Trial Outcomes & Findings for An Indian Multi-centric Phase IV Study to Assess the Safety of Crizanlizumab in Sickle Cell Disease Patients (NCT NCT04662931)

Results Overview

Number of participants with treatment emergent SAEs and SAEs grade \>=3. Adverse events were assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5. CTCAE ranges severity from Grade 1 through 5 being Grade 1 the lowest severity grade.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

140 participants

Primary outcome timeframe

Up to 15 months

Results posted on

2025-09-26

Participant Flow

Participants took part in 8 investigative sites in India.

During the screening period, which occurred within 35 days before enrollment, participants signed written informed consent according to local guidelines. All screening evaluations were performed during this period.

Participant milestones

Participant milestones
Measure	Crizanlizumab 5.0 mg/kg i.v. Crizanlizumab 5.0 mg/kg i.v. initial dose on Week 1 Day 1, second dose on Week 3 Day 1. Subsequently, Day 1 of every 4 weeks until Week 51, in addition of standard of care.
Overall Study STARTED	140
Overall Study COMPLETED	116
Overall Study NOT COMPLETED	24

Reasons for withdrawal

Reasons for withdrawal
Measure	Crizanlizumab 5.0 mg/kg i.v. Crizanlizumab 5.0 mg/kg i.v. initial dose on Week 1 Day 1, second dose on Week 3 Day 1. Subsequently, Day 1 of every 4 weeks until Week 51, in addition of standard of care.
Overall Study Withdrawal by Subject	17
Overall Study Death	3
Overall Study Lost to Follow-up	3
Overall Study Guardian Decision	1

Baseline Characteristics

An Indian Multi-centric Phase IV Study to Assess the Safety of Crizanlizumab in Sickle Cell Disease Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Crizanlizumab 5.0 mg/kg i.v. n=140 Participants Crizanlizumab 5.0 mg/kg i.v. initial dose on Week 1 Day 1, second dose on Week 3 Day 1. Subsequently, Day 1 of every 4 weeks until Week 51, in addition of standard of care.
Age, Continuous	26.2 years STANDARD_DEVIATION 10.67 • n=5 Participants
Sex: Female, Male Female	65 Participants n=5 Participants
Sex: Female, Male Male	75 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	137 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	1 Participants n=5 Participants
Race/Ethnicity, Customized Not reported	1 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 15 months

Population: The Safety Set included all participants who received at least one dose of study treatment.

Number of participants with treatment emergent SAEs and SAEs grade \>=3. Adverse events were assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5. CTCAE ranges severity from Grade 1 through 5 being Grade 1 the lowest severity grade.

Outcome measures

Outcome measures
Measure	Crizanlizumab 5.0 mg/kg i.v. n=140 Participants Crizanlizumab 5.0 mg/kg i.v. initial dose on Week 1 Day 1, second dose on Week 3 Day 1. Subsequently, Day 1 of every 4 weeks until Week 51, in addition of standard of care.
Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) Serious adverse events	3 Participants
Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) Serious adverse events grade >=3	3 Participants

SECONDARY outcome

Timeframe: Up to 15 months

Population: The Safety Set included all participants who received at least one dose of study treatment.

Number of participants with treatment emergent AEs, AEs grade \>=3, AEs led to study treatment discontinuation, AEs leading to dose adjustment/interruption, and AEs requiring additional therapy. Adverse events were assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.

Outcome measures

Outcome measures
Measure	Crizanlizumab 5.0 mg/kg i.v. n=140 Participants Crizanlizumab 5.0 mg/kg i.v. initial dose on Week 1 Day 1, second dose on Week 3 Day 1. Subsequently, Day 1 of every 4 weeks until Week 51, in addition of standard of care.
Number of Participants With Treatment Emergent Adverse Events (AEs) Adverse events	53 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) Adverse events grade >=3	6 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) AEs leading to discontinuation	3 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) AEs leading to dose adjustment/interruption	1 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) AEs requiring additional therapy	46 Participants

SECONDARY outcome

Timeframe: Up to 15 months

Population: The Safety Set included all participants who received at least one dose of study treatment.

The AESIs were designated medical events, infections, infusion-related reaction (IRR), infusion-related reaction new combined and pain events. Pain events are potential infusion-related reactions presenting as pain events (occurred on the day of infusion). IRR (Standard search): Standard search, excluding infusion site-reaction and investigating the most common, nonspecific, potential signs and symptoms indicative of IRRs, and occurring on the day of infusion. IRR (Combined search): Comprised of severe reactions (e.g. bronchospasm, anaphylactic reaction etc.), that occurs any time after infusion (regardless of grade and causality) and pain events on the day of infusion along with the events that are covered under standard search. Designated medical events (DMEs): European Medicines Agency, as well as EEA Member States released a list of DMEs, to identify reports of suspected ADRs that deserve special attention, irrespective of statistical criteria used to prioritize safety reviews.

Outcome measures

Outcome measures
Measure	Crizanlizumab 5.0 mg/kg i.v. n=140 Participants Crizanlizumab 5.0 mg/kg i.v. initial dose on Week 1 Day 1, second dose on Week 3 Day 1. Subsequently, Day 1 of every 4 weeks until Week 51, in addition of standard of care.
Number of Participants With Adverse Events of Special Interest (AESI) Designated medical events	1 Participants
Number of Participants With Adverse Events of Special Interest (AESI) Infections (All)	10 Participants
Number of Participants With Adverse Events of Special Interest (AESI) Infusion-related reaction (standard search)	2 Participants
Number of Participants With Adverse Events of Special Interest (AESI) Infusion-related reactions (IRR) (new combined search)	3 Participants
Number of Participants With Adverse Events of Special Interest (AESI) Pain events	2 Participants
Number of Participants With Adverse Events of Special Interest (AESI) Any AESI	18 Participants

Adverse Events

Crizanlizumab 5.0 mg/kg i.v.

Serious events: 3 serious events

Other events: 25 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	Crizanlizumab 5.0 mg/kg i.v. n=140 participants at risk Crizanlizumab 5.0 mg/kg i.v. initial dose on Week 1 Day 1, second dose on Week 3 Day 1. Subsequently, Day 1 of every 4 weeks until Week 51, in addition of standard of care.
General disorders Sudden cardiac death	0.71% 1/140 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period of 105 days, up to a maximum duration of approximately 15 months.
Injury, poisoning and procedural complications Road traffic accident	0.71% 1/140 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period of 105 days, up to a maximum duration of approximately 15 months.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.71% 1/140 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period of 105 days, up to a maximum duration of approximately 15 months.

Other adverse events

Other adverse events
Measure	Crizanlizumab 5.0 mg/kg i.v. n=140 participants at risk Crizanlizumab 5.0 mg/kg i.v. initial dose on Week 1 Day 1, second dose on Week 3 Day 1. Subsequently, Day 1 of every 4 weeks until Week 51, in addition of standard of care.
Blood and lymphatic system disorders Anaemia	3.6% 5/140 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period of 105 days, up to a maximum duration of approximately 15 months.
General disorders Pain	7.1% 10/140 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period of 105 days, up to a maximum duration of approximately 15 months.
General disorders Pyrexia	5.7% 8/140 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period of 105 days, up to a maximum duration of approximately 15 months.
Musculoskeletal and connective tissue disorders Arthralgia	4.3% 6/140 • Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period of 105 days, up to a maximum duration of approximately 15 months.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: + 1 862 778 8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER