Study of ALXN1820 in Healthy Adult Participants

Phase 1

Completed

Conditions: Healthy

Interventions: Drug: ALXN1820 SC
Drug: Placebo SC
Drug: ALXN1820 IV
Drug: Placebo IV

Registration Number: NCT04631562

Lead Sponsor: Alexion Pharmaceuticals, Inc.

Brief Summary: This is a Phase 1, randomized, double-blind, placebo-controlled single and multiple ascending dose study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of ALXN1820 administered subcutaneously (SC) (ALXN1820 SC) and intravenously (IV) (ALXN1820 IV).

Detailed Description: This study will include up to 10 different dosing cohorts, with each cohort consisting of 2 groups (ALXN1820 group, placebo group). Participants will be randomly assigned in a 3:1 ratio to each of these 2 groups, respectively, within all 10 cohorts, to receive either a single or multiple doses of ALXN1820 SC, a single dose of ALXN1820 IV, or a single or multiple doses of placebo.

The study will be conducted in healthy adult participants and will also include a multiple SC dose cohort in healthy participants of Japanese descent.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 66

Inclusion Criteria

Body weight 50 to 100 kilograms (kg); body mass index 17 to 32 kg/meter squared.
Cohort 9 only: Japanese participants (defined as those participants whose parents and grandparents are both Japanese and who have spent less than 5 years outside of Japan).
Satisfactory medical assessment.
Must follow protocol-specified contraception guidance while on treatment and for up to 6 months after last dose.
Vaccination requirement:
- Vaccination with tetravalent meningococcal conjugate vaccine at least 56 days and not more than 2 years, 6 months prior to dosing;
- Vaccination with serogroup B meningococcal vaccine at least 56 days prior to dosing, with a booster at least 28 days prior to dosing, with at least 28 days between the first and second injections.

Exclusion Criteria

Current/recurrent diseases or relevant medical history.
History of any Neisseria infection.
Hepatitis B/C, human immunodeficiency virus.
History of latent or active tuberculosis (TB), or positive TB test.
Active systemic infection within 14 days of dosing.
Risk of meningococcal infections due to living/working conditions.
History of complement deficiency or complement activity below the reference range.
Participation 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.
Acquired complement deficiencies (for example, those receiving eculizumab).

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
ALXN1820	ALXN1820 SC	Participants will receive ALXN1820 SC or ALXN1820 IV according to their assigned cohort. ALXN1820 SC will be evaluated in single and multiple ascending doses while ALXN1820 IV will be evaluated in a single dose cohort only.
ALXN1820	ALXN1820 IV	Participants will receive ALXN1820 SC or ALXN1820 IV according to their assigned cohort. ALXN1820 SC will be evaluated in single and multiple ascending doses while ALXN1820 IV will be evaluated in a single dose cohort only.
Placebo	Placebo SC	Participants will receive Placebo SC or Placebo IV according to their assigned cohort.
Placebo	Placebo IV	Participants will receive Placebo SC or Placebo IV according to their assigned cohort.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-related Adverse Events (TEAEs) For ALXN1820 SC And ALXN1820 IV	Cohorts 1 to 6: Baseline up to Day 127; Cohorts 8 to 9: Baseline up to Day 155	An adverse event (AE) was defined as any unfavorable and unintended sign (for example, including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or procedure, whether or not considered related to the medicinal product or procedure, which occurred during the course of the clinical study. TEAEs were defined as any AEs that commenced after the start of administration of study intervention. Serious AEs (SAEs) were defined as any untoward medical occurrence that met at least 1 of the following serious criteria: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, other medically important serious event. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Reported AEs' Section.

Secondary Outcome Measures

Name	Time	Method
Area Under The Concentration-time Curve (AUC) From Time 0 (Dosing) To Time Infinity (AUC0-inf) And AUC During The Dosing Interval (AUCtau) of Serum ALXN1820 For Single Dose Cohorts	Up to 126 days following the first day of dosing
Area Under The Concentration-time Curve During The Dosing Interval (AUCtau) Of Serum ALXN1820 For Multiple Dose Cohorts	Up to 154 days following the first day of dosing
Maximum Observed Serum Concentration (Cmax) Of Serum ALXN1820 For Single Dose Cohorts	Up to 126 days following the first day of dosing
Maximum Observed Serum Concentration (Cmax) Of Serum ALXN1820 For Multiple Dose Cohorts	Up to 154 days following the first day of dosing
Change From Baseline in Serum Concentrations Of Total Properdin For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts	Baseline, Day 127
Change From Baseline in Serum Concentrations Of Free Properdin For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts	Baseline, Day 127
Change From Baseline In Serum Concentrations of Total Properdin For ALXN1820 SC- Multiple Dose Cohorts	Baseline, Day 155
Change From Baseline In Serum Concentrations of Free Properdin For ALXN1820 SC- Multiple Dose Cohorts	Baseline, Day 155
Change From Baseline In Complement Alternative Pathway (CAP) Activity Using The Wieslab Alternative Pathway (AP) Assay For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts	Baseline, Day 127
Change From Baseline In Complement Alternative Pathway Activity Using The Wieslab Alternative Pathway Assay For ALXN1820 SC- Multiple Dose Cohorts	Baseline, Day 155
Absolute Bioavailability Of ALXN1820 SC	Baseline up to Day 127	The absolute bioavailability was expressed as ratio and was calculated as the geometric mean for the AUC\[0-inf\] for SC divided by the geometric mean for the AUC\[0-inf\] for IV. Least square means were calculated with cohort, treatment, and sequence as the fixed effects, and participant-participant (sequence) as a random effect.
Number Of Participants With Positive Antidrug Antibodies (ADAs) To ALXN1820 SC And ALXN1820 IV	Baseline up to Day 155