E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Sickle Cell Disease (SCD); vaso-occlusive episodes 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 efficacy of crovalimab compared with placebo |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the efficacy of crovalimab compared with placebo - To evaluate the safety and tolerability of crovalimab compared with placebo - To evaluate the pharmacokinetics of crovalimab - 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 - Male or female with confirmed diagnosis of HbSS (SCD genotype of sickle cell anemia) or HbSβ0 (SCD genotype of sickle cell beta zero thalassemia) - Two or more (>=2) to <=10 documented VOEs in the 12 months prior to randomization - If receiving concurrent SCD-directed therapy, the patient must have been on a stable dose for a minimum of 3 months prior to study enrollment. There should be no plans to modify the patients’ dosing throughout the study duration, other than for safety reasons. - If receiving erythropoietin, the patient must have been prescribed this medication for the preceding 3 months and be dose-stabilized for at least 3 months prior to study enrollment - Vaccination against N. meningitides serotypes A, C, W and Y - Vaccinations against H. influenza type B and S. pneumonia - Patients who have been vaccinated (partially or in full) against SARS-CoV-2 with a locally approved vaccine are eligible to be enrolled in the study, 3 days or longer after inoculation - Adequate hepatic and renal function - For women of childbearing potential, agreement to remain abstinent or use contraception during the treatment period and for 46 weeks (approximately 10.5 months) after the final dose of study treatment
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E.4 | Principal exclusion criteria |
- History of hematopoietic stem cell transplant - Participating in a chronic transfusion program and/or planning on undergoing an exchange transfusion during the duration of the study - History of hypersensitivity, allergic, or anaphylactic reactions to any ingredient contained in the study treatment - Received active treatment on another investigational trial within 28 days (or within five half-lives of that agent, whichever is greater) prior to screening visit, or plans to participate in another investigational drug trial - Hemoglobin <6 g/dL - Known or suspected hereditary complement deficiency - Active systemic bacterial, viral, or fungal infection within 14 days before first drug administration - Presence of fever (>=38 degrees Celsius) within 7 days before the first drug administration - Immunized with a live attenuated vaccine within 1 month before first drug administration - Pregnant or breastfeeding, or intending to become pregnant during the study or within 46 weeks (approximately 10.5 months) after the final dose of study treatment - Known HIV infection with documented CD4 count <200 cells/microliter within 24 weeks prior to screening - History of N. meningitidis infection within the prior 6 months
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Annualized rate of medical facility VOEs (AVR) |
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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. Annualized rate of home VOE captured by patient report 2. Annualized rate of uncomplicated medical facility VOE 3. Annualized rate of acute chest syndrome (ACS) 4. Annualized rate of days hospitalized for medical facility VOE 5. Annualized rate of days hospitalized for treatment of non-VOE complications of SCD 6. Change in hematologic measures from baseline to Week 49 7. Time to first medical facility VOE from randomization 8. Change in urinary albumin-creatinine ratio from baseline to Week 49 9. Change from baseline to Week 49 in tricuspid regurgitant jet velocity (TRV) 10. Proportion of patients with TRV >2.5 m/s at Week 49 11. Change from baseline to Week 49 in Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue score in adults
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-9. Baseline to Week 49 10. At Week 49 11. Baseline to Week 49
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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) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
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 |
France |
Netherlands |
Spain |
Italy |
Turkey |
United Kingdom |
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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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The end of this study is defined as the date when the last patient, last visit, occurs, which is defined as completion of 48 weeks of the study treatment, followed by the end of safety follow-up period of 24 weeks. In addition, the study treatment may be discontinued, the patient may discontinue from the study, or the Sponsor may decide to terminate the study or discontinue a site at any time. |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |