Clinical trial NCT06208488: A Study of Subcutaneous Gefurulimab Using Prefilled Syringe Versus Autoinjector in Healthy Adult Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Adult Participants
Keywords: Pharmacokinetics
Pharmacodynamics
Safety
Immunogenicity
Device Performance
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2024-01-17
Enrollment: 175
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Separate randomization lists will be produced for each weight stratum (ie, 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 (PFS-SD or AI) and injection site (abdomen, thigh, or upper arm).
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Area under the serum concentration-time curve from time zero to the last measurable concentration (AUClast)
timeFrame: Day 1 up to early discontinuation or Day 92
measure: Area under the serum concentration-time curve from time zero to time infinity (AUCinf)
timeFrame: Day 1 up to early discontinuation or Day 92
measure: Maximum (peak) concentration observed after study intervention administration (Cmax)
timeFrame: Day 1 up to early discontinuation or Day 92
Secondary outcomes:
measure: Time to maximum observed serum concentration (tmax)
timeFrame: Day 1 to Day 92
measure: Terminal elimination half-life (t½)
timeFrame: Day 1 to Day 92
measure: Apparent total body clearance of the study intervention from serum (CL/F)
timeFrame: Day 1 to Day 92
measure: Apparent volume of distribution (Vd/F)
timeFrame: Day 1 to Day 92
measure: Serum free C5 (complement component 5) concentrations
timeFrame: Day 1 to Day 92
measure: Number of subjects with TEAEs (treatment-emergent adverse event) and TESAEs (treatment-emergent serious adverse event)
timeFrame: From Admission (Day-1) to Day 92
measure: Incidence of antidrug antibody (ADA) to gefurulimab category of immune-response and titer
timeFrame: Day 1, Day 92
measure: Number of reported outcome of attempted full-dose administration via AI (autoinjector) or PFS-SD (prefilled syringe with needle safety device)
timeFrame: Day 1
measure: Number of reported device deficiencies/complaints and associated device investigations
timeFrame: Day 1
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Laval
country: Canada
facility: Research Site
state: Quebec
Study officials:
References: