Who may be eligible for the The Effect of Monoallelic Variants in the ALPL Gene on the Natural Course of Hypophosphatasia in Russia trial?

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Accepted Answer

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 symptomatic HPP confirmed by the presence of ALL of the following criteria:

1. reduced alkaline phosphatase (ALP) activity relative to age- and sex-specific reference ranges, confirmed by at least two separate measurements;
   2. the identification of a monoallelic pathogenic, likely pathogenic, or variant of uncertain significance in the ALPL gene on genetic testing;
   3. presence of clinically relevant manifestations\*, consistent with HPP, confirmed by at least one of the following: i. Musculoskeletal pain requiring medical intervention or limiting activities of daily living, present at screening or documented within the previous 12 months (e.g., based on medical records, functional test results, treatment prescriptions and/or rehabilitation interventions); chronic or recurrent pain lasting ≥3 months may be considered based on medical history beyond the 12-month period prior to screening, provided appropriate documentation is available; ii. Muscle weakness and/or reduced physical function (e.g., impaired mobility, increased fatigue), present at screening or documented within the previous 12 months (e.g., based on medical records, functional test results, treatment prescriptions and/or rehabilitation interventions); iii. History of fractures, pseudofractures, or delayed fracture healing, confirmed by medical documentation and/or imaging studies performed within 24 months prior to screening (provided no subsequent interventions have occurred that may have altered the findings; if such interventions have occurred, repeat imaging may be performed at the investigator's discretion, if applicable within routine clinical practice); iv. Skeletal abnormalities (e.g., radiographic signs of rickets/osteomalacia), confirmed by medical documentation and/or imaging studies performed within 24 months prior to screening (provided no subsequent interventions have occurred that may have altered the findings; if such interventions have occurred, repeat imaging may be performed at the investigator's discretion, if applicable within routine clinical practice); v. Dental manifestations (e.g., premature loss of deciduous teeth with intact roots before the age of 5 years without significant trauma), confirmed by medical and/or dental records; vi. Limitation in mobility, endurance, or activities of daily living, present at screening or documented within the previous 12 months based on routine clinical assessment using questionnaires, scales, functional tests and/or other relevant clinical tools used in routine practice; such tools may include, for example, the 6-minute walk test (6MWT), Timed Up-and-Go test, Chair-Rise test, Borg scale, IPAQ, PedsQL, EQ 5D-3L, bioimpedance measurements, and other methods used in routine clinical practice; if symptoms are present at screening, confirmation may be based on clinical assessments performed within 3 months prior to screening (provided there are no clinically significant changes in the patient's condition) or at the screening visit; vii. Need for analgesics, physiotherapy, and/or other supportive care for clinical manifestations of HPP, present at screening or during the period prior to screening, confirmed by at least one of the following criteria (based on medical records):

* regular use of analgesics (≥3 times per week for at least 4 consecutive weeks) within the previous 6 months, or escalation of analgesic therapy within the previous 6 months;
      * ≥1 structured course of physiotherapy and/or rehabilitation interventions prescribed for musculoskeletal manifestations of HPP within the previous 12 months, or ongoing sessions according to specialist recommendations;
      * use of non-pharmacological and/or medical measures to reduce symptoms and support function, including orthoses, insoles, assistive devices, local injections, or other symptomatic interventions; viii. Other clinical manifestations associated with HPP, in the investigator's opinion, present at screening or documented within the previous 12 months (based on clinical assessment and/or medical records).

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. Current 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. Monoallelic pathogenic, likely pathogenic, or variant of uncertain significance in the ALPL gene in the absence of clinically relevant manifestations of HPP at the time of screening and/or in medical history consistent with the inclusion criterion #5;
5. In the opinion of the investigator, the patient is not able to return for follow-up visits or obtain required follow-up studies;
6. Pregnant and breastfeeding women.

The Effect of Monoallelic Variants in the ALPL Gene on the Natural Course of Hypophosphatasia in Russia

What this study is about

Eligibility

Inclusion criteria

Exclusion criteria

Study description and what participation involves

Questions you could ask

More on hypophosphatasia

Important dates

Sponsor and research team

Central study contact

Participating sites (4)

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