ClinicalTrials.gg
CompletedNCT03264989Updated Oct 9, 2024Results posted

Pharmacokinetics and Pharmacodynamics Study of SEG101 (Crizanlizumab) in Sickle Cell Disease (SCD) Patients With Vaso- Occlusive Crisis (VOC)

A Phase 2 interventional study of crizanlizumab in Sickle Cell Disease (SCD), sponsored by Novartis Pharmaceuticals. Completed at 12 sites in United States. Open to participants aged 16 Years to 70 Years. Per ClinicalTrials.gov, last updated 2024-10-09.

Primary conditionVaso-Occlusive CrisesRegistry: Anemia, Sickle CellReclassifiedWhy we changed it
Registry
Anemia, Sickle Cell — the first condition term the registry derived for this study.
ClinicalTrials.gg
Vaso-Occlusive Crises
Why
  1. The study's title name Vaso-Occlusive Crises, a narrower term within Anemia, Sickle Cell.
Confidence
High: the new condition is named in the study's own title. Of 46 hand-checked studies reclassified this way, 72% were exactly right and 89% in the right disease family; the registry's first term was right for 4% (measured 2026-10-21). How we classify →
Wrong?
Tell us the study's main condition →

Sponsored by Novartis Pharmaceuticals (part of Novartis) · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
57
Allocation
Not applicable
Ages
16 Years to 70 Years
Sex
All
01

Where this study stands

Counted across the records on this site · 2026-11-12

Among 60 studies in Vaso-Occlusive Crises with a site in United States — 13 open to participants now, 15 under way, 5 of them phase 3. Vaso-Occlusive Crises · United States.

Enrollment
31st of 56
57 · median 63
Started
2017
the only one that year
Phase 2
18 of 60
4 open now
Registered
27th of 60
by date
Lead sponsor
4 of 60
Novartis Pharmaceuticals

Among the 60 studies in Vaso-Occlusive Crises with a site in United States, this one is the 31st largest by enrollment of the 56 interventional ones that give a count, is the only one that started in 2017, is one of 18 in phase 2, and was the 27th registered.

Vaso-Occlusive Crises

104 studies on the registry are indexed under Vaso-Occlusive Crises; 31 are open to participants now.

Browse Vaso-Occlusive Crises studies →

Open to participants now

13 of the 60 studies in Vaso-Occlusive Crises with a site in United States are open now. Recruiting first, the newest first:

8 more — sign in →

All 13 open studies →

A study can be open while its sites in United States have not opened yet or have stopped. Only those recruiting at a site in United States →

Who these studies take

Of the 17 Vaso-Occlusive Crises studies recruiting now, 7 (41%) set no upper age limit and 6 (35%) stop at 75 or younger; 10 take children under 18; 1 take healthy volunteers.

This study: 16 Years to 70 Years · all sexes · no healthy volunteers.

The full table on the hub →

This tab as a report to print or save as PDF → With an account.

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Watch this landscapeDownload CSVNarrow it in search →With an account: a weekly mail of what changed among 60 studies in Vaso-Occlusive Crises with a site in United States, or all of them as a file.
02

Study summary

The purpose of the CSEG101A2202 study was to characterize the Pharmacokinetic (PK) and Pharmacodynamic (PD) of SEG101/crizanlizumab and to evaluate the safety and efficacy of SEG101/crizanlizumab in sickle cell disease (SCD) patients.

Read the detailed description

Study CSEG101A2202 was designed as a Phase II, multicenter, open-label study. The first 45 patients (to identify 27 evaluable patients) were enrolled to the treatment group crizanlizumab 5.0 mg/kg to complete full Pharmacokinetic/Pharmacodynamic (PK/PD) sampling at week 1 and week 15. In all patients, trough PK/PD samples were collected prior to each dose. In addition, throughout the study (and when possible), all patients had blood drawn for serum to assess PK and PD drawn at times of onset and resolution of each VOC event, fever, or infection. Once the up to 45 patients were enrolled, 12 additional patients were enrolled to the exploratory treatment group and began at 7.5 mg/kg of crizanlizumab.

The study was initiated on 19-Dec-2017. This study provides five years follow up data that fully characterizes the safety, tolerability and treatment effect of the 5.0 mg/kg and 7.5 mg/kg doses of crizanlizumab along with the initially planned PK and PD data.

At the time of study closure, crizanlizumab 5.0 mg/kg was an FDA approved treatment in the United States (US) for patients with sickle-cell disease. Therefore, the patients treated with crizanlizumab 5.0 mg/kg dose were encouraged to transition to commercial supply of crizanlizumab. The patients treated with the not currently approved dose of crizanlizumab 7.5 mg/kg were allowed to join a multi-center, multi-national, rollover clinical trial (Study SEG101A2401B), for continued access to treatment with crizanlizumab.

03

Conditions studied

  • Sickle Cell Disease (SCD)

Browse trials for

Keywords

  • Sickle cell disease
  • SCD
  • sickle cell anemia
  • vaso-occlusive crisis
  • P-selectin
  • SEG101
  • crizanlizumab
  • monoclonal antibody
  • Anemia, Sickle Cell
  • HbS Disease
  • Hemoglobin SC Disease
  • Sickle Cell Disorders
  • Sickling Disorder Due to Hemoglobin S
04

In context

Vaso-Occlusive Crises Reclassified

104 studies on the registry are indexed under Vaso-Occlusive Crises; 31 are open to participants now.

This study's enrollment of 57 is below the median of 81 across 86 interventional studies indexed under Vaso-Occlusive Crises.

Browse Vaso-Occlusive Crises studies →

Lead sponsor

Novartis Pharmaceuticals is the lead sponsor of 2,718 studies on the registry; 221 are open to participants now.

Of its 585 completed or terminated interventional studies of FDA-regulated products, 438 (75%) have results posted.

Compared within Vaso-Occlusive Crises, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Anemia, Sickle Cell. The counts are of registry records indexed under each term, refreshed daily. How we classify →

05

Who can participate

Ages eligible
16 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Male and non-pregnant female patients 16-70 years of age (inclusive)
  • Confirmed diagnosis of sickle cell disease by electrophoresis or high-performance liquid chromatography (HPLC) [performed locally]. All sickle cell disease genotypes are eligible.
  • Experienced at least 1 VOC within the preceding 12 months prior to Screening, as determined by medical history.
  • If receiving HU/HC or erythropoietin stimulating agent, must have been receiving the drug for at least 6 months prior to Screening
  • Hemoglobin ≥4.0 g/dL. ≥1.0 x 109/L and count ≥75 x 109/L
  • Adequate renal and hepatic function as defined:
  • ≥45 mL/min/1.73 m2 calculated by CKD-EPI
  • ≤3 x
  • Direct (conjugated) ≤2 x ULN
  • performance status ≤2
  • Written (or assent/ parental consent for minor subjects) prior to any screening procedures

Exclusion criteria

Exclusion Criteria:

  • History of stem cell transplant.
  • Acute VOC ending 7 days prior to first dosing
  • Ongoing hospitalization prior to Screening
  • Received blood products within 30 days to first dosing
  • Participating in a chronic transfusion program (pre-planned series of transfusions for prophylactic purposes)
  • History of severe reactions to other monoclonal antibodies
  • Received a monoclonal antibody or immunoglobulin -based agent within 1 year of Screening, or has documented immunogenicity to a prior biologic.
  • Received active treatment on another trial within 30 days (or 5 half-lives of that agent, whichever is greater) prior to Screening
  • Significant active infection or immune deficiency (including chronic use of drugs)
  • Resting ≥470 msec at pretreatment (baseline) or other cardiac or cardiac repolarization abnormality
Terms in these criteria, in plain language(13)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

Absolute neutrophil count (ANC)

The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.

It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

GFR and eGFR (kidney filtering)

GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².

Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

ECOG performance status

A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.

0
Fully active, no restrictions.
1
Limited in strenuous activity, but walking and able to do light work, such as housework or office work.
2
Walking and able to look after yourself, but unable to work; up and about more than half of waking hours.
3
Able to look after yourself only in part; in bed or a chair more than half of waking hours.
4
Unable to look after yourself at all; in bed or a chair all day.

Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Hypersensitivity

An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

Immunosuppression

A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.

Read whether the line is about a condition or about medicines, and which medicines and doses it means.

QT and QTc

On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.

The study may name a correction formula and a limit in milliseconds, often around 450–480.

06

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
57 participants (actual)

Study arms

  • Experimental
    crizanlizumab

    SEG101 (crizanlizumab) drug at a dose of 5.0 mg/kg (or 7.5 mg/kg for exploratory group) by IV infusion.

    Drug: crizanlizumab

Interventions

  • Crizanlizumab was administered IV infusion over 30 minutes at the assigned dose on Week 1 Day 1, Week 3 Day 1, and then Day 1 of every 4-week cycle. Cycle = 28 days

    Also known as: SEG101

07

What researchers measure

Primary outcomes

  1. Pharmacokinetic (PK): AUCd15 and AUCtau of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients

    To characterize PK of crizanlizumab at 5.0 mg/kg in SCD patients. AUCd15: The AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1) after single dose AUCtau: The AUC calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1)

    Time frame: 1st dose: Day 1: (pre-dose, 0.5, 1, 2, 4, 6 & 24 hours post dose, Days 4, 8 & 15; 5th dose: Day 1 (pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post dose), Days 4, 8, 15, 22 & 29

  2. PK: Cmax of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients

    To characterize PK of crizanlizumab at 5.0 mg/kg in SCD patients. Cmax: The maximum (peak) observed serum drug concentration after dose administration (mass x volume-1).

    Time frame: After the starting dose (Week 1) and after multiple doses (steady state, Week 15)

  3. Pre-dose Concentrations Prior to Each Study Drug Dose

    To characterize PK of crizanlizumab at 5.0 mg/kg in SCD patients, by serum concentrations by treatment group. Data was collected prior to each study drug dose; From Week 3 (loading dose), pre-dose (trough) concentrations were obtained every 4 weeks.

    Time frame: Pre-dose at Day 1 on Weeks 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, 47, 51

  4. Percentage of P-selectin Inhibition After the Starting Dose (PD-AUCd15), After Multiple Doses (PD-AUCd29) of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients

    PD-AUCd15 and PD-AUCd29 were derived from the P-selectin inhibition data of week 1 and week 15, respectively. To characterize PD of crizanlizumab at 5.0 mg/kg in SCD patients The area under the curve (AUC) of percentage of P-selectin inhibition versus time profile after the starting dose (PD-AUCd15) and after multiple doses (PD-AUCd29) is being reported.

    Time frame: 1st dose: Day 1: (pre-dose, 0.5, 1, 2, 4, 6 & 24 hours post dose, Days 4, 8, 15; 5th dose: Day 1(pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post dose), Days 4, 8, 15, 22 & 29

  5. Percentage of P-selectin Inhibition Prior to Each Study Drug Dose of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients

    To characterize the PD effect of crizanlizumab in terms of Percentage of P-selectin inhibition prior to study drug dose at 5 mg/kg in CSD patients.

    Time frame: Pre-dose on Day 1 for Weeks 3, 7, 11, 15, 19, 23, 27, 31,35, 39, 43, 47, 51 (at 0 hr or pre-dose)

Secondary outcomes

  1. Annualized Rate of Vaso-occlusive Crisis (VOC) Events Leading to Healthcare Visit in Clinic/Emergency Room (ER)/Hospital

    To assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in Sickle cell disease (SCD) patients. Annualized rate of VOC=(Number of VOC reported until End date ×365.25)/(End date - date of first dose of study treatment+1). End date is defined as the minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and erythropoietin to treat SCD and or to prevent/reduce VOCs, cut-off date).

    Time frame: Baseline (Week 1) through approx. 45 months (median exposure to treatment)

  2. Annualized Rate of VOC Events Treated at Home (Based on Documentation by Health Care Provider Following Phone Contact With Patient)

    To assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients. Annualized rate of VOC=(Number of VOC reported until End date ×365.25)/(End date - date of first dose of study treatment+1). End date is defined as the minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and erythropoietin to treat SCD and or to prevent/reduce VOCs, cut-off date).

    Time frame: Baseline (Week 1) through approx. 45 months (median exposure to treatment)

  3. Annualized Rate of Total and VOC-related Hospitalizations and Emergency Room (ER) Visits

    To assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients. Annualized rate of hospitalizations and ER visits = number of hospitalizations and ER visits reported until end date × 365.25/(End date - treatment start date + 1). End date is defined as the minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and erythropoietin to treat SCD and or to prevent/reduce VOCs, cut-off date).

    Time frame: Baseine (Week 1) through approx. 45 months (median exposure to treatment)

  4. Annualized Days of Total and VOC-related Hospitalizations and Emergency Room (ER) Visits

    Assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients for hospitalizations and ER visits. Annualized days of all hospitalizations and ER visits = Number of days of all hospitalizations and ER visits × 365.25/(End date - treatment start date + 1). End date is defined as the minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and to treat SCD and or to prevent/reduce VOCs, cut-off date).

    Time frame: Baseline (Week 1) through approx. 45 months (median exposure to treatment)

  5. Annualized Rate of Each Subcategory of All VOC Events (Acute Chest Syndrome (ACS), Priapism, Uncomplicated Sickle Cell-vaso-occlusive Cisis (Uncomplicated SC-VOCs))

    Assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients. The baseline (BL) annualized rate of VOC is defined as the number of VOCs reported in the last 12 months in the eCRF. Annualized rate of VOC=(Number of VOC reported until End date ×365.25)/(End date - date of first dose of study treatment+1). End date is defined as the minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and erythropoietin to treat SCD and or to prevent/reduce VOCs, cut-off date).

    Time frame: Baseline (Week 1) through approx. 45 months (median exposure to treatment)

  6. Annualized Rate of VOC Events (Including Both Healthcare Visit and Home Treatment)

    Assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients. Annualized rate of VOC=(Number of VOC reported until End date ×365.25)/(End date -date of first dose of study treatment+1). End date is defined as th e minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and erythropoietin to treat SCD and or to prevent/reduce VOCs, cut-off date).

    Time frame: Baseline (Week 1) through approx. 45 months (median exposure to treatment)

  7. Number of Participants With Immunogenicity (IG) by Any Positive Status

    Assess safety and tolerability of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients by the percentage of participants with any positive status. Immunogenicity is the measurement of anti-drug antibodies (ADA) to crizanlizumab.

    Time frame: Baseline (Week 1), post-baseline (approx. 45 months (median exposure))

08

Results

Posted Apr 23, 2024
Limitations and caveats
This study provided a 5-year follow up (f/u) data that fully characterized the safety, tolerability \& treatment of the 5.0 mg/kg \& 7.5 mg/kg doses of crizanlizumab along with the initially planned PK \& PD data. As the goal of study f/u was reached, study was considered completed \& it was in line with the end of study as defined in the study protocol, the sponsor closed the study as the participants were no longer receiving intervention or being examined.

Participant flow

57 patients were enrolled sequentially to study the at 5 mg/kg arm and at 7.5 mg/kg.

Participant flow — Overall Study
MilestoneCrizanlizumab 5.0 mg/kgCrizanlizumab 7.5 mg/kg
Started4512
Completed00
Not completed4512
Withdrew: Lost to follow-up10
Withdrew: New therapy for study indication10
Withdrew: Protocol violation01
Withdrew: Patient decision130
Withdrew: Physician decision64
Withdrew: Adverse event21
Withdrew: Death11
Withdrew: Pregnancy20
Withdrew: End of study195

Outcome measures

PrimaryPharmacokinetic (PK): AUCd15 and AUCtau of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients

To characterize PK of crizanlizumab at 5.0 mg/kg in SCD patients. AUCd15: The AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1) after single dose AUCtau: The AUC calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1)

Time frame:
1st dose: Day 1: (pre-dose, 0.5, 1, 2, 4, 6 & 24 hours post dose, Days 4, 8 & 15; 5th dose: Day 1 (pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post dose), Days 4, 8, 15, 22 & 29
Reported as:
Mean · hr*μg/mL
Pharmacokinetic (PK): AUCd15 and AUCtau of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients
hr*μg/mLCrizanlizumab 5.0 mg/kg
Starting dose (Week 1): AUCd1513100 ± 2810
Steady State (Week 15): AUCtau20800 ± 5030
PrimaryPK: Cmax of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients

To characterize PK of crizanlizumab at 5.0 mg/kg in SCD patients. Cmax: The maximum (peak) observed serum drug concentration after dose administration (mass x volume-1).

Time frame:
After the starting dose (Week 1) and after multiple doses (steady state, Week 15)
Reported as:
Mean · μg/mL
PK: Cmax of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients
μg/mLCrizanlizumab 5.0 mg/kg
Starting dose (Week 1)102 ± 29.8
Steady State (Week 15)123 ± 36.4
PrimaryPre-dose Concentrations Prior to Each Study Drug Dose

To characterize PK of crizanlizumab at 5.0 mg/kg in SCD patients, by serum concentrations by treatment group. Data was collected prior to each study drug dose; From Week 3 (loading dose), pre-dose (trough) concentrations were obtained every 4 weeks.

Time frame:
Pre-dose at Day 1 on Weeks 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, 47, 51
Reported as:
Mean · μg/mL
Pre-dose Concentrations Prior to Each Study Drug Dose
μg/mLCrizanlizumab 5.0 mg/kg
Week (W) 3 Day 1 (D)1: 0 hrs pre-dose18.0 ± 6.42
W7 D1: 0 hrs pre-dose10.8 ± 5.21
W11 D1: 0 hrs pre-dose9.04 ± 5.04
W15 D1: 0 hrs pre-dose10.0 ± 5.39
W19 D1: 0 hrs pre-dose9.37 ± 4.95
W23 D1: 0 hrs pre-dose9.91 ± 5.09
W27 D1: 0 hrs pre-dose9.65 ± 4.03
W31 D1: 0 hrs pre-dose9.75 ± 4.66
W35 D1: 0 hrs pre-dose9.48 ± 4.60
W39 D1: 0 hrs pre-dose9.54 ± 5.47
W43 D1: 0 hrs pre-dose8.53 ± 5.24
W47 D1: 0 hrs pre-dose8.96 ± 4.31
W51 D1: 0 hrs pre-dose8.45 ± 4.88
PrimaryPercentage of P-selectin Inhibition After the Starting Dose (PD-AUCd15), After Multiple Doses (PD-AUCd29) of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients

PD-AUCd15 and PD-AUCd29 were derived from the P-selectin inhibition data of week 1 and week 15, respectively. To characterize PD of crizanlizumab at 5.0 mg/kg in SCD patients The area under the curve (AUC) of percentage of P-selectin inhibition versus time profile after the starting dose (PD-AUCd15) and after multiple doses (PD-AUCd29) is being reported.

Time frame:
1st dose: Day 1: (pre-dose, 0.5, 1, 2, 4, 6 & 24 hours post dose, Days 4, 8, 15; 5th dose: Day 1(pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post dose), Days 4, 8, 15, 22 & 29
Reported as:
Mean · hours*% of P-selectin inhibition
Percentage of P-selectin Inhibition After the Starting Dose (PD-AUCd15), After Multiple Doses (PD-AUCd29) of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients
hours*% of P-selectin inhibitionCrizanlizumab 5.0 mg/kg
Starting dose (Week 1): PD-AUCd1533200 ± 1830
Steady state (Week 15): PD-AUCd2966900 ± 5540
SecondaryAnnualized Rate of Vaso-occlusive Crisis (VOC) Events Leading to Healthcare Visit in Clinic/Emergency Room (ER)/Hospital

To assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in Sickle cell disease (SCD) patients. Annualized rate of VOC=(Number of VOC reported until End date ×365.25)/(End date - date of first dose of study treatment+1). End date is defined as the minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and erythropoietin to treat SCD and or to prevent/reduce VOCs, cut-off date).

Time frame:
Baseline (Week 1) through approx. 45 months (median exposure to treatment)
Reported as:
Median · number of events per year
Annualized Rate of Vaso-occlusive Crisis (VOC) Events Leading to Healthcare Visit in Clinic/Emergency Room (ER)/Hospital
number of events per yearCrizanlizumab 5.0 mg/kgCrizanlizumab 7.5 mg/kg
Baseline annualized rate of VOC4.00 (1.0 to 25.0)2.00 (1.0 to 9.0)
Annualized rate of VOC on treatment2.75 (0.0 to 17.3)0.97 (0.0 to 7.9)
SecondaryAnnualized Rate of VOC Events Treated at Home (Based on Documentation by Health Care Provider Following Phone Contact With Patient)

To assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients. Annualized rate of VOC=(Number of VOC reported until End date ×365.25)/(End date - date of first dose of study treatment+1). End date is defined as the minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and erythropoietin to treat SCD and or to prevent/reduce VOCs, cut-off date).

Time frame:
Baseline (Week 1) through approx. 45 months (median exposure to treatment)
Reported as:
Median · number of events per participant-year
Annualized Rate of VOC Events Treated at Home (Based on Documentation by Health Care Provider Following Phone Contact With Patient)
number of events per participant-yearCrizanlizumab 5.0 mg/kgCrizanlizumab 7.5 mg/kg
Annualized Rate of VOC Events Treated at Home (Based on Documentation by Health Care Provider Following Phone Contact With Patient)0.68 (0.21 to 2.17)0.71 (0.35 to 1.74)
SecondaryAnnualized Rate of Total and VOC-related Hospitalizations and Emergency Room (ER) Visits

To assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients. Annualized rate of hospitalizations and ER visits = number of hospitalizations and ER visits reported until end date × 365.25/(End date - treatment start date + 1). End date is defined as the minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and erythropoietin to treat SCD and or to prevent/reduce VOCs, cut-off date).

Time frame:
Baseine (Week 1) through approx. 45 months (median exposure to treatment)
Reported as:
Median · number of events per participant-year
Annualized Rate of Total and VOC-related Hospitalizations and Emergency Room (ER) Visits
number of events per participant-yearCrizanlizumab 5.0 mg/kgCrizanlizumab 7.5 mg/kg
Annualized rate (total)3.42 (0.0 to 57.8)2.47 (0.0 to 8.1)
Annualized rate (VOC related)3.34 (0.0 to 57.8)0.86 (0.0 to 7.9)
Hospitalizations/ER Annualized rate (total)2.46 (0.0 to 22.1)1.44 (0.0 to 7.9)
Hospitalizations/ER Annualized rate (VOC related)2.27 (0.0 to 22.1)0.48 (0.0 to 7.9)
SecondaryAnnualized Days of Total and VOC-related Hospitalizations and Emergency Room (ER) Visits

Assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients for hospitalizations and ER visits. Annualized days of all hospitalizations and ER visits = Number of days of all hospitalizations and ER visits × 365.25/(End date - treatment start date + 1). End date is defined as the minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and to treat SCD and or to prevent/reduce VOCs, cut-off date).

Time frame:
Baseline (Week 1) through approx. 45 months (median exposure to treatment)
Reported as:
Median · number of days per year
Annualized Days of Total and VOC-related Hospitalizations and Emergency Room (ER) Visits
number of days per yearCrizanlizumab 5.0 mg/kgCrizanlizumab 7.5 mg/kg
Annualized days (total)11.95 (0.0 to 86.2)3.17 (0.0 to 36.8)
Annualized days (VOC related)9.03 (0.0 to 86.2)1.57 (0.0 to 36.8)
Hospitalizations/ER Annualized days (total)10.31 (0.0 to 69.4)2.57 (0.0 to 36.8)
Hospitalizations/ER Annualized days (VOC related)7.27 (0.0 to 69.4)0.60 (0.0 to 36.8)
SecondaryAnnualized Rate of Each Subcategory of All VOC Events (Acute Chest Syndrome (ACS), Priapism, Uncomplicated Sickle Cell-vaso-occlusive Cisis (Uncomplicated SC-VOCs))

Assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients. The baseline (BL) annualized rate of VOC is defined as the number of VOCs reported in the last 12 months in the eCRF. Annualized rate of VOC=(Number of VOC reported until End date ×365.25)/(End date - date of first dose of study treatment+1). End date is defined as the minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and erythropoietin to treat SCD and or to prevent/reduce VOCs, cut-off date).

Time frame:
Baseline (Week 1) through approx. 45 months (median exposure to treatment)
Reported as:
Median · number of events per year
Annualized Rate of Each Subcategory of All VOC Events (Acute Chest Syndrome (ACS), Priapism, Uncomplicated Sickle Cell-vaso-occlusive Cisis (Uncomplicated SC-VOCs))
number of events per yearCrizanlizumab 5.0 mg/kgCrizanlizumab 7.5 mg/kg
BL annualized rate of VOC: ACS0.00 (0.0 to 2.0)0.00 (0.0 to 2.0)
Annualized rate of VOC on treatment: ACS0.62 (0.0 to 2.7)0.25 (0.0 to 0.6)
BL annualized rate of VOC: Priapism1.00 (0.0 to 4.0)—
Annualized rate of VOC on treatment: Priapism1.58 (0.0 to 3.8)—
BL annualized rate of VOC: Uncomplicated SC-VOCs3.00 (1.0 to 25.0)2.00 (1.0 to 9.0)
Annualized rate of VOC on treatment: Uncomplicated SC-VOCs2.58 (0.0 to 17.3)1.04 (0.0 to 7.9)
SecondaryAnnualized Rate of VOC Events (Including Both Healthcare Visit and Home Treatment)

Assess the efficacy of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients. Annualized rate of VOC=(Number of VOC reported until End date ×365.25)/(End date -date of first dose of study treatment+1). End date is defined as th e minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-glutamine or other therapies such as voxelotor and erythropoietin to treat SCD and or to prevent/reduce VOCs, cut-off date).

Time frame:
Baseline (Week 1) through approx. 45 months (median exposure to treatment)
Reported as:
Median · number of events per year
Annualized Rate of VOC Events (Including Both Healthcare Visit and Home Treatment)
number of events per yearCrizanlizumab 5.0 mg/kgCrizanlizumab 7.5 mg/kg
Annualized Rate of VOC Events (Including Both Healthcare Visit and Home Treatment)3.42 (0.0 to 17.3)1.65 (0.0 to 9.3)
SecondaryNumber of Participants With Immunogenicity (IG) by Any Positive Status

Assess safety and tolerability of crizanlizumab at 5.0 mg/kg and 7.5 mg/kg in SCD patients by the percentage of participants with any positive status. Immunogenicity is the measurement of anti-drug antibodies (ADA) to crizanlizumab.

Time frame:
Baseline (Week 1), post-baseline (approx. 45 months (median exposure))
Reported as:
Number · Participants
Number of Participants With Immunogenicity (IG) by Any Positive Status
ParticipantsCrizanlizumab 5.0 mg/kgCrizanlizumab 7.5 mg/kgAll Participants
Baseline: Positive000
Post-Baseline: Any Positive000
PrimaryPercentage of P-selectin Inhibition Prior to Each Study Drug Dose of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients

To characterize the PD effect of crizanlizumab in terms of Percentage of P-selectin inhibition prior to study drug dose at 5 mg/kg in CSD patients.

Time frame:
Pre-dose on Day 1 for Weeks 3, 7, 11, 15, 19, 23, 27, 31,35, 39, 43, 47, 51 (at 0 hr or pre-dose)
Reported as:
Mean · percentage of P-selectin inhibition
Percentage of P-selectin Inhibition Prior to Each Study Drug Dose of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients
percentage of P-selectin inhibitionCrizanlizumab 5.0 mg/kg
Week (W) 3 Day (D) 1: 0 hrs pre-dose97.3 ± 7.49
W7D1: 0 hrs pre-dose93.0 ± 17.1
W11D1: 0 hrs pre-dose87.8 ± 22.6
W15D1: 0 hrs pre-dose94.1 ± 12.8
WD19: 0 hrs pre-dose91.7 ± 18.5
W23D1: 0 hrs pre-dose93.2 ± 14.9
W27D1: 0 hrs pre-dose94.3 ± 13.0
W31D1: 0 hrs pre-dose92.4 ± 18.9
W35D1: 0 hrs pre-dose91.7 ± 14.7
W39D1: 0 hrs pre-dose88.5 ± 21.2
W43D1: 0 hrs pre-dose86.1 ± 24.8
W47D1: 0 hrs pre-dose92.1 ± 16.8
W51D1: 0 hrs pre-dose91.5 ± 17.6

Adverse events

Collected over All deaths, Serious Adverse Events, and Other Adverse Events for both 'Treatment phase' and 'Post-treatment follow-up phase' (up to 105 days after the last dose of study treatment) were reported. The median duration of exposure to crizanlizumab was 206.1 weeks in the 5.0 mg/kg dose group and 169.6 weeks in the 7.5 mg/kg dose group.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Crizanlizumab 5.0 mg/kg1/45 (2.2%)22/45 (48.9%)42/45 (93.3%)
Crizanlizumab 7.5 mg/kg1/12 (8.3%)6/12 (50%)11/12 (91.7%)
All Participants2/57 (3.5%)28/57 (49.1%)53/57 (93%)
Most frequent serious events
Showing 10 of 59
Most frequent serious events
EventCrizanlizumab 5.0 mg/kgCrizanlizumab 7.5 mg/kgAll Participants
AnaemiaBlood and lymphatic system disorders0/451/121/57
CytopeniaBlood and lymphatic system disorders0/451/121/57
Cardiac arrestCardiac disorders0/451/121/57
PyrexiaGeneral disorders1/451/122/57
CholelithiasisHepatobiliary disorders0/451/121/57
HypertransaminasaemiaHepatobiliary disorders0/451/121/57
Ischaemic hepatitisHepatobiliary disorders0/451/121/57
Anaphylactic reactionImmune system disorders0/451/121/57
AppendicitisInfections and infestations0/451/121/57
COVID-19Infections and infestations3/451/124/57
Most frequent other events
Showing 10 of 76
Most frequent other events
EventCrizanlizumab 5.0 mg/kgCrizanlizumab 7.5 mg/kgAll Participants
PyrexiaGeneral disorders13/453/1216/57
HypokalaemiaMetabolism and nutrition disorders12/452/1214/57
HeadacheNervous system disorders12/452/1214/57
VomitingGastrointestinal disorders4/453/127/57
Upper respiratory tract infectionInfections and infestations10/452/1212/57
ArthralgiaMusculoskeletal and connective tissue disorders8/452/1210/57
ConstipationGastrointestinal disorders3/452/125/57
DiarrhoeaGastrointestinal disorders4/452/126/57
NauseaGastrointestinal disorders6/452/128/57
Ocular icterusHepatobiliary disorders1/452/123/57

Baseline characteristics

Full Analysis Set (FAS): Consisted of all patients to whom crizanlizumab had been assigned and who received at least 1 dose of study treatment.

Age, Continuous
Age, Continuous(years)Crizanlizumab 5.0 mg/kgCrizanlizumab 7.5 mg/kgTotal
Mean32.3 ± 12.7126.8 ± 12.2531.2 ± 12.71
Age, Customized
Age, Customized(participants)Crizanlizumab 5.0 mg/kgCrizanlizumab 7.5 mg/kgTotal
16 - < 18 years123
18 - < 65 years431053
65 - < 70 years101
Sex: Female, Male
Sex: Female, Male(Participants)Crizanlizumab 5.0 mg/kgCrizanlizumab 7.5 mg/kgTotal
Female25631
Male20626
Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)Crizanlizumab 5.0 mg/kgCrizanlizumab 7.5 mg/kgTotal
Black or African American441256
White and Black or African American101
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Study locations

12 sites
  • Novartis Investigative Site
    Orange, Florida 32763, United States
  • Novartis Investigative Site
    Tampa, Florida 33606, United States
  • Childrens Healthcare of Atlanta .
    Atlanta, Georgia 30342, United States
  • Augusta University Georgia Patient Treatment
    Augusta, Georgia 30912, United States
  • University of Maryland Medical Ctr
    Baltimore, Maryland 21201, United States
  • Childrens Hospital at Montefiore
    Bronx, New York 10467, United States
  • Duke University Medical Center Patient Treatment
    Durham, North Carolina 27710, United States
  • East Carolina University East Carolina University
    Greenville, North Carolina 27858, United States
  • Childrens Hospital Of Philadelphia Patient Treatment
    Philadelphia, Pennsylvania 19104-4399, United States
  • Medical Uni of South Carolina Medical Univ of SC
    Charleston, South Carolina 29425, United States
  • M Francisco Gonzalez MD PA .
    Columbia, South Carolina 29203, United States
  • Carolina Blood and Cancer Care of South Carolina
    Rock Hill, South Carolina 29732, United States
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References and documents

Publications

  • Kanter J, Brown RC, Norris C, Nair SM, Kutlar A, Manwani D, Shah N, Tanaka C, Bodla S, Sanchez-Olle G, Albers U, Liles D. Pharmacokinetics, pharmacodynamics, safety, and efficacy of crizanlizumab in patients with sickle cell disease. Blood Adv. 2023 Mar 28;7(6):943-952. doi: 10.1182/bloodadvances.2022008209. PubMed 36355805 ↗

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: Yes — Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Data sharing details ↗ · www.clinicalstudydatarequest.com

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Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Dec 2017 to primary completion in Jun 2023, 66 months.

Results were first posted in Apr 2024, 9 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
Aug 4, 2017
First posted
Aug 29, 2017
StartActual
Dec 19, 2017
Primary completionActual
Jun 26, 2023
CompletionActual
Jun 26, 2023
Results first posted
Apr 23, 2024
Last update
Oct 9, 2024
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Oct 9, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT03264989
Responsible party
Sponsor
First posted
Aug 29, 2017
Start date
Dec 19, 2017
Primary completion
Jun 26, 2023
Completion
Jun 26, 2023
Results posted
Apr 23, 2024
Last update
Oct 9, 2024

Study contacts

Novartis Pharmaceuticals
study director · Novartis Pharmaceuticals

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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Studies of the drug tested here: Crizanlizumab

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