Safety, Efficacy, Pharmacokinetic, and Pharmacodynamic Study of ALXN1820 in Adult Participants With Sickle Cell Disease

Sickle Cell Disease (SCD) Clinical Trial

— PHOENIX  

Official title:

A Phase 2a, Randomized, Open-Label Study to Evaluate Multiple Dosing Regimens of Subcutaneous ALXN1820 in Adult Participants With Sickle Cell Disease

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05565092
• Other study ID #: ALXN1820-SCD-201
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 22, 2023
• Est. completion date: June 24, 2024

Study information

• Verified date: October 2023
• Source: Alexion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 30
• Est. completion date: June 24, 2024
• Est. primary completion date: June 24, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Confirmed diagnosis of SCD (HbSS, or HbSß0-thalassemia).

• Body weight = 40 kg (inclusive) at Screening.

• Must follow protocol-specified contraception guidance while on treatment and for up to 6 months after last dose.

• Hemoglobin between 5.5 and 10 g/dL at Screening

• Have had 1 to 10 VOCs in the past 12 months.

• 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.

• 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.

• 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:

• Planned initiation, termination, or dose alteration of hydroxyurea during the study.

• Receiving Voxelotor (OXBRYTA) or crizanlizumab (ADAKVEO) within 60 days of providing informed consent.

• Receiving treatment with recombinant human erythropoetins (eg, epoetin alfa).

• Treated with complement inhibitors within 6 months prior to the first dose.

• Patients who are on chronic transfusion or receive a transfusion within 60 days of first dose.

• Any significant disease or disorder which, in the opinion of the Investigator, may put the participant at risk.

• 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.

• Active systemic bacterial, viral, or fungal infection within 14 days prior to dosing.

• 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.

• 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.

• Severe renal impairment (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m2 ) or on chronic dialysis.

• History of allergy or hypersensitivity to excipients of ALXN1820 (eg, polysorbate 80).

• History of complement deficiency.

• History of N meningitidis, S pneumoniae, or H influenzae infection.

• 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.

• Participants who are pregnant or breastfeeding.

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease (SCD)

Intervention

Drug:
• ALXN1820
ALXN1820 will be administered subcutaneously.

Locations

Country	Name	City	State
France	Clinical Trial Site	La Tronche
France	Clinical Trial Site	Lille
France	Clinical Trial Site	Lyon
France	Clinical Trial Site	Mulhouse
United States	Clinical Trial Site	Atlanta	Georgia
United States	Clinical Trial Site	Aurora	Colorado
United States	Clinical Trial Site	Baltimore	Maryland
United States	Clinical Trial Site	Boston	Massachusetts
United States	Clinical Trial Site	Chapel Hill	North Carolina
United States	Clinical Trial Site	Hollywood	Florida
United States	Clinical Trial Site	Houston	Texas
United States	Clinical Trial Site	Indianapolis	Indiana
United States	Clinical Trial Site	Richmond	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Alexion

Countries where clinical trial is conducted

United States,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Pharmacokinetics (PK): Serum ALXN1820 Concentration		Baseline through Day 211 (Cohorts 1 and 2) and through Day 169 (Optional Cohort 3)
Secondary	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)
Secondary	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)
Secondary	Change From Baseline or Percent Change From Baseline in Complement Biomarkers Through Week 12 (Cohorts 1 and 2)	Changes in complement component Ba (Ba), complement component C3a (C3a), soluble complement component C5B-9 (sC5B9) will be measured by ELISA (capture & detection).	Baseline, Week 12
Secondary	Change From Baseline in Hemoglobin Level at Week 12 (Cohorts 1 and 2)		Baseline, Week 12
Secondary	Change From Baseline or Percent Change From Baseline in Hemolysis Markers at Week 12 (Cohorts 1 and 2)	Hemolysis markers will include lactate dehydrogenase, reticulocytes, and bilirubin.	Baseline, Week 12
Secondary	Change From Baseline in Hemopexin at Week 12 (Cohorts 1 and 2)		Baseline, Week 12
Secondary	Number of Participants With Antidrug Antibodies (ADAs) to ALXN1820		Baseline through Day 211 (Cohorts 1 and 2) and through Day 169 (Optional Cohort 3)