How a single ALPL gene change affects hypophosphatasia over time in Russia

The Effect of Monoallelic Variants in the ALPL Gene on the Natural Course of Hypophosphatasia (HPP) in Children and Adults in Russia

This observational study will follow children and adults with hypophosphatasia who carry one ALPL gene variant to see how their symptoms and health change during routine care in Russia.

Quick facts

• Study type: Observational
• Enrollment: 55 (estimated)
• Sex: All
• Sponsor: AstraZeneca (Industry-sponsored)
• Locations: 4 sites (Moscow and 3 other locations)
• Trial ID: NCT07390240 on ClinicalTrials.gov

What this trial studies

This is a non-interventional, multicenter cohort study enrolling children (≥4 years) and adults with hypophosphatasia who have a monoallelic pathogenic, likely pathogenic, or uncertain variant in the ALPL gene and persistently low alkaline phosphatase confirmed on at least two tests. Participants receive standard clinical care at participating centers while investigators collect clinical measures, laboratory data, genetic information, and patient-reported outcomes over time. The study excludes individuals with prior enzyme-replacement therapy, those with other conditions that mimic HPP, or those currently enrolled in other clinical studies. Collected data will be used to describe the natural course of HPP in monoallelic carriers and inform clinical management in routine practice.

Who should consider this trial

Good fit: Ideal candidates are people aged 4 years or older with confirmed low alkaline phosphatase on at least two measurements and a monoallelic pathogenic, likely pathogenic, or uncertain ALPL variant who have not received enzyme-replacement therapy and can provide consent.

Not a fit: People already receiving enzyme-replacement therapy, those with two pathogenic ALPL variants (biallelic disease), or those with other confirmed conditions that mimic HPP are unlikely to gain benefit from this observational study.

Why it matters

Potential benefit: If successful, the study could help doctors predict disease course and personalise monitoring and treatment for people with one ALPL variant.

How similar studies have performed: Enzyme-replacement therapy has shown benefit for severe biallelic HPP, but specific natural-history studies of monoallelic ALPL carriers are limited, so this observational approach addresses a relatively under-studied area.

Eligibility criteria

Inclusion criteria:

1. Age ≥4 to \<18 years, or ≥18 years at the time of enrollment;
2. Signed ICF for patients ≥18 years, or legal representatives (parents) of patients aged ≥4 to \<18 years;
3. Written informed assent (for patients aged ≥14 to \<18 years only);
4. No history of HPP treatment with enzyme-replacement therapy;
5. Diagnosis of HPP confirmed by:

   * reduced alkaline phosphatase (ALP) activity relative to age- and sex-specific reference ranges, confirmed by at least two separate measurements, AND
   * the identification of a monoallelic pathogenic, likely pathogenic, or variant of uncertain significance in the ALPL gene on genetic testing.

Exclusion Criteria:

1. Confirmed conditions presenting with clinical features overlapping with HPP, including but not limited to: cerebral palsy, Duchenne muscular dystrophy, limb-girdle muscular dystrophy (Erb-Roth dystrophy), acquired secondary myopathies of various etiologies;
2. Сurrent participation in any clinical study (patients participating in other non interventional studies may be included);
3. Homozygous or compound heterozygous mutation in the ALPL gene
4. In the opinion of the investigator, the patient is not able to return for follow-up visits or obtain required follow-up studies.
5. Pregnant and breastfeeding women.

Where this trial is running

Moscow and 3 other locations

• Research site — Moscow, Russia (Completed)
• Research Site — Moscow, Russia (Recruiting)
• Research Site — Rostov-on-Don, Russia (Recruiting)
• Research site — Saint Petersburg, Russia (Recruiting)

Study contacts

• Study coordinator: AstraZeneca Clinical Study Information Center

Conditions Hypophosphatasia