A Study of Subcutaneous Gefurulimab Using Prefilled Syringe Versus Autoinjector in Healthy Adult Participants

A Phase 1, Open-label, Randomized, Parallel-group Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety, Immunogenicity, and Device Performance of ALXN1720 (Gefurulimab) Administered Subcutaneously Using Prefilled Syringe Versus Autoinjector in Adult Healthy Participants

This study will evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety, immunogenicity, and device performance of gefurulimab.

Study Overview

• Status: Completed
• Conditions: Healthy Adult Participants
• Intervention / Treatment: Drug: Gefurulimab PFS-SD; Drug: Gefurulimab AI

Detailed Description

This is an open-label, randomized, parallel-group study.

The study consists of 2 periods: a Screening Period (up to 70 days), and an Evaluation Period of 92 days.

Separate randomization lists will be produced for each weight stratum (50 to < 70 kg, 70 to < 90 kg, and 90 to < 110 kg) and within each of the three weight strata, participants will be randomized 1:1:1:1:1:1 to one of the six combinations of device (prefilled syringe with needle safety device [PFS-SD] or autoinjector [AI]) and injection site (abdomen, thigh, or upper arm),

Participants will receive a single dose of 600 mg gefurulimab on Day 1, will be residential at the clinical unit until Day 5, will have visits on Day 8, quaque week (once a week) [qw] thereafter until Day 50, and quaque 2 week (once every two weeks) [q2w] from Day 50 until Day 92 during the Evaluation Period.

The total study duration is up to 162 days.

• Study Type: Interventional
• Enrollment (Actual): 175
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M9L 3A2
      • Research Site
  • Quebec
    • Laval, Quebec, Canada, h7v 4bc
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Participants must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
2. Body weight within ≥ 50 to < 110 kg and body mass index (BMI) within the range 18.5 to 30 kg/m2 (inclusive)
3. Participants who are healthy as determined by medical evaluation with no clinically significant or relevant abnormalities as determined by medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory evaluation.
4. QT interval corrected using Fridericia's formula (QTcF) ≤ 450 msec for male participants and ≤ 460 msec for female participants at Screening and prior to dosing on Day 1.
5. Documented vaccination against meningococcal infection from serogroups A, C, W, and Y and serogroup B.
6. Male and female participants should adhere to study-specific contraceptive methods.

Exclusion Criteria:

1. History of any Neisseria meningitidis infection.
2. History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, or neurological disorders.
3. Abnormal blood pressure as determined by the Investigator.
4. History of latent or active TB (Tuberculosis) or exposure to endemic areas.
5. Allergy to monoclonal antibodies.
6. Clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe posttreatment hypersensitivity reactions.
7. Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
8. Current or chronic history of liver disease.
9. Known hepatic or biliary abnormalities.
10. Active systemic bacterial, viral, or fungal infection within 14 days prior to dosing.
11. History of allergy or intolerance to penicillin or cephalosporin.
12. History of clinically significant allergic reaction (eg, anaphylaxis or angioedema) to any product.
13. Live vaccine(s) within 1 month prior to Screening or plans to receive such vaccines during the study.
14. Evidence of human immunodeficiency virus (HIV) infection (positive HIV type 1 or type 2 antibody).
15. Evidence of hepatitis B infection (positive hepatitis B surface antigen [HBsAg] or positive total hepatitis B core antibody [HBcAb] with negative surface antibody [anti-HBs]), or hepatitis C viral infection (positive HCV RNA).
16. Female participants who have a positive pregnancy test at Screening or Admission.
17. Positive prestudy drug/alcohol screen; positive result may be repeated once.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gefurulimab PFS-SD; Participants will be administered gefurulimab as a single dose of 600 mg by PFS-SD on the abdomen, thigh, or upper arm.	Drug: Gefurulimab PFS-SD; Participants will receive a single 600 mg dose of Gefurulimab PFS-SD subcutaneously (SC) on Day 1.; Other Names: ALXN1720
Experimental: Gefurulimab AI; Participants will be administered gefurulimab as a single dose of 600 mg by AI on the abdomen, thigh, or upper arm.	Drug: Gefurulimab AI; Participants will receive a single 600 mg dose of Gefurulimab AI subcutaneously (SC) on Day 1.; Other Names: ALXN1720

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the serum concentration-time curve from time zero to the last measurable concentration (AUClast)	The AUClast exposure in healthy participants following a single SC dose of 600 mg gefurulimab by AI comparable to the PK exposure using the PFS-SD will be assessed.	Day 1 up to early discontinuation or Day 92
Area under the serum concentration-time curve from time zero to time infinity (AUCinf)	The AUClinf exposure in healthy participants following a single SC dose of 600 mg gefurulimab by AI comparable to the PK exposure using the PFS-SD will be assessed.	Day 1 up to early discontinuation or Day 92
Maximum (peak) concentration observed after study intervention administration (Cmax)	The Cmax exposure in healthy participants following a single SC dose of 600 mg gefurulimab by AI comparable to the PK exposure using the PFS-SD will be assessed.	Day 1 up to early discontinuation or Day 92

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to maximum observed serum concentration (tmax)	The tmax of gefurulimab SC in healthy participants across devices, and injection sites will be assessed.	Day 1 to Day 92
Terminal elimination half-life (t½)	The t½ of gefurulimab SC in healthy participants across devices, and injection sites will be assessed.	Day 1 to Day 92
Apparent total body clearance of the study intervention from serum (CL/F)	The CL/F of gefurulimab SC in healthy participants across devices, and injection sites will be assessed.	Day 1 to Day 92
Apparent volume of distribution (Vd/F)	The Vd/F of gefurulimab SC in healthy participants across devices, and injection sites will be assessed.	Day 1 to Day 92
Serum free C5 (complement component 5) concentrations	The serum free C5 concentrations of gefurulimab SC in healthy participants across devices and injection sites will be assessed.	Day 1 to Day 92
Number of subjects with TEAEs (treatment-emergent adverse event) and TESAEs (treatment-emergent serious adverse event)	The safety and tolerability of gefurulimab SC in healthy participants across devices and injection sites will be evaluated.	From Admission (Day-1) to Day 92
Incidence of antidrug antibody (ADA) to gefurulimab category of immune-response and titer	The immunogenicity of gefurulimab SC administered with either PFS-SD or AI in healthy participants will be assessed.	Day 1, Day 92
Number of reported outcome of attempted full-dose administration via AI (autoinjector) or PFS-SD (prefilled syringe with needle safety device)	The performance of the AI and PFS-SD in the administration of gefurulimab SC in healthy participants will be assessed.	Day 1
Number of reported device deficiencies/complaints and associated device investigations	The performance of the AI and PFS-SD in the administration of gefurulimab SC in healthy participants will be assessed.	Day 1

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals, Inc.
• Collaborators: Parexel

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2023
• Primary Completion (Actual): September 17, 2024
• Study Completion (Actual): September 28, 2024

Study Registration Dates

• First Submitted: November 6, 2023
• First Submitted That Met QC Criteria: January 5, 2024
• First Posted (Actual): January 17, 2024

Study Record Updates

• Last Update Posted (Actual): October 23, 2024
• Last Update Submitted That Met QC Criteria: October 21, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; Immunogenicity; Pharmacodynamics; Device Performance
• Other Study ID Numbers: ALXN1720-HV-103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPINPhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No