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

Healthy Adult Participants Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06208488
• Other study ID #: ALXN1720-HV-103
• Status: Recruiting
• Phase: Phase 1
• Start date: November 22, 2023
• Est. completion date: April 1, 2025

Study information

• Verified date: January 2024
• Source: Alexion Pharmaceuticals, Inc.
• Contact: Alexion Pharmaceuticals, Inc. (Sponsor)
• Phone: 1-855-752-2356
• Email: clinicaltrials[@]alexion.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 174
• Est. completion date: April 1, 2025
• Est. primary completion date: April 1, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Adult Participants

Intervention

Drug:
• Gefurulimab PFS-SD
Participants will receive a single 600 mg dose of Gefurulimab PFS-SD subcutaneously (SC) on Day 1.
• Gefurulimab AI
Participants will receive a single 600 mg dose of Gefurulimab AI subcutaneously (SC) on Day 1.

Locations

Country	Name	City	State
Canada	Research Site	Laval	Quebec
Canada	Research Site	Toronto	Ontario
United Kingdom	Research Site	Harrow

Sponsors (2)

Lead Sponsor	Collaborator
Alexion Pharmaceuticals, Inc.	Parexel

Countries where clinical trial is conducted

Canada,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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