A Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ALE1 in Healthy Adults and Adults with Hypophosphatasia in order to Identify Suitable Doses of ALE1

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Alesta Therapeutics B.V.

Participant type

Healthy volunteers, Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05], Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Decision date (initial)

2025-11-19

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Alesta Therapeutics B.V.

External identifiers

EU CT number

2025-522378-36-00

ClinicalTrials.gov

NCT07179640

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Safety, Pharmacokinetic

To investigate the safety and tolerability of ALE1 in healthy adult participants and adult patients with HPP following single and multiple-ascending oral dose administrations.

Secondary objectives 4

1. To investigate the plasma and urine pharmacokinetic characteristics of single and multiple ascending oral doses of ALE1 in healthy adult participants and adult patients with HPP.
2. To investigate the blood pharmacodynamic response to single and multiple-ascending oral doses of ALE1 in healthy adult participants and adult patients with HPP.
3. To investigate whether ALE1 pharmacokinetics show dose proportionality after single and multiple-ascending oral doses of ALE1 in healthy adult participants and adult patients with HPP.
4. To investigate the effect of food on the pharmacokinetics of ALE1 following a single oral dose administration in healthy adult participants.

Conditions and MedDRA coding

Hypophosphatasia

Regulatory references

Scientific advice from competent authorities

Federal Institute For Drugs And Medical Devices

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Aged ≥ 18 to ≤ 65 years (inclusive) at the time of signing the ICF.
2. Part 1: 1) Participants are overtly healthy as determined by a medical evaluation.
3. Part 1: 2) No concurrent medical conditions or significant medical history, in the opinion of the investigator.
4. Part 2: 1) Documented ALPL gene variant.

Exclusion criteria 6

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Number and severity of treatment emergent adverse events (TEAEs) in healthy participants and patients with hypophosphatasia (HPP) with increasing oral doses of ALE1

Secondary endpoints 4

1. Pharmacokinetic parameters of single and multiple ascending doses of ALE1.
2. Pharmacodynamic biomarker levels in blood samples of single and multiple ascending doses of ALE1.
3. Dose proportionality in pharmacokinetic parameters in single and multiple ascending doses of ALE1.
4. Effect of food on ALE1 pharmacokinetic parameters.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Alesta Therapeutics B.V.

Sponsor organisation

Alesta Therapeutics B.V.

Address

Galileiweg 8

City

Leiden

Postcode

2333 BD

Country

Netherlands

Scientific contact point

Organisation

Alesta Therapeutics B.V.

Contact name

Medical Information

Public contact point

Organisation

Alesta Therapeutics B.V.

Contact name

Medical Information

Third parties 9

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications