A Study of a Single Subcutaneous Dose of ALXN1210 in Healthy Adult Participants

NCT05288829 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: ALXN1210-SC-1012016-001617-24
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluated the safety and tolerability of a single dose of ALXN1210 subcutaneous (SC) compared to ALXN1210 intravenous (IV) in healthy participants and to determine the absolute bioavailability of ALXN1210 SC.

Conditions

Healthy

Keywords

Pharmacokinetics; Pharmacodynamics; ALXN1210; Safety; Immunogenicity

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  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 AEs with a start date or time on or after the first dose of the study drug. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.

  Baseline up to Day 200

• Absolute Bioavailability of ALXN1210 SC

  The absolute bioavailability of ALXN1210 SC is reported as the area under the serum concentration versus time curve from time 0 extrapolated to infinity (AUCinf) geometric mean of the ALXN1210 SC group divided by the AUCinf geometric mean of the ALXN1210 IV group\*100. Linear mixed model with fixed and random effects for the participant was used.

  Predose , end of infusion (EOI); 30 minutes post EOI; 2, 4, and 8 hours post start of infusion; and from Day 2 up to Day 150

Secondary Outcomes (3)

• Percent Change From Baseline in Free Complement Protein C5 Concentration At Day 8

  Baseline, Day 8

• Percent Change From Baseline In Chicken Red Blood Cell Hemolysis At Day 8

  Baseline, Day 8

• Number of Participants With Positive Antidrug Antibodies (ADAs) to ALXN1210

  Baseline up to Day 200

Study Arms (3)

ALXN1210 SC

EXPERIMENTAL

Participants received ALXN1210 SC.

Drug: ALXN1210 SC

ALXN1210 IV

EXPERIMENTAL

Participants received ALXN1210 IV.

Drug: ALXN1210 IV

Placebo SC

PLACEBO COMPARATOR

Participants received placebo SC.

Drug: Placebo

Interventions

ALXN1210 SC DRUG

All doses of ALXN1210 SC were administered by four 100-milligram (mg) SC injections of 1 milliliter (mL) each in the abdominal area. All four 1-mL injections were administered over a 15-minute period with at least 15 minutes between the end of injection in 1 participant and the start of injection in the next participant.

Also known as: Ravulizumab, Ultomiris

ALXN1210 SC

ALXN1210 IV DRUG

All doses of ALXN1210 IV were administered by IV infusion, using IV sets with in-line filters, at a maximum rate of 333 mL/hour, excluding interruption for safety or technical reason. There were at least 15 minutes between the end-of-infusion/injection in 1 participant and the start-of infusion/injection in the next participant.

Also known as: Ravulizumab, Ultomiris

ALXN1210 IV

Placebo DRUG

All doses of placebo SC were administered by four 100-mg SC injections of 1 mL each in the abdominal area. All four 1-mL injections were administered over a 15-minute period with at least 15 minutes between the end of injection in 1 participant and the start of injection in the next participant.

Placebo SC

Eligibility Criteria

• Age: 25 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Body mass index from 18 through 29.9 kilogram (kg)/square meter, inclusive, and weight between 50 and 100 kg, inclusive.
• QT interval corrected using Fridericia's formula ≤ 450 milliseconds (msec) for males and ≤ 470 msec for females at Screening and prior to dosing on Day 1.
• Was willing and was able to give written informed consent and complied with the study visit schedule.
• Documented vaccination with tetravalent meningococcal conjugate vaccine at least 56 days and not more than 3 years prior to dosing. Documentation must have included a positive serum bactericidal antibody titer to confirm an immune response before study drug administration.
• Vaccination with serogroup B meningococcal vaccine at least 56 days prior to dosing on Day 1, with a booster administered at least 28 days prior to dosing on Day 1, with at least 28 days between the first and second injections.
• Female participants of childbearing potential, if heterosexually active, must use highly effective contraception.

You may not qualify if:

• Participants who were in intimate and prolonged contact with (defined as living under the same roof or providing personal care to) people younger than 2 years of age or older than 65 years of age, or who were either immunocompromised or had 1 of the following underlying medical conditions: anatomic or functional asplenia (including sickle cell disease); congenital complement, properdin, factor D, or primary antibody deficiencies; acquired complement deficiencies (for example, those receiving eculizumab); or human immunodeficiency virus (HIV).
• Participants who were one of the following: professionals exposed to environments of greater risk for meningococcal disease; research, industrial, and clinical laboratory personnel routinely exposed to Neisseria meningitidis; military personnel during recruit training (military personnel could have been at increased risk of meningococcal infection when accommodated in close quarters); daycare center workers; those living on a college or university campus; and those who planned to travel during the course of the study to or had travelled to endemic areas for meningococcal meningitis (for example, India, Sub-Saharan Africa, or pilgrimage to Saudi Arabia for Hajj) within the past 6 months.
• History of any Neisseria infection.
• History of unexplained, recurrent infection, or infection requiring treatment with systemic antibiotics within 90 days prior to dosing.
• Evidence of HIV infection (HIV-1 or HIV-2 antibody titer).
• Acute or chronic hepatitis B virus infection. Hepatitis B surface antigen (HBsAg) testing was required for all participants prior to enrollment. Participants with positive HBsAg were not enrolled. For participants with negative HBsAg, the following testing algorithm was required: If hepatitis B core antibody (HBcAb) was negative, the participant was eligible to enroll and If HBcAb was positive, the hepatitis B surface antibody (HBsAb) was tested. (If both HBcAb and HBsAb were positive, the participant was eligible to enroll and If HBcAb was positive and HBsAb was negative, the participant was not enrolled.)
• Acute or chronic hepatitis C virus infection (evidenced by antibody titer).
• Active systemic viral or fungal infection within 14 days prior to dosing.
• Positive or indeterminate QuantiFERON-TB test which indicated possible tuberculosis (TB) infection.
• History of latent or active TB or exposure to endemic areas within 8 weeks prior to the Screening visit.
• Female participants who are breastfeeding or are heterosexually active and unwilling to practice contraception and are not postmenopausal.
• Positive serum pregnancy test at Screening or on Day -1.
• Serum creatinine greater than the upper limit of normal (ULN) of the reference range of the testing laboratory at Screening or on Day -1.
• Alanine aminotransferase or aspartate aminotransferase \> ULN of the reference range of the testing laboratory at Screening or \> 1.5\*ULN of the reference range of the testing laboratory on Day -1.
• Any of the following hematology results: hemoglobin \< 130 grams (g)/liter for males and \< 115 g/L for females, hematocrit \< 0.37 L/L for males and \< 0.33 L/L for females, white blood cell count \< 3.0\*10\^3/microliter (μL), absolute neutrophil count \< 2.0\*10\^3/μL, and platelet count \< 150 or \> 400\*10\^3/μL at Screening or on Day -1. Complete blood count clinical laboratory results that were considered clinically relevant and unacceptable by the Investigator at Day -1.

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (1)

Clinical Trial Site

London, United Kingdom

Location

MeSH Terms

Interventions

ravulizumab

Results Point of Contact

• Title: Alexion Pharmaceuticals, Inc.
• Organization: Alexion Pharmaceuticals, Inc.

clinicaltrials@alexion.com

855-752-2356

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: This was a partially blinded study. During Cohorts 1a and 1b dosing, participants, study site medical/nursing staff, and other study site staff involved in the safety evaluations were blinded to study drug assignment. The pharmacy staff who prepared the SC injections and the research physician responsible for study drug administration was not blinded. In addition, a data manager responsible for masking some of the PK data was not blinded. Alexion staff were unblinded only on specific occasions (eg, to monitor that the SC injections were being prepared appropriately, to determine reportability of serious adverse events \[AEs\]), and refrained from sharing any information on study drug assignment with the study site staff. During Cohort 2, however, participants and study site staff were made aware of the treatment being administered.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2022
• First Posted: March 21, 2022
• Study Start: August 19, 2016
• Primary Completion: July 18, 2017
• Study Completion: July 18, 2017
• Last Updated: May 1, 2023
• Results First Posted: May 1, 2023

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR

Locations

GB (1)