A Study of Multiple Doses of ALXN1210 in Healthy Adult Participants

NCT05288673 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: ALXN1210-HV-1022014-005495-29
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluated the safety and tolerability of multiple doses of ALXN1210 (400 and 800 milligrams \[mg\]) following intravenous (IV) administration to healthy participants.

Conditions

Healthy

Keywords

ALXN1210; Pharmacokinetics; Pharmacodynamics

Outcome Measures

Primary Outcomes (1)

• 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 that occurred on or after the date and time of study drug administration, or those that first occurred before dosing but worsened in frequency or severity after study drug administration. 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 309

Secondary Outcomes (8)

• Area Under The Serum Concentration Versus Time Curve From Time Zero To Infinity (AUCinf) of ALXN1210

  Predose, end of infusion, 30 minutes, 4 hours, 8 hours and 24 hours post start of infusion on Day 1 up to Day 309

• Area Under The Serum Concentration From Time Zero To The Time of The Last Quantifiable Concentration (AUCt) of ALXN1210

  Predose, end of infusion, 30 minutes, 4 hours, 8 hours and 24 hours post start of infusion on Day 1 up to Day 309

• Maximum Observed Serum Concentration (Cmax) of ALXN1210

  Predose, end of infusion, 30 minutes, 4 hours, 8 hours and 24 hours post start of infusion on Day 1 up to Day 309

• Percent Change From Baseline in Free Complement Protein C5 Concentration at Day 113

  Baseline, Day 113

• Percent Change From Baseline in Total C5 Concentration at Day 113

  Baseline, Day 113

Study Arms (3)

ALXN1210 400 mg

EXPERIMENTAL

Participants received ALXN1210 every 28 days.

Drug: ALXN1210

ALXN1210: 800 mg

EXPERIMENTAL

Participants received ALXN1210 every 28 days.

Drug: ALXN1210

Placebo

PLACEBO COMPARATOR

Participants received placebo every 28 days.

Drug: Placebo

Interventions

ALXN1210 DRUG

ALXN1210 was administered by IV infusion over 5 periods, 1 dose per period: Period 1, induction; Periods 2-5, maintenance. Participants received a total of 5 doses of 400 or 800 mg, each administered every 28 days.

Also known as: Ultomiris, Ravulizumab

ALXN1210 400 mg; ALXN1210: 800 mg

Placebo DRUG

Placebo was administered by IV infusion over 5 periods, 1 dose per period. Participants received the same volume and infusion rate as specified for each ALXN1210 dose (400 or 800 mg).

Placebo

Eligibility Criteria

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

You may qualify if:

• Healthy male and female participants ≥ 25 and ≤ 55 years old; smokers (no more than 10 cigarettes daily), former smokers (at the Investigator's discretion), or nonsmokers.
• 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 the Fridericia formula) ≤ 450 milliseconds (ms) for males and ≤ 470 ms for females at Screening and prior to dosing on Day 1.
• Participant was willing and able to give written informed consent and comply with the study visit schedule.
• Documented vaccination with tetravalent meningococcal conjugate vaccine (MCV4) at least 56 days and not more than 3 years prior to dosing. Documentation must have included a positive serum bactericidal antibody test to confirm an immune response before the study drug administration.
• Vaccination with serogroup B 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.
• Male participants with a female spouse/partner of childbearing potential or a pregnant or breastfeeding spouse or partner were required to use barrier contraception (male condom) during the treatment period and for at least 6 months after the last dose of ALXN1210.

You may not qualify if:

• Participants who had intimate and prolonged contact (defined as living under the same roof or providing personal care) with individuals who were either immunocompromised, or had specific underlying medical conditions (persons with anatomic or functional asplenia \[including sickle cell disease\]; persons with congenital complement, properdin, factor D, or primary antibody deficiencies, persons with acquired complement deficiencies \[for example, those receiving eculizumab\], and persons with human immunodeficiency virus \[HIV\]) or with persons younger than 2 years of age or older than 65 years of age
• 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 may be at increased risk when accommodated in close quarters); daycare center workers; those living on a college or university campus; or 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, pilgrimage to Saudi Arabia for Hajj) within the past 6 months
• History of any Neisseria infection
• History of unexplained recurrent infection or infection that required treatment with systemic antibiotics within the last 90 days prior to dosing
• HIV infection (evidenced by HIV-1 or HIV-2 antibody titer)
• Acute or chronic hepatitis B virus infection (evidenced by the presence of hepatitis B surface antigen or immunoglobulin M antibodies against hepatitis B core antigen)
• 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 indicating possible tuberculosis infection
• History of latent or active tuberculosis or exposure to endemic areas within 8 weeks prior to the screening visit
• Female participants who were breastfeeding or were of childbearing potential, including any female who had experienced menarche and who had not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who was pregnant, breastfeeding, or not postmenopausal.
• Positive serum pregnancy test at Screening or Day -1
• Serum creatinine \> upper limit of normal (ULN) of the reference range of the testing laboratory at Screening or 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 at Day -1.
• Any of the following hematology results: hemoglobin \< 135 grams (g)/L for males and \< 120 g/L for females; hematocrit \< 0.41 L/L for males and \< 0.36 L/L for females; white blood cells \< 3.5\*10\^3/microliter (μL) or \> ULN of the testing laboratory reference range; absolute neutrophils \< 1.5\*10\^3/μL (\< 1.0\*10\^3/μL for black race participants) or \> ULN of the testing laboratory reference range; and platelets \< the lower limit of normal of the testing laboratory reference range or \> 450\*10\^3/μL at Screening or Day -1; or complete blood count clinical laboratory results considered as 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

8557522356

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Participants and on-site medical/nursing staff at the study site were blinded to study drug/dose assignment. The pharmacy staff who prepared ALXN1210 or placebo, however, was not blinded to study drug assignment, but all other site staff, including the Investigator and personnel administering study drug, was blinded. Sponsor staff was unblinded as needed (for example, to monitor the pharmacy), but did not share any information on study drug assignment with the site staff.
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2022
• First Posted: March 21, 2022
• Study Start: July 28, 2015
• Primary Completion: September 1, 2016
• Study Completion: September 1, 2016
• Last Updated: May 9, 2023
• Results First Posted: May 9, 2023

Record last verified: 2022-06

Data Sharing

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

Locations

GB (1)