Trial Outcomes & Findings for Safety Extension Trial of Inhaled Molgramostim in Autoimmune Pulmonary Alveolar Proteinosis (NCT NCT03482752)

Last Updated: 2024-07-03

Results Overview

The primary objective of this trial was safety assessed by adverse event (AE) reporting. Definitions and reporting procedures for AEs were done according to current regulatory standards. AEs were collected by the investigator by a non-leading question and by reporting events directly observed or spontaneously volunteered by participants. Participants were also encouraged to contact the clinic in between visits if they experienced AEs or had any concerns. Treatment-emergent was defined as events occurring on study drug and up to 7 days after last dose of study drug.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

60 participants

Primary outcome timeframe

139 weeks

Results posted on

2024-07-03

Participant Flow

SAV006-03 was an open-label extension trial for participants who had completed the IMPALA study. Among the 30 clinical sites enrolling participants in IMPALA, 13 sites participated in SAV006-03. First participant was enrolled on 16 April 2018 and last participant completed the study on 14 January 2021.

Participant milestones

Participant milestones
Measure	Molgramostim Nebulizer Solution (300 μg) Open-label treatment with molgramostim nebulizer solution (300 μg) administered intermittently (repetitive cycles of 7 days of treatment followed by 7 days off-treatment). Molgramostim: 300 µg inhaled molgramostim in cycles of once daily administration for 7 days, then 7 days off treatment.
Overall Study STARTED	60
Overall Study Safety Analysis Set	59
Overall Study COMPLETED	56
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Molgramostim Nebulizer Solution (300 μg) Open-label treatment with molgramostim nebulizer solution (300 μg) administered intermittently (repetitive cycles of 7 days of treatment followed by 7 days off-treatment). Molgramostim: 300 µg inhaled molgramostim in cycles of once daily administration for 7 days, then 7 days off treatment.
Overall Study Withdrawal by Subject	2
Overall Study Lost to Follow-up	1
Overall Study 1 participant died 24 days after last dose ie outside the definition of treatment-emergent	1

Baseline Characteristics

Safety Extension Trial of Inhaled Molgramostim in Autoimmune Pulmonary Alveolar Proteinosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Molgramostim Nebulizer Solution (300 μg) n=60 Participants Open-label treatment with molgramostim nebulizer solution (300 μg) administered intermittently (repetitive cycles of 7 days of treatment followed by 7 days off-treatment). Molgramostim: 300 µg inhaled molgramostim in cycles of once daily administration for 7 days, then 7 days off treatment.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	55 Participants n=5 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants
Age, Continuous	46.8 years STANDARD_DEVIATION 13.5 • n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants
Sex: Female, Male Male	36 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	54 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants
Region of Enrollment Greece	4 participants n=5 Participants
Region of Enrollment Netherlands	6 participants n=5 Participants
Region of Enrollment Turkey	7 participants n=5 Participants
Region of Enrollment Denmark	3 participants n=5 Participants
Region of Enrollment United Kingdom	4 participants n=5 Participants
Region of Enrollment Italy	9 participants n=5 Participants
Region of Enrollment Israel	4 participants n=5 Participants
Region of Enrollment France	4 participants n=5 Participants
Region of Enrollment Germany	12 participants n=5 Participants
Region of Enrollment Russia	7 participants n=5 Participants

PRIMARY outcome

Timeframe: 139 weeks

Population: Safety analysis set.

Outcome measures

Outcome measures
Measure	Molgramostim Nebulizer Solution (300 μg) n=59 Participants Open-label treatment with molgramostim nebulizer solution (300 μg) administered intermittently (repetitive cycles of 7 days of treatment followed by 7 days off-treatment). Molgramostim: 300 µg inhaled molgramostim in cycles of once daily administration for 7 days, then 7 days off treatment.
Number of Treatment-emergent Adverse Events (TEAEs)	165 events

PRIMARY outcome

Timeframe: 139 weeks

Population: Safety analysis set.

Serious TEAEs were defined as any untoward medicinal occurrence or effect that at any dose: * Results in death * Is life-threatening * Requires hospitalisation or prolongation of existing hospitalisation * Results in persistent or significant disability or incapacity * Is a congenital abnormality or birth defect * May jeopardise the participant or may require medical intervention to prevent one or more of the outcomes listed above (Important Medical Events).

Outcome measures

Outcome measures
Measure	Molgramostim Nebulizer Solution (300 μg) n=59 Participants Open-label treatment with molgramostim nebulizer solution (300 μg) administered intermittently (repetitive cycles of 7 days of treatment followed by 7 days off-treatment). Molgramostim: 300 µg inhaled molgramostim in cycles of once daily administration for 7 days, then 7 days off treatment.
Number of Serious TEAEs	8 events

PRIMARY outcome

Timeframe: 139 weeks

Population: Safety analysis set.

All AEs were assessed by the investigator for causality (unlikely, possible, probable, not applicable) according to current regulatory standards. AEs which had a 'possible' or 'probable' causality were classified as ADRs.

Outcome measures

Outcome measures
Measure	Molgramostim Nebulizer Solution (300 μg) n=59 Participants Open-label treatment with molgramostim nebulizer solution (300 μg) administered intermittently (repetitive cycles of 7 days of treatment followed by 7 days off-treatment). Molgramostim: 300 µg inhaled molgramostim in cycles of once daily administration for 7 days, then 7 days off treatment.
Number of Treatment-emergent Adverse Drug Reactions (ADRs)	3 events

PRIMARY outcome

Timeframe: 139 weeks

Population: Safety analysis set.

Outcome measures

Outcome measures
Measure	Molgramostim Nebulizer Solution (300 μg) n=59 Participants Open-label treatment with molgramostim nebulizer solution (300 μg) administered intermittently (repetitive cycles of 7 days of treatment followed by 7 days off-treatment). Molgramostim: 300 µg inhaled molgramostim in cycles of once daily administration for 7 days, then 7 days off treatment.
Number of TEAEs Leading to Treatment Discontinuation	0 events

Adverse Events

Molgramostim Nebulizer Solution (300 μg)

Serious events: 8 serious events

Other events: 38 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Molgramostim Nebulizer Solution (300 μg) n=59 participants at risk Open-label treatment with molgramostim nebulizer solution (300 μg) administered intermittently (repetitive cycles of 7 days of treatment followed by 7 days off-treatment). Molgramostim: 300 µg inhaled molgramostim in cycles of once daily administration for 7 days, then 7 days off treatment.
Respiratory, thoracic and mediastinal disorders Alveolar proteinosis	5.1% 3/59 • Number of events 3 • Adverse events (AEs) were collected from the baseline visit up to a follow-up telephone call, which occurred 2 weeks after study completion (maximum duration 139 weeks). AEs were collected by the investigator by a non-leading question and by reporting events directly observed or spontaneously volunteered by participants. Participants were also encouraged to contact the clinic in between visits if they experienced AEs or had any concerns.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.7% 1/59 • Number of events 1 • Adverse events (AEs) were collected from the baseline visit up to a follow-up telephone call, which occurred 2 weeks after study completion (maximum duration 139 weeks). AEs were collected by the investigator by a non-leading question and by reporting events directly observed or spontaneously volunteered by participants. Participants were also encouraged to contact the clinic in between visits if they experienced AEs or had any concerns.
Musculoskeletal and connective tissue disorders Back pain	1.7% 1/59 • Number of events 1 • Adverse events (AEs) were collected from the baseline visit up to a follow-up telephone call, which occurred 2 weeks after study completion (maximum duration 139 weeks). AEs were collected by the investigator by a non-leading question and by reporting events directly observed or spontaneously volunteered by participants. Participants were also encouraged to contact the clinic in between visits if they experienced AEs or had any concerns.
Infections and infestations HIV infection CDC Group IV subgroup A	1.7% 1/59 • Number of events 1 • Adverse events (AEs) were collected from the baseline visit up to a follow-up telephone call, which occurred 2 weeks after study completion (maximum duration 139 weeks). AEs were collected by the investigator by a non-leading question and by reporting events directly observed or spontaneously volunteered by participants. Participants were also encouraged to contact the clinic in between visits if they experienced AEs or had any concerns.
Infections and infestations Laryngitis	1.7% 1/59 • Number of events 1 • Adverse events (AEs) were collected from the baseline visit up to a follow-up telephone call, which occurred 2 weeks after study completion (maximum duration 139 weeks). AEs were collected by the investigator by a non-leading question and by reporting events directly observed or spontaneously volunteered by participants. Participants were also encouraged to contact the clinic in between visits if they experienced AEs or had any concerns.
Infections and infestations Cellulitis	1.7% 1/59 • Number of events 1 • Adverse events (AEs) were collected from the baseline visit up to a follow-up telephone call, which occurred 2 weeks after study completion (maximum duration 139 weeks). AEs were collected by the investigator by a non-leading question and by reporting events directly observed or spontaneously volunteered by participants. Participants were also encouraged to contact the clinic in between visits if they experienced AEs or had any concerns.

Other adverse events

Other adverse events
Measure	Molgramostim Nebulizer Solution (300 μg) n=59 participants at risk Open-label treatment with molgramostim nebulizer solution (300 μg) administered intermittently (repetitive cycles of 7 days of treatment followed by 7 days off-treatment). Molgramostim: 300 µg inhaled molgramostim in cycles of once daily administration for 7 days, then 7 days off treatment.
Respiratory, thoracic and mediastinal disorders Cough	11.9% 7/59 • Number of events 7 • Adverse events (AEs) were collected from the baseline visit up to a follow-up telephone call, which occurred 2 weeks after study completion (maximum duration 139 weeks). AEs were collected by the investigator by a non-leading question and by reporting events directly observed or spontaneously volunteered by participants. Participants were also encouraged to contact the clinic in between visits if they experienced AEs or had any concerns.
Respiratory, thoracic and mediastinal disorders Alveolar proteinosis	6.8% 4/59 • Number of events 5 • Adverse events (AEs) were collected from the baseline visit up to a follow-up telephone call, which occurred 2 weeks after study completion (maximum duration 139 weeks). AEs were collected by the investigator by a non-leading question and by reporting events directly observed or spontaneously volunteered by participants. Participants were also encouraged to contact the clinic in between visits if they experienced AEs or had any concerns.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.1% 3/59 • Number of events 4 • Adverse events (AEs) were collected from the baseline visit up to a follow-up telephone call, which occurred 2 weeks after study completion (maximum duration 139 weeks). AEs were collected by the investigator by a non-leading question and by reporting events directly observed or spontaneously volunteered by participants. Participants were also encouraged to contact the clinic in between visits if they experienced AEs or had any concerns.
General disorders Fatigue	5.1% 3/59 • Number of events 3 • Adverse events (AEs) were collected from the baseline visit up to a follow-up telephone call, which occurred 2 weeks after study completion (maximum duration 139 weeks). AEs were collected by the investigator by a non-leading question and by reporting events directly observed or spontaneously volunteered by participants. Participants were also encouraged to contact the clinic in between visits if they experienced AEs or had any concerns.
Musculoskeletal and connective tissue disorders Arthralgia	6.8% 4/59 • Number of events 6 • Adverse events (AEs) were collected from the baseline visit up to a follow-up telephone call, which occurred 2 weeks after study completion (maximum duration 139 weeks). AEs were collected by the investigator by a non-leading question and by reporting events directly observed or spontaneously volunteered by participants. Participants were also encouraged to contact the clinic in between visits if they experienced AEs or had any concerns.
Infections and infestations Nasopharyngitis	11.9% 7/59 • Number of events 7 • Adverse events (AEs) were collected from the baseline visit up to a follow-up telephone call, which occurred 2 weeks after study completion (maximum duration 139 weeks). AEs were collected by the investigator by a non-leading question and by reporting events directly observed or spontaneously volunteered by participants. Participants were also encouraged to contact the clinic in between visits if they experienced AEs or had any concerns.
Infections and infestations Respiratory tract infection	6.8% 4/59 • Number of events 7 • Adverse events (AEs) were collected from the baseline visit up to a follow-up telephone call, which occurred 2 weeks after study completion (maximum duration 139 weeks). AEs were collected by the investigator by a non-leading question and by reporting events directly observed or spontaneously volunteered by participants. Participants were also encouraged to contact the clinic in between visits if they experienced AEs or had any concerns.
Infections and infestations COVID-19	6.8% 4/59 • Number of events 4 • Adverse events (AEs) were collected from the baseline visit up to a follow-up telephone call, which occurred 2 weeks after study completion (maximum duration 139 weeks). AEs were collected by the investigator by a non-leading question and by reporting events directly observed or spontaneously volunteered by participants. Participants were also encouraged to contact the clinic in between visits if they experienced AEs or had any concerns.
Infections and infestations Bronchitis	5.1% 3/59 • Number of events 6 • Adverse events (AEs) were collected from the baseline visit up to a follow-up telephone call, which occurred 2 weeks after study completion (maximum duration 139 weeks). AEs were collected by the investigator by a non-leading question and by reporting events directly observed or spontaneously volunteered by participants. Participants were also encouraged to contact the clinic in between visits if they experienced AEs or had any concerns.
Infections and infestations Pneumonia	5.1% 3/59 • Number of events 4 • Adverse events (AEs) were collected from the baseline visit up to a follow-up telephone call, which occurred 2 weeks after study completion (maximum duration 139 weeks). AEs were collected by the investigator by a non-leading question and by reporting events directly observed or spontaneously volunteered by participants. Participants were also encouraged to contact the clinic in between visits if they experienced AEs or had any concerns.

Additional Information

Raymond D Pratt, Chief Medical Officer

Savara Inc

Phone: +1 512 784 8757

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place