Healthy Adult Participants
Conditions
Keywords
Pharmacokinetics, Pharmacodynamics, Safety, Immunogenicity, Device Performance
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.
Interventions
DRUGGefurulimab PFS-SD
Participants will receive a single 600 mg dose of Gefurulimab PFS-SD subcutaneously (SC) on Day 1.
DRUGGefurulimab AI
Participants will receive a single 600 mg dose of Gefurulimab AI subcutaneously (SC) on Day 1.
Sponsors
Parexel
Alexion Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
This is an open-label study. To avoid potential bias and maintain the data integrity, the analysis and reporting performed before database lock for Primary Analysis, ie, dry run/blinded data review for Primary Analysis, will be based on blinded data in which the treatment information is based on a dummy randomization schedule.
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).
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the serum concentration-time curve from time zero to the last measurable concentration (AUClast) | Day 1 up to early discontinuation or Day 92 | 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. |
| Area under the serum concentration-time curve from time zero to time infinity (AUCinf) | Day 1 up to early discontinuation or Day 92 | 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. |
| Maximum (peak) concentration observed after study intervention administration (Cmax) | Day 1 up to early discontinuation or Day 92 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Apparent total body clearance of the study intervention from serum (CL/F) | Day 1 to Day 92 | The CL/F of gefurulimab SC in healthy participants across devices, and injection sites will be assessed. |
| Apparent volume of distribution (Vd/F) | Day 1 to Day 92 | The Vd/F of gefurulimab SC in healthy participants across devices, and injection sites will be assessed. |
| Serum free C5 (complement component 5) concentrations | Day 1 to Day 92 | The serum free C5 concentrations of gefurulimab SC in healthy participants across devices and injection sites will be assessed. |
| Number of reported device deficiencies/complaints and associated device investigations | Day 1 | The performance of the AI and PFS-SD in the administration of gefurulimab SC in healthy participants will be assessed. |
| Incidence of antidrug antibody (ADA) to gefurulimab category of immune-response and titer | Day 1, Day 92 | The immunogenicity of gefurulimab SC administered with either PFS-SD or AI in healthy participants will be assessed. |
| Number of reported outcome of attempted full-dose administration via AI (autoinjector) or PFS-SD (prefilled syringe with needle safety device) | Day 1 | The performance of the AI and PFS-SD in the administration of gefurulimab SC in healthy participants will be assessed. |
| Number of subjects with TEAEs (treatment-emergent adverse event) and TESAEs (treatment-emergent serious adverse event) | From Admission (Day-1) to Day 92 | The safety and tolerability of gefurulimab SC in healthy participants across devices and injection sites will be evaluated. |
| Time to maximum observed serum concentration (tmax) | Day 1 to Day 92 | The tmax of gefurulimab SC in healthy participants across devices, and injection sites will be assessed. |
| Terminal elimination half-life (t½) | Day 1 to Day 92 | The t½ of gefurulimab SC in healthy participants across devices, and injection sites will be assessed. |
Countries
Canada
Outcome results
None listed