Study of ALXN1820 in Healthy Adult Participants

Healthy Clinical Trial

Official title:

A Phase 1, Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Study of Subcutaneous and Intravenous ALXN1820 in Healthy Participants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04631562
• Other study ID #: ALXN1820-HV-101
• Status: Completed
• Phase: Phase 1
• Start date: January 8, 2021
• Est. completion date: September 1, 2022

Study information

• Verified date: August 2023
• Source: Alexion Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: September 1, 2022
• Est. primary completion date: September 1, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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).

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• ALXN1820 SC
ALXN1820 SC will be administered as a manual SC push or SC infusion via a syringe pump. Doses will range from 12.5 milligrams (mg) to a maximum of 2250 mg. Multiple dosing duration will range from 3 to 5 weeks.
• ALXN1820 IV
ALXN1820 IV (450 mg) will be administered as an IV infusion.
• Placebo SC
Placebo SC will be administered as a manual SC push or SC infusion via a syringe pump.
• Placebo IV
Placebo IV will be administered as an IV infusion.

Locations

Country	Name	City	State
Australia	Clinical Study Site	Herston
United Kingdom	Clinical Study Site	London

Sponsors (2)

Lead Sponsor	Collaborator
Alexion Pharmaceuticals, Inc.	Syneos Health

Countries where clinical trial is conducted

Australia,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-related Adverse Events (TEAEs) For ALXN1820 SC And ALXN1820 IV	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.	Cohorts 1 to 6: Baseline up to Day 127; Cohorts 8 to 9: Baseline up to Day 155
Secondary	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
Secondary	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
Secondary	Maximum Observed Serum Concentration (Cmax) Of Serum ALXN1820 For Single Dose Cohorts		Up to 126 days following the first day of dosing
Secondary	Maximum Observed Serum Concentration (Cmax) Of Serum ALXN1820 For Multiple Dose Cohorts		Up to 154 days following the first day of dosing
Secondary	Change From Baseline in Serum Concentrations Of Total Properdin For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts		Baseline, Day 127
Secondary	Change From Baseline in Serum Concentrations Of Free Properdin For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts		Baseline, Day 127
Secondary	Change From Baseline In Serum Concentrations of Total Properdin For ALXN1820 SC- Multiple Dose Cohorts		Baseline, Day 155
Secondary	Change From Baseline In Serum Concentrations of Free Properdin For ALXN1820 SC- Multiple Dose Cohorts		Baseline, Day 155
Secondary	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
Secondary	Change From Baseline In Complement Alternative Pathway Activity Using The Wieslab Alternative Pathway Assay For ALXN1820 SC- Multiple Dose Cohorts		Baseline, Day 155
Secondary	Number Of Participants With Positive Antidrug Antibodies (ADAs) To ALXN1820 SC And ALXN1820 IV		Baseline up to Day 155
Secondary	Absolute Bioavailability Of ALXN1820 SC	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.	Baseline up to Day 127