Trial Outcomes & Findings for CSL312 (Garadacimab) in the Prevention of Hereditary Angioedema Attacks (NCT NCT04656418)

Results Overview

Time-normalized number of HAE attacks per month during treatment was calculated per participant as: \[number of HAE attacks / length of participant treatment in days\] \* 30.4375.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

64 participants

Primary outcome timeframe

First injection up to 6 months

Results posted on

2023-06-29

Participant Flow

Participants were enrolled at study centers in Canada, Germany, Hungary, Israel, Japan, Netherlands, and the United States from 27 January 2021 to 07 June 2022.

A total of 80 participants were screened, of which 64 participants were randomized and received the loading dose in the treatment period.

Participant milestones

Participant milestones
Measure	CSL312 Participants received a CSL312 loading dose of 400 mg as two 200 mg subcutaneous (SC) injections in Month 1 along with CSL312 of 200 mg SC injections, once monthly from Months 2 to 6.	Placebo Participants received a CSL312 matched loading dose of placebo as two SC injections in Month 1 along with CSL312 matched placebo SC injections, once monthly from Months 2 to 6.
Overall Study STARTED	39	25
Overall Study Intention-to-treat (ITT) Analysis Set	39	25
Overall Study Safety Analysis Set	39	25
Overall Study COMPLETED	38	22
Overall Study NOT COMPLETED	1	3

Reasons for withdrawal

Reasons for withdrawal
Measure	CSL312 Participants received a CSL312 loading dose of 400 mg as two 200 mg subcutaneous (SC) injections in Month 1 along with CSL312 of 200 mg SC injections, once monthly from Months 2 to 6.	Placebo Participants received a CSL312 matched loading dose of placebo as two SC injections in Month 1 along with CSL312 matched placebo SC injections, once monthly from Months 2 to 6.
Overall Study Withdrawal by Subject	1	3

Baseline Characteristics

CSL312 (Garadacimab) in the Prevention of Hereditary Angioedema Attacks

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CSL312 n=39 Participants Participants received a CSL312 loading dose of 400 mg as two 200 mg SC injections in Month 1 along with CSL312 of 200 mg SC injections, once monthly from Months 2 to 6.	Placebo n=25 Participants Participants received a CSL312 matched loading dose of placebo as two SC injections in Month 1 along with CSL312 matched placebo SC injections, once monthly from Months 2 to 6.	Total n=64 Participants Total of all reporting groups
Age, Continuous	43.3 years STANDARD_DEVIATION 17.45 • n=5 Participants	37.8 years STANDARD_DEVIATION 12.80 • n=7 Participants	41.2 years STANDARD_DEVIATION 15.92 • n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	14 Participants n=7 Participants	38 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	11 Participants n=7 Participants	26 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	37 Participants n=5 Participants	23 Participants n=7 Participants	60 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	33 Participants n=5 Participants	22 Participants n=7 Participants	55 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Canada	5 participants n=5 Participants	3 participants n=7 Participants	8 participants n=5 Participants
Region of Enrollment Netherlands	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment Hungary	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants	9 participants n=7 Participants	21 participants n=5 Participants
Region of Enrollment Japan	4 participants n=5 Participants	2 participants n=7 Participants	6 participants n=5 Participants
Region of Enrollment Israel	7 participants n=5 Participants	2 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment Germany	7 participants n=5 Participants	8 participants n=7 Participants	15 participants n=5 Participants

PRIMARY outcome

Timeframe: First injection up to 6 months

Population: ITT analysis set included all the randomized participants who provided written informed consent and underwent study screening procedures. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis.

Time-normalized number of HAE attacks per month during treatment was calculated per participant as: \[number of HAE attacks / length of participant treatment in days\] \* 30.4375.

Outcome measures

Outcome measures
Measure	CSL312 n=39 Participants Participants received a CSL312 loading dose of 400 mg as two 200 mg SC injections in Month 1 along with CSL312 of 200 mg SC injections, once monthly from Months 2 to 6.	Placebo n=24 Participants Participants received a CSL312 matched loading dose of placebo as two SC injections in Month 1 along with CSL312 matched placebo SC injections, once monthly from Months 2 to 6.
Time-Normalized Number of Hereditary Angioedema (HAE) Attacks Per Month During Treatment Period	0.27 number of HAE attacks per month Standard Deviation 0.683	2.01 number of HAE attacks per month Standard Deviation 1.341

SECONDARY outcome

Timeframe: 6 months, first 3-months and second 3-months of treatment period

Population: ITT analysis set included all the randomized participants who provided written informed consent and underwent study screening procedures. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available for analysis at the specified time point.

Percentage change in the time-normalized number of HAE attacks was calculated within a participant as: 100 \* \[1 - (time-normalized number of HAE attacks per month during treatment period / time-normalized number of HAE attacks per month during run-in period)\]. Time-normalized number of HAE attacks per month during treatment period was calculated per participant as: \[number of HAE attacks / length of participant treatment in days\] \* 30.4375.

Outcome measures

Outcome measures
Measure	CSL312 n=39 Participants Participants received a CSL312 loading dose of 400 mg as two 200 mg SC injections in Month 1 along with CSL312 of 200 mg SC injections, once monthly from Months 2 to 6.	Placebo n=24 Participants Participants received a CSL312 matched loading dose of placebo as two SC injections in Month 1 along with CSL312 matched placebo SC injections, once monthly from Months 2 to 6.
Percentage Change in the Time-normalized Number of HAE Attacks Per Month During the Treatment Period Compared to the Run-in Period 6 Months of Treatment	90.67 percentage change in HAE attacks/month Standard Deviation 22.433	20.21 percentage change in HAE attacks/month Standard Deviation 42.661
Percentage Change in the Time-normalized Number of HAE Attacks Per Month During the Treatment Period Compared to the Run-in Period First 3-months of Treatment	91.10 percentage change in HAE attacks/month Standard Deviation 21.255	18.89 percentage change in HAE attacks/month Standard Deviation 53.837
Percentage Change in the Time-normalized Number of HAE Attacks Per Month During the Treatment Period Compared to the Run-in Period Second 3-months of Treatment	90.12 percentage change in HAE attacks/month Standard Deviation 25.624	29.87 percentage change in HAE attacks/month Standard Deviation 55.529

SECONDARY outcome

Timeframe: 6 months, first 3-months and second 3-months of treatment period

Population: ITT analysis set included all the randomized participants who provided written informed consent and underwent study screening procedures. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available for analysis at the specified time point.

Time-normalized number of HAE attacks per month requiring on-demand treatment was calculated per participant as: \[number of HAE attacks requiring on-demand treatment / length of participant in days\] \* 30.4375.

Outcome measures

Outcome measures
Measure	CSL312 n=63 Total number of HAE attacks Participants received a CSL312 loading dose of 400 mg as two 200 mg SC injections in Month 1 along with CSL312 of 200 mg SC injections, once monthly from Months 2 to 6.	Placebo n=264 Total number of HAE attacks Participants received a CSL312 matched loading dose of placebo as two SC injections in Month 1 along with CSL312 matched placebo SC injections, once monthly from Months 2 to 6.
Time-Normalized Number of HAE Attacks Per Month Requiring On-Demand Treatment 6 Months of Treatment	0.23 number of HAE attacks per month Standard Deviation 0.663	1.86 number of HAE attacks per month Standard Deviation 1.412
Time-Normalized Number of HAE Attacks Per Month Requiring On-Demand Treatment First 3-months of Treatment	0.24 number of HAE attacks per month Standard Deviation 0.748	1.76 number of HAE attacks per month Standard Deviation 1.378
Time-Normalized Number of HAE Attacks Per Month Requiring On-Demand Treatment Second 3-months of Treatment	0.23 number of HAE attacks per month Standard Deviation 0.610	1.80 number of HAE attacks per month Standard Deviation 1.626

SECONDARY outcome

Timeframe: 6 months, first 3-months and second 3-months of treatment period

Population: ITT analysis set included all the randomized participants who provided written informed consent and underwent study screening procedures. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available for analysis at the specified time point.

Time-normalized number of moderate or severe HAE attacks per month during treatment period was calculated per participant as: \[number of moderate or severe HAE attacks / length of participant treatment in days\] \* 30.4375.

Outcome measures

Outcome measures
Measure	CSL312 n=63 Total number of HAE attacks Participants received a CSL312 loading dose of 400 mg as two 200 mg SC injections in Month 1 along with CSL312 of 200 mg SC injections, once monthly from Months 2 to 6.	Placebo n=264 Total number of HAE attacks Participants received a CSL312 matched loading dose of placebo as two SC injections in Month 1 along with CSL312 matched placebo SC injections, once monthly from Months 2 to 6.
Time-Normalized Number of Moderate or Severe HAE Attacks Per Month 6 Months of Treatment	0.13 number of HAE attacks per month Standard Deviation 0.296	1.35 number of HAE attacks per month Standard Deviation 1.166
Time-Normalized Number of Moderate or Severe HAE Attacks Per Month First 3-months of Treatment	0.12 number of HAE attacks per month Standard Deviation 0.305	1.25 number of HAE attacks per month Standard Deviation 1.091
Time-Normalized Number of Moderate or Severe HAE Attacks Per Month Second 3-months of Treatment	0.13 number of HAE attacks per month Standard Deviation 0.320	1.24 number of HAE attacks per month Standard Deviation 1.296

SECONDARY outcome

Timeframe: First 3-months and second 3-months of treatment period

Population: ITT analysis set included all the randomized participants who provided written informed consent and underwent study screening procedures. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available for analysis at the specified time point.

Time-normalized number of HAE attacks per month during treatment was calculated per participant as: \[number of HAE attacks / length of participant treatment in days\] \* 30.4375.

Outcome measures

Outcome measures
Measure	CSL312 n=39 Participants Participants received a CSL312 loading dose of 400 mg as two 200 mg SC injections in Month 1 along with CSL312 of 200 mg SC injections, once monthly from Months 2 to 6.	Placebo n=24 Participants Participants received a CSL312 matched loading dose of placebo as two SC injections in Month 1 along with CSL312 matched placebo SC injections, once monthly from Months 2 to 6.
Time-normalized Number of HAE Attacks Per Month in the First 3-months and Second 3-months of Treatment Period First 3-months of Treatment	0.26 number of HAE attacks per month Standard Deviation 0.749	1.97 number of HAE attacks per month Standard Deviation 1.287
Time-normalized Number of HAE Attacks Per Month in the First 3-months and Second 3-months of Treatment Period Second 3-months of Treatment	0.28 number of HAE attacks per month Standard Deviation 0.652	1.86 number of HAE attacks per month Standard Deviation 1.603

SECONDARY outcome

Timeframe: 6 months, first 3-months and second 3-months of treatment period

Population: ITT analysis set included all randomized participants who provided written informed consent and underwent study screening procedures. 'Overall number of participants analyzed' indicates number of participants with data available for outcome measure (OM) analysis. 'Number analyzed' indicates number of participants with data available for analysis at specified time point. As pre-specified in protocol and SAP, data for this OM was reported for participants of CSL312 and Placebo Comparison group.

Relative difference in means in the time-normalized number of HAE attacks per month CSL312 to Placebo was calculated as: 100 \* \[(mean time-normalized number of HAE attacks for CSL312 - mean time-normalized number of HAE attacks for placebo) / mean time-normalized number of HAE attacks for placebo\]. Time-normalized number of HAE attacks per month during treatment was calculated per participant as: \[number of HAE attacks / length of participant treatment in days\] \* 30.4375.

Outcome measures

Outcome measures
Measure	CSL312 n=63 Participants Participants received a CSL312 loading dose of 400 mg as two 200 mg SC injections in Month 1 along with CSL312 of 200 mg SC injections, once monthly from Months 2 to 6.	Placebo Participants received a CSL312 matched loading dose of placebo as two SC injections in Month 1 along with CSL312 matched placebo SC injections, once monthly from Months 2 to 6.
Relative Difference in Means in the Time-Normalized Number of HAE Attacks Per Month Between CSL312 to Placebo 6 Months of Treatment	-86.51 number of HAE attacks per month Interval -95.68 to -57.84	—
Relative Difference in Means in the Time-Normalized Number of HAE Attacks Per Month Between CSL312 to Placebo First 3-months of Treatment	-86.64 number of HAE attacks per month Interval -95.87 to -56.76	—
Relative Difference in Means in the Time-Normalized Number of HAE Attacks Per Month Between CSL312 to Placebo Second 3-months of Treatment	-85.01 number of HAE attacks per month Interval -95.62 to -48.74	—

SECONDARY outcome

Timeframe: Up to 6 months

Population: ITT analysis set included all the randomized participants who provided written informed consent and underwent study screening procedures. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis.

SGART is a self-assessment by the participant and measures the subject's overall treatment response to the investigational product using the following ratings: 0 (none: worse or no response at all, not acceptable), 1 (poor: very little response, not acceptable), 2 (fair: some response, acceptable but could be better), 3 (good: good response, acceptable), and 4 (excellent: excellent response, as good as can be imagined).

Outcome measures

Outcome measures
Measure	CSL312 n=38 Participants Participants received a CSL312 loading dose of 400 mg as two 200 mg SC injections in Month 1 along with CSL312 of 200 mg SC injections, once monthly from Months 2 to 6.	Placebo n=24 Participants Participants received a CSL312 matched loading dose of placebo as two SC injections in Month 1 along with CSL312 matched placebo SC injections, once monthly from Months 2 to 6.
Percentage of Participants With a Response to Subject's Global Assessment of Response to Therapy (SGART) None	2.6 percentage of participants	41.7 percentage of participants
Percentage of Participants With a Response to Subject's Global Assessment of Response to Therapy (SGART) Poor	7.9 percentage of participants	16.7 percentage of participants
Percentage of Participants With a Response to Subject's Global Assessment of Response to Therapy (SGART) Fair	7.9 percentage of participants	8.3 percentage of participants
Percentage of Participants With a Response to Subject's Global Assessment of Response to Therapy (SGART) Good	15.8 percentage of participants	20.8 percentage of participants
Percentage of Participants With a Response to Subject's Global Assessment of Response to Therapy (SGART) Excellent	65.8 percentage of participants	12.5 percentage of participants

SECONDARY outcome

Timeframe: From first dose of study drug up to 3 months after the last injection (approximately 8 months)

Population: Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.

AE is any untoward medical occurrence in a participant administered with an investigational product which does not necessarily have a causal relationship with treatment, can be any unfavorable and unintended sign, symptom, or disease temporally associated with use of an investigational product, whether or not considered related to product. SAE is any untoward medical occurrence that results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, is a congenital anomaly or birth defect, or is a medically significant event. An AESI is an AE of scientific and medical concern specific to sponsor's product or program, for which ongoing monitoring and rapid communication by investigator to sponsor is appropriate.

Outcome measures

Outcome measures
Measure	CSL312 n=39 Participants Participants received a CSL312 loading dose of 400 mg as two 200 mg SC injections in Month 1 along with CSL312 of 200 mg SC injections, once monthly from Months 2 to 6.	Placebo n=25 Participants Participants received a CSL312 matched loading dose of placebo as two SC injections in Month 1 along with CSL312 matched placebo SC injections, once monthly from Months 2 to 6.
Number of Participants With at Least One Adverse Event (AE), Serious Adverse Event (SAE), and AEs of Special Interest (AESI) AE	25 Participants	15 Participants
Number of Participants With at Least One Adverse Event (AE), Serious Adverse Event (SAE), and AEs of Special Interest (AESI) SAE	1 Participants	0 Participants
Number of Participants With at Least One Adverse Event (AE), Serious Adverse Event (SAE), and AEs of Special Interest (AESI) AESI	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 8 months

Population: Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.

Outcome measures

Outcome measures
Measure	CSL312 n=39 Participants Participants received a CSL312 loading dose of 400 mg as two 200 mg SC injections in Month 1 along with CSL312 of 200 mg SC injections, once monthly from Months 2 to 6.	Placebo n=25 Participants Participants received a CSL312 matched loading dose of placebo as two SC injections in Month 1 along with CSL312 matched placebo SC injections, once monthly from Months 2 to 6.
Number of Participants With CSL312-induced Anti-CSL312 Antibodies	1 Participants	0 Participants

SECONDARY outcome

Timeframe: From first dose of study drug up to 3 months after the last injection (approximately 8 months)

Population: Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.

Laboratory assessments included: Hematology, biochemistry, urinalysis, and coagulation parameters.

Outcome measures

Outcome measures
Measure	CSL312 n=39 Participants Participants received a CSL312 loading dose of 400 mg as two 200 mg SC injections in Month 1 along with CSL312 of 200 mg SC injections, once monthly from Months 2 to 6.	Placebo n=25 Participants Participants received a CSL312 matched loading dose of placebo as two SC injections in Month 1 along with CSL312 matched placebo SC injections, once monthly from Months 2 to 6.
Number of Participants With Clinically Significant Abnormalities in Laboratory Assessments Reported as Treatment Emergent Adverse Events (TEAEs)	1 Participants	2 Participants

SECONDARY outcome

Timeframe: From first dose of study drug up to 3 months after the last injection (approximately 8 months)

Population: Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product. The percentage of participants are rounded off to the single decimal point.

AE is any untoward medical occurrence in a participant administered with an investigational product which does not necessarily have a causal relationship with treatment, can be any unfavorable and unintended sign, symptom, or disease temporally associated with use of an investigational product, whether or not considered related to product. SAE is any untoward medical occurrence that results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, is a congenital anomaly or birth defect, or is a medically significant event. An AESI is an AE of scientific and medical concern specific to sponsor's product or program, for which ongoing monitoring and rapid communication by investigator to sponsor is appropriate.

Outcome measures

Outcome measures
Measure	CSL312 n=39 Participants Participants received a CSL312 loading dose of 400 mg as two 200 mg SC injections in Month 1 along with CSL312 of 200 mg SC injections, once monthly from Months 2 to 6.	Placebo n=25 Participants Participants received a CSL312 matched loading dose of placebo as two SC injections in Month 1 along with CSL312 matched placebo SC injections, once monthly from Months 2 to 6.
Percentage of Participants With at Least One AE, SAE, and AESI AE	64.1 percentage of participants	60.0 percentage of participants
Percentage of Participants With at Least One AE, SAE, and AESI SAE	2.6 percentage of participants	0 percentage of participants
Percentage of Participants With at Least One AE, SAE, and AESI AESI	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Up to 6 months

Population: Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product. The percentage of participants are rounded off to the single decimal point.

Outcome measures

Outcome measures
Measure	CSL312 n=39 Participants Participants received a CSL312 loading dose of 400 mg as two 200 mg SC injections in Month 1 along with CSL312 of 200 mg SC injections, once monthly from Months 2 to 6.	Placebo n=25 Participants Participants received a CSL312 matched loading dose of placebo as two SC injections in Month 1 along with CSL312 matched placebo SC injections, once monthly from Months 2 to 6.
Percentage of Participants With CSL312-induced Anti-CSL312 Antibodies	2.6 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: From first dose of study drug up to 3 months after the last injection (approximately 8 months)

Population: Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product. The percentage of participants are rounded off to the single decimal point.

Laboratory assessments included: Hematology, biochemistry, urinalysis, and coagulation parameters.

Outcome measures

Outcome measures
Measure	CSL312 n=39 Participants Participants received a CSL312 loading dose of 400 mg as two 200 mg SC injections in Month 1 along with CSL312 of 200 mg SC injections, once monthly from Months 2 to 6.	Placebo n=25 Participants Participants received a CSL312 matched loading dose of placebo as two SC injections in Month 1 along with CSL312 matched placebo SC injections, once monthly from Months 2 to 6.
Percentage of Participants With Clinically Significant Abnormalities in Laboratory Assessments Reported as TEAEs	2.6 percentage of participants	8.0 percentage of participants

Adverse Events

CSL312

Serious events: 1 serious events

Other events: 17 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	CSL312 n=39 participants at risk Participants received a CSL312 loading dose of 400 mg as two 200 mg SC injections in Month 1 along with CSL312 of 200 mg SC injections, once monthly from Months 2 to 6.	Placebo n=25 participants at risk Participants received a CSL312 matched loading dose of placebo as two SC injections in Month 1 along with CSL312 matched placebo SC injections, once monthly from Months 2 to 6.
Congenital, familial and genetic disorders Hereditary angioedema	2.6% 1/39 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.	0.00% 0/25 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.

Other adverse events

Additional Information

Study Director

CSL Behring

Phone: 610-878-4000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	CSL312 n=39 participants at risk Participants received a CSL312 loading dose of 400 mg as two 200 mg SC injections in Month 1 along with CSL312 of 200 mg SC injections, once monthly from Months 2 to 6.	Placebo n=25 participants at risk Participants received a CSL312 matched loading dose of placebo as two SC injections in Month 1 along with CSL312 matched placebo SC injections, once monthly from Months 2 to 6.
Gastrointestinal disorders Diarrhoea	5.1% 2/39 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.	4.0% 1/25 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.
Gastrointestinal disorders Abdominal pain	5.1% 2/39 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.	0.00% 0/25 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.
Infections and infestations Upper respiratory tract infection	10.3% 4/39 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.	8.0% 2/25 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.
Infections and infestations Nasopharyngitis	7.7% 3/39 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.	4.0% 1/25 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.
Infections and infestations COVID-19	0.00% 0/39 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.	12.0% 3/25 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.
Infections and infestations Gastrointestinal infection	5.1% 2/39 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.	4.0% 1/25 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.
Infections and infestations Conjunctivitis	5.1% 2/39 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.	0.00% 0/25 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.
Infections and infestations Sinusitis	5.1% 2/39 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.	0.00% 0/25 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.
Infections and infestations Urinary tract infection	5.1% 2/39 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.	0.00% 0/25 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.
General disorders Fatigue	0.00% 0/39 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.	12.0% 3/25 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.
General disorders Injection site erythema	2.6% 1/39 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.	8.0% 2/25 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.
General disorders Pyrexia	2.6% 1/39 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.	8.0% 2/25 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.
Nervous system disorders Headache	7.7% 3/39 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.	16.0% 4/25 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.
Gastrointestinal disorders Nausea	0.00% 0/39 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.	8.0% 2/25 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.
Musculoskeletal and connective tissue disorders Back pain	5.1% 2/39 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.	4.0% 1/25 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/39 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.	8.0% 2/25 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.1% 2/39 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.	4.0% 1/25 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.
Eye disorders Visual impairment	5.1% 2/39 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.	0.00% 0/25 • From first dose of study drug up to 3 months after the last injection (approximately 8 months) Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.