Trial Outcomes & Findings for Efficacy Multicentre Trial of ImmunoTherapy Vaccination With Abagovomab to Treat Ovarian Cancer Patients (NCT NCT00418574)

Last Updated: 2011-11-24

Results Overview

The Recurrence free survival correspond to the time from date of randomization to documented disease recurrence or death. Disease recurrence is defined as the appearance of any lesion or development of tumor-related symptoms evaluated by medical examination and must be confirmed by a documented CT scan.

Recruitment status

TERMINATED

Study phase

PHASE2/PHASE3

Target enrollment

888 participants

Primary outcome timeframe

Every 12 weeks up to recurrence or up to 3 months after last administered dose

Results posted on

2011-11-24

Participant Flow

Study population was recruited in 139 sites (Hospitals/University Clinics) distributed in Europe (Belgium, Czech Republic, France, Germany, Hungary, Italy, Poland and Spain) and US. Date of first patient randomised: 08 December 2006 Date of last patient randomised: 26 December 2008

Participant milestones

Participant milestones
Measure	Abagovomab 2 mg/ml SC, every 2 weeks (for the first 4 doses - induction phase) and then every 4 weeks (maintenance phase)	Placebo 2 mg/ml SC, every 2 weeks (for the first 4 doses - induction phase) and then every 4 weeks (maintenance phase)
Overall Study STARTED	593	295
Overall Study TREATED	592	294
Overall Study COMPLETED	545	272
Overall Study NOT COMPLETED	48	23

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Efficacy Multicentre Trial of ImmunoTherapy Vaccination With Abagovomab to Treat Ovarian Cancer Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Abagovomab n=593 Participants 2 mg/ml SC, every 2 weeks (for the first 4 doses - induction phase) and then every 4 weeks (maintenance phase)	Placebo n=295 Participants 2 mg/ml SC, every 2 weeks (for the first 4 doses - induction phase) and then every 4 weeks (maintenance phase)	Total n=888 Participants Total of all reporting groups
Age, Categorical <=18 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	447 Participants n=5 Participants	227 Participants n=7 Participants	674 Participants n=5 Participants
Age, Categorical >=65 years	145 Participants n=5 Participants	68 Participants n=7 Participants	213 Participants n=5 Participants
Age Continuous	56.4 years STANDARD_DEVIATION 10.57 • n=5 Participants	56.0 years STANDARD_DEVIATION 10.47 • n=7 Participants	56.3 years STANDARD_DEVIATION 10.53 • n=5 Participants
Sex/Gender, Customized Female	593 participants n=5 Participants	295 participants n=7 Participants	888 participants n=5 Participants
Region of Enrollment France	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment United States	91 participants n=5 Participants	47 participants n=7 Participants	138 participants n=5 Participants
Region of Enrollment Hungary	17 participants n=5 Participants	8 participants n=7 Participants	25 participants n=5 Participants
Region of Enrollment Czech Republic	54 participants n=5 Participants	28 participants n=7 Participants	82 participants n=5 Participants
Region of Enrollment Poland	53 participants n=5 Participants	25 participants n=7 Participants	78 participants n=5 Participants
Region of Enrollment Spain	55 participants n=5 Participants	48 participants n=7 Participants	103 participants n=5 Participants
Region of Enrollment Belgium	19 participants n=5 Participants	4 participants n=7 Participants	23 participants n=5 Participants
Region of Enrollment Germany	206 participants n=5 Participants	93 participants n=7 Participants	299 participants n=5 Participants
Region of Enrollment Italy	97 participants n=5 Participants	40 participants n=7 Participants	137 participants n=5 Participants
Histology of ovarian tumor Serous/papillary	481 participants n=5 Participants	245 participants n=7 Participants	726 participants n=5 Participants
Histology of ovarian tumor Endometrioid	38 participants n=5 Participants	21 participants n=7 Participants	59 participants n=5 Participants
Histology of ovarian tumor Mucinous	6 participants n=5 Participants	3 participants n=7 Participants	9 participants n=5 Participants
Histology of ovarian tumor Undifferentiated	14 participants n=5 Participants	7 participants n=7 Participants	21 participants n=5 Participants
Histology of ovarian tumor Mixed tumor	18 participants n=5 Participants	7 participants n=7 Participants	25 participants n=5 Participants
Histology of ovarian tumor Others	33 participants n=5 Participants	12 participants n=7 Participants	45 participants n=5 Participants
Histology of ovarian tumor missing	3 participants n=5 Participants	0 participants n=7 Participants	3 participants n=5 Participants
Eastern Cooperative Oncology Group Performance Status (ECOG-PS) 0	460 participants n=5 Participants	240 participants n=7 Participants	700 participants n=5 Participants
Eastern Cooperative Oncology Group Performance Status (ECOG-PS) 1	131 participants n=5 Participants	55 participants n=7 Participants	186 participants n=5 Participants
Eastern Cooperative Oncology Group Performance Status (ECOG-PS) 2	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Grade of histologic differentiation G1-G2	160 participants n=5 Participants	82 participants n=7 Participants	242 participants n=5 Participants
Grade of histologic differentiation G3-G4	365 participants n=5 Participants	185 participants n=7 Participants	550 participants n=5 Participants
Grade of histologic differentiation GX	12 participants n=5 Participants	4 participants n=7 Participants	16 participants n=5 Participants
Grade of histologic differentiation not done	56 participants n=5 Participants	24 participants n=7 Participants	80 participants n=5 Participants
International Federation of Gynecology and Obstetrics (FIGO) stage III	513 participants n=5 Participants	252 participants n=7 Participants	765 participants n=5 Participants
International Federation of Gynecology and Obstetrics (FIGO) stage IV	80 participants n=5 Participants	42 participants n=7 Participants	122 participants n=5 Participants
International Federation of Gynecology and Obstetrics (FIGO) stage missing	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Tumor size after debulking surgery <= 1 cm	479 participants n=5 Participants	232 participants n=7 Participants	711 participants n=5 Participants
Tumor size after debulking surgery > 1 cm	114 participants n=5 Participants	63 participants n=7 Participants	177 participants n=5 Participants
Serum CA-125 after 3rd chemotherapy cycle <= 35 U/ml	479 participants n=5 Participants	239 participants n=7 Participants	718 participants n=5 Participants
Serum CA-125 after 3rd chemotherapy cycle > 35 U/ml	114 participants n=5 Participants	55 participants n=7 Participants	169 participants n=5 Participants
Serum CA-125 after 3rd chemotherapy cycle missing	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants

PRIMARY outcome

Timeframe: Every 12 weeks up to recurrence or up to 3 months after last administered dose

Population: intention to treat (ITT) population (i.e. all randomized patients)

Outcome measures

Outcome measures
Measure	Abagovomab n=593 Participants 2 mg/ml SC, every 2 weeks (for the first 4 doses - induction phase) and then every 4 weeks (maintenance phase)	Placebo n=295 Participants 2 mg/ml SC, every 2 weeks (for the first 4 doses - induction phase) and then every 4 weeks (maintenance phase)
Recurrence Free Survival Evaluated by Clinical Event Adjudication Committee (CEAC)	403 days Interval 323.0 to 414.0	402 days Interval 323.0 to 487.0

SECONDARY outcome

Timeframe: 2 years

Population: intention to treat (ITT) population (i.e. all randomized patients)

2 years survival rate

Outcome measures

Outcome measures
Measure	Abagovomab n=593 Participants 2 mg/ml SC, every 2 weeks (for the first 4 doses - induction phase) and then every 4 weeks (maintenance phase)	Placebo n=295 Participants 2 mg/ml SC, every 2 weeks (for the first 4 doses - induction phase) and then every 4 weeks (maintenance phase)
Overall Survival	80 Percentage of participants	79 Percentage of participants

SECONDARY outcome

Timeframe: Along treatment administration and up to double blind observation period. i.e. for each patient after the first dose administration till the f inal study visit, or within 12 weeks of the last dose

Population: Safety population (i.e. All randomized patients who received at least one dose treatment administration)

Safety was analyzed in all patients who received at least 1 dose administration. Adverse event (AE) are defined as events which started on or after the first dose of study medication and on or before the date of the final study visit, or within 12 weeks of the last dose if the final study visit was not performed.

Outcome measures

Outcome measures
Measure	Abagovomab n=592 Participants 2 mg/ml SC, every 2 weeks (for the first 4 doses - induction phase) and then every 4 weeks (maintenance phase)	Placebo n=294 Participants 2 mg/ml SC, every 2 weeks (for the first 4 doses - induction phase) and then every 4 weeks (maintenance phase)
Safety Patients with at least 1 Adverse Event (AE)	564 participants	278 participants
Safety Patients with at least 1 Adverse Drug Reaction ADR	507 participants	246 participants
Safety Patients with at least 1 Serious Adverse Event SAE	141 participants	72 participants
Safety Patients with at least 1 Serious ADR (SADR)	10 participants	3 participants
Safety Patients with at least 1 AE leading to withdrawal	93 participants	57 participants
Safety Patients with at least 1 AE resulted in death	8 participants	4 participants

SECONDARY outcome

Timeframe: at baseline, at week 10 after first dose administration and at final study visit (at week 4 or week 12 after the last administered dose, as appropriate)

Population: Participants who received abagovomab (evaluable population)and have baseline serum sample: 576 at baseline; 538 at week 10 after first dose intake; 449 at the final study visit

Time course of immunologic parameters (anti-anti-idiotypic antibody - Ab3) will be assessed in all patients, by comparing levels at baseline (week 0), at week 10 after first dose administration and at end of treatment (at week 4 or week 12 after the last administered dose, as appropriate).

Outcome measures

Outcome measures
Measure	Abagovomab n=576 Participants 2 mg/ml SC, every 2 weeks (for the first 4 doses - induction phase) and then every 4 weeks (maintenance phase)	Placebo 2 mg/ml SC, every 2 weeks (for the first 4 doses - induction phase) and then every 4 weeks (maintenance phase)
Time Course of Immunoresponse Ab3 (week 10)	63550 ng/ml Interval 0.0 to 777000.0	—
Time Course of Immunoresponse Ab3 (end of treatment)	493000 ng/ml Interval 0.0 to 2720000.0	—
Time Course of Immunoresponse Ab3 (baseline)	0 ng/ml Interval 0.0 to 118000.0	—

Adverse Events

Abagovomab

Serious events: 141 serious events

Other events: 532 other events

Deaths: 0 deaths

Placebo

Serious events: 72 serious events

Other events: 261 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Research Director

Menarini Ricerche SpA

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The only disclosure restriction on the PI is that result communications shall be exchanged and discussed with the sponsor 60 days prior to submission for publication or presentation.
Publication restrictions are in place

Restriction type: OTHER

Measure	Abagovomab n=592 participants at risk 2 mg/ml SC, every 2 weeks (for the first 4 doses - induction phase) and then every 4 weeks (maintenance phase)	Placebo n=294 participants at risk 2 mg/ml SC, every 2 weeks (for the first 4 doses - induction phase) and then every 4 weeks (maintenance phase)
Gastrointestinal disorders Diarrhoea (excl infective)	16.6% 98/592 • Number of events 177 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)	13.9% 41/294 • Number of events 64 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)
Gastrointestinal disorders Flatulence, bloating and distension	7.6% 45/592 • Number of events 69 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)	8.5% 25/294 • Number of events 33 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)
Gastrointestinal disorders Gastrointestinal and abdominal pains (excl oral and throat)	30.9% 183/592 • Number of events 300 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)	27.6% 81/294 • Number of events 125 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)
Gastrointestinal disorders Gastrointestinal atonic and hypomotility disorders NEC	13.9% 82/592 • Number of events 115 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)	12.9% 38/294 • Number of events 54 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)
Gastrointestinal disorders Nausea and vomiting symptoms	22.0% 130/592 • Number of events 325 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)	21.8% 64/294 • Number of events 138 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)
General disorders Asthenic conditions	32.3% 191/592 • Number of events 431 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)	30.3% 89/294 • Number of events 240 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)
General disorders Febrile disorders	11.3% 67/592 • Number of events 111 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)	13.6% 40/294 • Number of events 73 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)
General disorders Feelings and sensations NEC	5.7% 34/592 • Number of events 42 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)	4.8% 14/294 • Number of events 25 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)
General disorders General signs and symptoms NEC	7.4% 44/592 • Number of events 75 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)	6.5% 19/294 • Number of events 25 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)
General disorders Injection site reactions	78.9% 467/592 • Number of events 4906 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)	75.5% 222/294 • Number of events 2352 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)
General disorders Oedema NEC	10.3% 61/592 • Number of events 82 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)	10.9% 32/294 • Number of events 39 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)
General disorders Pain and discomfort NEC	6.2% 37/592 • Number of events 44 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)	6.8% 20/294 • Number of events 22 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)
Infections and infestations Lower respiratory tract and lung infections	7.3% 43/592 • Number of events 49 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)	2.7% 8/294 • Number of events 8 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)
Infections and infestations Upper respiratory tract infections	24.0% 142/592 • Number of events 242 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)	23.8% 70/294 • Number of events 124 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)
Infections and infestations Urinary tract infections	13.5% 80/592 • Number of events 114 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)	9.2% 27/294 • Number of events 33 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)
Investigations Physical examination procedures	5.6% 33/592 • Number of events 46 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)	6.8% 20/294 • Number of events 33 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)
Musculoskeletal and connective tissue disorders Bone related signs and symptoms	6.9% 41/592 • Number of events 59 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)	8.8% 26/294 • Number of events 44 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)
Musculoskeletal and connective tissue disorders Joint related signs and symptoms	22.6% 134/592 • Number of events 263 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)	22.8% 67/294 • Number of events 112 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)
Musculoskeletal and connective tissue disorders Muscle pains	10.0% 59/592 • Number of events 104 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)	11.9% 35/294 • Number of events 59 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue pain and discomfort	28.9% 171/592 • Number of events 355 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)	26.9% 79/294 • Number of events 212 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)
Nervous system disorders Headaches NEC	14.0% 83/592 • Number of events 227 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)	12.9% 38/294 • Number of events 86 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)
Nervous system disorders Neurological signs and symptoms NEC	7.1% 42/592 • Number of events 63 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)	8.5% 25/294 • Number of events 30 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)
Nervous system disorders Peripheral neuropathies NEC	7.8% 46/592 • Number of events 57 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)	8.5% 25/294 • Number of events 28 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)
Psychiatric disorders Disturbances in initiating and maintaining sleep	5.2% 31/592 • Number of events 37 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)	5.8% 17/294 • Number of events 24 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)
Renal and urinary disorders Bladder and urethral symptoms	6.4% 38/592 • Number of events 47 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)	8.5% 25/294 • Number of events 30 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)
Respiratory, thoracic and mediastinal disorders Breathing abnormalities	8.1% 48/592 • Number of events 59 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)	7.8% 23/294 • Number of events 26 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)
Respiratory, thoracic and mediastinal disorders Coughing and associated symptoms	7.3% 43/592 • Number of events 51 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)	8.5% 25/294 • Number of events 31 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)
Skin and subcutaneous tissue disorders Erythemas	6.8% 40/592 • Number of events 76 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)	7.5% 22/294 • Number of events 37 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)
Skin and subcutaneous tissue disorders Pruritus NEC	5.1% 30/592 • Number of events 50 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)	5.1% 15/294 • Number of events 16 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)
Skin and subcutaneous tissue disorders Rashes, eruptions and exanthems NEC	5.6% 33/592 • Number of events 47 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)	6.5% 19/294 • Number of events 23 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)
Vascular disorders Peripheral vascular disorders NEC	8.3% 49/592 • Number of events 62 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)	8.8% 26/294 • Number of events 35 • 4 years Adverse Events monitored throughout the observation period, at each visit prior dosing (every 2 weeks during the induction phase, every 4 weeks during the maintenance phase)