Crizanlizumab for Sickle Cell Disease

Recruiting at 38 trial locations

Overseen By Novartis Pharmaceuticals

Age: Any Age

Sex: Any

Trial Phase: Phase 4

Sponsor: Novartis Pharmaceuticals

Must be taking: Crizanlizumab

Disqualifiers: Pregnancy, Grade 3 AEs, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 10 years or until treatment becomes commercially available

130 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial focuses on continuing access to crizanlizumab, a treatment for sickle cell disease (SCD). The goal is to ensure that individuals already benefiting from crizanlizumab in a previous Novartis-sponsored study can continue receiving it. Participants must have completed the earlier study and be benefiting from the treatment, as determined by their doctor. This trial is for those who have adhered to their visit schedules and are prepared to continue with their treatment plan. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, providing an opportunity to continue benefiting from it.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial investigator to understand how your current medications might interact with the study treatment.

What is the safety track record for crizanlizumab?

Research has shown that crizanlizumab is generally well-tolerated by people with sickle cell disease. In earlier studies, crizanlizumab effectively blocked P-selectin, a molecule involved in inflammation, which helped reduce pain crises. The safety of crizanlizumab, especially at the recommended dose of 5.0 mg/kg monthly, suggests it is safe to use. Most patients did not experience severe side effects.

In another study, people taking a higher dose of crizanlizumab had significantly fewer pain crises compared to those taking a placebo. This suggests that the treatment helps manage sickle cell disease with a manageable safety profile. Overall, extensive research has shown crizanlizumab to be safe. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Crizanlizumab is unique because it targets P-selectin, a key molecule involved in the obstruction of blood flow in sickle cell disease. Unlike other treatments that focus primarily on managing symptoms and pain, crizanlizumab works by preventing the underlying cause of vaso-occlusive crises, which can lead to severe pain episodes. Researchers are excited about crizanlizumab because it offers a new way to reduce these painful events and potentially improve the quality of life for patients with sickle cell disease.

What is the effectiveness track record for crizanlizumab in treating sickle cell disease?

Research has shown that crizanlizumab effectively treats sickle cell disease by blocking a protein called P-selectin, which helps cells stick together. This action may prevent blockages in blood vessels. One study found that patients taking crizanlizumab experienced fewer painful blockages, known as vaso-occlusive crises, compared to those taking a placebo. Specifically, patients on crizanlizumab averaged 1.63 crises per year, while those on a placebo averaged 2.98. The FDA has approved crizanlizumab for managing sickle cell disease, supporting its effectiveness. Overall, evidence suggests crizanlizumab can help reduce painful episodes for people with sickle cell disease. ^{1 6 7 8 9}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for patients with Sickle Cell Disease who are already participating in a Novartis-sponsored Crizanlizumab study and have seen benefits. They must have completed the previous study's treatment schedule, shown commitment to visit schedules, and be willing to continue visits. Pregnant or nursing women, those not using effective contraception, or anyone with unresolved severe side effects from prior treatments cannot join.

Inclusion Criteria

I am in a Novartis study for SCD, benefiting from crizanlizumab, and have met all study requirements.

I (or my guardian if I'm under 18) have signed the consent form.

Patient has demonstrated compliance to the planned visit schedule in the parent study, and in the opinion of the investigator has shown willingness and ability to comply with future visit schedules

Exclusion Criteria

Pregnant or nursing women

Concurrent participation in any other investigational clinical trial other than the parent study or plan to participate in any other investigational clinical trial

I have SCD and cannot continue with crizanlizumab as per the main study.

Timeline for a Trial Participant

Treatment

Participants continue receiving Crizanlizumab treatment at the same dose/schedule as in the parent study

10 years or until treatment becomes commercially available

Safety Follow-up

A safety follow-up visit is conducted 105 days after the last administration of study treatment

105 days

Long-term Follow-up

Participants are monitored for continued access to Crizanlizumab until it becomes commercially available or no longer needed

Up to 10 years

What Are the Treatments Tested in This Trial?

Interventions

• Crizanlizumab

Trial Overview

The trial provides continued access to Crizanlizumab for individuals with Sickle Cell Disease who benefited from earlier trials. It's designed as a rollover study where participants receive ongoing Crizanlizumab therapy under the supervision of investigators at multiple centers internationally.

How Is the Trial Designed?

Group I: Crizanlizumab Experimental Treatment 1 Intervention

All participants will receive crizanlizumab (SEG101) at the same dose/schedule as in the parent study.

Crizanlizumab is already approved in United States for the following indications:

Approved in United States as Adakveo for:

• Prevention of recurrent vaso-occlusive crises in sickle cell disease patients aged 16 years and older

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

Crizanlizumab effectively reduces the frequency of vaso-occlusive crises (VOCs) in patients with sickle cell disease, showing a significant reduction in the annualized rate of VOCs after more than 12 months of treatment, with a median reduction of -0.88 and -0.93 for the 5.0 mg/kg and 7.5 mg/kg doses, respectively.

The treatment demonstrated a favorable safety profile, with only one treatment-related adverse event reported and no serious treatment-related adverse events, indicating that crizanlizumab can be safely administered over long periods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics, safety, and efficacy of crizanlizumab in patients with sickle cell disease. Kanter, J., Brown, RC., Norris, C., et al.[2023]

Dasatinib has been approved by the FDA as a treatment for pediatric chronic myeloid leukemia, providing a new therapeutic option for young patients.

As the second tyrosine kinase inhibitor approved for this condition, dasatinib can be used in both first- and second-line treatment, expanding the choices available for managing this type of leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dasatinib Approved for Pediatric CML. [2019]

Crizanlizumab is the first monoclonal antibody approved for sickle cell disease, specifically designed to reduce the frequency of vaso-occlusive pain crises, based on data from a phase 2 clinical trial.

This medication is administered as a monthly intravenous infusion for patients aged 16 and older, showing efficacy in crisis prevention, although concerns about cost and long-term safety remain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crizanlizumab for the Prevention of Vaso-Occlusive Pain Crises in Sickle Cell Disease. Stevens, DL., Hix, M., Gildon, BL.[2022]

Crizanlizumab may help reduce acute care visits for patients with sickle cell disease, especially among those who frequently use hospital services, with a significant decrease from an average of 40 visits to 16 after starting treatment.

Despite its potential benefits, the study found a high discontinuation rate, with only five out of fifteen patients remaining on crizanlizumab six months after starting, indicating a need for further research into the reasons for discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Data of Crizanlizumab in Sickle Cell Disease: A Single-Center Analysis. Cheplowitz, H., Block, S., Groesbeck, J., et al.[2023]

Crizanlizumab, a monoclonal antibody targeting P-selectin, received conditional marketing authorization in the EU for preventing recurrent vaso-occlusive crises in sickle cell disease patients aged 16 and older, showing a 45.3% reduction in annual pain crises at a high dose compared to placebo.

The treatment was found to have a similar safety profile to placebo, with common side effects including infusion-related reactions and arthralgia, indicating that crizanlizumab is both effective and relatively safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European Medicines Agency Review of Crizanlizumab for the Prevention of Recurrent Vaso-Occlusive Crises in Patients With Sickle Cell Disease. Delgado, J., Voltz, C., Stain, M., et al.[2021]

Imatinib, the first tyrosine-kinase inhibitor (TKI) for chronic myeloid leukemia (CML), has significantly improved patient outcomes since its introduction 10 years ago.

Second generation TKIs like dasatinib and nilotinib are more effective and better tolerated than imatinib, suggesting they may soon become the standard first-line treatment for CML, with a future goal of achieving curative therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current therapy of chronic myeloid leukemia]. Koskela, H., Koskenvesa, P., Mustjoki, S., et al.[2022]

Imatinib, a first-line treatment for chronic myeloid leukemia (CML), often leads to intolerance in patients, prompting the need for second- and third-generation tyrosine kinase inhibitors (TKIs) like ponatinib, which is effective against all BCR-ABL1 mutants, including those resistant to other TKIs.

There is a lack of consistent definitions of intolerance across clinical trials, which complicates the assessment of adverse events and their impact on patient quality of life, highlighting the need for better evaluation methods and consideration of ponatinib for patients who cannot tolerate other TKIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intolerance to tyrosine kinase inhibitors in chronic myeloid leukemia: the possible role of ponatinib. Breccia, M., Efficace, F., Iurlo, A., et al.[2019]

Crizanlizumab, a new treatment for sickle cell disease (SCD), has shown promise in reducing the annual rates of vaso-occlusive crises (VOC) with a favorable safety profile, marking a significant advancement in therapy options beyond hydroxyurea.

While hydroxyurea has been effective in decreasing VOC and hospitalizations, adherence to this treatment can be challenging due to side effects; crizanlizumab offers a new approach that may improve patient compliance and outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profile of crizanlizumab and its potential in the prevention of pain crises in sickle cell disease: evidence to date. Riley, TR., Riley, TT.[2020]

Crizanlizumab is a monoclonal antibody that effectively reduces the frequency of vaso-occlusive crises (VOCs) in patients with sickle cell disease by blocking P-selectin, which is crucial for cell adhesion and inflammation.

Approved in the USA in November 2019 for adults and pediatric patients aged 16 and older, crizanlizumab is also under review in the EU and being studied for use in myelofibrosis, indicating its potential versatility in treating blood-related conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crizanlizumab: First Approval. Blair, HA.[2020]

A patient with chronic myeloid leukemia (CML) carrying the T315I mutation, which is resistant to other treatments, showed a complete response to ponatinib therapy, with the mutation burden dropping to undetectable levels.

Before treatment with ponatinib, the patient had a high level of BCR-ABL1 transcripts (18%), but after therapy, this level significantly decreased to just 0.011%, indicating the drug's efficacy in overcoming resistance to previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical activity of ponatinib in one patient with chronic myeloid leukemia in chronic phase with e19a2 transcript and T315I mutation. Ferri, CA., Bianchini, M., Bengió, RM., et al.[2015]

Imatinib (Gleevec) has significantly improved survival rates for patients with chronic myeloid leukemia in chronic phase (CML-CP), transforming a previously poor prognosis into one comparable to that of healthy individuals of similar age.

While newer TKIs like nilotinib (Tasigna) and dasatinib (Sprycel) offer faster responses and are effective for patients who cannot tolerate or are resistant to imatinib, they have not demonstrated a survival advantage over long-term imatinib treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is imatinib still an acceptable first-line treatment for CML in chronic phase? Goldman, JM., Marin, D.[2017]

Citations

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11533247/

final results from the phase II SOLACE-adults study

In conclusion, crizanlizumab at both doses reached levels of exposure that caused sustained inhibition of P-selectin, had tolerable safety, and ...

2.

thelancet.com

thelancet.com/journals/lanhae/article/PIIS2352-3026(24)00384-3/abstract

Crizanlizumab with or without hydroxyurea in patients ...

Crizanlizumab 5·0 mg/kg exhibits a favorable safety profile in patients with sickle cell disease: pooled data from two phase II studies

3.

hematologyadvisor.com

hematologyadvisor.com/news/sickle-cell-disease-scd-crizanlizumab-stand-trial-efficacy-benefit/

No Efficacy Benefit With Crizanlizumab in the STAND Trial ...

The primary analysis of the phase 3 STAND trial showed no significant improvement in the rate of vaso-occlusive crisis or associated health care visits.

4.

fda.gov

fda.gov/drugs/resources-information-approved-drugs/fda-approves-crizanlizumab-tmca-sickle-cell-disease

FDA approves crizanlizumab-tmca for sickle cell disease

Patients receiving crizanlizumab-tmca, 5 mg/kg, had a lower median annual rate of VOC compared to those receiving placebo (1.63 vs. 2.98, p= ...

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01895361

NCT01895361 | Study to Assess Safety and Impact of ...

By stopping these cell-cell interactions, SelG1 may prevent small blood vessels from becoming blocked and therefore reduce the occurrence and severity of pain ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01895361

NCT01895361 | Study to Assess Safety and Impact of ...

Pharmacokinetics, pharmacodynamics, safety, and efficacy of crizanlizumab in patients with sickle cell disease. Blood Adv. 2023 Mar 28;7(6):943-952. doi ...

7.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40088922/

Crizanlizumab with or without hydroxyurea in patients ...

The STAND study aimed to evaluate the efficacy and safety of two doses (5·0 mg/kg and 7·5 mg/kg) of crizanlizumab in sickle cell disease. Herein, we report the ...

8.

ashpublications.org

ashpublications.org/blood/article/142/Supplement%201/1139/505806/Safety-Profile-of-Crizanlizumab-5-0-Mg-Kg-in

Safety Profile of Crizanlizumab 5.0 Mg/Kg in Sickle Cell Disease

This pooled analysis assesses the safety of the recommended dosage of crizanlizumab (5.0 mg/kg monthly) in treated patients. Methods: Safety was ...

9.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa1611770

Crizanlizumab for the Prevention of Pain Crises in Sickle ...

The annual crisis rate was 32.1% lower with high-dose crizanlizumab than with placebo among patients receiving hydroxyurea and 50.0% lower among ...