E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Sickle cell disease (SCD); vaso-occlusive episodes (VOE) in SCD |
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E.1.1.1 | Medical condition in easily understood language |
Sickle cell disease is an inherited red blood cell disorder that affects hemoglobin and leads to painful episodes (also known as vaso-occlusive episodes [VOE]). |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10040644 |
E.1.2 | Term | Sickle cell disease |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10072397 |
E.1.2 | Term | Vaso-occlusive crisis |
E.1.2 | System Organ Class | 100000004851 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To evaluate the safety of crovalimab compared with placebo |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the pharmacokinetics (PK) of crovalimab • To evaluate the pharmacodynamics (PD) of crovalimab • To evaluate the efficacy of crovalimab compared with placebo • To evaluate the immune response to crovalimab
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Signed ICF or Assent Form (as determined by patient’s age and individual site and country standards) • Age >=12 to =<55 years • Body weight >=40 kg • Confirmed diagnosis of HbSS (SCD genotype of sickle cell anemia) or HbSβ0 (SCD genotype of sickle cell beta zero thalassemia) • Vaccination against Neisseria meningitidis • Vaccinations against H. influenzae type B and S. pneumoniae • Diagnosis of an acute uncomplicated VOE, that requires admission to a hospital/acute medical facility and treatment with parenteral opioid analgesics • Adequate hepatic and renal function • Hemoglobin >=5 g/dL • Platelet count >=100,000/µL • Patients receiving sickle cell therapies must be on a stable dose for >=28 days • For female patients of childbearing potential, an agreement to remain abstinent or use contraception for 6 months after the dose of study treatment
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E.4 | Principal exclusion criteria |
• More than 10 VOEs within the last 12 months prior to presentation, that have required a medical facility visit • Pain related to the current VOE ongoing for >48 hours • Acute pain related to avascular necrosis, hepatic or splenic sequestration, or priapism • Pain atypical of an acute uncomplicated VOE • Evidence of or suspicion of ACS • Evidence or high suspicion of a severe systemic infection • Major surgery and/or hospitalization for any reason within 30 days prior to VOE presentation • History of Neisseria meningitidis infection within 6 months prior • Known HIV infection with a documented CD4 count <200 cells/µL • Transfusion or receipt of blood products within 3 months or current participation in a chronic transfusion protocol • Immunized with a live attenuated vaccine within 30 days • History of hematopoietic stem cell transplant • Known or suspected hereditary complement deficiency • Pregnant or breastfeeding, or intending to become pregnant during the study or within 6 months after the study drug administration • 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
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E.5 End points |
E.5.1 | Primary end point(s) |
1. 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) 2. Change from baseline in targeted vital signs and clinical laboratory test results 3. Incidence and severity of infusion-related reactions and hypersensitivity
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Serum concentrations of crovalimab over time 2. Relationships between drug exposure and pharmacodynamics, efficacy or safety endpoints of crovalimab 3. Change over time in PD markers (CH50, free C5, sC5b-9) 4. Time to improvement of the primary acute uncomplicated VOE from baseline 5. Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs during the study
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-3. Baseline to Day 84 4. Baseline to hospital discharge (up to 84 days) 5. Baseline to Day 84
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Brazil |
United States |
France |
Italy |
Spain |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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LPLV or the date at which the last data point is received from the last patient on study, whichever occurs later. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |