Phase 1
Completed N=48
Safety and Tolerability, Pharmacokinetic, and Pharmacodynamic Study of ALXN1910 in Healthy Participants
Healthy
Source: ClinicalTrials.gov NCT05307978 ↗
Enrolled (actual)
48
Serious AEs
2.1%
Results posted
Feb 2025
Primary outcomePrimary: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) — 3; 3; 4; 3 Participants
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).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) |
3; 3; 4; 3; 5; 4 | — |
| SECONDARY Maximum Observed Serum Concentration (Cmax) |
1.034; 0.3172; 3.113; 0.3807; 1.230; 4.257 | — |
| SECONDARY Time to Maximum Observed Serum Concentration (Tmax) |
0.48; 107.85; 0.52; 108.02; 95.99; 84.14 | — |
| SECONDARY Apparent Terminal Elimination Half Life (t1/2) |
166.1; 215.1; 194.9; 207.5; 271.3; 263.5 | — |
| SECONDARY Terminal-phase Elimination Rate Constant (λz) |
0.004172; 0.003222; 0.003556; 0.003341; 0.002555; 0.002631 | — |
| SECONDARY AUC From Time Zero to the Last Quantifiable Concentratio (AUCt) |
69.52; 102.4; 219.0; 120.9; 484.3; 1606 | — |
| SECONDARY AUC From Time Zero Extrapolated to Infinity (AUC∞) |
89.43; 168.0; 244.5; 157.8; 517.8; 1699 | — |
| SECONDARY AUC From Time Zero to 168h (AUC0-168) |
53.06; 40.83; 142.1; 49.73; 161.9; 573.3 | — |
| SECONDARY Percentage of AUC∞ Obtained by Extrapolation Beyond Tlast (%AUCex) |
24.03; 22.89; 10.41; 16.89; 6.418; 5.133 | — |
| SECONDARY Total Body Clearance (for IV Cohorts) or Apparent Clearance (for SC Cohorts) (CL or CL/F) |
0.05591; 0.08926; 0.06135; 0.09507; 0.08691; 0.07945 | — |
| SECONDARY Volume of Distribution (for IV Cohorts) or Apparent Volume of Distribution (for SC Cohorts) (Vd or Vd/F) |
12.56; 27.12; 17.25; 28.46; 34.02; 30.20 | — |
| SECONDARY Plasma Concentration of Inorganic Pyrophosphate (PPi) |
1.677; 1.783; 1.580; 1.683; 1.577; 1.525 | — |
| SECONDARY Plasma Concentration of Pyridoxal (PL) |
2.000; 2.133; 2.000; 2.092; 2.000; 2.182 | — |
| SECONDARY Plasma Concentration of Pyridoxal 5-Phosphate (PLP) |
10.187; 10.332; 9.817; 15.883; 11.503; 13.940 | — |
| SECONDARY Plasma Concentration of Pyridoxic Acid (PA) |
2.613; 3.088; 2.988; 3.590; 2.750; 3.797 | — |
| SECONDARY Number of Participants With Positive Treatment-Emergent Antidrug Antibodies (ADAs) |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Geometric Mean Ratio (GMR) of Area Under the Curve (AUC∞) Values of Subcutaneous (SC) Versus Intravenous (IV) Serum Concentration of ALXN1910 |
168.05; 244.51 | — |
| SECONDARY Maximum Observed Serum Concentration (Cmax) in Japanese and Non-Japanese Participants |
0.32; 0.38 | — |
| SECONDARY AUC From Time Zero to the Last Quantifiable Concentration (AUCt) in Japanese and Non-Japanese Participants |
102.37; 120.94 | — |
| SECONDARY AUC From Time Zero Extrapolated to Infinity (AUC∞) in Japanese and Non-Japanese Participants |
168.05; 157.78 | — |
| SECONDARY Change From Baseline in Inorganic Pyrophosphate Concentration in Japanese and Non-Japanese Participants |
-0.195; -0.152; -0.357; -0.251; -0.355; -0.176 | — |
| SECONDARY Change From Baseline in Pyridoxal-5-phosphate Concentration in Japanese and Non-Japanese Participants |
-0.430; -4.957; -1.220; 2.193; -0.412; 13.693 | — |
| SECONDARY Change From Baseline in Pyridoxal Concentration in Japanese and Non-Japanese Participants |
-0.093; -0.061; -0.171; 0.789; 0.190; 2.981 | — |
| SECONDARY Change From Baseline in Pyridoxic Acid Concentration in Japanese and Non-Japanese Participants |
-0.316; -0.725; 0.182; 1.267; -0.238; 6.278 | — |
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).
Data sourced from ClinicalTrials.gov (NCT05307978). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.