Clinical trial NCT05565092: Safety, Efficacy, Pharmacokinetic, and Pharmacodynamic Study of ALXN1820 in Adult Participants With Sickle Cell Disease
Official title: A Phase 2a, Randomized, Open-Label Study to Evaluate Multiple Dosing Regimens of Subcutaneous ALXN1820 in Adult Participants With Sickle Cell Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Sickle Cell Disease (SCD)
Keywords: Sickle Cell Disease
ALXN1820
SCD
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2022-10-04
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

* Confirmed diagnosis of SCD (HbSS, or HbSβ0-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.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events
timeFrame: Baseline through Day 211 (Cohorts 1 and 2) and through Day 169 (Optional Cohort 3)
Secondary outcomes:
measure: Pharmacokinetics: Serum ALXN1820 Concentration
timeFrame: Baseline through Day 211 (Cohorts 1 and 2) and through Day 169 (Optional Cohort 3)
measure: Change From Baseline in Serum Concentration of Total and Free Properdin Through Day 211 (Cohorts 1 and 2) and Day 169 (Optional Cohort 3)
timeFrame: Baseline through Day 211 (Cohorts 1 and 2) and Day 169 (Optional Cohort 3)
measure: Change From Baseline Complement Alternative Pathway Activity Through Day 211 (Cohorts 1 and 2) and Day 169 (Optional Cohort 3)
timeFrame: Baseline through Day 211 (Cohorts 1 and 2) and Day 169 (Optional Cohort 3)
measure: Change From Baseline in Complement Biomarkers Through Week 12 (Cohorts 1 and 2)
timeFrame: Baseline, Week 12
measure: Change From Baseline in Hemoglobin Level at Week 12 (Cohorts 1 and 2)
timeFrame: Baseline, Week 12
measure: Change From Baseline in Hemolysis Markers at Week 12 (Cohorts 1 and 2)
timeFrame: Baseline, Week 12
measure: Change From Baseline in Hemopexin at Week 12 (Cohorts 1 and 2)
timeFrame: Baseline, Week 12
measure: Number of Participants With Antidrug Antibodies to ALXN1820
timeFrame: Baseline through Day 211 (Cohorts 1 and 2) and through Day 169 (Optional Cohort 3)
Other outcomes:
Locations:
city: Hollywood
country: United States
facility: Research Site
state: Florida
city: Indianapolis
country: United States
facility: Research Site
state: Indiana
Study officials:
References: