A study evaluating the safety, pharmacokinetics, pharmacodynamics, and efficacy of crovalimab for the management of acute uncomplicated vaso-occlusive episodes in participants with sickle cell disease
- Conditions
- Sickle cell disease (SCD)vaso-occlusive episodes in SCDPain crisisvaso-occlusive episodes (VOE) in SCDHaematological Disorders
- Registration Number
- ISRCTN89975936
- Lead Sponsor
- F.Hoffmann-La Roche Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 30
Current inclusion criteria as of 09/02/2023:
1. Age >=12 to =<55 years
2. Body weight >=40 kg
3. Confirmed diagnosis of HbSS (SCD genotype of sickle cell anemia) or HbSß0 (SCD genotype of sickle cell beta zero thalassemia)
4. Vaccination against Neisseria meningitidis
5. Vaccinations against H. influenzae type B and S. pneumoniae
6. Participants vaccinated against SARS-CoV-2 are eligible, as long as it has been 3 days or more after inoculation with the vaccine.
7. Diagnosis of an acute uncomplicated VOE, that requires admission to a hospital/acute medical facility and treatment with parenteral opioid analgesics
8. Adequate hepatic and renal function
9. Hemoglobin >=5 grams/deciliter (g/dL)
10. Platelet count >=100,000/microliter (µL)
11. Participants receiving sickle cell therapies must be on a stable dose for >=28 days
12. For female patients of childbearing potential, an agreement to remain abstinent or use contraception for 6 months after the dose of study treatment
_____
Previous inclusion criteria:
1. Signed ICF or Assent Form (as determined by patient’s age and individual site and country standards)
2. Age >=12 to =<55 years
3. Body weight >=40 kg
4. Confirmed diagnosis of HbSS (SCD genotype of sickle cell anemia) or HbSß0 (SCD genotype of sickle cell beta zero thalassemia)
5. Vaccination against Neisseria meningitidis
6. Vaccinations against H. influenzae type B and S. pneumoniae
7. Diagnosis of an acute uncomplicated VOE, that requires admission to a hospital/acute medical facility and treatment with parenteral opioid analgesics
8. Adequate hepatic and renal function
9. Hemoglobin >=5 g/dL
10. Platelet count >=100,000/µL
11. Patients receiving sickle cell therapies must be on a stable dose for >=28 days
12. For female patients of childbearing potential, an agreement to remain abstinent or use contraception for 6 months after the dose of study treatment
Current exclusion criteria as of 09/02/2023:
1. More than 10 VOEs within the last 12 months prior to presentation, that have required a medical facility visit
2. Pain related to the current VOE ongoing for >48 hours
3. Acute pain related to avascular necrosis, hepatic or splenic sequestration, or priapism
4. Pain atypical of an acute uncomplicated VOE
5. Evidence of or suspicion of ACS
6. Evidence or high suspicion of a severe systemic infection
7. Major surgery and/or hospitalization for any reason within 30 days
8. History of Neisseria meningitidis infection within 6 months prior
9. Known HIV infection with a documented CD4 count <200 cells/µL
10. Transfusion or receipt of blood products within 3 months or current participation in a chronic transfusion protocol
11. Immunized with a live attenuated vaccine within 30 days
12. History of hematopoietic stem cell transplant
13. Known or suspected hereditary complement deficiency
14. Pregnant or breastfeeding, or intending to become pregnant during the study or within 322 days (approximately 10.5 months) after the study drug administration.
15. Participation in another interventional treatment study with an investigational agent or use of any experimental therapy within the prior 28 days or within five half-lives of that investigational product, whichever was greater
_____
Previous exclusion criteria:
1. More than 10 VOEs within the last 12 months prior to presentation, that have required a medical facility visit
2. Pain related to the current VOE ongoing for >48 hours
3. Acute pain related to avascular necrosis, hepatic or splenic sequestration, or priapism
4. Pain atypical of an acute uncomplicated VOE
5. Evidence of or suspicion of ACS
6. Evidence or high suspicion of a severe systemic infection
7. Major surgery and/or hospitalization for any reason within 30 days
8. History of Neisseria meningitidis infection within 6 months prior
9. Known HIV infection with a documented CD4 count <200 cells/µL
10. Transfusion or receipt of blood products within 3 months or current participation in a chronic transfusion protocol
11. Immunized with a live attenuated vaccine within 30 days
12. History of hematopoietic stem cell transplant
13. Known or suspected hereditary complement deficiency
14. Pregnant or breastfeeding, or intending to become pregnant during the study or within 6 months after the study drug administration
15. Participation in another interventional treatment study with an investigational agent or use of any experimental therapy within the prior 28 days or within five half-lives of that investigational product, whichever was greater
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Current primary outcome measure as of 09/02/2023: <br><br>1. Percentage of participants with adverse events (AEs), measured from Baseline up to Day 322<br>2. Percentage of participants with infusion-related reactions and hypersensitivity, measured from Baseline up to Day 84<br><br>_____<br><br>Previous primary outcome measure:<br><br>Incidence and severity of adverse events, with severity determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.0 (CTCAE v5.0) measured at Screening visit 2, during study treatment, within 30 mins post-infusion, 12 hours post-infusion, day 2 - day 14, day of discharge, post-discharge day 28, day 46, day 64, and day 84
- Secondary Outcome Measures
Name Time Method