Clinical trial NCT05307978: Safety and Tolerability, Pharmacokinetic, and Pharmacodynamic Study of ALXN1910 in Healthy Participants
Official title: A Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study of Subcutaneously and Intravenously Administered ALXN1910 in Healthy Adult Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: ALXN1910
Safety
Pharmacokinetics
Pharmacodynamics
Japanese Descent
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2022-04-01
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: This is a Phase 1, randomized, double-blind, placebo-controlled study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of single ascending doses (SADs) of ALXN1910 subcutaneous (SC) and SAD of ALXN1910 intravenous (IV).


Eligibility criteria: Inclusion Criteria:

* Healthy participants
* Participants of Japanese descent are defined as: First generation (born to 2 Japanese parents and 4 Japanese grandparents).
* Participants of Japanese descent must be between 20 and 55 years of age.

Exclusion Criteria:

* Current or recurrent disease
* Current or relevant history of physical or psychiatric illness.
* Any other significant disease or disorder that, in the opinion of the Investigator, may put the participant at risk.
* History of significant allergic reaction (eg, anaphylaxis or angioedema) to any product (eg, food, pharmaceutical).
* Female participants who are pregnant or breastfeeding.
* Major surgery or hospitalization within 90 days prior to dosing on Day1.
* History of exposure to asfotase alfa.
* History of allergy or hypersensitivity to excipients of asfotase alfa or ALXN1910 (eg,sodium phosphate, sodium chloride).

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
timeFrame: Day 1 (postdose) through Day 75
Secondary outcomes:
measure: Maximum Observed Serum Concentration (Cmax)
timeFrame: Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75
measure: Time to Maximum Observed Serum Concentration (Tmax)
timeFrame: Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75
measure: Apparent Terminal Elimination Half Life (t1/2)
timeFrame: Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75
measure: Terminal-phase Elimination Rate Constant (λz)
timeFrame: Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75
measure: AUC From Time Zero to the Last Quantifiable Concentratio (AUCt)
timeFrame: Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75
measure: AUC From Time Zero Extrapolated to Infinity (AUC∞)
timeFrame: Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75
measure: AUC From Time Zero to 168h (AUC0-168)
timeFrame: Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75
measure: Percentage of AUC∞ Obtained by Extrapolation Beyond Tlast (%AUCex)
timeFrame: Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75
measure: Total Body Clearance (for IV Cohorts) or Apparent Clearance (for SC Cohorts) (CL or CL/F)
timeFrame: Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75
measure: Volume of Distribution (for IV Cohorts) or Apparent Volume of Distribution (for SC Cohorts) (Vd or Vd/F)
timeFrame: Days 1 through 5 (predose and up to 96 hours postdose), postdose on Days 6, 7, 8, 15, 22, 29, 36, 43, and 75
measure: Plasma Concentration of Inorganic Pyrophosphate (PPi)
timeFrame: Day 1 (predose), 2, 3, 5, 8, 15, 22, 29, 36, 43, and 75
measure: Plasma Concentration of Pyridoxal (PL)
timeFrame: Day 1 (predose), 2, 3, 5, 8, 15, 22, 29, 36, 43, and 75
measure: Plasma Concentration of Pyridoxal 5-Phosphate (PLP)
timeFrame: Day 1 (predose), 2, 3, 5, 8, 15, 22, 29, 36, 43, and 75
measure: Plasma Concentration of Pyridoxic Acid (PA)
timeFrame: Day 1 (predose), 2, 3, 5, 8, 15, 22, 29, 36, 43, and 75
measure: Number of Participants With Positive Treatment-Emergent Antidrug Antibodies (ADAs)
timeFrame: Day 1 (postdose) through Day 75
measure: Geometric Mean Ratio (GMR) of Area Under the Curve (AUC∞) Values of Subcutaneous (SC) Versus Intravenous (IV) Serum Concentration of ALXN1910
timeFrame: Up to Day 75
measure: Maximum Observed Serum Concentration (Cmax) in Japanese and Non-Japanese Participants
timeFrame: Up to Day 75
measure: AUC From Time Zero to the Last Quantifiable Concentration (AUCt) in Japanese and Non-Japanese Participants
timeFrame: Up to Day 75
measure: AUC From Time Zero Extrapolated to Infinity (AUC∞) in Japanese and Non-Japanese Participants
timeFrame: Up to Day 75
measure: Change From Baseline in Inorganic Pyrophosphate Concentration in Japanese and Non-Japanese Participants
timeFrame: Day 2, 15, 22, 43, and 75
measure: Change From Baseline in Pyridoxal-5-phosphate Concentration in Japanese and Non-Japanese Participants
timeFrame: Day 2, 15, 22, 43, and 75
measure: Change From Baseline in Pyridoxal Concentration in Japanese and Non-Japanese Participants
timeFrame: Day 2, 15, 22, 43, and 75
measure: Change From Baseline in Pyridoxic Acid Concentration in Japanese and Non-Japanese Participants
timeFrame: Day 2, 15, 22, 43, and 75
Other outcomes:
Locations:
city: Harrow
country: United Kingdom
facility: Clinical Trial Site
Study officials:
References: