ALE1 safety, dosing, and activity in adults with and without hypophosphatasia

A Randomised, Placebo Controlled, Double-Blind, Single-Ascending Dose And Multiple-Ascending Dose First-In-Human Study To Investigate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Orally Administered ALE1 With Or Without Food In Healthy Adult Subjects And Adult Patients With Hypophosphatasia

Researchers will try different doses of ALE1 to check safety and how the drug acts in healthy adults and adults with hypophosphatasia.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years to 50 Years
• Sex: All
• Sponsor: Alesta Therapeutics (industry)
• Locations: 2 sites (Grafton, Auckland and 1 other locations)
• Trial ID: NCT07179640 on ClinicalTrials.gov

What this trial studies

This randomized, placebo-controlled, double-blind Phase 1/2a trial tests single and multiple doses of ALE1 to characterize safety, tolerability, pharmacokinetics, and pharmacodynamics. The study enrolls overtly healthy adults and adults with genetically confirmed hypophosphatasia to identify suitable dose regimens. Key exclusions include prior enzyme replacement or other advanced therapies for HPP, recent fractures, and disorders affecting bone or mineral metabolism. Safety labs, PK sampling, and PD markers related to alkaline phosphatase activity will guide dose selection.

Who should consider this trial

Good fit: Ideal participants are adults with a documented ALPL gene variant who are medically stable, have not received prior enzyme replacement or advanced HPP therapies, and are willing to attend in-person study visits; the trial also enrolls healthy adult volunteers for safety comparisons.

Not a fit: Patients with other bone or mineral disorders, recent fractures, uncontrolled parathyroid disease, or prior exposure to ERT or gene therapies are unlikely to benefit from this early-phase dosing study.

Why it matters

Potential benefit: If successful, ALE1 could offer a new treatment option that improves biochemical markers and symptoms of hypophosphatasia in adults.

How similar studies have performed: Enzyme replacement therapy such as asfotase alfa has improved outcomes in HPP, so targeting alkaline phosphatase pathways is a proven approach, but ALE1 itself is a novel agent with limited clinical data to date.

Eligibility criteria

Key Inclusion Criteria Part 1:

1. Participants are overtly healthy as determined by a medical evaluation
2. No concurrent medical conditions or significant medical history, in the opinion of the investigator.

Key Inclusion Criteria Part 2:

1\. Documented ALPL gene variant

Key Exclusion Criteria Part 1:

1\. History of conditions affecting bone or mineral metabolism

Key Exclusion Criteria Part 2:

1. Previous treatment with an enzyme replacement therapy (ERT) or any advanced therapeutic agent (e.g., gene therapy) for the treatment of hypophosphatasia (HPP) or any treatment for osteoporotic diseases
2. Previous exposure to any medication or investigational agent potentially affecting bone structure, muscle volume, muscle strength, or muscle or nerve function
3. Diagnosis of hyperparathyroidism
4. Diagnosis of hypoparathyroidism, unless secondary to HPP
5. New fracture within 12 weeks before first dosing

Where this trial is running

Grafton, Auckland and 1 other locations

• New Zealand Clinical Research — Grafton, Auckland, New Zealand (RECRUITING)
• Fortrea Clinical Research Unit — Leeds, United Kingdom (RECRUITING)

Conditions: Hypophosphatasia, hypophosphatasia