E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Sickle Cell Disease (HbSS and HBSß thalassemia). |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the safety and tolerability of ALXN1820 Subcutanaous (SC) in patients with Sickle Cells Disease (SCD) |
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E.2.2 | Secondary objectives of the trial |
- To assess the multiple-dose PK of ALXN1820 SC - To assess the PD effects of ALXN1820 SC - To assess the effect of ALXN1820 on complement biomarkers - To assess the effect of ALXN1820 on hemolysis - To assess the immunogenicity of ALXN1820 SC
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Participant must be 18 to 65 years of age inclusive, at the time of signing the informed consent 2.Confirmed diagnosis of SCD (HbSS, or HbSβ0-thalassemia) 3.Body weight greater than 40 kg (inclusive) at Screening. 4.Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Female participants of childbearing potential and male participants with female partners of childbearing potential must be willing to follow protocol-specified contraception guidance while on treatment and for at least 6 months after last dose of study drug Other : 5.Hemoglobin between 5.5 and 10 g/dL at Screening. 6.Have had 1 to 10 VOCs in the past 12 months. 7.Patients receiving hydroxyurea must have been on a stable dose for ≥ 3months prior to providing informed consent, with no anticipated need for dose adjustment during the study. For patients who previously used hydroxyurea but are not currently on hydroxyurea, treatment (due to non-responsiveness, intolerance, or unwillingness to take hydroxyurea), hydroxyurea treatment have been discontinued at least 30 days prior to providing informed consent. 8.Patients will be vaccinated with MCV4 and serogroup B meningococcal vaccinations at least 14 days before dosing, if not already vaccinated within 3 years before the first dose (or per national/local guidelines). Participants who initiate study intervention treatment less than 14 days after receiving a meningococcal vaccine must receive treatment with appropriate prophylactic antibiotics until at least 2 weeks after vaccination. 9.Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae vaccination are up to date according to current national/local vaccination guidelines for patients with sickle cell disease. 10.Must be willing to abide by all study requirements and restrictions.
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E.4 | Principal exclusion criteria |
1.Planned initiation, termination, or dose alteration of hydroxyurea during the study. 2.Receiving Voxelotor (OXBRYTA) or crizanlizumab (ADAKVEO) within 60 days of providing informed consent. 3.Receiving treatment with recombinant human erythropoetins (eg, epoetin alfa). 4.Treated with complement inhibitors within 6 months prior to the first dose. 5.Patients who are on chronic transfusion or receive a transfusion within 60 days of first dose. 6.Any significant disease or disorder which, in the opinion of the Investigator, may put the participant at risk. 7.History of complement deficiency 8.History of N.meningitidis, S.pneumoniae, or H influenzae infection. 9.History of malignancy with the exception of a nonmelanoma skin cancer or carcinoma in situ of the cervix that has been treated with no evidence of recurrence within 5 years. 10.Evidence of hepatitis B (positive hepatitis surface antigen [HBsAg] or positive core antibody (anti-HBc) with negative surface antibody [anti-HBs]) or hepatitis C viral infection (HCV antibody positive, except for patients with documented successful treatment and documented sustained virologic response [SVR]) at Screening. 11.Active systemic bacterial, viral, or fungal infection within 14 days prior to dosing. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety assessed by incidence of TEAEs and SAEs, physical examination, vital sign measurements, clinical laboratory, and electrocardiogram results |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
through Day 211 (Cohorts 1 and 2) and through Day 169 (Optional Cohort 3) |
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E.5.2 | Secondary end point(s) |
- Serum ALXN1820 multiple-dose PK profiles - Change in serum concentrations of total and free properdin over time - Change in CAP activity using the Wieslab AP assay - Change from baseline in complement biomarkers - Change from baseline in hemoglobin levels - Change from baseline in hemolysis markers - Incidence of ADAs to ALXN1820 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
through Day 211 (Cohorts 1 and 2) and through Day 169 (Optional Cohort 3)
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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 | Yes |
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 | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | No |
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 |
Canada |
India |
United States |
France |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |