Safety, Efficacy, Pharmacokinetic, and Pharmacodynamic Study of ALXN1820 in Adult Participants With Sickle Cell Disease
Study Details
Study Description
Brief Summary
The primary objective of this study is to assess the safety and tolerability of ALXN1820 SC (subcutaneous) in participants with SCD (Sickle Cell Disease).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ALXN1820 300 mg once weekly Participants will receive 300 milligrams (mg) once weekly (QW). |
Drug: ALXN1820
ALXN1820 will be administered subcutaneously.
|
| Experimental: ALXN1820 600 mg once every 4 weeks Participants will receive 600 mg once every 4 weeks (Q4W). |
Drug: ALXN1820
ALXN1820 will be administered subcutaneously.
|
| Experimental: ALXN1820 300 mg once every 2 weeks (Optional cohort) Participants will receive 300 mg once every 2 weeks (Q2W). |
Drug: ALXN1820
ALXN1820 will be administered subcutaneously.
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [Baseline through Day 211 (Cohorts 1 and 2) and through Day 169 (Optional Cohort 3)]
Secondary Outcome Measures
- Pharmacokinetics (PK): Serum ALXN1820 Concentration [Baseline through Day 211 (Cohorts 1 and 2) and through Day 169 (Optional Cohort 3)]
- Change From Baseline in Serum Concentration of Total and Free Properdin Through Day 211 (Cohorts 1 and 2) and Day 169 (Optional Cohort 3) [Baseline through Day 211 (Cohorts 1 and 2) and Day 169 (Optional Cohort 3)]
- Change From Baseline Complement Alternative Pathway (CAP) Activity Through Day 211 (Cohorts 1 and 2) and Day 169 (Optional Cohort 3) [Baseline through Day 211 (Cohorts 1 and 2) and Day 169 (Optional Cohort 3)]
- Change From Baseline or Percent Change From Baseline in Complement Biomarkers Through Week 12 (Cohorts 1 and 2) [Baseline, Week 12]
Changes in complement component Ba (Ba), complement component C3a (C3a), soluble complement component C5B-9 (sC5B9) will be measured by ELISA (capture & detection).
- Change From Baseline in Hemoglobin Level at Week 12 (Cohorts 1 and 2) [Baseline, Week 12]
- Change From Baseline or Percent Change From Baseline in Hemolysis Markers at Week 12 (Cohorts 1 and 2) [Baseline, Week 12]
Hemolysis markers will include lactate dehydrogenase, reticulocytes, and bilirubin.
- Change From Baseline in Hemopexin at Week 12 (Cohorts 1 and 2) [Baseline, Week 12]
- Number of Participants With Antidrug Antibodies (ADAs) to ALXN1820 [Baseline through Day 211 (Cohorts 1 and 2) and through Day 169 (Optional Cohort 3)]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Confirmed diagnosis of SCD (HbSS, or HbSβ0-thalassemia).
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Body weight ≥ 40 kg (inclusive) at Screening.
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Must follow protocol-specified contraception guidance while on treatment and for up to 6 months after last dose.
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Hemoglobin between 5.5 and 10 g/dL at Screening
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Have had 1 to 10 VOCs in the past 12 months.
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Patients receiving hydroxyurea must have been on a stable dose for ≥ 3 months prior to providing informed consent, with no anticipated need for dose adjustment during the study.
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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.
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Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae vaccination are up to date according to current national/local vaccination guidelines for patients with SCD.
Exclusion Criteria:
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Planned initiation, termination, or dose alteration of hydroxyurea during the study.
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Receiving Voxelotor (OXBRYTA) or crizanlizumab (ADAKVEO) within 60 days of providing informed consent.
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Receiving treatment with recombinant human erythropoetins (eg, epoetin alfa).
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Treated with complement inhibitors within 6 months prior to the first dose.
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Patients who are on chronic transfusion or receive a transfusion within 60 days of first dose.
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Any significant disease or disorder which, in the opinion of the Investigator, may put the participant at risk.
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Hepatitis B (positive hepatitis surface antigen [HBsAg] or positive core antibody (anti-HBc) with negative surface antibody [anti-HBs]) or hepatitis C viral infection (hepatitis C virus [HCV] antibody positive, except for patients with documented successful treatment and documented sustained virologic response) at Screening.
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Active systemic bacterial, viral, or fungal infection within 14 days prior to dosing.
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Participation (ie, last protocol-required study visit) in a clinical study within 90 days or 5 half-lives of the investigational agent, whichever is longer, before initiation of dosing on Day 1.
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Participation in more than 1 clinical study of a monoclonal antibody (mAb), or participation in a clinical study of a mAb within the 6 months or 5 half-lives of the mAb, whichever is longer, prior to Screening, during which the participant was exposed to the active study drug.
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Severe renal impairment (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m2 ) or on chronic dialysis.
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History of allergy or hypersensitivity to excipients of ALXN1820 (eg, polysorbate 80).
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History of complement deficiency.
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History of N meningitidis, S pneumoniae, or H influenzae infection.
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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.
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Participants who are pregnant or breastfeeding.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Alexion Pharmaceuticals
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ALXN1820-SCD-201