Trial Outcomes & Findings for A Noninferiority Study of Alglucosidase Alfa Manufactured at the 160 L and 4000 L Scales in Treatment Naïve Patients With Infantile-Onset Pompe Disease (NCT NCT01597596)

Last Updated: 2016-01-18

Results Overview

Cardiac function was measured by the left ventricular mass Z-score (LVM-Z). Z-Scores indicate the number of standard deviations (SD) from the mean in a normal distribution. A negative change from baseline indicates a decrease and positive change from baseline indicates an increase in LVM Z-score. The normal range is -2 to 2 and greater than 2 may indicate left ventricular hypertrophy.

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

4 participants

Primary outcome timeframe

Baseline, Week 52

Results posted on

2016-01-18

Participant Flow

The study was conducted between 21 August 2012 and 1 December 2014.

A total of 5 participants were screened and 4 participants were treated.

Participant milestones

Participant milestones
Measure	Alglucosidase Alfa 4000 L Material (Non-US Participants) Alglucosidase alfa (4000 L material) 20 mg/kg intravenous (IV) infusion every other week (QOW) for 52 weeks.	Alglucosidase Alfa 160 L Material (US Participants) Alglucosidase alfa (160 L material) 20 mg/kg IV infusion QOW for 52 weeks.
Overall Study STARTED	1	3
Overall Study COMPLETED	0	2
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Alglucosidase Alfa 4000 L Material (Non-US Participants) Alglucosidase alfa (4000 L material) 20 mg/kg intravenous (IV) infusion every other week (QOW) for 52 weeks.	Alglucosidase Alfa 160 L Material (US Participants) Alglucosidase alfa (160 L material) 20 mg/kg IV infusion QOW for 52 weeks.
Overall Study Study terminated by sponsor	1	0
Overall Study Physician Decision	0	1

Baseline Characteristics

A Noninferiority Study of Alglucosidase Alfa Manufactured at the 160 L and 4000 L Scales in Treatment Naïve Patients With Infantile-Onset Pompe Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Alglucosidase Alfa 4000 L Material (Non-US Participants) n=1 Participants Alglucosidase alfa (4000 L material) 20 mg/kg IV infusion QOW for 52 weeks.	Alglucosidase Alfa 160 L Material (US Participants) n=3 Participants Alglucosidase alfa (160 L material) 20 mg/kg IV infusion QOW for 52 weeks.	Total n=4 Participants Total of all reporting groups
Age, Continuous	0.3 years n=5 Participants	0.5 years STANDARD_DEVIATION 0.28 • n=7 Participants	0.4 years STANDARD_DEVIATION 0.14 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 52

Population: Full analysis population defined as all participants who receive at least 1 infusion of alglucosidase alfa. For this endpoint no participants were analyzed in 'Algucosidase Alfa 4000 L material' arm at Baseline and Week 52. One participant from 'Algucosidase Alfa 160 L Material' arm was discontinued from study at Week 31 due to physician's decision

Outcome measures

Outcome measures
Measure	Alglucosidase Alfa 4000 L Material (Non-US Participants) Alglucosidase alfa (4000 L material) 20 mg/kg IV infusion QOW for 52 weeks.	Alglucosidase Alfa 160 L Material (US Participants) n=2 Participants Alglucosidase alfa (160 L material) 20 mg/kg IV infusion QOW for 52 weeks.
Change From Baseline in Cardiac Function at Week 52	—	-5.06 Z-score Standard Deviation 1.103

SECONDARY outcome

Timeframe: Up to Week 52

Population: Full analysis population.

Outcome measures

Outcome measures
Measure	Alglucosidase Alfa 4000 L Material (Non-US Participants) n=1 Participants Alglucosidase alfa (4000 L material) 20 mg/kg IV infusion QOW for 52 weeks.	Alglucosidase Alfa 160 L Material (US Participants) n=3 Participants Alglucosidase alfa (160 L material) 20 mg/kg IV infusion QOW for 52 weeks.
Percentage of Participants With Estimated Probability of Survival	100 percentage of participants	100 percentage of participants

SECONDARY outcome

Timeframe: Up to Week 52

Population: Full analysis population.

Invasive ventilator-free survival was defined as the time during which the participant is alive and not invasively ventilated. Number of Participants with invasive ventilator-free survival were reported.

Outcome measures

Outcome measures
Measure	Alglucosidase Alfa 4000 L Material (Non-US Participants) n=1 Participants Alglucosidase alfa (4000 L material) 20 mg/kg IV infusion QOW for 52 weeks.	Alglucosidase Alfa 160 L Material (US Participants) n=3 Participants Alglucosidase alfa (160 L material) 20 mg/kg IV infusion QOW for 52 weeks.
Number of Participants With Invasive Ventilator-Free Survival	1 participants	2 participants

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: Full analysis population. For this endpoint no participants were analyzed in 'Algucosidase Alfa 4000 L material' arm at Baseline and Week 52. One participant from 'Algucosidase Alfa 160 L Material' arm was discontinued from study at Week 31 due to physician's decision.

Motor development status was assessed by the Gross Motor Function Measure - 88 Scale (GMFM-88) total percent scores. GMFM-88 is an 88-item measure to detect gross motor function. It consists of 5 categories: lying and rolling; sitting; crawling and kneeling; standing; walking, running and jumping. Each item was scored on a 4-point Likert scale (0 = cannot do; 1 = initiates \[\<10% of the task\]; 2 = partially completes \[10% to \<100% of the task\]; 3 = task completion). The score for each dimension was expressed as a percentage of the maximum score for that dimension. Total score ranges from 0% to 100%, where higher scores indicate better motor functions.

Outcome measures

Outcome measures
Measure	Alglucosidase Alfa 4000 L Material (Non-US Participants) Alglucosidase alfa (4000 L material) 20 mg/kg IV infusion QOW for 52 weeks.	Alglucosidase Alfa 160 L Material (US Participants) n=2 Participants Alglucosidase alfa (160 L material) 20 mg/kg IV infusion QOW for 52 weeks.
Change From Baseline in Motor Development Status at Week 52	—	48.65 percentage of maximum total score Standard Deviation 17.183

Adverse Events

Alglucosidase Alfa 4000 L Material (Non-US Participants)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Alglucosidase Alfa 160 L Material (US Participants)

Serious events: 3 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Alglucosidase Alfa 4000 L Material (Non-US Participants) n=1 participants at risk Alglucosidase alfa (4000 L material) 20 mg/kg IV infusion QOW for 52 weeks.	Alglucosidase Alfa 160 L Material (US Participants) n=3 participants at risk Alglucosidase alfa (160 L material) 20 mg/kg IV infusion QOW for 52 weeks.
Cardiac disorders Cardiac failure	0.00% 0/1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 52) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the period from the first infusion date to the date that the last data were collected). Analysis was carried out on full analysis population.	33.3% 1/3 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 52) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the period from the first infusion date to the date that the last data were collected). Analysis was carried out on full analysis population.
General disorders Pyrexia	0.00% 0/1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 52) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the period from the first infusion date to the date that the last data were collected). Analysis was carried out on full analysis population.	33.3% 1/3 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 52) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the period from the first infusion date to the date that the last data were collected). Analysis was carried out on full analysis population.
Infections and infestations Adenovirus infection	0.00% 0/1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 52) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the period from the first infusion date to the date that the last data were collected). Analysis was carried out on full analysis population.	33.3% 1/3 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 52) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the period from the first infusion date to the date that the last data were collected). Analysis was carried out on full analysis population.
Infections and infestations Lobar pneumonia	0.00% 0/1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 52) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the period from the first infusion date to the date that the last data were collected). Analysis was carried out on full analysis population.	33.3% 1/3 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 52) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the period from the first infusion date to the date that the last data were collected). Analysis was carried out on full analysis population.
Infections and infestations Otitis media acute	0.00% 0/1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 52) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the period from the first infusion date to the date that the last data were collected). Analysis was carried out on full analysis population.	33.3% 1/3 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 52) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the period from the first infusion date to the date that the last data were collected). Analysis was carried out on full analysis population.
Infections and infestations Respiratory syncytial virus infection	0.00% 0/1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 52) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the period from the first infusion date to the date that the last data were collected). Analysis was carried out on full analysis population.	33.3% 1/3 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 52) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the period from the first infusion date to the date that the last data were collected). Analysis was carried out on full analysis population.
Infections and infestations Upper respiratory tract infection	0.00% 0/1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 52) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the period from the first infusion date to the date that the last data were collected). Analysis was carried out on full analysis population.	33.3% 1/3 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 52) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the period from the first infusion date to the date that the last data were collected). Analysis was carried out on full analysis population.
Nervous system disorders Hypotonia	0.00% 0/1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 52) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the period from the first infusion date to the date that the last data were collected). Analysis was carried out on full analysis population.	33.3% 1/3 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 52) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the period from the first infusion date to the date that the last data were collected). Analysis was carried out on full analysis population.
Nervous system disorders Syncope	0.00% 0/1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 52) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the period from the first infusion date to the date that the last data were collected). Analysis was carried out on full analysis population.	33.3% 1/3 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 52) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the period from the first infusion date to the date that the last data were collected). Analysis was carried out on full analysis population.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 52) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the period from the first infusion date to the date that the last data were collected). Analysis was carried out on full analysis population.	33.3% 1/3 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 52) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the period from the first infusion date to the date that the last data were collected). Analysis was carried out on full analysis population.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 52) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the period from the first infusion date to the date that the last data were collected). Analysis was carried out on full analysis population.	33.3% 1/3 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 52) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the period from the first infusion date to the date that the last data were collected). Analysis was carried out on full analysis population.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/1 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 52) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the period from the first infusion date to the date that the last data were collected). Analysis was carried out on full analysis population.	33.3% 1/3 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 52) regardless of seriousness or relationship to investigational product. Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (the period from the first infusion date to the date that the last data were collected). Analysis was carried out on full analysis population.

Other adverse events

Additional Information

Trial Transparency Team

Sanofi

Email: Contact [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Publication restrictions are in place

Restriction type: OTHER