Clinical trial NCT04980248: Study of ALXN1850 in Participants With Hypophosphatasia (HPP)
Official title: A Phase 1, Open-label, Dose-escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ALXN1850 in Adults With Hypophosphatasia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypophosphatasia
Keywords: HPP
enzyme replacement therapy
low alkaline phosphatase
tissue-nonspecific alkaline phosphatase
TNSALP
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2021-07-28
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Study participants will be enrolled into 3 cohorts in a sequential fashion.
Primary purpose: BASIC_SCIENCE

Brief summary: This is an open-label, dose-escalating study to assess safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and immunogenicity of ALXN1850 when given intravenous (IV) and subcutaneous (SC) to adults with HPP.


Eligibility criteria: Inclusion Criteria:

* Confirmed clinical diagnosis of HPP
* Not anticipated to require further treatment with enzyme replacement therapy to treat participant's HPP after study completion
* Willing and able to follow protocol-specified contraception requirements
* Willing and able to give informed consent

Exclusion Criteria:

* Primary or secondary hyperparathyroidism or hypoparathyroidism
* Fracture within 12 weeks of screening
* Current or relevant history of unstable physical or psychiatric illness
* Significant allergies
* Asfotase alfa use within 6 months and/or positive for asfotase alfa antidrug antibody/neutralizing antibodies

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
timeFrame: Day 1 up to Day 85
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of ALXN1850 Following Intravenous (IV) Dose, Subcutaneous (SC) Dose 1, SC Dose 2 and SC Dose 3
timeFrame: Predose, 2, 6 and 12 hours postdose on Days 1, 15, 22 and 29
measure: Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity Following IV Dose of ALXN1850
timeFrame: Predose, 2, 6 and 12 hours postdose on Days 1, 15, 22 and 29
measure: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Dosing Interval (AUCtau) Following SC Dose 1, SC Dose 2 and SC Dose 3
timeFrame: Predose, 2, 6 and 12 hour postdose on Days 1, 15, 22 and 29
measure: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Dosing Interval (AUCtau) Values of the First SC Versus IV Administration of ALXN1850
timeFrame: Predose, 2, 6 and 12 hour postdose on Days 1, 15, 22 and 29
measure: Absolute Change From Baseline in Plasma Concentration of Pyridoxal-5' Phosphate (PLP) at Week 1
timeFrame: Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
measure: Absolute Change From Baseline in Plasma Concentration of Inorganic Pyrophosphate (PPi) at Week 1
timeFrame: Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
measure: Absolute Change From Baseline in Plasma Concentration of Pyridoxal Phosphate/ Pyridoxal (PLP/PL) Ratio at Week 1
timeFrame: Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
measure: Percent Change From Baseline in Plasma Concentration of PLP at Week 1
timeFrame: Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
measure: Percent Change From Baseline in Plasma Concentration of PPi at Week 1
timeFrame: Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
measure: Percent Change From Baseline in Plasma Concentration of PLP/PL Ratio Over Time at Week 1
timeFrame: Baseline, 1 Week post Day 1 IV dose and 1 Week post Day 29 SC dose 3
measure: Number of Participants With Anti-drug Antibody (ADA) Positive and Neutralizing Antibody (NAb) Positive Status
timeFrame: Baseline up to Day 85
Other outcomes:
Locations:
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Austin
country: United States
facility: Research Site
state: Texas
Study officials:
References: