating the risk; therefore, Vertex paused screening, enrollment, and dosing in Study 001 on 25 April 2025. Vertex is evaluating potential additional risk mitigation measures to improve tolerability of study drug.
On 30 April 2025, an ad hoc IDMC meeting was held. The IDMC agreed with Vertex's decision to pause screening, enrollment and dosing in Study 001. The IDMC also agreed to reconvene at a later date to discuss additional potential risk mitigation measures.

Benefit-risk balance changed

No

Treatment stopped

Yes

Temporary halt TH-81059

Halt date

2025-04-25

Member states concerned

Sweden

Publication date

2025-05-02

Reason

Sponsor decision

Explanation

Vertex has paused screening, enrollment, and dosing in Study VX21-522-001 (Study 001) as of 25 April 2025, due to signs and symptoms of fever and dyspnea, decline in percent predicted forced expiratory volume in 1 second (ppFEV1), and CT scan showing ground glass opacities, in 2 subjects recently dosed with VX-522 in multiple ascending dose (MAD) Cohort 1 Treatment Arm 2 (T2). One of these subjects (Subject 320-001) experienced a SUSAR (MedWatch #2025-004733), while the other subject (Subject 207-002) had non-serious adverse events (AEs) of moderate severity. The AEs in these subjects have either rapidly resolved or are improving following discontinuation of study drug and treatment with antibiotics and corticosteroids.
The study is paused while Vertex is evaluating potential additional risk mitigation measures to improve tolerability of study drug. Vertex will ensure agreement with the Independent Data Monitoring Committee (IDMC) and Health Authorities prior to study restart.
Vertex convened an IDMC meeting on 30 April 2025 to (1) review the data in these 2 subjects, (2) inform the IDMC of Vertex’s decision to pause screening, enrollment, and dosing in Study 001, and (3) propose to reconvene at a later date to discuss additional potential risk mitigation measures. The IDMC agreed with Vertex’s decision for Study 001 and agreed to reconvene at a later date.
No subjects are currently dosing with study drug and no subjects are in the Run-in Period or screening. We continue to follow the subjects in the Safety Follow-up Period, as required per protocol.

Please see the attached letter for more details.

Follow-up measures

Following this event, Vertex reviewed the safety data and made the following recommendations:
• Dosing with study drug in Subject 320-001 should not be resumed.
• Given the rapid resolution of AEs in Subject 320-001 after drug discontinuation, completion of dosing to Day 28 in the other 2 subjects in Cohort 1 T2, the fact that acute respiratory signs and symptoms can be clinically monitored and managed, and the high unmet medical need in patients who cannot be treated with CFTR modulators, Vertex recommended that dosing with VX-522 may proceed with the next subject in Cohort 1 T2.
This recommendation was discussed with the IDMC on 02 April 2025 and the IDMC agreed with Vertex’s recommendation. The IDMC stated that the study could continue without modification and considered it acceptable to initiate dosing of the next subject.
The next subject (Subject 207-002) was dosed with VX-522 in combination with IVA on 08 April 2025. On Day 5, Subject 207-002 had a non-serious, moderate AE of infective PEx of CF with symptoms of dyspnea, fever, and findings of decline in ppFEV1 and ground glass opacities which resulted in study drug discontinuation on Day 9. The events are improving rapidly following study drug discontinuation and initiation of antibiotics and corticosteroids.
Vertex assessed that these AEs likely represent a pulmonary inflammatory response to VX-522 and the current mitigation measures of inhaled steroids and bronchodilators are insufficient in mitigating the risk; therefore, Vertex paused screening, enrollment, and dosing in Study 001 on 25 April 2025. Vertex is evaluating potential additional risk mitigation measures to improve tolerability of study drug.
On 30 April 2025, an ad hoc IDMC meeting was held. The IDMC agreed with Vertex's decision to pause screening, enrollment and dosing in Study 001. The IDMC also agreed to reconvene at a later date to discuss additional potential risk mitigation measures.

Benefit-risk balance changed

No

Treatment stopped

Yes

Temporary halt TH-35181

Halt date

2024-07-01

Member states concerned

Belgium

Publication date

2024-07-16

Reason

Sponsor decision

Explanation

Vertex has temporarily paused dosing in Study VX21-522-001 as of 01Jul2024 to amend the protocol with changes aimed at improving tolerability to VX-522 during the multiple ascending dose (MAD) portion of the study. The study will resume once the protocol changes are in place.

Follow-up measures

Vertex is also submitting a substantial amendment to update the protocol today on 16th July 2024. The trial will resume once the protocol has been approved.

Benefit-risk balance changed

No

Treatment stopped

Yes