Crizanlizumab for Sickle Cell Disease

(STAND Trial)

Recruiting at 67 trial locations

Overseen By Novartis Pharmaceuticals

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must be taking: Hydroxyurea, L-glutamine, Erythropoietin

Must not be taking: Selectin agents

Disqualifiers: Stem cell transplant, Chronic transfusion, ECG abnormalities, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 year

259 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to compare the efficacy and safety of 2 doses of crizanlizumab (5.0 mg/kg and 7.5 mg/kg) versus placebo in adolescent and adult sickle cell disease (SCD) patients with history of vaso-occlusive crisis (VOC) leading to healthcare visit.

Will I have to stop taking my current medications?

The trial requires that if you are taking hydroxyurea (HU/HC), L-glutamine, or an erythropoietin stimulating agent, you must have been on a stable dose for at least 3 months before the trial and plan to continue it during the study. If you are not taking these medications, you must not have taken them for at least 6 months before joining the trial.

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

Crizanlizumab has been shown to reduce the frequency of painful episodes called vaso-occlusive crises in people with sickle cell disease. Studies, including a phase 2 trial and real-world data, indicate that patients experienced fewer hospital visits for pain and needed less pain medication after receiving Crizanlizumab. ^{1 2 3 4 5}

Is crizanlizumab safe for humans?

Crizanlizumab has been studied for sickle cell disease and is generally considered safe, with common side effects including infusion-related reactions, joint pain, diarrhea, and nausea. Long-term safety data is still being gathered, but current studies show similar rates of serious side effects compared to a placebo. ^{1 2 4 5 6}

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

Crizanlizumab is unique for treating Sickle Cell Disease because it works by targeting P-selectin, a protein that plays a key role in the inflammation and blockage of blood vessels, which are common issues in this condition. This mechanism of action is different from other treatments that primarily focus on managing pain or increasing red blood cell production. ^{7 8 9 10 11}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

Adolescents and adults aged 12 years and older with sickle cell disease who have had at least two vaso-occlusive crises (VOC) leading to healthcare visits in the past year. Participants must meet specific health criteria, including certain blood counts and organ function levels, but cannot be part of a chronic transfusion program or have had a stem cell transplant.

Inclusion Criteria

I have had a pain crisis needing a doctor's visit and pain medication, with no other cause than a blockage in my blood vessels.

I've been on a stable dose of HU/HC or L-glutamine for 6 months, with at least one pain crisis despite treatment.

I have been diagnosed with Sickle Cell Disease through a blood test.

Exclusion Criteria

I have been treated with crizanlizumab or a similar medication.

My family has a history of long QT syndrome or Torsades de Pointes.

History or current diagnosis of ECG abnormalities indicating significant risk of safety such as:

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 5 mg/kg or 7.5 mg/kg of crizanlizumab or placebo, with or without hydroxyurea/hydroxycarbamide therapy

1 year

Multiple visits for dosing and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term Follow-up

Participants are monitored for long-term outcomes such as VOC rates and safety over 5 years

5 years

Treatment Details

Interventions

• Crizanlizumab
• Placebo

Trial Overview The trial is testing the effectiveness and safety of two different doses of Crizanlizumab (5.0 mg/kg and 7.5 mg/kg) compared to a placebo in reducing VOCs for those with sickle cell disease. Patients are randomly assigned to receive either one of the drug doses or a placebo.

Participant Groups

Group I: Crizanlizumab (SEG101) at 7.5 mg/kg Experimental Treatment 1 Intervention

Participants received Crizanlizumab (SEG101) at 7.5 mg/kg

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

Participants received Crizanlizumab (SEG101) at 5.0 mg/kg

Group III: Placebo Placebo Group 1 Intervention

Participants received the placebo drug.

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 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 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, 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, 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]

Subcutaneous risankizumab, a selective anti-IL-23 antibody, has been shown to be an effective maintenance therapy for patients with moderately to severely active Crohn's disease, achieving higher rates of clinical remission and endoscopic response compared to placebo in a study involving 542 participants.

The treatment was well tolerated, with adverse event rates similar across all groups, indicating that risankizumab could be a safe new option for patients who need ongoing management of their condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risankizumab as maintenance therapy for moderately to severely active Crohn's disease: results from the multicentre, randomised, double-blind, placebo-controlled, withdrawal phase 3 FORTIFY maintenance trial. Ferrante, M., Panaccione, R., Baert, F., et al.[2022]

A systematic review of 28 studies found that infliximab and adalimumab were more effective than certolizumab pegol and tofacitinib for inducing and maintaining remission in Crohn's disease, highlighting their superior efficacy.

CT-P13 (a biosimilar of infliximab) was shown to be more effective than several biological agents and JAK1 inhibitors for both inducing remission and maintaining steroid-free remission, suggesting it should be recommended for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review and Network Meta-Analysis: Comparative Efficacy and Safety of Biosimilars, Biologics and JAK1 Inhibitors for Active Crohn Disease. Wu, G., Yang, Y., Liu, M., et al.[2021]

Certolizumab pegol is effective in treating moderate-to-severe Crohn's disease and rheumatoid arthritis, outperforming placebo in maintaining clinical response in patients who did not respond adequately to conventional therapies.

Patients must be screened for tuberculosis and vaccinated against live infections before starting treatment, as the drug can increase the risk of serious infections, and it should not be used alongside anakinra due to heightened infection risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Certolizumab pegol for the treatment of Crohn's disease. Baker, DE.[2010]

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

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

3. England pubmed.ncbi.nlm.nih.gov

EXPRESS: Real-World Experience of Patients with Sickle Cell Disease Treated with Crizanlizumab. [2023]

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

Crizanlizumab: First Approval. [2020]

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

The European Medicines Agency Review of Crizanlizumab for the Prevention of Recurrent Vaso-Occlusive Crises in Patients With Sickle Cell Disease. [2021]

7. England pubmed.ncbi.nlm.nih.gov

A Phase 2b, Randomised, Double-blind, Placebo-controlled, Parallel-arm, Multicenter Study Evaluating the Safety and Efficacy of Tesnatilimab in Patients with Moderately to Severely Active Crohn's Disease. [2023]

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

A randomised placebo-controlled multicentre trial of intravenous semapimod HCl for moderate to severe Crohn's disease. [2012]

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

Risankizumab as maintenance therapy for moderately to severely active Crohn's disease: results from the multicentre, randomised, double-blind, placebo-controlled, withdrawal phase 3 FORTIFY maintenance trial. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Systematic Review and Network Meta-Analysis: Comparative Efficacy and Safety of Biosimilars, Biologics and JAK1 Inhibitors for Active Crohn Disease. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Certolizumab pegol for the treatment of Crohn's disease. [2010]