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Clinical Trial Results:
A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study of MTAU9937a in Patients With Moderate Alzheimer’s Disease

Summary
EudraCT number	2018-003398-87
Trial protocol	ES
Global end of trial date

Results information
Results version number	v2(current)
This version publication date	20 Sep 2022
First version publication date	31 Jul 2022
Other versions	v1
Version creation reason

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

GN40040

ISRCTN number

US NCT number

NCT03828747

WHO universal trial number (UTN)

Sponsor organisation name

F. Hoffmann-La Roche AG

Sponsor organisation address

Grenzacherstrasse 124, Basel, Switzerland, CH-4070

Public contact

F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.com

Scientific contact

F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.com

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

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?

Analysis stage

Interim

Date of interim/final analysis

20 Jul 2021

Is this the analysis of the primary completion data?

Yes

Primary completion date

20 Jul 2021

Global end of trial reached?

Main objective of the trial

The objective of this trial was to evaluate the clinical efficacy, safety, pharmacokinetics, and pharmacodynamics of semorinemab in participants with moderate AD.

Protection of trial subjects

All study subjects were required to read and sign and Informed Consent Form.

Background therapy

Evidence for comparator

Actual start date of recruitment

30 Jan 2019

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

3 Months

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

France: 22

Country: Number of subjects enrolled

Poland: 43

Country: Number of subjects enrolled

Spain: 36

Country: Number of subjects enrolled

United States: 171

Worldwide total number of subjects

272

EEA total number of subjects

101

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

209

85 years and over

Subject disposition

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Recruitment details

The study was conducted at 49 centers in 4 countries.

Screening details

A total of 272 participants were enrolled at 49 centers. 5 participants did not receive blinded treatment. These 267 participants represented the Safety Analysis population and data for this population is presented here.

Period 1 title

Double-Blind Treatment Period

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Semorinemab

Arm description

Semorinemab will be administered intravenously in the double-blind treatment period and will be administered intravenously in the optional open-label extension period.

Arm type

Experimental

Investigational medicinal product name

Semorinemab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants will receive semorinemab every 2 weeks (Q2W) for the first three doses of the double-blind treatment period and every 4 weeks (Q4W) thereafter during the double-blind treatment period. Semorinemab will be administered Q4W in the OLE period.

Investigational medicinal product name

[18F]GTP1

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

[18F]GTP1 was administered as a solution for intravenous (IV) use, as part of positron emission tomography (PET) imaging.

Placebo

Arm description

Placebo was administered intravenously in the double-blind treatment period and semorinemab will be administered intravenously in the optional open-label extension.

Arm type

Placebo

Investigational medicinal product name

[18F]GTP1

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

[18F]GTP1 was administered as a solution for IV use, as part of PET imaging.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received placebo Q2W for the first three doses of the double-blind treatment period and Q4W thereafter during the double-blind treatment period.

Number of subjects in period 1 ^[1]	Semorinemab	Placebo
Started	135	132
Cohort 1	78 ^[2]	86 ^[3]
Cohort 2	57 ^[4]	46 ^[5]
Completed	104	96
Not completed	31	36
Consent withdrawn by subject	19	21
Physician decision	-	3
Adverse Event	6	6
Death	1	2
Various reasons	5	3
Lost to follow-up	-	1

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: 5 participants didn't receive blinded treatment.
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: We are showing the number or participants, per cohort who started in each arm to be consistent with the clinicaltrials.gov posting
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: We are showing the number or participants, per cohort who started in each arm to be consistent with the clinicaltrials.gov posting
[4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: We are showing the number or participants, per cohort who started in each arm to be consistent with the clinicaltrials.gov posting
[5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: We are showing the number or participants, per cohort who started in each arm to be consistent with the clinicaltrials.gov posting

Period 2 title

Open-Label Extension

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Semorinemab

Arm description

Semorinemab will be administered intravenously in the double-blind treatment period and will be administered intravenously in the optional open-label extension period.

Arm type

Experimental

Investigational medicinal product name

Semorinemab

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

[18F]GTP1

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

[18F]GTP1 was administered as a solution for intravenous (IV) use, as part of positron emission tomography (PET) imaging.

Placebo

Arm description

Placebo was administered intravenously in the double-blind treatment period and semorinemab will be administered intravenously in the optional open-label extension.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received placebo Q2W for the first three doses of the double-blind treatment period and Q4W thereafter during the double-blind treatment period.

Investigational medicinal product name

[18F]GTP1

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

[18F]GTP1 was administered as a solution for IV use, as part of PET imaging.

Number of subjects in period 2 ^[6]	Semorinemab	Placebo
Started	104	95
Completed	0	0
Not completed	104	95
Consent withdrawn by subject	19	16
Adverse Event	3	4
Death	-	2
Various reasons	1	1
Lost to follow-up	4	-
Continuing on study	77	72

Notes
[6] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: The number of participants starting this period differs from those that completed the previous period as this was an optional open-label extension for participants to join.

Baseline characteristics

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Reporting group title

Semorinemab

Reporting group description

Semorinemab will be administered intravenously in the double-blind treatment period and will be administered intravenously in the optional open-label extension period.

Reporting group title

Placebo

Reporting group description

Placebo was administered intravenously in the double-blind treatment period and semorinemab will be administered intravenously in the optional open-label extension.

Reporting group values	Semorinemab	Placebo	Total
Number of subjects	135	132	267
Age Categorical
Units: Participants
In utero	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	0	0	0
Adolescents (12-17 years)	0	0	0
Adults (18-64 years)	30	18	48
From 65-84 years	99	106	205
85 years and over	6	8	14
Age Continuous
Units: years
arithmetic mean (standard deviation)	71.6 ± 8.2	73.1 ± 8.0	-
Gender Categorical
Units: Participants
Female	93	80	173
Male	42	52	94
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	4	3	7
Not Hispanic or Latino	116	111	227
Unknown or Not Reported	15	18	33
Race (NIH/OMB)
Units: Subjects
Asian	1	0	1
Black or African American	4	5	9
White	121	115	236
Unknown or Not Reported	9	12	21

Subject analysis set title

Semorinemab (Modified ITT)

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

The modified intent-to-treat population included all randomized participants who received at least one dose of study drug and had at least one baseline and one postbaseline ADAS-Cog11 score. For ADCS-ADL, CDR-SB and MMSE, participants also had the respective score at the given time point.

Subject analysis set title

Placebo (Modified ITT)

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Subject analysis sets values	Semorinemab (Modified ITT)	Placebo (Modified ITT)
Number of subjects	123	115
Age Categorical
Units: Participants
In utero	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0
Newborns (0-27 days)	0	0
Infants and toddlers (28 days-23 months)	0	0
Children (2-11 years)	0	0
Adolescents (12-17 years)	0	0
Adults (18-64 years)	29	17
From 65-84 years	89	92
85 years and over	5	6
Age Continuous
Units: years
arithmetic mean (standard deviation)	71.2 ± 8.2	72.8 ± 8.2
Gender Categorical
Units: Participants
Female	84	70
Male	39	45
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	4	2
Not Hispanic or Latino	104	97
Unknown or Not Reported	15	16
Race (NIH/OMB)
Units: Subjects
Asian	1	0
Black or African American	4	4
White	109	101
Unknown or Not Reported	9	10

End points

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Reporting group title

Semorinemab

Reporting group description

Semorinemab will be administered intravenously in the double-blind treatment period and will be administered intravenously in the optional open-label extension period.

Reporting group title

Placebo

Reporting group description

Placebo was administered intravenously in the double-blind treatment period and semorinemab will be administered intravenously in the optional open-label extension.

Reporting group title

Semorinemab

Reporting group description

Semorinemab will be administered intravenously in the double-blind treatment period and will be administered intravenously in the optional open-label extension period.

Reporting group title

Placebo

Reporting group description

Placebo was administered intravenously in the double-blind treatment period and semorinemab will be administered intravenously in the optional open-label extension.

Subject analysis set title

Semorinemab (Modified ITT)

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Subject analysis set title

Placebo (Modified ITT)

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Primary: Change From Baseline to Last Visit of Double-Blind Treatment Period in Cognitive Function as Measured by the Alzheimer’s Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11)

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End point title

Change From Baseline to Last Visit of Double-Blind Treatment Period in Cognitive Function as Measured by the Alzheimer’s Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11)

End point description

The Alzheimer’s Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11) is an 11 item cognitive subscale used to quantify the areas of cognitive function most often affected in Alzheimer's disease. The total score ranges from 0-70 with lower scores indicating better cognitive function.

End point type

Primary

End point timeframe

Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2

End point values	Semorinemab (Modified ITT)	Placebo (Modified ITT)
Number of subjects analysed	123	115
Units: Units on a scale
least squares mean (standard error)
Baseline	23.93 ± 0.533	24.09 ± 0.589
Change from Baseline at Week 49 (Cohort 1 and 2)	3.96 ± 0.658	6.85 ± 0.643
Change from Baseline at Week 61 (only Cohort 2)	5.71 ± 0.907	8.47 ± 0.965

Week 49

Comparison groups

Semorinemab (Modified ITT) v Placebo (Modified ITT)

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0008

Method

Mixed models analysis

Parameter type

Least Squares Mean Difference

Point estimate

-2.89

Confidence interval

level

95%

sides

2-sided

lower limit

-4.56

upper limit

-1.21

Variability estimate

Standard error of the mean

Dispersion value

0.849

Week 61

Comparison groups

Semorinemab (Modified ITT) v Placebo (Modified ITT)

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0351

Method

Mixed models analysis

Parameter type

Least Squares Mean Difference

Point estimate

-2.75

Confidence interval

level

95%

sides

2-sided

lower limit

-5.31

upper limit

-0.2

Variability estimate

Standard error of the mean

Dispersion value

1.287

Primary: Change From Baseline to Last Visit of Double-Blind Treatment Period in Functional Capacities as Measured by the Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL)

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End point title

Change From Baseline to Last Visit of Double-Blind Treatment Period in Functional Capacities as Measured by the Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL)

End point description

A scale used to quantify performance of activities of daily living. Scores on the ADCS-ADL range from 0-78, with higher scores indicating better ADL function.

End point type

Primary

End point timeframe

Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2

End point values	Semorinemab (Modified ITT)	Placebo (Modified ITT)
Number of subjects analysed	123	115
Units: Units on a scale
least squares mean (standard error)
Baseline	62.03 ± 0.764	59.74 ± 0.842
Change from Baseline at Week 49 (Cohort 1 and 2)	-7.63 ± 1.002	-6.80 ± 0.974
Change from Baseline at Week 61 (only Cohort 2)	-9.29 ± 1.343	-7.57 ± 1.462

Week 49

Comparison groups

Semorinemab (Modified ITT) v Placebo (Modified ITT)

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5207

Method

Mixed models analysis

Parameter type

Least Squares Mean Difference

Point estimate

-0.83

Confidence interval

level

95%

sides

2-sided

lower limit

-3.39

upper limit

1.72

Variability estimate

Standard error of the mean

Dispersion value

1.295

Week 61

Comparison groups

Semorinemab (Modified ITT) v Placebo (Modified ITT)

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3704

Method

Mixed models analysis

Parameter type

Least Squares Mean Difference

Point estimate

-1.72

Confidence interval

level

95%

sides

2-sided

lower limit

-5.5

upper limit

2.07

Variability estimate

Standard error of the mean

Dispersion value

1.911

Secondary: Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB)

Top of page

End point title

Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB)

End point description

A scale used to quantify the severity of symptoms of dementia. The CDR-SB is obtained through interviews of patients and informants, and disease severity is rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a 5-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment (personal care is scored on a 4-point scale without a 0.5 rating available). The CDR-SB score is obtained by summing each of the domain box scores, with scores ranging from 0 to 18, with the higher values representing more severe impairment.

End point type

Secondary

End point timeframe

Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2

End point values	Semorinemab (Modified ITT)	Placebo (Modified ITT)
Number of subjects analysed	123	115
Units: Units on a scale
least squares mean (standard error)
Baseline	6.23 ± 0.156	6.51 ± 0.182
Change from Baseline at Week 49 (Cohort 1 and 2)	1.80 ± 0.217	1.54 ± 0.214
Change from Baseline at Week 61 (only Cohort 2)	2.45 ± 0.367	2.28 ± 0.393

Week 49

Comparison groups

Semorinemab (Modified ITT) v Placebo (Modified ITT)

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3501

Method

Mixed models analysis

Parameter type

Least Squares Mean Difference

Point estimate

0.26

Confidence interval

level

95%

sides

2-sided

lower limit

-0.29

upper limit

0.82

Variability estimate

Standard error of the mean

Dispersion value

0.282

Week 61

Comparison groups

Semorinemab (Modified ITT) v Placebo (Modified ITT)

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7431

Method

Mixed models analysis

Parameter type

Least Squares Mean Difference

Point estimate

0.17

Confidence interval

level

95%

sides

2-sided

lower limit

-0.87

upper limit

1.22

Variability estimate

Standard error of the mean

Dispersion value

0.525

Secondary: Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE)

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End point title

Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE)

End point description

The Mini Mental State Examination (MMSE) is a brief clinical cognitive examination commonly used to screen for dementia and other cognitive deficits that has a total score of 0-30. Higher scores indicate better cognitive function.

End point type

Secondary

End point timeframe

Baseline to Week 49 for Cohorts 1 and 2, and Baseline to Week 61 for Cohort 2

End point values	Semorinemab (Modified ITT)	Placebo (Modified ITT)
Number of subjects analysed	123	115
Units: Units on a scale
least squares mean (standard error)
Baseline	18.38 ± 0.182	18.15 ± 0.197
Change from Baseline at Week 49 (Cohort 1 and 2)	-2.86 ± 0.330	-3.12 ± 0.325
Change from Baseline at Week 61 (only Cohort 2)	-3.14 ± 0.429	-4.22 ± 0.466

Week 49

Comparison groups

Semorinemab (Modified ITT) v Placebo (Modified ITT)

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5366

Method

Mixed models analysis

Parameter type

Least Squares Mean Difference

Point estimate

0.27

Confidence interval

level

95%

sides

2-sided

lower limit

-0.58

upper limit

1.11

Variability estimate

Standard error of the mean

Dispersion value

0.429

Week 61

Comparison groups

Semorinemab (Modified ITT) v Placebo (Modified ITT)

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0851

Method

Mixed models analysis

Parameter type

Least Squares Mean Difference

Point estimate

1.08

Confidence interval

level

95%

sides

2-sided

lower limit

-0.15

upper limit

2.3

Variability estimate

Standard error of the mean

Dispersion value

0.618

Secondary: Percentage of Participants with Adverse Events

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End point title

Percentage of Participants with Adverse Events

End point description

An Adverse Event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

End point type

Secondary

End point timeframe

Baseline up to Clinical Cut Off Date (CCOD) of July 20, 2021 (approximately 2.5 years)

End point values	Semorinemab	Placebo
Number of subjects analysed	135	132
Units: Percentage of Participants
number (not applicable)	83.7	81.1

No statistical analyses for this end point

Secondary: Serum Concentration of RO7105705 at Specified Timepoints

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End point title

Serum Concentration of RO7105705 at Specified Timepoints

End point description

Data collection is ongoing and the results will be disclosed within 1 year from Study Completion

End point type

Secondary

End point timeframe

Weeks 1,3,5,9,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,3,5,9,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.

End point values	Semorinemab	Placebo
Number of subjects analysed	0 ^[1]	0 ^[2]
Units: ug/mL
arithmetic mean (standard deviation)	±	±

Notes
[1] - Data collection is ongoing and the results will be disclosed within 1 year from Study Completion
[2] - Data collection is ongoing and the results will be disclosed within 1 year from Study Completion

No statistical analyses for this end point

Secondary: Serum concentration of RO7105705 at specified timepoints

Top of page

End point title

Serum concentration of RO7105705 at specified timepoints

End point description

Data collection is ongoing and the results will be disclosed within 1 year from Study Completion

End point type

Secondary

End point timeframe

Weeks 1,3,5,9,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,3,5,9,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.

End point values	Semorinemab	Placebo
Number of subjects analysed	0 ^[3]	0 ^[4]
Units: ug/mL
arithmetic mean (standard deviation)	±	±

Notes
[3] - Data collection is ongoing and the results will be disclosed within 1 year from Study Completion
[4] - Data collection is ongoing and the results will be disclosed within 1 year from Study Completion

No statistical analyses for this end point

Secondary: Incidence of anti-drug antibodies (ADAs) during the study relative to the prevalence of ADAs at baseline

Top of page

End point title

Incidence of anti-drug antibodies (ADAs) during the study relative to the prevalence of ADAs at baseline

End point description

Data collection is ongoing and the results will be disclosed within 1 year from Study Completion

End point type

Secondary

End point timeframe

Weeks 1,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.

End point values	Semorinemab	Placebo
Number of subjects analysed	0 ^[5]	0 ^[6]
Units: Participants
number (not applicable)

Notes
[5] - Data collection is ongoing and the results will be disclosed within 1 year from Study Completion
[6] - Data collection is ongoing and the results will be disclosed within 1 year from Study Completion

No statistical analyses for this end point

Secondary: Relationship between ADA Status and Percentage of Participants with Adverse Events

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End point title

Relationship between ADA Status and Percentage of Participants with Adverse Events

End point description

Descriptive statistics will be used for assessment. Data collection is ongoing and the results will be disclosed within 1 year from Study Completion

End point type

Secondary

End point timeframe

Up to 57 weeks for Cohort 1, and up to 69 weeks for Cohort 2.

End point values	Semorinemab	Placebo
Number of subjects analysed	0 ^[7]	0 ^[8]
Units: Percentage of Participants
number (not applicable)

Notes
[7] - Data collection is ongoing and the results will be disclosed within 1 year from Study Completion
[8] - Data collection is ongoing and the results will be disclosed within 1 year from Study Completion

No statistical analyses for this end point

Secondary: Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period in Cognitive Function as Measured by the Alzheimer’s Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11)

Top of page

End point title

Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period in Cognitive Function as Measured by the Alzheimer’s Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11)

End point description

Descriptive statistics will be used for assessment. A 70-point scale used to quantify the areas of cognitive function most often affected in Alzheimer's disease. Lower scores indicate better cognitive function. Data collection is ongoing and the results will be disclosed within 1 year from Study Completion

End point type

Secondary

End point timeframe

Baseline to Week 49 for Cohort 1, and Baseline to Week 61 for Cohort 2

End point values	Semorinemab	Placebo
Number of subjects analysed	0 ^[9]	0 ^[10]
Units: Units on a Scale
least squares mean (standard error)	±	±

Notes
[9] - Data collection is ongoing and the results will be disclosed within 1 year from Study Completion
[10] - Data collection is ongoing and the results will be disclosed within 1 year from Study Completion

No statistical analyses for this end point

Secondary: Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period in Functional Capacities as Measured by the Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL)

Top of page

End point title

Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period in Functional Capacities as Measured by the Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL)

End point description

Descriptive statistics will be used for assessment. A scale used to quantify performance of activities of daily living. Scores on the ADCS-ADL range from 0-78, with higher scores indicating better ADL function. Data collection is ongoing and the results will be disclosed within 1 year from Study Completion

End point type

Secondary

End point timeframe

Baseline to Week 49 for Cohort 1, and Baseline to Week 61 for Cohort 2

End point values	Semorinemab	Placebo
Number of subjects analysed	0 ^[11]	0 ^[12]
Units: Units on a scale
least squares mean (standard error)	±	±

Notes
[11] - Data collection is ongoing and the results will be disclosed within 1 year from Study Completion
[12] - Data collection is ongoing and the results will be disclosed within 1 year from Study Completion

No statistical analyses for this end point

Secondary: Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB)

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End point title

Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB)

End point description

Descriptive statistics will be used for assessment. A scale used to quantify the severity of symptoms of dementia. The CDR-SB is obtained through interviews of patients and informants, and disease severity is rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a 5-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment (personal care is scored on a 4-point scale without a 0.5 rating available). The CDR-SOB score is obtained by summing each of the domain box scores, with scores ranging from 0 to 18, with the higher values representing more severe impairment. Data collection is ongoing and the results will be disclosed within 1 year from Study Completion

End point type

Secondary

End point timeframe

Baseline to Week 49 for Cohort 1, and Baseline to Week 61 for Cohort 2

End point values	Semorinemab	Placebo
Number of subjects analysed	0 ^[13]	0 ^[14]
Units: Units on a scale
least squares mean (standard error)	±	±

Notes
[13] - Data collection is ongoing and the results will be disclosed within 1 year from Study Completion
[14] - Data collection is ongoing and the results will be disclosed within 1 year from Study Completion

No statistical analyses for this end point

Secondary: Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE)

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End point title

Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE)

End point description

Descriptive statistics will be used for assessment. The Mini Mental State Examination (MMSE) is a brief clinical cognitive examination commonly used to screen for dementia and other cognitive deficits that has a total score of 0-30. Higher scores indicate better cognitive function. Data collection is ongoing and the results will be disclosed within 1 year from Study Completion

End point type

Secondary

End point timeframe

Baseline to Week 49 for Cohort 1, and Baseline to Week 61 for Cohort 2

End point values	Semorinemab	Placebo
Number of subjects analysed	0 ^[15]	0 ^[16]
Units: Units on a scale
least squares mean (standard error)	±	±

Notes
[15] - Data collection is ongoing and the results will be disclosed within 1 year from Study Completion
[16] - Data collection is ongoing and the results will be disclosed within 1 year from Study Completion

No statistical analyses for this end point

Secondary: Relationship Between ADA Status and Serum Concentration of RO7105705 at Specified Timepoints

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End point title

Relationship Between ADA Status and Serum Concentration of RO7105705 at Specified Timepoints

End point description

Descriptive statistics will be used for assessment. Data collection is ongoing and the results will be disclosed within 1 year from Study Completion

End point type

Secondary

End point timeframe

Weeks 1,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.

End point values	Semorinemab	Placebo
Number of subjects analysed	0 ^[17]	0 ^[18]
Units: ug/ml
arithmetic mean (standard deviation)	±	±

Notes
[17] - Data collection is ongoing and the results will be disclosed within 1 year from Study Completion
[18] - Data collection is ongoing and the results will be disclosed within 1 year from Study Completion

No statistical analyses for this end point

Secondary: Relationship Between ADA Status and Incidence of Anti-Drug Antibodies (ADAs) During the Study Relative to the Prevalence of ADAs at Baseline

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End point title

Relationship Between ADA Status and Incidence of Anti-Drug Antibodies (ADAs) During the Study Relative to the Prevalence of ADAs at Baseline

End point description

Descriptive statistics will be used for assessment. Data collection is ongoing and the results will be disclosed within 1 year from Study Completion

End point type

Secondary

End point timeframe

Weeks 1,13,25,37,49, and at treatment discontinuation (up to Week 48) for Cohort 1. Weeks 1,13,25,37,49,61, and at treatment discontinuation (up to Week 60) for Cohort 2.

End point values	Semorinemab	Placebo
Number of subjects analysed	0 ^[19]	0 ^[20]
Units: Percentage of Participants
number (not applicable)

Notes
[19] - Data collection is ongoing and the results will be disclosed within 1 year from Study Completion
[20] - Data collection is ongoing and the results will be disclosed within 1 year from Study Completion

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Baseline up to CCOD of July 20, 2021 (approximately 2.5 years)

Adverse event reporting additional description

The safety population included all randomized participants who received at least one dose of either semorinemab or placebo.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.1

Reporting group title

Placebo

Reporting group description

Placebo was administered intravenously in the double-blind treatment period and semorinemab will be administered intravenously in the optional open-label extension.‌

Reporting group title

Semorinemab (OLE)

Reporting group description

Semorinemab will be administered intravenously in the double-blind treatment period and will be administered intravenously in the optional open-label extension period.

Reporting group title

Semorinemab (Double Blind)

Reporting group description

Semorinemab will be administered intravenously in the double-blind treatment period and will be administered intravenously in the optional open-label extension period.

Serious adverse events	Placebo	Semorinemab (OLE)	Semorinemab (Double Blind)
Total subjects affected by serious adverse events
subjects affected / exposed	22 / 132 (16.67%)	14 / 194 (7.22%)	22 / 135 (16.30%)
number of deaths (all causes)	4	0	1
number of deaths resulting from adverse events	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Transitional cell carcinoma recurrent
subjects affected / exposed	0 / 132 (0.00%)	0 / 194 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma
subjects affected / exposed	0 / 132 (0.00%)	0 / 194 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Adenocarcinoma metastatic
subjects affected / exposed	0 / 132 (0.00%)	0 / 194 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Invasive ductal breast carcinoma
subjects affected / exposed	0 / 132 (0.00%)	0 / 194 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal neoplasm
subjects affected / exposed	1 / 132 (0.76%)	0 / 194 (0.00%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ovarian cancer
subjects affected / exposed	0 / 132 (0.00%)	0 / 194 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bladder cancer recurrent
subjects affected / exposed	0 / 132 (0.00%)	1 / 194 (0.52%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular disorders
Peripheral artery thrombosis
subjects affected / exposed	0 / 132 (0.00%)	0 / 194 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Aortic aneurysm
subjects affected / exposed	1 / 132 (0.76%)	0 / 194 (0.00%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Peripheral artery aneurysm
subjects affected / exposed	0 / 132 (0.00%)	1 / 194 (0.52%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypotension
subjects affected / exposed	0 / 132 (0.00%)	1 / 194 (0.52%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Death
subjects affected / exposed	1 / 132 (0.76%)	0 / 194 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1
Non-cardiac chest pain
subjects affected / exposed	1 / 132 (0.76%)	0 / 194 (0.00%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
subjects affected / exposed	1 / 132 (0.76%)	0 / 194 (0.00%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Agitation
subjects affected / exposed	3 / 132 (2.27%)	2 / 194 (1.03%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Aggression
subjects affected / exposed	0 / 132 (0.00%)	1 / 194 (0.52%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Investigations
SARS-CoV-2 test positive
subjects affected / exposed	0 / 132 (0.00%)	0 / 194 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Femoral neck fracture
subjects affected / exposed	0 / 132 (0.00%)	0 / 194 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hip fracture
subjects affected / exposed	2 / 132 (1.52%)	0 / 194 (0.00%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Head injury
subjects affected / exposed	1 / 132 (0.76%)	0 / 194 (0.00%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Patella fracture
subjects affected / exposed	0 / 132 (0.00%)	0 / 194 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Joint dislocation
subjects affected / exposed	0 / 132 (0.00%)	0 / 194 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Craniocerebral injury
subjects affected / exposed	0 / 132 (0.00%)	0 / 194 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
Bradycardia
subjects affected / exposed	0 / 132 (0.00%)	0 / 194 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	0 / 132 (0.00%)	0 / 194 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac failure
subjects affected / exposed	1 / 132 (0.76%)	0 / 194 (0.00%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Stress cardiomyopathy
subjects affected / exposed	0 / 132 (0.00%)	0 / 194 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Arrhythmia
subjects affected / exposed	0 / 132 (0.00%)	1 / 194 (0.52%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Sinus node dysfunction
subjects affected / exposed	0 / 132 (0.00%)	1 / 194 (0.52%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Upper motor neurone lesion
subjects affected / exposed	0 / 132 (0.00%)	0 / 194 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	1 / 132 (0.76%)	3 / 194 (1.55%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cerebrovascular accident
subjects affected / exposed	1 / 132 (0.76%)	0 / 194 (0.00%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Seizure
subjects affected / exposed	1 / 132 (0.76%)	0 / 194 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Dysarthria
subjects affected / exposed	0 / 132 (0.00%)	0 / 194 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Subarachnoid haemorrhage
subjects affected / exposed	0 / 132 (0.00%)	0 / 194 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Leukocytosis
subjects affected / exposed	0 / 132 (0.00%)	0 / 194 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Inguinal hernia strangulated
subjects affected / exposed	0 / 132 (0.00%)	0 / 194 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hernial eventration
subjects affected / exposed	1 / 132 (0.76%)	0 / 194 (0.00%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	2 / 132 (1.52%)	1 / 194 (0.52%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Colitis
subjects affected / exposed	0 / 132 (0.00%)	0 / 194 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholelithiasis
subjects affected / exposed	1 / 132 (0.76%)	0 / 194 (0.00%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cholecystitis
subjects affected / exposed	0 / 132 (0.00%)	1 / 194 (0.52%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Chronic Exacerbated Cholecystitis on the Background of Urolithiasis
subjects affected / exposed	0 / 132 (0.00%)	1 / 194 (0.52%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Renal failure
subjects affected / exposed	0 / 132 (0.00%)	0 / 194 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nephrolithiasis
subjects affected / exposed	1 / 132 (0.76%)	0 / 194 (0.00%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hydronephrosis
subjects affected / exposed	1 / 132 (0.76%)	0 / 194 (0.00%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
COVID-19
subjects affected / exposed	2 / 132 (1.52%)	1 / 194 (0.52%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 1	0 / 0
Pneumonia
subjects affected / exposed	2 / 132 (1.52%)	0 / 194 (0.00%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 132 (0.00%)	1 / 194 (0.52%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	1 / 132 (0.76%)	0 / 194 (0.00%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 132 (0.00%)	0 / 194 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cystitis
subjects affected / exposed	0 / 132 (0.00%)	0 / 194 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
COVID-19 pneumonia
subjects affected / exposed	0 / 132 (0.00%)	1 / 194 (0.52%)	0 / 135 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	1 / 132 (0.76%)	0 / 194 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diabetic metabolic decompensation
subjects affected / exposed	0 / 132 (0.00%)	0 / 194 (0.00%)	1 / 135 (0.74%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Placebo	Semorinemab (OLE)	Semorinemab (Double Blind)
Total subjects affected by non serious adverse events
subjects affected / exposed	71 / 132 (53.79%)	52 / 194 (26.80%)	77 / 135 (57.04%)
Injury, poisoning and procedural complications
Infusion related reaction
subjects affected / exposed	5 / 132 (3.79%)	3 / 194 (1.55%)	14 / 135 (10.37%)
occurrences all number	9	3	30
Fall
subjects affected / exposed	19 / 132 (14.39%)	9 / 194 (4.64%)	14 / 135 (10.37%)
occurrences all number	28	16	19
Vascular disorders
Hypertension
subjects affected / exposed	5 / 132 (3.79%)	3 / 194 (1.55%)	8 / 135 (5.93%)
occurrences all number	5	3	10
Nervous system disorders
Dizziness
subjects affected / exposed	9 / 132 (6.82%)	3 / 194 (1.55%)	8 / 135 (5.93%)
occurrences all number	11	4	8
Headache
subjects affected / exposed	9 / 132 (6.82%)	2 / 194 (1.03%)	11 / 135 (8.15%)
occurrences all number	10	3	14
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	5 / 132 (3.79%)	2 / 194 (1.03%)	7 / 135 (5.19%)
occurrences all number	6	2	7
Psychiatric disorders
Agitation
subjects affected / exposed	5 / 132 (3.79%)	5 / 194 (2.58%)	8 / 135 (5.93%)
occurrences all number	5	5	8
Insomnia
subjects affected / exposed	2 / 132 (1.52%)	4 / 194 (2.06%)	7 / 135 (5.19%)
occurrences all number	2	4	7
Depression
subjects affected / exposed	6 / 132 (4.55%)	0 / 194 (0.00%)	10 / 135 (7.41%)
occurrences all number	6	0	10
Anxiety
subjects affected / exposed	12 / 132 (9.09%)	4 / 194 (2.06%)	9 / 135 (6.67%)
occurrences all number	12	4	11
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	4 / 132 (3.03%)	7 / 194 (3.61%)	7 / 135 (5.19%)
occurrences all number	4	7	7
Infections and infestations
Urinary tract infection
subjects affected / exposed	16 / 132 (12.12%)	10 / 194 (5.15%)	10 / 135 (7.41%)
occurrences all number	19	11	14
Nasopharyngitis
subjects affected / exposed	3 / 132 (2.27%)	0 / 194 (0.00%)	9 / 135 (6.67%)
occurrences all number	3	0	10

More information

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Were there any global substantial amendments to the protocol? Yes

16 Apr 2020

The following updates were made: [1] The study design was revised to assign randomized participants to one of up to three cohorts; [2] Endpoints, statistical consideration and analysis plans were updated; [3] For participants in Cohorts 2 and 3, study drug administration was revised for those who missed 2 or more infusions; [4] During the double-blind treatment period, additional clinical outcome assessments (COAs) could be administered remotely due to the COVID-19 pandemic; [5] End of study and length of study were updated; [6] Due to COVID-19 travel restrictions, some study activities could be performed in the participants home or alternate location; [6] Guidance was provided for monitoring participant's signs or symptoms suggestive of new clinically significant neurologic abnormalities; [7] Schedules of activities for the double-blind treatment period and OLE period were added for Cohorts 2 and 3; [8] Mandatory cerebrospinal fluid collection by lumbar puncture was removed.

29 Jun 2020

The following updates were made; [1] Participants who completed blinded study drug treatment through Week 45 without any missed doses of study drug were eligible to revert to the Cohort 1 Schedule of Activities continue to OLE. Participants who were active in the double-blind treatment period when Protocol Version 4 was implemented who either completed the Cohort 2 Week 49 visit, continued in Cohort 2; [2] Up to 100 participants could be recruited into the study; [3] The option to administer study drug infusion in the participant's home or in an approved alternate location during the COVID-19 pandemic was clarified; [4] Approval by the Medical Monitor for daily treatment with medications from selected drug classes could be permitted during the OLE.

14 Dec 2021

The following updates were made; [1] Cohort 3 was removed; [2] The option to enroll up to 100 additional participants was removed as it was deemed unnecessary; [3] [18F]GTP1 PET was removed during the OLE at Week 145 for Cohort 1, Week 157 for Cohort 2, and at treatment discontinuation visit (for both cohorts); [4] OLE COAs, with the exception of the Columbia-Suicide Severity Rating Scale, were removed at Week 121 for Cohort 1 and Week 133 for Cohort 2; [5] The collection of serum PK and ADA samples was reduced to only once during the OLE, at Week 97 for Cohort 1 and Week 109 for Cohort 2; [6] The Medical Monitor changed.

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.

None reported

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Clinical trials

Clinical Trial Results: A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study of MTAU9937a in Patients With Moderate Alzheimer’s Disease

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change From Baseline to Last Visit of Double-Blind Treatment Period in Cognitive Function as Measured by the Alzheimer’s Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11)

Primary: Change From Baseline to Last Visit of Double-Blind Treatment Period in Cognitive Function as Measured by the Alzheimer’s Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11)

Primary: Change From Baseline to Last Visit of Double-Blind Treatment Period in Functional Capacities as Measured by the Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL)

Primary: Change From Baseline to Last Visit of Double-Blind Treatment Period in Functional Capacities as Measured by the Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL)

Secondary: Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB)

Secondary: Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB)

Secondary: Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE)

Secondary: Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE)

Secondary: Percentage of Participants with Adverse Events

Secondary: Percentage of Participants with Adverse Events

Secondary: Serum Concentration of RO7105705 at Specified Timepoints

Secondary: Serum Concentration of RO7105705 at Specified Timepoints

Secondary: Serum concentration of RO7105705 at specified timepoints

Secondary: Serum concentration of RO7105705 at specified timepoints

Secondary: Incidence of anti-drug antibodies (ADAs) during the study relative to the prevalence of ADAs at baseline

Secondary: Incidence of anti-drug antibodies (ADAs) during the study relative to the prevalence of ADAs at baseline

Secondary: Relationship between ADA Status and Percentage of Participants with Adverse Events

Secondary: Relationship between ADA Status and Percentage of Participants with Adverse Events

Secondary: Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period in Cognitive Function as Measured by the Alzheimer’s Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11)

Secondary: Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period in Cognitive Function as Measured by the Alzheimer’s Disease Assessment Scale, Cognitive Subscale, 11-Item Version (ADAS-Cog11)

Secondary: Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period in Functional Capacities as Measured by the Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL)

Secondary: Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period in Functional Capacities as Measured by the Alzheimer's Disease Cooperative Study-Daily Living Inventory (ADCS-ADL)

Secondary: Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB)

Secondary: Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period on the Clinical Dementia Rating-Sum of Boxes (CDR-SB)

Secondary: Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE)

Secondary: Relationship Between ADA Status and Change From Baseline to Last Visit of Double-Blind Treatment Period on the Mini-Mental State Examination (MMSE)

Secondary: Relationship Between ADA Status and Serum Concentration of RO7105705 at Specified Timepoints

Secondary: Relationship Between ADA Status and Serum Concentration of RO7105705 at Specified Timepoints

Secondary: Relationship Between ADA Status and Incidence of Anti-Drug Antibodies (ADAs) During the Study Relative to the Prevalence of ADAs at Baseline

Secondary: Relationship Between ADA Status and Incidence of Anti-Drug Antibodies (ADAs) During the Study Relative to the Prevalence of ADAs at Baseline

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study of MTAU9937a in Patients With Moderate Alzheimer’s Disease