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Clinical Trial Results:
A Multi-Center, Double-Blind, Randomized, Placebo-Controlled, Parallel Group Trial, Investigating the Efficacy and Safety of Repeated Lamazym Treatment of Subjects with alpha-Mannosidosis.

Summary
EudraCT number	2012-000979-17
Trial protocol	DE DK BE ES SE
Global end of trial date	02 May 2014

Results information
Results version number	v2(current)
This version publication date	29 Jul 2016
First version publication date	09 Aug 2015
Other versions	v1
Version creation reason	Correction of full data set Correction of Sponsor organisation name and address.

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

rhLAMAN-05

ISRCTN number

US NCT number

NCT01681953

WHO universal trial number (UTN)

Other trial identifiers

EudraCT: 2012-000979-17

Sponsor organisation name

Zymenex A/S

Sponsor organisation address

Roskildevej 12C, Hilleroed, Denmark, 3400

Public contact

Clinical Trial Transparency, Chiesi Farmaceutici SpA, clinicaltrials_info@chiesi.com

Scientific contact

Clinical Trial Transparency, Chiesi Farmaceutici SpA, clinicaltrials_info@chiesi.com

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-001056-PIP02-12

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

02 May 2014

Is this the analysis of the primary completion data?

Yes

Primary completion date

02 May 2014

Global end of trial reached?

Yes

Global end of trial date

02 May 2014

Was the trial ended prematurely?

Main objective of the trial

The overall objective of this trial is to evaluate the efficacy and safety of repeated Lamazym i.v. treatment, compared with placebo, in subjects 5-35 years of age with alpha-Mannosidosis

Protection of trial subjects

The study was conducted in accordance with the Declaration of Helsinki, Good Clinical Practice (GCP) guidelines and local law requirements. Other than routine care, no specific measures for protection of trial subjects were implemented.

Background therapy

Evidence for comparator

Actual start date of recruitment

10 Sep 2012

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Spain: 3

Country: Number of subjects enrolled

Sweden: 1

Country: Number of subjects enrolled

Belgium: 3

Country: Number of subjects enrolled

Denmark: 4

Country: Number of subjects enrolled

France: 6

Country: Number of subjects enrolled

Germany: 8

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Twenty-five (25) patients were randomized to Lamazym (n=15) or Placebo (n=10). No patients withdrew from the rhLAMAN-05 trial

Screening details

A total of 26 patients were screened in the rhLAMAN-05 trial. There was one screening failure due to level of IgE not compatible with exclusion criteria.

Period 1 title

Overall trial (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer, Assessor

Blinding implementation details

A double-blind, randomized, parallel group trial design has been chosen. The randomization (in a 3:2 ratio) into active or Placebo group was stratified on age and was used to allocate the patients into blocks. Within the blocks, a standard randomization into active and Placebo was performed.

Are arms mutually exclusive

Yes

Lamazym

Arm description

Intravenous (i.v.) dosing of Lamazym at a dose level of 1 mg/kg body weight.

Arm type

Experimental

Investigational medicinal product name

Lamazym

Investigational medicinal product code

Other name

recombinant human alpha-mannosidase

Pharmaceutical forms

Powder and solution for solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Intravenous (i.v.) dosing of Lamazym at a dose level of 1 mg/kg body weight. Weekly i.v.dosing of Lamazym through 12 months was planned; a minimum of 49 infusions and a maximum of 55 infusions were administered to each patient.

Placebo

Arm description

Intravenous (i.v.) dosing of Placebo at a dose level of 1 mg/kg body weight

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous (i.v.) dosing of Placebo at a dose level of 1 mg/kg body weight. Weekly i.v.dosing of placebo through 12 months was planned; a minimum of 49 infusions and a maximum of 55 infusions were administered to each patient.

Number of subjects in period 1	Lamazym	Placebo
Started	15	10
Completed	15	10

Baseline characteristics

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Reporting group title

Lamazym

Reporting group description

Intravenous (i.v.) dosing of Lamazym at a dose level of 1 mg/kg body weight.

Reporting group title

Placebo

Reporting group description

Intravenous (i.v.) dosing of Placebo at a dose level of 1 mg/kg body weight

Reporting group values	Lamazym	Placebo	Total
Number of subjects	15	10	25
Age categorical
Units: Subjects
Children (2-11 years)	4	2	6
Adolescents (12-17 years)	3	3	6
Adults (18-64 years)	8	5	13
Age continuous
Units: years
arithmetic mean (standard deviation)	18.5 ± 9	19.7 ± 8.9	-
Gender categorical
Units: Subjects
Female	6	5	11
Male	9	5	14

Subject analysis set title

Lamazym - Full Analysis Set (FAS)

Subject analysis set type

Full analysis

Subject analysis set description

The Full Analysis Set (FAS) included 25 patients, i.e all randomized subjects who received at least one dose of the study treatment and with at least one post-baseline efficacy measurement

Subject analysis set title

Lamazym - Safety

Subject analysis set type

Safety analysis

Subject analysis set description

The safety analysis set included 25 patients, i.e. all randomised patients who received at least one dose of the study treatment

Subject analysis set title

Lamazym - Per protocol

Subject analysis set type

Per protocol

Subject analysis set description

The Per-Protocol analysis Set (PP) included 25 patients, i.e all all patients from the FAS who did not have substantial deviations to the protocol

Subject analysis set title

Lamazym - PK

Subject analysis set type

Sub-group analysis

Subject analysis set description

The PK analysis set (PK) included 25 patients, i.e. all patients from the safety population and treated with Lamazym excluding patients without any valid PK measurement or with major protocol deviations significantly affecting PK. During the blinded data review, all patients were included in the PK analysis set, but only the 15 patients treated with Lamazym were then analyzed.

Subject analysis set title

Placebo - Full Analysis Set (FAS)

Subject analysis set type

Full analysis

Subject analysis set description

The Full Analysis Set (FAS) included 25 patients, i.e all randomized subjects who received at least one dose of the study treatment and with at least one post-baseline efficacy measurement

Subject analysis set title

Placebo - Safety

Subject analysis set type

Safety analysis

Subject analysis set description

The safety analysis set included 25 patients, i.e. all randomised patients who received at least one dose of the study treatment

Subject analysis set title

Placebo - Per protocol

Subject analysis set type

Per protocol

Subject analysis set description

The Per-Protocol analysis Set (PP) included 25 patients, i.e all all patients from the FAS who did not have substantial deviations to the protocol

Subject analysis set title

Placebo - PK

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis sets values	Lamazym - Full Analysis Set (FAS)	Lamazym - Safety	Lamazym - Per protocol	Lamazym - PK	Placebo - Full Analysis Set (FAS)	Placebo - Safety	Placebo - Per protocol	Placebo - PK
Number of subjects	15	15	15	15	10	10	10	10
Age categorical
Units: Subjects
Children (2-11 years)	4	4	4	4	2	2	2
Adolescents (12-17 years)	3	3	3	3	3	3	3
Adults (18-64 years)	8	8	8	8	5	5	5
Age continuous
Units: years
arithmetic mean (standard deviation)	18.5 ± 9	18.5 ± 9	18.5 ± 9	18.5 ± 9	19.7 ± 8.9	19.7 ± 8.9	19.7 ± 8.9	±
Gender categorical
Units: Subjects
Female	6	6	6	6	5	5	5
Male	9	9	9	9	5	5	5

End points

Top of page

Reporting group title

Lamazym

Reporting group description

Intravenous (i.v.) dosing of Lamazym at a dose level of 1 mg/kg body weight.

Reporting group title

Placebo

Reporting group description

Intravenous (i.v.) dosing of Placebo at a dose level of 1 mg/kg body weight

Subject analysis set title

Lamazym - Full Analysis Set (FAS)

Subject analysis set type

Full analysis

Subject analysis set description

The Full Analysis Set (FAS) included 25 patients, i.e all randomized subjects who received at least one dose of the study treatment and with at least one post-baseline efficacy measurement

Subject analysis set title

Lamazym - Safety

Subject analysis set type

Safety analysis

Subject analysis set description

The safety analysis set included 25 patients, i.e. all randomised patients who received at least one dose of the study treatment

Subject analysis set title

Lamazym - Per protocol

Subject analysis set type

Per protocol

Subject analysis set description

The Per-Protocol analysis Set (PP) included 25 patients, i.e all all patients from the FAS who did not have substantial deviations to the protocol

Subject analysis set title

Lamazym - PK

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

Placebo - Full Analysis Set (FAS)

Subject analysis set type

Full analysis

Subject analysis set description

The Full Analysis Set (FAS) included 25 patients, i.e all randomized subjects who received at least one dose of the study treatment and with at least one post-baseline efficacy measurement

Subject analysis set title

Placebo - Safety

Subject analysis set type

Safety analysis

Subject analysis set description

The safety analysis set included 25 patients, i.e. all randomised patients who received at least one dose of the study treatment

Subject analysis set title

Placebo - Per protocol

Subject analysis set type

Per protocol

Subject analysis set description

The Per-Protocol analysis Set (PP) included 25 patients, i.e all all patients from the FAS who did not have substantial deviations to the protocol

Subject analysis set title

Placebo - PK

Subject analysis set type

Sub-group analysis

Subject analysis set description

Primary: Change from baseline to week 52 in serum oligosaccharides

Top of page

End point title

Change from baseline to week 52 in serum oligosaccharides

End point description

End point type

Primary

End point timeframe

Serum oligosaccharides concentration was measured at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: μmol/L
arithmetic mean (standard deviation)	-5.1 ± 1.2	-1.6 ± 1.7

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

-3.5

Confidence interval

level

95%

sides

2-sided

lower limit

-4.37

upper limit

-2.62

Primary: Change from baseline to week 52 in the 3-minute stair climb test (3MSCT)

Top of page

End point title

Change from baseline to week 52 in the 3-minute stair climb test (3MSCT)

End point description

The 3MSCT measures the number of steps climbed up in 3 minutes and it was performed in accordance with the guidelines. The test was performed twice, and the better result of the 2 tests was used.

End point type

Primary

End point timeframe

The 3MSCT was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: steps/min
arithmetic mean (standard deviation)	0.6 ± 8.6	-2.4 ± 5.5

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.406

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

2.62

Confidence interval

level

95%

sides

2-sided

lower limit

-3.81

upper limit

9.05

Secondary: Change from baseline to week 52 in 6 minute walk test (6MWT)

Top of page

End point title

Change from baseline to week 52 in 6 minute walk test (6MWT)

End point description

Change from baseline to week 52 in 6MWT was included as a prioritized secondary endpoint

End point type

Secondary

End point timeframe

The 6MWT was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: meters
arithmetic mean (standard deviation)	4.4 ± 46.12	-4.6 ± 40.79

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.692

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

7.35

Confidence interval

level

95%

sides

2-sided

lower limit

-30.76

upper limit

45.46

Secondary: Change from baseline to week 52 in FVC percent of predicted normal value (FVC %)

Top of page

End point title

Change from baseline to week 52 in FVC percent of predicted normal value (FVC %)

End point description

Change from baseline to week 52 in FVC% was included as a prioritized secondary endpoint

End point type

Secondary

End point timeframe

FVC% was measured at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	14	9
Units: percent
arithmetic mean (standard deviation)	8.17 ± 9.85	2 ± 12.61

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.278

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

5.91

Confidence interval

level

95%

sides

2-sided

lower limit

-4.78

upper limit

16.6

Secondary: Change from baseline to week 26 in the BOT2 test - Running Speed and Agility

Top of page

End point title

Change from baseline to week 26 in the BOT2 test - Running Speed and Agility

End point description

End point type

Secondary

End point timeframe

The Bruininks-Oseretsky (BOT2) test of motor proficiency was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: points
arithmetic mean (standard deviation)	-0.93 ± 2.22	-0.3 ± 2.67

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.434

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

-0.85

Confidence interval

level

95%

sides

2-sided

lower limit

-3.08

upper limit

1.37

Secondary: Change from baseline to week 52 in the BOT2 test - Running Speed and Agility

Top of page

End point title

Change from baseline to week 52 in the BOT2 test - Running Speed and Agility

End point description

End point type

Secondary

End point timeframe

The BOT2 test was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	9
Units: points
arithmetic mean (standard deviation)	-0.07 ± 3.03	-0.78 ± 1.48

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.998

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.17

upper limit

2.16

Secondary: Change from baseline to week 26 in the BOT2 test - Body coordination

Top of page

End point title

Change from baseline to week 26 in the BOT2 test - Body coordination

End point description

End point type

Secondary

End point timeframe

The BOT2 test was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: points
arithmetic mean (standard deviation)	-0.27 ± 4.93	0.8 ± 4.32

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.451

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

-1.52

Confidence interval

level

95%

sides

2-sided

lower limit

-5.64

upper limit

2.59

Secondary: Change from baseline to week 52 in the BOT2 test - Body coordination

Top of page

End point title

Change from baseline to week 52 in the BOT2 test - Body coordination

End point description

End point type

Secondary

End point timeframe

The BOT2 test was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	9
Units: points
arithmetic mean (standard deviation)	0.93 ± 5.18	0.8 ± 5.24

Lamazym vs Placebo

Comparison groups

Placebo - Full Analysis Set (FAS) v Lamazym - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.272

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

2.59

Confidence interval

level

95%

sides

2-sided

lower limit

-2.04

upper limit

7.22

Secondary: Change from baseline to week 26 in the BOT2 test - Fine Manual Control

Top of page

End point title

Change from baseline to week 26 in the BOT2 test - Fine Manual Control

End point description

End point type

Secondary

End point timeframe

The BOT2 test was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: Points
arithmetic mean (standard deviation)	-0.07 ± 6.51	-0.9 ± 5.78

Lamzym vs Placebo

Comparison groups

Placebo - Full Analysis Set (FAS) v Lamazym - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.937

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

0.18

Confidence interval

level

95%

sides

2-sided

lower limit

-4.43

upper limit

4.78

Secondary: Change from baseline to week 52 in the BOT2 test - Fine Manual Control

Top of page

End point title

Change from baseline to week 52 in the BOT2 test - Fine Manual Control

End point description

End point type

Secondary

End point timeframe

The BOT2 test was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	9
Units: points
arithmetic mean (standard deviation)	2.73 ± 6.39	1.33 ± 5.59

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.381

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

2.31

Confidence interval

level

95%

sides

2-sided

lower limit

-2.86

upper limit

7.48

Secondary: Change from baseline to week 26 in the BOT2 test - Manual Coordination

Top of page

End point title

Change from baseline to week 26 in the BOT2 test - Manual Coordination

End point description

End point type

Secondary

End point timeframe

The BOT2 test was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: points
arithmetic mean (standard deviation)	1.47 ± 7.69	-0.1 ± 3.38

Lamzym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.688

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

1.04

Confidence interval

level

95%

sides

2-sided

lower limit

-4.25

upper limit

6.33

Secondary: Change from baseline to week 52 in the BOT2 test - Manual Coordination

Top of page

End point title

Change from baseline to week 52 in the BOT2 test - Manual Coordination

End point description

End point type

Secondary

End point timeframe

The BOT2 test was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	9
Units: points
arithmetic mean (standard deviation)	2.8 ± 6.46	-0.1 ± 3.38

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.787

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

-0.65

Confidence interval

level

95%

sides

2-sided

lower limit

-5.33

upper limit

4.04

Secondary: Change from baseline to week 26 in the BOT2 test - Total

Top of page

End point title

Change from baseline to week 26 in the BOT2 test - Total

End point description

End point type

Secondary

End point timeframe

Change from baseline to week 52 in the BOT2 test - Manual Coordination

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: points
arithmetic mean (standard deviation)	0.2 ± 12.8	-0.5 ± 12.26

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.875

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

-0.79

Confidence interval

level

95%

sides

2-sided

lower limit

-11.02

upper limit

9.45

Secondary: Change from baseline to week 52 in the BOT2 test - Total

Top of page

End point title

Change from baseline to week 52 in the BOT2 test - Total

End point description

End point type

Secondary

End point timeframe

The BOT2 test was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	9
Units: points
arithmetic mean (standard deviation)	6.4 ± 13.38	-0.33 ± 9.59

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.344

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

4.54

Confidence interval

level

95%

sides

2-sided

lower limit

-4.86

upper limit

13.94

Secondary: Change from baseline to week 26 in the Leiter R – Design Analogies

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End point title

Change from baseline to week 26 in the Leiter R – Design Analogies

End point description

End point type

Secondary

End point timeframe

The Leiter R cognitive function test was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: years
arithmetic mean (standard deviation)	0.16 ± 1.11	0.4 ± 1.18

No statistical analyses for this end point

Secondary: Change from baseline to week 52 in the Leiter R – Design Analogies

Top of page

End point title

Change from baseline to week 52 in the Leiter R – Design Analogies

End point description

End point type

Secondary

End point timeframe

The Leiter R cognitive function test was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	10	10
Units: years
arithmetic mean (standard deviation)	0.81 ± 1.47	0.64 ± 1

No statistical analyses for this end point

Secondary: Change from baseline to week 26 in the Leiter R – Figure Ground

Top of page

End point title

Change from baseline to week 26 in the Leiter R – Figure Ground

End point description

End point type

Secondary

End point timeframe

The Leiter R cognitive function test was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: years
arithmetic mean (standard deviation)	0.07 ± 1.15	0.11 ± 1.2

No statistical analyses for this end point

Secondary: Change from baseline to week 52 in the Leiter R – Figure Ground

Top of page

End point title

Change from baseline to week 52 in the Leiter R – Figure Ground

End point description

End point type

Secondary

End point timeframe

The Leiter R cognitive function test was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: years
arithmetic mean (standard deviation)	0.37 ± 1.15	0 ± 1.08

No statistical analyses for this end point

Secondary: Change from baseline to week 26 in the Leiter R – Form Completion

Top of page

End point title

Change from baseline to week 26 in the Leiter R – Form Completion

End point description

End point type

Secondary

End point timeframe

The Leiter R cognitive function test was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: years
arithmetic mean (standard deviation)	0.26 ± 1.38	-0.22 ± 1.36

No statistical analyses for this end point

Secondary: Change from baseline to week 52 in the Leiter R – Form Completion

Top of page

End point title

Change from baseline to week 52 in the Leiter R – Form Completion

End point description

End point type

Secondary

End point timeframe

The Leiter R cognitive function test was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: years
arithmetic mean (standard deviation)	0.63 ± 1.52	0.22 ± 0.69

No statistical analyses for this end point

Secondary: Change from baseline to week 26 in the Leiter R – Paper Folding

Top of page

End point title

Change from baseline to week 26 in the Leiter R – Paper Folding

End point description

End point type

Secondary

End point timeframe

The Leiter R cognitive function test was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	9
Units: years
arithmetic mean (standard deviation)	-0.87 ± 2.19	-0.25 ± 2.54

No statistical analyses for this end point

Secondary: Change from baseline to week 52 in the Leiter R – Paper Folding

Top of page

End point title

Change from baseline to week 52 in the Leiter R – Paper Folding

End point description

End point type

Secondary

End point timeframe

The Leiter R cognitive function test was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	9
Units: years
arithmetic mean (standard deviation)	0.21 ± 2.26	-0.31 ± 2.37

No statistical analyses for this end point

Secondary: Change from baseline to week 26 in the Leiter R – Repeated Pattern

Top of page

End point title

Change from baseline to week 26 in the Leiter R – Repeated Pattern

End point description

End point type

Secondary

End point timeframe

The Leiter R cognitive function test was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	9
Units: years
arithmetic mean (standard deviation)	0.39 ± 0.78	-0.44 ± 1.83

No statistical analyses for this end point

Secondary: Change from baseline to week 52 in the Leiter R – Repeated Pattern

Top of page

End point title

Change from baseline to week 52 in the Leiter R – Repeated Pattern

End point description

End point type

Secondary

End point timeframe

The Leiter R cognitive function test was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	9
Units: years
arithmetic mean (standard deviation)	0.09 ± 0.64	-0.69 ± 1.89

No statistical analyses for this end point

Secondary: Change from baseline to week 26 in the Leiter R – Sequential Order

Top of page

End point title

Change from baseline to week 26 in the Leiter R – Sequential Order

End point description

End point type

Secondary

End point timeframe

The Leiter R cognitive function test was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	9
Units: years
arithmetic mean (standard deviation)	-0.26 ± 1.95	0.57 ± 0.8

No statistical analyses for this end point

Secondary: Change from baseline to week 52 in the Leiter R – Sequential Order

Top of page

End point title

Change from baseline to week 52 in the Leiter R – Sequential Order

End point description

End point type

Secondary

End point timeframe

The Leiter R cognitive function test was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	9
Units: years
arithmetic mean (standard deviation)	-0.34 ± 1.79	0.27 ± 1.24

No statistical analyses for this end point

Secondary: Change from baseline to week 26 in the Leiter R – Associated Pairs

Top of page

End point title

Change from baseline to week 26 in the Leiter R – Associated Pairs

End point description

End point type

Secondary

End point timeframe

The Leiter R cognitive function test was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: years
arithmetic mean (standard deviation)	0.13 ± 1.89	0.59 ± 1.45

No statistical analyses for this end point

Secondary: Change from baseline to week 52 in the Leiter R – Associated Pairs

Top of page

End point title

Change from baseline to week 52 in the Leiter R – Associated Pairs

End point description

End point type

Secondary

End point timeframe

The Leiter R cognitive function test was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: years
least squares mean (standard deviation)	0.18 ± 2.54	-0.14 ± 1.59

No statistical analyses for this end point

Secondary: Change from baseline to week 26 in the Leiter R – Forward Memory

Top of page

End point title

Change from baseline to week 26 in the Leiter R – Forward Memory

End point description

End point type

Secondary

End point timeframe

The Leiter R cognitive function test was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: years
arithmetic mean (standard deviation)	-0.46 ± 2.76	0.52 ± 1.16

No statistical analyses for this end point

Secondary: Change from baseline to week 52 in the Leiter R – Forward Memory

Top of page

End point title

Change from baseline to week 52 in the Leiter R – Forward Memory

End point description

End point type

Secondary

End point timeframe

The Leiter R cognitive function test was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: years
arithmetic mean (standard deviation)	0.91 ± 2.34	0.32 ± 1.37

No statistical analyses for this end point

Secondary: Change from baseline to week 26 in the Leiter R – Total Equivalence Age AM

Top of page

End point title

Change from baseline to week 26 in the Leiter R – Total Equivalence Age AM

End point description

End point type

Secondary

End point timeframe

The Leiter R cognitive function test was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: years
arithmetic mean (standard deviation)	0.1 ± 1.33	0.27 ± 0.62

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.702

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

-0.18

Confidence interval

level

95%

sides

2-sided

lower limit

-1.09

upper limit

0.73

Secondary: Change from baseline to week 52 in the Leiter R – Total Equivalence Age AM

Top of page

End point title

Change from baseline to week 52 in the Leiter R – Total Equivalence Age AM

End point description

End point type

Secondary

End point timeframe

The Leiter R cognitive function test was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: years
arithmetic mean (standard deviation)	0.02 ± 1.41	0.11 ± 1.02

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.681

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

-0.18

Confidence interval

level

95%

sides

2-sided

lower limit

-1.09

upper limit

0.73

Secondary: Change from baseline to week 26 in the Leiter R – Total Equivalence Age VR

Top of page

End point title

Change from baseline to week 26 in the Leiter R – Total Equivalence Age VR

End point description

End point type

Secondary

End point timeframe

The Leiter R cognitive function test was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: years
arithmetic mean (standard deviation)	-0.01 ± 0.67	0.1 ± 0.52

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.454

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

-0.17

Confidence interval

level

95%

sides

2-sided

lower limit

-0.62

upper limit

0.29

Secondary: Change from baseline to week 52 in the Leiter R – Total Equivalence Age VR

Top of page

End point title

Change from baseline to week 52 in the Leiter R – Total Equivalence Age VR

End point description

End point type

Secondary

End point timeframe

The Leiter R cognitive function test was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: years
arithmetic mean (standard deviation)	0.17 ± 0.71	0.16 ± 0.65

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.864

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

-0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-0.57

upper limit

0.48

Secondary: Change from baseline to week 26 in CSF oligosaccharides

Top of page

End point title

Change from baseline to week 26 in CSF oligosaccharides

End point description

End point type

Secondary

End point timeframe

CSF oligosaccharides concentration was measured at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: μmol/L
arithmetic mean (standard deviation)	1.4 ± 2.1	0.4 ± 1.7

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.327

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

0.83

Confidence interval

level

95%

sides

2-sided

lower limit

-0.89

upper limit

2.56

Secondary: Change from baseline to week 52 in CSF oligosaccharides

Top of page

End point title

Change from baseline to week 52 in CSF oligosaccharides

End point description

End point type

Secondary

End point timeframe

CSF oligosaccharides concentration was measured at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: μmol/L
arithmetic mean (standard deviation)	-0.4 ± 1.2	-0.5 ± 0.9

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.897

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

0.06

Confidence interval

level

95%

sides

2-sided

lower limit

-0.82

upper limit

0.93

Secondary: Change from baseline to week 26 in CSF Tau Protein concentration

Top of page

End point title

Change from baseline to week 26 in CSF Tau Protein concentration

End point description

End point type

Secondary

End point timeframe

CSF biomarkers (Tau Protein, Neurofilament Protein and Glial Fibrillary Acidic Protein) concentration was measured at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: ng/L
arithmetic mean (standard deviation)	13.8 ± 80.6	-69.1 ± 80.1

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.01

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

95.32

Confidence interval

level

95%

sides

2-sided

lower limit

24.96

upper limit

165.69

Secondary: Change from baseline to week 52 in CSF Tau Protein concentration

Top of page

End point title

Change from baseline to week 52 in CSF Tau Protein concentration

End point description

End point type

Secondary

End point timeframe

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: ng/L
arithmetic mean (standard deviation)	-61 ± 117.5	-60.1 ± 70.2

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.356

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

32.48

Confidence interval

level

95%

sides

2-sided

lower limit

-39.01

upper limit

103.96

Secondary: Change from baseline to week 26 in CSF Neurofilament Protein concentration

Top of page

End point title

Change from baseline to week 26 in CSF Neurofilament Protein concentration

End point description

End point type

Secondary

End point timeframe

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: ng/L
arithmetic mean (standard deviation)	26 ± 173.6	-224 ± 608.3

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.143

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

101.03

Confidence interval

level

95%

sides

2-sided

lower limit

-36.94

upper limit

239

Secondary: Change from baseline to week 52 in CSF Neurofilament Protein concentration

Top of page

End point title

Change from baseline to week 52 in CSF Neurofilament Protein concentration

End point description

End point type

Secondary

End point timeframe

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: ng/L
arithmetic mean (standard deviation)	-15.3 ± 87.2	-112 ± 598

Lamazym vs Placebo

Comparison groups

Placebo - Full Analysis Set (FAS) v Lamazym - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.639

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

-35.09

Confidence interval

level

95%

sides

2-sided

lower limit

-188.3

upper limit

118.09

Secondary: Change from baseline to week 26 in CSF Glial Fibrillary Acidic Protein concentration

Top of page

End point title

Change from baseline to week 26 in CSF Glial Fibrillary Acidic Protein concentration

End point description

End point type

Secondary

End point timeframe

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: ng/L
arithmetic mean (standard deviation)	42 ± 188.4	-8 ± 106.5

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.573

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

37.63

Confidence interval

level

95%

sides

2-sided

lower limit

-99.18

upper limit

174.43

Secondary: Change from baseline to week 52 in CSF Glial Fibrillary Acidic Protein concentration

Top of page

End point title

Change from baseline to week 52 in CSF Glial Fibrillary Acidic Protein concentration

End point description

End point type

Secondary

End point timeframe

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: ng/L
arithmetic mean (standard deviation)	107.3 ± 187.6	141 ± 231.9

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.575

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

-46.85

Confidence interval

level

95%

sides

2-sided

lower limit

-218.1

upper limit

124.38

Secondary: Change from baseline to week 26 in FEV1

Top of page

End point title

Change from baseline to week 26 in FEV1

End point description

End point type

Secondary

End point timeframe

Pulmonary function test were performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	10	8
Units: liters
arithmetic mean (standard deviation)	0.23 ± 0.28	-0.04 ± 0.24

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.057

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

0.26

Confidence interval

level

95%

sides

2-sided

lower limit

-0.01

upper limit

0.52

Secondary: Change from baseline to week 52 in FEV1

Top of page

End point title

Change from baseline to week 52 in FEV1

End point description

End point type

Secondary

End point timeframe

Pulmonary function test were performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	12	9
Units: liters
arithmetic mean (standard deviation)	0.32 ± 0.34	0.2 ± 0.12

Lamazym vs Placebo

Comparison groups

Placebo - Full Analysis Set (FAS) v Lamazym - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.608

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

0.06

Confidence interval

level

95%

sides

2-sided

lower limit

-0.18

upper limit

0.31

Secondary: Change from baseline to Visit 26 in FEV1 Percent of predicted normal value

Top of page

End point title

Change from baseline to Visit 26 in FEV1 Percent of predicted normal value

End point description

End point type

Secondary

End point timeframe

Pulmonary function test were performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	10	8
Units: percent
arithmetic mean (standard deviation)	6.1 ± 9.54	-1.38 ± 6.91

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.023

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

10.29

Confidence interval

level

95%

sides

2-sided

lower limit

1.43

upper limit

19.16

Secondary: Change from baseline to Visit 52 in FEV1 Percent of predicted normal value

Top of page

End point title

Change from baseline to Visit 52 in FEV1 Percent of predicted normal value

End point description

End point type

Secondary

End point timeframe

Pulmonary function test were performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	12	9
Units: percent
arithmetic mean (standard deviation)	6.5 ± 8.66	4.44 ± 4.69

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.618

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

1.77

Confidence interval

level

95%

sides

2-sided

lower limit

-5.2

upper limit

8.74

Secondary: Change from baseline to Visit 26 in FVC

Top of page

End point title

Change from baseline to Visit 26 in FVC

End point description

End point type

Secondary

End point timeframe

Pulmonary function test were performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	11	8
Units: liters
arithmetic mean (standard deviation)	0.24 ± 0.32	-0.03 ± 0.17

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.101

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

0.29

Confidence interval

level

95%

sides

2-sided

lower limit

-0.06

upper limit

0.64

Secondary: Change from baseline to Visit 52 in FVC

Top of page

End point title

Change from baseline to Visit 52 in FVC

End point description

End point type

Secondary

End point timeframe

Pulmonary function test were performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	12	9
Units: liters
arithmetic mean (standard deviation)	0.4 ± 0.41	0.11 ± 0.5

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.202

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

0.27

Confidence interval

level

95%

sides

2-sided

lower limit

-0.14

upper limit

0.68

Secondary: Change from baseline to Visit 26 in PEF

Top of page

End point title

Change from baseline to Visit 26 in PEF

End point description

End point type

Secondary

End point timeframe

Pulmonary function test were performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	11	8
Units: L/s
arithmetic mean (standard deviation)	0.92 ± 0.73	0.04 ± 0.62

Lamazym vs Placebo

Comparison groups

Placebo - Full Analysis Set (FAS) v Lamazym - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.009

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.24

upper limit

1.66

Secondary: Change from baseline to Visit 52 in PEF

Top of page

End point title

Change from baseline to Visit 52 in PEF

End point description

End point type

Secondary

End point timeframe

Pulmonary function test were performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	12	9
Units: L/s
arithmetic mean (standard deviation)	1 ± 0.9	0.68 ± 0.87

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.837

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

0.09

Confidence interval

level

95%

sides

2-sided

lower limit

-0.73

upper limit

0.9

Secondary: Change from baseline to Visit 26 in Pure tone audiometry (PTA) - air conduction left ear

Top of page

End point title

Change from baseline to Visit 26 in Pure tone audiometry (PTA) - air conduction left ear

End point description

End point type

Secondary

End point timeframe

PTA (pure tone audiometry) was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: dbHL
arithmetic mean (standard deviation)	0.59 ± 7.08	-1.09 ± 10.74

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.419

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

2.79

Confidence interval

level

95%

sides

2-sided

lower limit

-4.24

upper limit

9.82

Secondary: Change from baseline to Visit 52 in Pure tone audiometry (PTA) - air conduction left ear

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End point title

Change from baseline to Visit 52 in Pure tone audiometry (PTA) - air conduction left ear

End point description

End point type

Secondary

End point timeframe

Pure tone audiometry was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: dbHL
arithmetic mean (standard deviation)	0.95 ± 8.03	0.76 ± 7.83

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.626

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

1.44

Confidence interval

level

95%

sides

2-sided

lower limit

-4.62

upper limit

7.5

Secondary: Change from baseline to Visit 26 in Pure tone audiometry (PTA) - air conduction right ear

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End point title

Change from baseline to Visit 26 in Pure tone audiometry (PTA) - air conduction right ear

End point description

End point type

Secondary

End point timeframe

Pure tone audiometry was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: dbHL
arithmetic mean (standard deviation)	1.08 ± 9.05	-1.44 ± 10.61

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.467

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

3.07

Confidence interval

level

95%

sides

2-sided

lower limit

-5.54

upper limit

11.67

Secondary: Change from baseline to Visit 52 in Pure tone audiometry (PTA) - air conduction right ear

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End point title

Change from baseline to Visit 52 in Pure tone audiometry (PTA) - air conduction right ear

End point description

End point type

Secondary

End point timeframe

Pure tone audiometry was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: dbHL
arithmetic mean (standard deviation)	1.94 ± 11.34	-1.89 ± 8.99

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.313

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

4.58

Confidence interval

level

95%

sides

2-sided

lower limit

-4.64

upper limit

13.81

Secondary: Change from baseline to Visit 26 in Pure tone audiometry (PTA) - bone conduction best ear

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End point title

Change from baseline to Visit 26 in Pure tone audiometry (PTA) - bone conduction best ear

End point description

End point type

Secondary

End point timeframe

Pure tone audiometry was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	14	10
Units: dbHL
arithmetic mean (standard deviation)	3.21 ± 3.49	-0.71 ± 5.46

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.027

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

4.21

Confidence interval

level

95%

sides

2-sided

lower limit

0.48

upper limit

7.94

Secondary: Change from baseline to Visit 52 in Pure tone audiometry (PTA) - bone conduction best ear

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End point title

Change from baseline to Visit 52 in Pure tone audiometry (PTA) - bone conduction best ear

End point description

End point type

Secondary

End point timeframe

Pure tone audiometry was performed at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	14	10
Units: dbHL
arithmetic mean (standard deviation)	2.36 ± 5.21	0.13 ± 5.89

Lamazym vs Placebo

Comparison groups

Lamazym - Full Analysis Set (FAS) v Placebo - Full Analysis Set (FAS)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.217

Method

ANCOVA

Parameter type

adjusted mean difference

Point estimate

2.87

Confidence interval

level

95%

sides

2-sided

lower limit

-1.68

upper limit

7.42

Secondary: Change from baseline to Visit 26 in CHAQ score - Disability Index

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End point title

Change from baseline to Visit 26 in CHAQ score - Disability Index

End point description

End point type

Secondary

End point timeframe

Health Questionnaires were administered at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: digit
arithmetic mean (standard deviation)	-0.06 ± 0.38	0.16 ± 0.41

No statistical analyses for this end point

Secondary: Change from baseline to Visit 52 in CHAQ score - Disability Index

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End point title

Change from baseline to Visit 52 in CHAQ score - Disability Index

End point description

End point type

Secondary

End point timeframe

Health Questionnaires were administered at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	15	10
Units: digit
arithmetic mean (standard deviation)	-0.01 ± 0.32	0.18 ± 0.36

No statistical analyses for this end point

Secondary: Change from baseline to Visit 26 in CHAQ score - VAS pain

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End point title

Change from baseline to Visit 26 in CHAQ score - VAS pain

End point description

End point type

Secondary

End point timeframe

Health Questionnaires were administered at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	14	9
Units: digit
arithmetic mean (standard deviation)	0.2 ± 0.79	0.3 ± 0.8

No statistical analyses for this end point

Secondary: Change from baseline to Visit 52 in CHAQ score - VAS pain

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End point title

Change from baseline to Visit 52 in CHAQ score - VAS pain

End point description

End point type

Secondary

End point timeframe

Health Questionnaires were administered at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	14	9
Units: digit
arithmetic mean (standard deviation)	0.19 ± 0.69	0.15 ± 0.71

No statistical analyses for this end point

Secondary: Change from baseline to Visit 26 in CHAQ score - VAS general

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End point title

Change from baseline to Visit 26 in CHAQ score - VAS general

End point description

End point type

Secondary

End point timeframe

Health Questionnaires were administered at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	14	10
Units: digit
arithmetic mean (standard deviation)	0.03 ± 0.63	0.41 ± 0.81

No statistical analyses for this end point

Secondary: Change from baseline to Visit 52 in CHAQ score - VAS general

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End point title

Change from baseline to Visit 52 in CHAQ score - VAS general

End point description

End point type

Secondary

End point timeframe

Health Questionnaires were administered at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	14	10
Units: digit
arithmetic mean (standard deviation)	0.51 ± 0.93	0.44 ± 0.62

No statistical analyses for this end point

Secondary: Change from baseline to Visit 26 in EQ-5D-5L VAS

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End point title

Change from baseline to Visit 26 in EQ-5D-5L VAS

End point description

End point type

Secondary

End point timeframe

Health Questionnaires were administered at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	14	10
Units: digit
arithmetic mean (standard deviation)	5.71 ± 16.94	3 ± 15.85

No statistical analyses for this end point

Secondary: Change from baseline to Visit 52 in EQ-5D-5L VAS

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End point title

Change from baseline to Visit 52 in EQ-5D-5L VAS

End point description

End point type

Secondary

End point timeframe

Health Questionnaires were administered at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	14	10
Units: digit
arithmetic mean (standard deviation)	2 ± 17.95	3.7 ± 15.71

No statistical analyses for this end point

Secondary: Change from baseline to Visit 26 in EQ-5D-5L Index

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End point title

Change from baseline to Visit 26 in EQ-5D-5L Index

End point description

End point type

Secondary

End point timeframe

Health Questionnaires were administered at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	14	8
Units: digit
arithmetic mean (standard deviation)	0.06 ± 0.12	0.04 ± 0.09

No statistical analyses for this end point

Secondary: Change from baseline to Visit 52 in EQ-5D-5L Index

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End point title

Change from baseline to Visit 52 in EQ-5D-5L Index

End point description

End point type

Secondary

End point timeframe

Health Questionnaires were administered at baseline (Visit 0), at Midterm evaluation (Visit 26a) and at End evaluation (Visit 52a)

End point values	Lamazym - Full Analysis Set (FAS)	Placebo - Full Analysis Set (FAS)
Number of subjects analysed	14	8
Units: digit
arithmetic mean (standard deviation)	0.04 ± 0.09	0.03 ± 0.16

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Adverse events were assessed at baseline, at midterm evaluation (visit 26a) and at end evaluation (visit 52a)

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

16.0

Reporting group title

Placebo - Safety

Reporting group description

Intravenous (i.v.) dosing of Placebo at a dose level of 1 mg/kg body weight

Reporting group title

Lamazym - Safety

Reporting group description

Intravenous (i.v.) dosing of Lamazym at a dose level of 1 mg/kg body weight.

Serious adverse events	Placebo - Safety	Lamazym - Safety
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 10 (0.00%)	5 / 15 (33.33%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events	0	0
Renal and urinary disorders
Renal failure
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Joint swelling
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Knee deformity
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Sjogren's syndrome
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Sepsis
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 1%

Non-serious adverse events	Placebo - Safety	Lamazym - Safety
Total subjects affected by non serious adverse events
subjects affected / exposed	9 / 10 (90.00%)	15 / 15 (100.00%)
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	5 / 10 (50.00%)	6 / 15 (40.00%)
occurrences all number	11	11
Chills
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	7
Oedema peripheral
subjects affected / exposed	1 / 10 (10.00%)	1 / 15 (6.67%)
occurrences all number	4	1
Fatigue
subjects affected / exposed	1 / 10 (10.00%)	1 / 15 (6.67%)
occurrences all number	1	1
Catheter site pain
subjects affected / exposed	1 / 10 (10.00%)	0 / 15 (0.00%)
occurrences all number	1	0
Infusion site oedema
subjects affected / exposed	1 / 10 (10.00%)	0 / 15 (0.00%)
occurrences all number	1	0
Immune system disorders
Hypersensitivity
subjects affected / exposed	0 / 10 (0.00%)	2 / 15 (13.33%)
occurrences all number	0	5
Seasonal allergy
subjects affected / exposed	1 / 10 (10.00%)	0 / 15 (0.00%)
occurrences all number	1	0
Food allergy
subjects affected / exposed	1 / 10 (10.00%)	0 / 15 (0.00%)
occurrences all number	1	0
Respiratory, thoracic and mediastinal disorders
Epistaxis
subjects affected / exposed	1 / 10 (10.00%)	1 / 15 (6.67%)
occurrences all number	3	4
Nasal congestion
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Cough
subjects affected / exposed	1 / 10 (10.00%)	0 / 15 (0.00%)
occurrences all number	1	0
Asthma
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Dyspnoea
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Psychiatric disorders
Agitation
subjects affected / exposed	1 / 10 (10.00%)	0 / 15 (0.00%)
occurrences all number	2	0
Stress
subjects affected / exposed	1 / 10 (10.00%)	0 / 15 (0.00%)
occurrences all number	1	0
Psychotic behaviour
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Insomnia
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Hallucination
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Depression
subjects affected / exposed	1 / 10 (10.00%)	0 / 15 (0.00%)
occurrences all number	1	0
Investigations
Cardiac murmur
subjects affected / exposed	1 / 10 (10.00%)	0 / 15 (0.00%)
occurrences all number	1	0
Blood bilirubin decreased
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Amylase increased
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Alanine aminotransferase increased
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Injury, poisoning and procedural complications
Excoriation
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	4
Fall
subjects affected / exposed	1 / 10 (10.00%)	0 / 15 (0.00%)
occurrences all number	2	0
Contusion
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	2
Head injury
subjects affected / exposed	1 / 10 (10.00%)	0 / 15 (0.00%)
occurrences all number	1	0
Arthropod sting
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Post lumbar puncture syndrome
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Wrist fracture
subjects affected / exposed	1 / 10 (10.00%)	0 / 15 (0.00%)
occurrences all number	1	0
Wound
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Sunburn
subjects affected / exposed	1 / 10 (10.00%)	0 / 15 (0.00%)
occurrences all number	1	0
Congenital, familial and genetic disorders
Hydrocele
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Cardiac disorders
Tachycardia
subjects affected / exposed	1 / 10 (10.00%)	0 / 15 (0.00%)
occurrences all number	1	0
Bradycardia
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Nervous system disorders
Headache
subjects affected / exposed	3 / 10 (30.00%)	5 / 15 (33.33%)
occurrences all number	9	7
Dizziness
subjects affected / exposed	2 / 10 (20.00%)	1 / 15 (6.67%)
occurrences all number	2	1
Syncope
subjects affected / exposed	0 / 10 (0.00%)	2 / 15 (13.33%)
occurrences all number	0	2
Loss of consciousness
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Aphonia
subjects affected / exposed	1 / 10 (10.00%)	0 / 15 (0.00%)
occurrences all number	1	0
Blood and lymphatic system disorders
Lymphadenopathy
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Ear and labyrinth disorders
Ear discomfort
subjects affected / exposed	2 / 10 (20.00%)	0 / 15 (0.00%)
occurrences all number	2	0
Ear congestion
subjects affected / exposed	1 / 10 (10.00%)	0 / 15 (0.00%)
occurrences all number	1	0
Eye disorders
Eyelid oedema
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	3
Conjunctival hyperaemia
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Eye pruritus
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Ocular hyperaemia
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Eye irritation
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Gastrointestinal disorders
Vomiting
subjects affected / exposed	4 / 10 (40.00%)	3 / 15 (20.00%)
occurrences all number	6	5
Diarrhoea
subjects affected / exposed	3 / 10 (30.00%)	2 / 15 (13.33%)
occurrences all number	3	2
Toothache
subjects affected / exposed	0 / 10 (0.00%)	2 / 15 (13.33%)
occurrences all number	0	3
Constipation
subjects affected / exposed	1 / 10 (10.00%)	1 / 15 (6.67%)
occurrences all number	1	1
Dental caries
subjects affected / exposed	1 / 10 (10.00%)	1 / 15 (6.67%)
occurrences all number	1	1
Oral mucosal blistering
subjects affected / exposed	1 / 10 (10.00%)	0 / 15 (0.00%)
occurrences all number	2	0
Lip blister
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	2
Mouth ulceration
subjects affected / exposed	1 / 10 (10.00%)	0 / 15 (0.00%)
occurrences all number	2	0
Nausea
subjects affected / exposed	1 / 10 (10.00%)	1 / 15 (6.67%)
occurrences all number	1	1
Rectal haemorrhage
subjects affected / exposed	1 / 10 (10.00%)	0 / 15 (0.00%)
occurrences all number	2	0
Tongue injury
subjects affected / exposed	1 / 10 (10.00%)	0 / 15 (0.00%)
occurrences all number	1	0
Abdominal pain
subjects affected / exposed	1 / 10 (10.00%)	0 / 15 (0.00%)
occurrences all number	1	0
Inguinal hernia
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Haemorrhoids
subjects affected / exposed	1 / 10 (10.00%)	0 / 15 (0.00%)
occurrences all number	1	0
Gingival swelling
subjects affected / exposed	1 / 10 (10.00%)	0 / 15 (0.00%)
occurrences all number	1	0
Gastrooesophageal reflux disease
subjects affected / exposed	1 / 10 (10.00%)	0 / 15 (0.00%)
occurrences all number	1	0
Mouth cyst
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Food poisoning
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Abdominal pain upper
subjects affected / exposed	1 / 10 (10.00%)	0 / 15 (0.00%)
occurrences all number	1	0
Skin and subcutaneous tissue disorders
Urticaria
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Cold sweat
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Acne
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Hyperhidrosis
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Rash
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Blister
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Scar pain
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Vitiligo
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Renal and urinary disorders
Pollakiuria
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 10 (10.00%)	3 / 15 (20.00%)
occurrences all number	6	4
Pain in extremity
subjects affected / exposed	1 / 10 (10.00%)	1 / 15 (6.67%)
occurrences all number	4	1
Back pain
subjects affected / exposed	1 / 10 (10.00%)	2 / 15 (13.33%)
occurrences all number	1	2
Muscle spasms
subjects affected / exposed	1 / 10 (10.00%)	0 / 15 (0.00%)
occurrences all number	2	0
Pain in jaw
subjects affected / exposed	1 / 10 (10.00%)	0 / 15 (0.00%)
occurrences all number	1	0
Neck pain
subjects affected / exposed	1 / 10 (10.00%)	0 / 15 (0.00%)
occurrences all number	1	0
Myalgia
subjects affected / exposed	1 / 10 (10.00%)	0 / 15 (0.00%)
occurrences all number	1	0
Spondylolisthesis
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Infections and infestations
Nasopharyngitis
subjects affected / exposed	7 / 10 (70.00%)	10 / 15 (66.67%)
occurrences all number	16	30
Urinary tract infection
subjects affected / exposed	1 / 10 (10.00%)	1 / 15 (6.67%)
occurrences all number	3	1
Ear infection
subjects affected / exposed	1 / 10 (10.00%)	2 / 15 (13.33%)
occurrences all number	1	2
Acute tonsillitis
subjects affected / exposed	0 / 10 (0.00%)	2 / 15 (13.33%)
occurrences all number	0	2
Influenza
subjects affected / exposed	0 / 10 (0.00%)	2 / 15 (13.33%)
occurrences all number	0	2
Gastroenteritis
subjects affected / exposed	0 / 10 (0.00%)	2 / 15 (13.33%)
occurrences all number	0	2
Wound infection
subjects affected / exposed	1 / 10 (10.00%)	0 / 15 (0.00%)
occurrences all number	1	0
Pharyngotonsillitis
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Tinea versicolour
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Tooth infection
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Paronychia
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Otitis externa
subjects affected / exposed	1 / 10 (10.00%)	0 / 15 (0.00%)
occurrences all number	1	0
Herpes simplex
subjects affected / exposed	1 / 10 (10.00%)	0 / 15 (0.00%)
occurrences all number	1	0
Cystitis
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Oral herpes
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Otitis media
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Parotitis
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Metabolism and nutrition disorders
Iron deficiency
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1
Decreased appetite
subjects affected / exposed	0 / 10 (0.00%)	1 / 15 (6.67%)
occurrences all number	0	1

More information

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Were there any global substantial amendments to the protocol? Yes

16 Jul 2012

The Amendment 1 concerns the following points: - Exclusion criteria; - Safety laboratory assessments; - Recording of data; - End of trial recordings; - Monitoring and data quality assurance; - Data Management; - Case report forms; - Record retention.

26 Jul 2012

The Amendment 2 concerns the Exclusion criteria.

26 Oct 2012

The Amendment 3 concerns the following points: - Synopsis; -Trial design; - Patient population and selection; - Recruitment; - Packaging and labelling; - Table 9.1; - Baseline (Visit 0); - Power and sample size.

19 Mar 2013

The Amendment 4 concerns the following points: - Synopsis; - Trial design.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

No limitations or caveats are applicable to this summary

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Clinical trials

Clinical Trial Results: A Multi-Center, Double-Blind, Randomized, Placebo-Controlled, Parallel Group Trial, Investigating the Efficacy and Safety of Repeated Lamazym Treatment of Subjects with alpha-Mannosidosis.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change from baseline to week 52 in serum oligosaccharides

Primary: Change from baseline to week 52 in serum oligosaccharides

Primary: Change from baseline to week 52 in the 3-minute stair climb test (3MSCT)

Primary: Change from baseline to week 52 in the 3-minute stair climb test (3MSCT)

Secondary: Change from baseline to week 52 in 6 minute walk test (6MWT)

Secondary: Change from baseline to week 52 in 6 minute walk test (6MWT)

Secondary: Change from baseline to week 52 in FVC percent of predicted normal value (FVC %)

Secondary: Change from baseline to week 52 in FVC percent of predicted normal value (FVC %)

Secondary: Change from baseline to week 26 in the BOT2 test - Running Speed and Agility

Secondary: Change from baseline to week 26 in the BOT2 test - Running Speed and Agility

Secondary: Change from baseline to week 52 in the BOT2 test - Running Speed and Agility

Secondary: Change from baseline to week 52 in the BOT2 test - Running Speed and Agility

Secondary: Change from baseline to week 26 in the BOT2 test - Body coordination

Secondary: Change from baseline to week 26 in the BOT2 test - Body coordination

Secondary: Change from baseline to week 52 in the BOT2 test - Body coordination

Secondary: Change from baseline to week 52 in the BOT2 test - Body coordination

Secondary: Change from baseline to week 26 in the BOT2 test - Fine Manual Control

Secondary: Change from baseline to week 26 in the BOT2 test - Fine Manual Control

Secondary: Change from baseline to week 52 in the BOT2 test - Fine Manual Control

Secondary: Change from baseline to week 52 in the BOT2 test - Fine Manual Control

Secondary: Change from baseline to week 26 in the BOT2 test - Manual Coordination

Secondary: Change from baseline to week 26 in the BOT2 test - Manual Coordination

Secondary: Change from baseline to week 52 in the BOT2 test - Manual Coordination

Secondary: Change from baseline to week 52 in the BOT2 test - Manual Coordination

Secondary: Change from baseline to week 26 in the BOT2 test - Total

Secondary: Change from baseline to week 26 in the BOT2 test - Total

Secondary: Change from baseline to week 52 in the BOT2 test - Total

Secondary: Change from baseline to week 52 in the BOT2 test - Total

Secondary: Change from baseline to week 26 in the Leiter R – Design Analogies

Secondary: Change from baseline to week 26 in the Leiter R – Design Analogies

Secondary: Change from baseline to week 52 in the Leiter R – Design Analogies

Secondary: Change from baseline to week 52 in the Leiter R – Design Analogies

Secondary: Change from baseline to week 26 in the Leiter R – Figure Ground

Secondary: Change from baseline to week 26 in the Leiter R – Figure Ground

Secondary: Change from baseline to week 52 in the Leiter R – Figure Ground

Secondary: Change from baseline to week 52 in the Leiter R – Figure Ground

Secondary: Change from baseline to week 26 in the Leiter R – Form Completion

Secondary: Change from baseline to week 26 in the Leiter R – Form Completion

Secondary: Change from baseline to week 52 in the Leiter R – Form Completion

Secondary: Change from baseline to week 52 in the Leiter R – Form Completion

Secondary: Change from baseline to week 26 in the Leiter R – Paper Folding

Secondary: Change from baseline to week 26 in the Leiter R – Paper Folding

Secondary: Change from baseline to week 52 in the Leiter R – Paper Folding

Secondary: Change from baseline to week 52 in the Leiter R – Paper Folding

Secondary: Change from baseline to week 26 in the Leiter R – Repeated Pattern

Secondary: Change from baseline to week 26 in the Leiter R – Repeated Pattern

Secondary: Change from baseline to week 52 in the Leiter R – Repeated Pattern

Secondary: Change from baseline to week 52 in the Leiter R – Repeated Pattern

Secondary: Change from baseline to week 26 in the Leiter R – Sequential Order

Secondary: Change from baseline to week 26 in the Leiter R – Sequential Order

Secondary: Change from baseline to week 52 in the Leiter R – Sequential Order

Secondary: Change from baseline to week 52 in the Leiter R – Sequential Order

Secondary: Change from baseline to week 26 in the Leiter R – Associated Pairs

Secondary: Change from baseline to week 26 in the Leiter R – Associated Pairs

Secondary: Change from baseline to week 52 in the Leiter R – Associated Pairs

Secondary: Change from baseline to week 52 in the Leiter R – Associated Pairs

Secondary: Change from baseline to week 26 in the Leiter R – Forward Memory

Secondary: Change from baseline to week 26 in the Leiter R – Forward Memory

Secondary: Change from baseline to week 52 in the Leiter R – Forward Memory

Secondary: Change from baseline to week 52 in the Leiter R – Forward Memory

Secondary: Change from baseline to week 26 in the Leiter R – Total Equivalence Age AM

Secondary: Change from baseline to week 26 in the Leiter R – Total Equivalence Age AM

Secondary: Change from baseline to week 52 in the Leiter R – Total Equivalence Age AM

Secondary: Change from baseline to week 52 in the Leiter R – Total Equivalence Age AM

Secondary: Change from baseline to week 26 in the Leiter R – Total Equivalence Age VR

Secondary: Change from baseline to week 26 in the Leiter R – Total Equivalence Age VR

Secondary: Change from baseline to week 52 in the Leiter R – Total Equivalence Age VR

Secondary: Change from baseline to week 52 in the Leiter R – Total Equivalence Age VR

Secondary: Change from baseline to week 26 in CSF oligosaccharides

Secondary: Change from baseline to week 26 in CSF oligosaccharides

Clinical Trial Results:
A Multi-Center, Double-Blind, Randomized, Placebo-Controlled, Parallel Group Trial, Investigating the Efficacy and Safety of Repeated Lamazym Treatment of Subjects with alpha-Mannosidosis.