Crizanlizumab for Sickle Cell Disease

(SPARKLE Trial)

Recruiting at 18 trial locations

Overseen By Novartis Pharmaceuticals

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Disqualifiers: Stroke, Intracranial hemorrhage, Transfusion, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 52 weeks

315 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called crizanlizumab to determine its effectiveness in helping people with Sickle Cell Disease (SCD) who frequently experience painful events known as vaso-occlusive crises (VOCs). The researchers aim to assess whether crizanlizumab can safely reduce the frequency of these crises compared to a placebo (a substance with no active medication). They seek participants who have experienced 4 to 12 VOCs in the past year that required medical care. This study might suit someone with SCD who regularly faces these painful episodes and is either currently on or not using hydroxyurea (a standard SCD treatment). As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for SCD.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on hydroxyurea/hydroxycarbamide or an erythropoietin stimulating agent, you must have been on a stable dose for at least 3 months and plan to continue it during the study.

Is there any evidence suggesting that crizanlizumab is likely to be safe for humans?

Research has shown that crizanlizumab is generally well-tolerated by people with sickle cell disease. Studies have found that a dose of 5.0 mg/kg is safe and doesn't cause significant problems for most users.

In one study, patients taking crizanlizumab experienced fewer pain crises compared to those who received a placebo, suggesting it might help reduce pain without major side effects. Another study with young patients, aged 12 to under 18, confirmed that this dose was safe over two years.

Overall, research indicates that crizanlizumab is a tolerable treatment option for sickle cell disease. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Sickle Cell Disease?

Crizanlizumab is unique because it targets P-selectin, a molecule that plays a key role in the clumping of red blood cells seen in sickle cell disease. This is different from most standard treatments like hydroxyurea, which works by increasing fetal hemoglobin levels. Researchers are excited about Crizanlizumab because it may reduce the frequency of painful crises in patients with sickle cell disease, potentially offering a new avenue for relief that directly addresses the underlying mechanisms of the disease.

What evidence suggests that crizanlizumab might be an effective treatment for Sickle Cell Disease?

Research has shown that crizanlizumab, which participants in this trial may receive, can help reduce pain crises in people with sickle cell disease. One study found that crizanlizumab lowered the number of painful blockages in blood flow and hospital visits by 45% and 41%, respectively. Another study demonstrated that crizanlizumab significantly reduced sickle cell-related pain crises compared to a placebo. However, results are mixed, as another study did not show a significant improvement in reducing pain crises. Overall, the treatment has shown promise in reducing pain episodes for some patients with sickle cell disease. ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adolescents and adults aged 12 years and older with confirmed Sickle Cell Disease (SCD). They must have experienced 4 to 12 vaso-occlusive crises (VOCs) in the past year. If they're on hydroxyurea/hydroxycarbamide, it should be a stable dose for at least 3 months before the study.

Inclusion Criteria

I am 12 years old or older.

I have been diagnosed with sickle cell disease through a blood test.

I've had 4 to 12 severe pain crises managed by a doctor in the last year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Crizanlizumab 5 mg/kg or placebo, with or without hydroxyurea/hydroxycarbamide therapy, for the management of vaso-occlusive crises

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for long-term safety and efficacy outcomes, including adverse events and immunogenicity

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Crizanlizumab

Trial Overview The SPARKLE study is testing Crizanlizumab (5 mg/kg) against a placebo to see if it's effective and safe in reducing VOCs in SCD patients. This includes those taking hydroxyurea/hydroxycarbamide, with participants randomly assigned to either group.

How Is the Trial Designed?

Group I: Crizanlizumab (SEG101) at 5.0 mg/kg Experimental Treatment 1 Intervention

Participants receive Crizanlizumab (SEG101) at 5.0 mg/kg and standard of care.

Group II: Placebo Placebo Group 1 Intervention

Participants receive the placebo drug and standard of care.

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

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 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]

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]

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 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 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]

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]

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]

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]

Citations

1. 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. sciencedirect.com sciencedirect.com/science/article/pii/S0268960X25000438

Review Evidence and gaps in clinical outcomes of novel ... In the SUSTAIN study, a 5-mg/kg dose of crizanlizumab reduced the occurrence of vaso-occlusive crises (VOCs) and hospitalizations by 45 % and 41 %, respectively ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1611770

Crizanlizumab for the Prevention of Pain Crises in Sickle ... In patients with sickle cell disease, crizanlizumab therapy resulted in a significantly lower rate of sickle cell–related pain crises than placebo.

5. 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.

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. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/180/530345/Pharmacokinetics-Pharmacodynamics-Safety-and

Pharmacokinetics/Pharmacodynamics, Safety, and Efficacy of ... The initial data from the 2-year analysis of 50 patients with SCD aged 12 to <18 years showed that crizanlizumab 5.0 mg/kg was safe and well ...