Crizanlizumab for Sickle Cell Disease

Recruiting at 34 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

Trial Summary

What is the purpose of this trial?

This is a multi-center multi-national rollover study to allow continued access to crizanlizumab for patients with sickle cell disease (SCD) who are on crizanlizumab treatment in a Novartis-sponsored study (parent study) and are benefiting from the treatment as judged by the investigator.

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 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 has been studied for safety in patients with sickle cell disease, showing similar rates of adverse events (unwanted effects) compared to a placebo. Common side effects include infusion-related reactions, joint pain, diarrhea, and nausea, but no serious treatment-related adverse events were reported. ^{1 2 4 5 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

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 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, 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]

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, 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]

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. Canada pubmed.ncbi.nlm.nih.gov

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

2. 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]

3. 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]

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

Crizanlizumab: First Approval. [2020]

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

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

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

Clinical activity of ponatinib in one patient with chronic myeloid leukemia in chronic phase with e19a2 transcript and T315I mutation. [2015]

9. England pubmed.ncbi.nlm.nih.gov

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

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]