Crovalimab for Sickle Cell Disease

(CROSSWALK-a Trial)

Recruiting at 33 trial locations

Overseen By Reference Study ID Number: BO42452 https://forpatients.roche.com/

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Hoffmann-La Roche

Disqualifiers: Frequent VOEs, Severe infection, HIV, others

Compensation: Varies

Number of Visits: 1

Duration: 1 day

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing crovalimab, a medication, to see if it can help treat severe pain crises in people with sickle cell disease. The study focuses on adults and adolescents who need hospital care for their pain. Researchers will check how the body handles crovalimab and its effects to ensure it is safe and effective.

Do I need to stop my current medications to join the trial?

The protocol does not specify if you need to stop your current medications. However, if you are on SCD-directed therapies, you must be on a stable dose for at least 28 days before joining the trial.

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 sickle cell disease-directed therapies, you must be on a stable dose for at least 28 days before joining the trial.

What data supports the idea that Crovalimab for Sickle Cell Disease is an effective drug?

The available research does not provide any data on Crovalimab for Sickle Cell Disease. The articles focus on other treatments for different conditions, such as chronic lymphocytic leukemia and hematologic malignancies, but do not mention Crovalimab or its effectiveness for Sickle Cell Disease. ^{1 2 3 4 5}

What safety data is available for Crovalimab in treating Sickle Cell Disease?

The provided research does not contain specific safety data for Crovalimab in the treatment of Sickle Cell Disease. The studies mentioned focus on other treatments such as hydroxyurea, L-glutamine, voxelotor, crizanlizumab, and adalimumab for different conditions. Therefore, no relevant safety data for Crovalimab is available in the given research. ^{6 7 8 9 10}

Is the drug Crovalimab a promising treatment for Sickle Cell Disease?

The information provided does not mention Crovalimab specifically, but it highlights Crizanlizumab as a promising drug for Sickle Cell Disease. Crizanlizumab helps reduce the frequency of painful episodes in patients, making it a valuable option for managing the disease. ^{11 12 13 14 15}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults and teens with Sickle Cell Disease who weigh at least 40 kg, have had certain vaccinations, stable sickle cell therapies if any, good liver/kidney function, and not pregnant. They must be hospitalized for a pain crisis but can't join if they've had recent surgeries, severe infections, many pain crises in the past year or are on other experimental treatments.

Inclusion Criteria

My liver and kidneys are working well.

I have been on a stable dose of my sickle cell treatment for at least 28 days.

I am hospitalized for a painful sickle cell crisis needing strong pain medication.

Exclusion Criteria

I've had over 10 pain crises needing hospital visits in the last year.

My pain from the current episode has lasted more than 48 hours.

I have had a stem cell transplant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intravenous (IV) infusion of Crovalimab or placebo based on body weight

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety, pharmacokinetics, pharmacodynamics, and efficacy after treatment

12 weeks

Multiple visits (in-person and/or virtual)

Treatment Details

Interventions

• Crovalimab
• Placebo

Trial Overview The study tests Crovalimab against a placebo to manage acute uncomplicated Vaso-Occlusive Episodes (VOE) requiring hospital care in Sickle Cell Disease patients. It focuses on safety while also checking how the body processes and responds to Crovalimab and its initial effectiveness.

Participant Groups

Group I: Crovalimab Experimental Treatment 1 Intervention

Participants will receive a single intravenous (IV) infusion of Crovalimab based on body weight.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive a single IV infusion of matching Placebo.

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Findings from Research

In a phase 2 study of 342 untreated patients with non-del(11q) chronic lymphocytic leukemia (CLL), the combination of fludarabine plus lenalidomide (FR+L) and fludarabine plus cyclophosphamide (FCR) showed significantly better 2-year progression-free survival (PFS) rates (72% and 74%, respectively) compared to the historical control rate of 60%.

The study found that FR+L and FCR not only improved PFS but also demonstrated longer median overall survival (OS), with FCR achieving a median OS of 101 months, suggesting that incorporating lenalidomide into treatment regimens could enhance outcomes for CLL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide consolidation benefits patients with CLL receiving chemoimmunotherapy: results for CALGB 10404 (Alliance). Byrd, JC., Ruppert, AS., Heerema, NA., et al.[2020]

Monoclonal antibodies like rituximab, alemtuzumab, and gemtuzumab ozogamicin are effective treatments for various blood cancers, including malignant lymphoma and different types of leukemia, showcasing their role in modern cancer therapy.

New targeted therapies such as dasatinib and nilotinib are being used for chronic myelogenous leukemia patients who become resistant to imatinib, while drugs like thalidomide and bortezomib are proving effective in treating multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Novel medical treatment modalities in hematology]. Hasselbalch, HC., Birgens, H., Dufva, IH., et al.[2022]

In 2016, significant advancements in hematologic cancer treatment were made with the approval of venetoclax, a first-in-class B-cell lymphoma 2 inhibitor, and nivolumab, the first immune checkpoint inhibitor for hematologic malignancies, enhancing patient management options.

The approval of defibrotide for veno-occlusive disease and expanded uses for anti-CD20 and anti-CD38 monoclonal antibodies indicate a growing arsenal of targeted therapies, each with specific mechanisms of action and clinical contexts for use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel and Expanded Oncology Drug Approvals of 2016-PART 2: New Options in the Management of Hematologic Malignancies. Knepper, TC., Saller, J., Walko, CM.[2018]

Ofatumumab is an effective treatment option for patients with relapsed or refractory chronic lymphocytic leukemia (CLL) who have not responded to previous therapies like fludarabine and alemtuzumab, demonstrating activity against rituximab-resistant CLL cell lines.

The review highlights that front-line chemoimmunotherapy has improved overall survival rates in CLL compared to traditional chemotherapy, showcasing advancements in treatment strategies over the past decade.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The emerging role of ofatumumab in the treatment of chronic lymphocytic leukemia. Nabhan, C., Kay, NE.[2021]

Anti-CD20 antibodies, such as rituximab, ofatumumab, and obinutuzumab, have significantly improved response rates and survival in patients with chronic lymphocytic leukemia when added to chemotherapy regimens.

Newer anti-CD20 antibodies like ocaratuzumab, veltuzumab, and ublituximab are currently being tested in clinical trials, potentially expanding treatment options and allowing for combinations with novel small molecule agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dancing partners at the ball: Rational selection of next generation anti-CD20 antibodies for combination therapy of chronic lymphocytic leukemia in the novel agents era. Butler, LA., Tam, CS., Seymour, JF.[2018]

In a study of 27 children with Crohn disease who had previously failed infliximab treatment, adalimumab (ADA) was found to be effective in 70% of the patients after a median follow-up of 16 months.

ADA treatment was associated with a significant decrease in inflammatory markers (C-reactive protein and orosomucoid) without serious adverse effects, indicating it is a safe option for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of adalimumab after infliximab failure in pediatric Crohn disease. Fumery, M., Jacob, A., Sarter, H., et al.[2022]

In a real-world study comparing new sickle cell disease treatments (L-glutamine, voxelotor, crizanlizumab) to hydroxyurea, the rates of adverse events (AEs) were found to be lower than those reported in clinical trials, indicating a potentially safer profile for these new agents.

The study revealed that the types of AEs varied by treatment, emphasizing the importance of effective communication between patients and physicians to better understand and manage patient-reported symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative pharmacovigilance assessment of adverse events associated with the use of hydroxyurea, L-glutamine, voxelotor, and crizanlizumab in sickle cell disease. Chen, M., Hankins, JS., Zhang, M., et al.[2023]

In a study of 117 Crohn's disease patients who previously failed anti-TNF therapy, those on a high-dose adalimumab regimen (40 mg weekly or 80 mg every other week) experienced a significantly longer time to treatment failure (6.6 years) compared to those on a standard-dose regimen (40 mg every other week), which had a median time to failure of 3.0 years.

The high-dose regimen also demonstrated a lower hazard rate of treatment failure (hazard ratio: 0.27), indicating it is more effective, while safety profiles were similar between high-dose and standard-dose groups, with no significant difference in adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of higher adalimumab maintenance therapy versus standard dose in anti-tumor necrosis factor experienced Crohn's disease patients: A propensity-score matched cohort analysis. Narula, N., Wong, ECL., AlRamdan, R., et al.[2022]

The review highlights that while treatments for Crohn's disease and ulcerative colitis, such as azathioprine, mercaptopurine, methotrexate, and biologic therapies, can be effective, they are associated with a range of adverse events, including serious complications like infections and malignancies.

It emphasizes the importance of gastroenterologists communicating the risks and benefits of these therapies to patients, and provides strategies for discussing when it may be appropriate to modify or discontinue treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in IBD: to stop or continue immune suppressant and biologic treatment. McLean, LP., Cross, RK.[2023]

In a study of 118 patients with Crohn's disease treated with adalimumab, 81.3% achieved a clinical response (complete or partial) within one year, demonstrating its effectiveness in real-world clinical practice.

Adalimumab was generally well tolerated, but 54% of patients experienced adverse events, with 11% facing serious adverse events, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab for Crohn's disease in clinical practice at Mayo clinic: the first 118 patients. Swoger, JM., Loftus, EV., Tremaine, WJ., et al.[2018]

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 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]

Current therapies for sickle cell anemia, such as hydroxyurea, work by increasing fetal hemoglobin (Hb F) levels, which helps reduce the harmful effects of sickle hemoglobin (Hb S) polymerization.

Emerging treatments are being explored that target various mechanisms, including increasing cell volume to lower Hb S concentration, inhibiting adhesion molecules to prevent vaso-occlusion, and promoting vasodilation through nitric oxide and antioxidants, potentially leading to improved patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Promising therapies in sickle cell disease. Raghupathy, R., Billett, HH.[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]

References

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

Lenalidomide consolidation benefits patients with CLL receiving chemoimmunotherapy: results for CALGB 10404 (Alliance). [2020]

2. Denmark pubmed.ncbi.nlm.nih.gov

[Novel medical treatment modalities in hematology]. [2022]

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

Novel and Expanded Oncology Drug Approvals of 2016-PART 2: New Options in the Management of Hematologic Malignancies. [2018]

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

The emerging role of ofatumumab in the treatment of chronic lymphocytic leukemia. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Dancing partners at the ball: Rational selection of next generation anti-CD20 antibodies for combination therapy of chronic lymphocytic leukemia in the novel agents era. [2018]

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

Efficacy and safety of adalimumab after infliximab failure in pediatric Crohn disease. [2022]

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

Comparative pharmacovigilance assessment of adverse events associated with the use of hydroxyurea, L-glutamine, voxelotor, and crizanlizumab in sickle cell disease. [2023]

8. Australia pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of higher adalimumab maintenance therapy versus standard dose in anti-tumor necrosis factor experienced Crohn's disease patients: A propensity-score matched cohort analysis. [2022]

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

Adverse events in IBD: to stop or continue immune suppressant and biologic treatment. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Adalimumab for Crohn's disease in clinical practice at Mayo clinic: the first 118 patients. [2018]

11. 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]

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

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

13. Canada pubmed.ncbi.nlm.nih.gov

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

14. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Promising therapies in sickle cell disease. [2019]

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

Crizanlizumab: First Approval. [2020]