Sickle Cell Disease (SCD)Phase 2NCT03264989

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

A Phase 2 study testing crizanlizumab in people with Sickle Cell Disease (SCD), run by Novartis Pharmaceuticals at 12 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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 more about this study

Who is it for?: Ages 16 to 70 years
Conditions the study is for: Sickle Cell Disease (SCD)
What is being tested?: crizanlizumab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 57 participants
Where: 12 sitesUnited States
Study dates: 19 Dec 2017to 26 Jun 2023
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 16 to 70 years
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Male and non-pregnant female patients 16-70 years of age (inclusive)
Confirmed diagnosis of sickle cell disease by hemoglobin 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. Absolute neutrophil count ≥1.0 x 109/L and platelet count ≥75 x 109/L
Adequate renal and hepatic function as defined:

Show all 11Show fewer

GFR ≥45 mL/min/1.73 m2 calculated by CKD-EPI
ALT ≤3 x ULN
Direct (conjugated) bilirubin ≤2 x ULN
ECOG performance status ≤2
Written informed consent (or assent/ parental consent for minor subjects) prior to any screening procedures

Who cannot join

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 hypersensitivity reactions to other monoclonal antibodies

Show all 10Show fewer

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 investigational 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 immunosuppressive drugs)
Resting QTcF ≥470 msec at pretreatment (baseline) or other cardiac or cardiac repolarization abnormality

Trial locations and contacts

12 sites in 1 country.

City, postcode or hospital

12 sites in 1 country

United States12 sites

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

Other trials in United States

About this study

Official title: A Phase 2, Multicenter, Open-Label Study to Assess PK/PD of SEG101 (Crizanlizumab), With or Without Hydroxyurea/Hydroxycarbamide, in Sickle Cell Patients With Vaso-Occlusive Crisis

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.

Conditions: Sickle Cell Disease (SCD)
Being tested: crizanlizumab
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
Medical subject headings: Anemia, Sickle Cell, Vaso-Occlusive Crises, Hemoglobin SC Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

crizanlizumabDrug
Also called SEG101
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

Study groups in NCT03264989
Study group	Role	What they receive
crizanlizumab	Experimental	SEG101 (crizanlizumab) drug at a dose of 5.0 mg/kg (or 7.5 mg/kg for exploratory group) by IV infusion. Receives: Drug: crizanlizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

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)
Measured: 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
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).
Measured: After the starting dose (Week 1) and after multiple doses (steady state, Week 15)
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.
Measured: Pre-dose at Day 1 on Weeks 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, 47, 51
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.
Measured: 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
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.
Measured: 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 (7)

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).
Measured: Baseline (Week 1) through approx. 45 months (median exposure to treatment)
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).
Measured: Baseline (Week 1) through approx. 45 months (median exposure to treatment)
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).
Measured: Baseine (Week 1) through approx. 45 months (median exposure to treatment)
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).
Measured: Baseline (Week 1) through approx. 45 months (median exposure to treatment)
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).
Measured: Baseline (Week 1) through approx. 45 months (median exposure to treatment)
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).
Measured: Baseline (Week 1) through approx. 45 months (median exposure to treatment)
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.
Measured: Baseline (Week 1), post-baseline (approx. 45 months (median exposure))

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

19 Dec 201726 Jun 2023

First posted29 Aug 2017
Study start19 Dec 2017
Primary completion26 Jun 2023
Study completion26 Jun 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Sickle Cell Disease (SCD)Studies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 57 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03264989
Sponsor's protocol ID: CSEG101A2202
Status last verified: Oct 2024
First submitted: 4 Aug 2017
Last updated: 9 Oct 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: 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

Publications

Kanter J, Mennito S, Nair SM, Manwani D, Kutlar A, Shah N, Keefe D, Madhamshetty H, Nassin M, Reshetnyak E, Mendonza AE, Liles D. Pharmacokinetics, pharmacodynamics, safety, and efficacy of crizanlizumab in patients with sickle cell disease: final results from the phase II SOLACE-adults study. Ther Adv Hematol. 2024 Nov 3;15:20406207241292508. doi: 10.1177/20406207241292508. eCollection 2024.
PubMed 39497751
Sy SKB, Tanaka C, Grosch K. Population Pharmacokinetics and Pharmacodynamics of Crizanlizumab in Healthy Subjects and Patients with Sickle Cell Disease. Clin Pharmacokinet. 2023 Feb;62(2):249-266. doi: 10.1007/s40262-022-01193-4. Epub 2022 Dec 18.
PubMed 36529836
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

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingPhase 1/2
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Long-term Mitapivat Dosing in Subjects With Stable Sickle Cell Disease: An Extension of a Phase I Pilot Study of Mitapivat
Sickle Cell Disease, Hemolytic Anemia
RecruitingObservational study
HPC Offered for PRESERVE Expansion
Bone Marrow Transplant (BMT)
RecruitingPhase 1
Study to Evaluate the Safety and Tolerability of Escalating Doses of Fostamatinib in Subjects With Stable Sickle Cell Disease
Sickle Cell Disorders, Sickle Cell Disease
RecruitingPhase 4
Clinical and Biomarker Effects of Depot Medroxyprogesterone Acetate in Females With Sickle Cell Disease
Sickle Cell Disease (SCD), Vaso-Occlusive Pain Episode in Sickle Cell Disease
Not yet recruitingPhase 1
Buprenorphine for the Management of Pain in Children With Sickle Cell Disease
Sickle Cell Disease (SCD), Sickle Cell Disease Vaso-occlusive Crisis

All Sickle Cell Disease (SCD) trials

Study at a glance

From the registry record, last updated by the sponsor on 9 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2, Multicenter, Open-Label Study to Assess PK/PD of SEG101 (Crizanlizumab), With or Without Hydroxyurea/Hydroxycarbamide, in Sickle Cell Patients With Vaso-Occlusive Crisis
ClinicalTrials.gov ID: NCT03264989
Acronym / sponsor ID: CSEG101A2202
Conditions: Sickle Cell Disease (SCD)
Keywords: Sickle cell disease, SCD, sickle cell anemia, vaso-occlusive crisis, P-selectin, SEG101, crizanlizumab, monoclonal antibody
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 57 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 19 Dec 2017 (actual)
Primary completion: 26 Jun 2023 (actual)
Study completion: 26 Jun 2023 (actual)
First posted: 29 Aug 2017 (actual)
Results: Posted 23 Apr 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
crizanlizumab	Experimental	Drug: crizanlizumabSEG101 (crizanlizumab) drug at a dose of 5.0 mg/kg (or 7.5 mg/kg for exploratory group) by IV infusion.

Who may qualify

Ages: 16 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (11 listed)

Male and non-pregnant female patients 16-70 years of age (inclusive)
Confirmed diagnosis of sickle cell disease by hemoglobin 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. Absolute neutrophil count ≥1.0 x 109/L and platelet count ≥75 x 109/L

Key exclusion criteria (10 listed)

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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
crizanlizumabAlso: SEG101Crizanlizumab 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	Drug	crizanlizumab

Primary outcome

Pharmacokinetic (PK): AUCd15 and AUCtau of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients
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
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)
PK: Cmax of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients
Time frame: After the starting dose (Week 1) and after multiple doses (steady state, Week 15)
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).
Pre-dose Concentrations Prior to Each Study Drug Dose
Time frame: Pre-dose at Day 1 on Weeks 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, 47, 51
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.
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
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
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.
Percentage of P-selectin Inhibition Prior to Each Study Drug Dose of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) 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)
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.

7 secondary outcomes

Annualized Rate of Vaso-occlusive Crisis (VOC) Events Leading to Healthcare Visit in Clinic/Emergency Room (ER)/Hospital
Time frame: Baseline (Week 1) through approx. 45 months (median exposure to treatment)
Annualized Rate of VOC Events Treated at Home (Based on Documentation by Health Care Provider Following Phone Contact With Patient)
Time frame: Baseline (Week 1) through approx. 45 months (median exposure to treatment)
Annualized Rate of Total and VOC-related Hospitalizations and Emergency Room (ER) Visits
Time frame: Baseine (Week 1) through approx. 45 months (median exposure to treatment)
Annualized Days of Total and VOC-related Hospitalizations and Emergency Room (ER) Visits
Time frame: Baseline (Week 1) through approx. 45 months (median exposure to treatment)
Annualized Rate of Each Subcategory of All VOC Events (Acute Chest Syndrome (ACS), Priapism, Uncomplicated Sickle Cell-vaso-occlusive Cisis (Uncomplicated SC-VOCs))
Time frame: Baseline (Week 1) through approx. 45 months (median exposure to treatment)
Annualized Rate of VOC Events (Including Both Healthcare Visit and Home Treatment)
Time frame: Baseline (Week 1) through approx. 45 months (median exposure to treatment)
Number of Participants With Immunogenicity (IG) by Any Positive Status
Time frame: Baseline (Week 1), post-baseline (approx. 45 months (median exposure))

Results and safety

Results posted to the registry on 23 Apr 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Crizanlizumab 5.0 mg/kg	45	0
Crizanlizumab 7.5 mg/kg	12	0

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

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. Mean (Standard Deviation). Unit: hr*μg/mL

Measure	Crizanlizumab 5.0 mg/kg n = 45
Starting dose (Week 1): AUCd15	13100 (2810)
Steady State (Week 15): AUCtau	20800 (5030)

Population analysed: The PK analysis set 1 (PAS1) included all patients who provided at least one evaluable PK profile in the 5.0 mg/kg arm.

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

Time frame: After the starting dose (Week 1) and after multiple doses (steady state, Week 15). Mean (Standard Deviation). Unit: μg/mL

Measure	Crizanlizumab 5.0 mg/kg n = 45
Starting dose (Week 1)	102 (29.8)
Steady State (Week 15)	123 (36.4)

Population analysed: The PK analysis set 1 (PAS1) included all patients who provided at least one evaluable PK profile in the 5.0 mg/kg arm. The Cmax analysis was done on all participants including those for at starting dose (n =42) and steady state (n = 36).

Primary outcome: Pre-dose Concentrations Prior to Each Study Drug Dose

Time frame: Pre-dose at Day 1 on Weeks 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, 47, 51. Mean (Standard Deviation). Unit: μg/mL

Measure	Crizanlizumab 5.0 mg/kg n = 45
Week (W) 3 Day 1 (D)1: 0 hrs pre-dose	18.0 (6.42)
W7 D1: 0 hrs pre-dose	10.8 (5.21)
W11 D1: 0 hrs pre-dose	9.04 (5.04)
W15 D1: 0 hrs pre-dose	10.0 (5.39)
W19 D1: 0 hrs pre-dose	9.37 (4.95)
W23 D1: 0 hrs pre-dose	9.91 (5.09)
W27 D1: 0 hrs pre-dose	9.65 (4.03)
W31 D1: 0 hrs pre-dose	9.75 (4.66)

Population analysed: PK Analysis set 2 (PAS2): Included all patients who received at least one planned treatment of 5 mg/kg and provided at least one corresponding evaluable PK concentration.

Primary outcome: 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

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. Mean (Standard Deviation). Unit: hours*% of P-selectin inhibition

Measure	Crizanlizumab 5.0 mg/kg n = 43
Starting dose (Week 1): PD-AUCd15	33200 (1830)
Steady state (Week 15): PD-AUCd29	66900 (5540)

Population analysed: PDS1 included all patients who provided at least 1 evaluable PD profile. The P-selectin inhibition analysis was done on all participants including those starting dose (n = 36) and steady state (n = 33).

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: 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.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Crizanlizumab 5.0 mg/kg	22 of 45 (48.9%)	42 of 45 (93.3%)	1 of 45
Crizanlizumab 7.5 mg/kg	6 of 12 (50%)	11 of 12 (91.7%)	1 of 12
All Participants	28 of 57 (49.1%)	53 of 57 (93%)	2 of 57

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 39497751Kanter J, Mennito S, Nair SM, Manwani D, Kutlar A, Shah N, Keefe D, Madhamshetty H, Nassin M, Reshetnyak E, Mendonza AE, Liles D. Pharmacokinetics, pharmacodynamics, safety, and efficacy of crizanlizumab in patients with sickle cell disease: final results from the phase II SOLACE-adults study. Ther Adv Hematol. 2024 Nov 3;15:20406207241292508. doi: 10.1177/20406207241292508. eCollection 2024.
Derived from this study: PubMed 36529836Sy SKB, Tanaka C, Grosch K. Population Pharmacokinetics and Pharmacodynamics of Crizanlizumab in Healthy Subjects and Patients with Sickle Cell Disease. Clin Pharmacokinet. 2023 Feb;62(2):249-266. doi: 10.1007/s40262-022-01193-4. Epub 2022 Dec 18.
Derived from this study: PubMed 36355805Kanter 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.
A Plain Language Trial Summary is available on www.novctrd.comLink provided by the sponsor.
Individual participant dataSharing planned: 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

Related trials for Sickle Cell Disease (SCD)

Active, not recruitingPhase 1/2
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Long-term Mitapivat Dosing in Subjects With Stable Sickle Cell Disease: An Extension of a Phase I Pilot Study of Mitapivat
Sickle Cell Disease, Hemolytic Anemia
RecruitingObservational study
HPC Offered for PRESERVE Expansion
Bone Marrow Transplant (BMT)
RecruitingPhase 1
Study to Evaluate the Safety and Tolerability of Escalating Doses of Fostamatinib in Subjects With Stable Sickle Cell Disease
Sickle Cell Disorders, Sickle Cell Disease
RecruitingPhase 4
Clinical and Biomarker Effects of Depot Medroxyprogesterone Acetate in Females With Sickle Cell Disease
Sickle Cell Disease (SCD), Vaso-Occlusive Pain Episode in Sickle Cell Disease
Not yet recruitingPhase 1
Buprenorphine for the Management of Pain in Children With Sickle Cell Disease
Sickle Cell Disease (SCD), Sickle Cell Disease Vaso-occlusive Crisis

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Novartis Pharmaceuticals study director

Novartis Pharmaceuticals

12 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing crizanlizumab in people with Sickle Cell Disease (SCD), run by Novartis Pharmaceuticals at 12 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pharmacokinetic (PK): AUCd15 and AUCtau of Crizanlizumab at 5.0 mg/kg in Sickle Cell Disease (SCD) Patients (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). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03264989, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2024.