Clinical trial NCT04631562: Study of ALXN1820 in Healthy Adult Participants
Official title: A Phase 1, Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Study of Subcutaneous and Intravenous ALXN1820 in Healthy Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: ALXN1820
Properdin
Pharmacodynamics
Pharmacokinetics
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Syneos Health
First posted: 2020-11-17
Enrollment: 66
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Number of Participants With Treatment-related Adverse Events (TEAEs) For ALXN1820 SC And ALXN1820 IV
timeFrame: Cohorts 1 to 6: Baseline up to Day 127; Cohorts 8 to 9: Baseline up to Day 155
Secondary outcomes:
measure: 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
timeFrame: Up to 126 days following the first day of dosing
measure: Area Under The Concentration-time Curve During The Dosing Interval (AUCtau) Of Serum ALXN1820 For Multiple Dose Cohorts
timeFrame: Up to 154 days following the first day of dosing
measure: Maximum Observed Serum Concentration (Cmax) Of Serum ALXN1820 For Single Dose Cohorts
timeFrame: Up to 126 days following the first day of dosing
measure: Maximum Observed Serum Concentration (Cmax) Of Serum ALXN1820 For Multiple Dose Cohorts
timeFrame: Up to 154 days following the first day of dosing
measure: Change From Baseline in Serum Concentrations Of Total Properdin For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts
timeFrame: Baseline, Day 127
measure: Change From Baseline in Serum Concentrations Of Free Properdin For ALXN1820 SC And ALXN1820 IV-Single Dose Cohorts
timeFrame: Baseline, Day 127
measure: Change From Baseline In Serum Concentrations of Total Properdin For ALXN1820 SC- Multiple Dose Cohorts
timeFrame: Baseline, Day 155
measure: Change From Baseline In Serum Concentrations of Free Properdin For ALXN1820 SC- Multiple Dose Cohorts
timeFrame: Baseline, Day 155
measure: 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
timeFrame: Baseline, Day 127
measure: Change From Baseline In Complement Alternative Pathway Activity Using The Wieslab Alternative Pathway Assay For ALXN1820 SC- Multiple Dose Cohorts
timeFrame: Baseline, Day 155
measure: Number Of Participants With Positive Antidrug Antibodies (ADAs) To ALXN1820 SC And ALXN1820 IV
timeFrame: Baseline up to Day 155
measure: Absolute Bioavailability Of ALXN1820 SC
timeFrame: Baseline up to Day 127
Other outcomes:
Locations:
city: Herston
country: Australia
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
Study officials:
References: