Crizanlizumab for Sickle Cell Disease

(SPARKLE Trial)

Recruiting in Palo Alto (17 mi)

+7 other locations

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Novartis Pharmaceuticals

Disqualifiers: Stroke, Intracranial hemorrhage, Transfusion, others

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

A phase III, multi-center, randomized, placebo-controlled, double-blind study to assess efficacy and safety of crizanlizumab (5 mg/kg) versus placebo, with or without hydroxyurea/hydroxycarbamide therapy, in adolescent and adult Sickle Cell Disease patients with frequent vaso-occlusive crises.

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.

What data supports the effectiveness of the drug crizanlizumab for sickle cell disease?

Crizanlizumab has been shown to reduce the frequency of painful episodes in sickle cell disease by 45.3% compared to a placebo in a clinical trial. It is approved for use in patients aged 16 and older to help prevent these painful crises. ^{1 2 3 4 5}

Is crizanlizumab safe for humans?

Crizanlizumab, used for sickle cell disease, has been generally safe in studies, with common side effects including infusion reactions, joint pain, diarrhea, and nausea. Serious side effects were rare, and no treatment-related serious adverse events were reported. ^{1 2 3 4 6}

What makes the drug Crizanlizumab unique for treating Sickle Cell Disease?

Crizanlizumab is unique because it targets P-selectin, a protein that plays a key role in the inflammation and blockage of blood vessels in Sickle Cell Disease, helping to reduce pain crises. This mechanism is different from other treatments that primarily focus on managing symptoms or increasing fetal hemoglobin levels. ^{7 8 9 10 11}

Research Team

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Crizanlizumab (Monoclonal Antibodies)

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.

Participant Groups

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.

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

Findings from Research

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]

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]

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 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]

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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Crizanlizumab: First Approval. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Crizanlizumab for the Prevention of Vaso-Occlusive Pain Crises in Sickle Cell Disease. [2022]

3. Canada pubmed.ncbi.nlm.nih.gov

Real-World Data of Crizanlizumab in Sickle Cell Disease: A Single-Center Analysis. [2023]

4. United States 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. [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

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

6. United States pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics, safety, and efficacy of crizanlizumab in patients with sickle cell disease. [2023]

7. Finland pubmed.ncbi.nlm.nih.gov

[Current therapy of chronic myeloid leukemia]. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Intolerance to tyrosine kinase inhibitors in chronic myeloid leukemia: the possible role of ponatinib. [2019]

9. England 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. [2015]

10. United States pubmed.ncbi.nlm.nih.gov

Is imatinib still an acceptable first-line treatment for CML in chronic phase? [2017]

11. United States pubmed.ncbi.nlm.nih.gov

Dasatinib Approved for Pediatric CML. [2019]