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
Overview
- Phase
- Phase 1
- Intervention
- Gefurulimab PFS-SD
- Conditions
- Healthy Adult Participants
- Sponsor
- Alexion Pharmaceuticals, Inc.
- Enrollment
- 175
- Locations
- 1
- Primary Endpoint
- Maximum (peak) concentration observed after study intervention administration (Cmax)
- Status
- Completed
- Last Updated
- last year
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
- •Body weight within ≥ 50 to \< 110 kg and body mass index (BMI) within the range 18.5 to 30 kg/m2 (inclusive)
- •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.
- •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
- •Documented vaccination against meningococcal infection from serogroups A, C, W, and Y and serogroup B.
- •Male and female participants should adhere to study-specific contraceptive methods.
Exclusion Criteria
- •History of any Neisseria meningitidis infection.
- •History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, or neurological disorders.
- •Abnormal blood pressure as determined by the Investigator.
- •History of latent or active TB (Tuberculosis) or exposure to endemic areas.
- •Allergy to monoclonal antibodies.
- •Clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe posttreatment hypersensitivity reactions.
- •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.
- •Current or chronic history of liver disease.
- •Known hepatic or biliary abnormalities.
- •Active systemic bacterial, viral, or fungal infection within 14 days prior to dosing.
Arms & Interventions
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.
Intervention: Gefurulimab PFS-SD
Gefurulimab AI
Participants will be administered gefurulimab as a single dose of 600 mg by AI on the abdomen, thigh, or upper arm.
Intervention: Gefurulimab AI
Outcomes
Primary Outcomes
Maximum (peak) concentration observed after study intervention administration (Cmax)
Time Frame: 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.
Area under the serum concentration-time curve from time zero to the last measurable concentration (AUClast)
Time Frame: 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)
Time Frame: 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.
Secondary Outcomes
- Apparent volume of distribution (Vd/F)(Day 1 to Day 92)
- Time to maximum observed serum concentration (tmax)(Day 1 to Day 92)
- Serum free C5 (complement component 5) concentrations(Day 1 to Day 92)
- Incidence of antidrug antibody (ADA) to gefurulimab category of immune-response and titer(Day 1, Day 92)
- Terminal elimination half-life (t½)(Day 1 to Day 92)
- Number of subjects with TEAEs (treatment-emergent adverse event) and TESAEs (treatment-emergent serious adverse event)(From Admission (Day-1) to Day 92)
- Apparent total body clearance of the study intervention from serum (CL/F)(Day 1 to Day 92)
- Number of reported outcome of attempted full-dose administration via AI (autoinjector) or PFS-SD (prefilled syringe with needle safety device)(Day 1)
- Number of reported device deficiencies/complaints and associated device investigations(Day 1)