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The effect of monoallelic variants in the ALPL gene on the natural course of hypophosphatasia (HPP) in children and adults in Russia (ATLANTIS)
Non-interventional, multi-center, cohort study for evaluation of clinical and patient reported outcomes in routine care settings
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| Measure | Description | Time Frame |
|---|---|---|
| (1) Mean age (in full years) at the HPP diagnosis; | In order to achieve the primary objectives, the following variables will be estimated | Day 0 (Visit 1) |
| (2) Mean age at the onset of initial HPP symptoms (including separately any, skeletal, and non-skeletal symptoms); | In order to achieve the primary objectives, the following variables will be estimated | Day 0 (Visit 1) |
| (3) Proportions of male and female patients | In order to achieve the primary objectives, the following variables will be estimated | Day 0 (Visit 1) |
| (4) Proportions of adults and children at baseline (childhood- and adult-onset HPP); | In order to achieve the primary objectives, the following variables will be estimated | Day 0 (Visit 1) |
| (5) Proportion of patients with a family history of HPP in a first-degree relative | In order to achieve the primary objectives, the following variables will be estimated | Day 0 (Visit 1) |
| (6) Proportions of patients with specific skeletal and non-skeletal manifestation locations/sites affected at baseline: |
| Day 0 (Visit 1) |
| (7) Proportions of patients with history and/or presence of specific skeletal manifestations at baseline: |
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Inclusion criteria:
Age ≥4 to <18 years, or ≥18 years at the time of enrollment;
Signed ICF for patients ≥18 years, or legal representatives (parents) of patients aged ≥4 to <18 years;
Written informed assent (for patients aged ≥14 to <18 years only);
No history of HPP treatment with enzyme-replacement therapy;
Diagnosis of HPP confirmed by:
Exclusion Criteria:
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This multicenter observational study will include 55 paediatric and adult patients newly diagnosed with HPP who carry monoallelic variants in the ALPL gene and are monitored by physicians of various specialties at 5 clinical centers in Moscow and Saint Petersburg, Russian Federation.
For inclusion to this study, patients should have a documented history of at least 2 reduced alkaline phosphatase (ALP) values relative to age- and sex-specific reference range measured on separate occasions and an HPP diagnosis, but no history of enzyme-replacement therapy. The specific study inclusion and exclusion criteria are described in the sections below.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| AstraZeneca Clinical Study Information Center | Contact | 1-877-240-9479 | information.center@astrazeneca.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research site | Completed | Moscow | Russia | |||
| Research Site |
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
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| ID | Term |
|---|---|
| D007014 | Hypophosphatasia |
| ID | Term |
|---|---|
| D008664 | Metal Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
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|
| Day 0 (Visit 1) |
| (8) Proportions of patients with history and/or presence of specific dental manifestations at baseline: |
| Day 0 (Visit 1) |
| (9) Proportions of patients with history and/or presence of specific muscular manifestations at baseline: |
| Day 0 (Visit 1) |
| (10) Proportions of patients with history and/or presence of specific rheumatologic manifestations at baseline: |
| Day 0 (Visit 1) |
| (11) Proportions of patients with history and/or presence of specific renal manifestations at baseline: |
| Day 0 (Visit 1) |
| (12) Proportions of patients with history and/or presence of specific respiratory manifestations at baseline: |
| Day 0 (Visit 1) |
| (13) Proportions of patients with history and/or presence of specific neurologic / psychiatric manifestations at baseline: |
| Day 0 (Visit 1) |
| (14) Proportions of patients with history and/or presence of other specific manifestations at baseline: |
| Day 0 (Visit 1) |
| (15) Median Standard Deviation Score (SDS) for height at baseline (for patients aged <18 years at the respective timepoints only); | In order to achieve the primary objectives, the following variables will be estimated | Day 0 (Visit 1) |
| (16) Proportion of patients with short stature at baseline (SDS for height <-2.0); | In order to achieve the primary objectives, the following variables will be estimated | Day 0 (Visit 1) |
| (17) Proportions of patients with other non-specific comorbidities at baseline; | In order to achieve the primary objectives, the following variables will be estimated | Day 0 (Visit 1) |
| (18) Proportions of patients with a history and/or presence of specific radiologic signs (X-ray of both hands, posteroanterior view on a single film including the distal forearms) at baseline: |
| Day 0 (Visit 1) |
| (19) Proportions of patients with history and/or presence of specific radiologic signs (radiography of both lower limbs, posteroanterior view on a single full-length film, including the distal lower legs) at baseline: |
| Day 0 (Visit 1) |
| (20) Proportions of patients with history and/or presence of specific radiologic signs on standing spine radiographs in anteroposterior and lateral views (preferably full-length) at baseline |
Children unable to maintain an upright position during radiography may undergo the examination in the supine position in anteroposterior and lateral views). | Day 0 (Visit 1) |
| (21) Proportions of patients with history and/or presence of specific radiologic signs on skull radiographs in anteroposterior and lateral views at baseline: |
| Day 0 (Visit 1) |
| (22) Proportions of patients with history and/or presence of specific radiologic signs on foot radiographs in anteroposterior and lateral views (in the presence of clinical signs of a pathological "march" fracture) at baseline: |
| Day 0 (Visit 1) |
| (23) Median Rickets Severity Scale (RSS) at baseline (only for children ≤14 years at the respective timepoints); | In order to achieve the primary objectives, the following variables will be estimated | Day 0 (Visit 1) |
| (24) Proportions of patients with history and/or presence of specific laboratory findings at baseline: |
| Day 0 (Visit 1) |
| (25) a Mean and median values of specific laboratory findings at baseline: | a) ALP (U/L) | Day 0 (Visit 1) |
| (26) Proportions of patients with specific ALPL gene mutations (for each gene variant); | In order to achieve the primary objectives, the following variables will be estimated | Day 0 (Visit 1) |
| (27) Mean and median number of fractures at baseline; | In order to achieve the primary objectives, the following variables will be estimated | Day 0 (Visit 1) |
| (28) Mean and median number of dental losses at baseline; | In order to achieve the primary objectives, the following variables will be estimated | Day 0 (Visit 1) |
| (29) Mean and median 6-Minute Walk Test (6MWT) distance (m) at baseline (only for patients ≥5 years); | In order to achieve the primary objectives, the following variables will be estimated | Day 0 (Visit 1) |
| (30) Proportion of patients with decreased 6MWT distance (m) at baseline (<80% of the predicted norm, only for patients ≥5 years); | In order to achieve the primary objectives, the following variables will be estimated | Day 0 (Visit 1) |
| (31) Mean and median Chair-Rise Test time (s) at baseline (only for patients ≥18 years); | In order to achieve the primary objectives, the following variables will be estimated | Day 0 (Visit 1) |
| (32) Mean and median Timed Up and Go (TUG) Test time (s) at baseline (only for adults ≥18 years); | In order to achieve the primary objectives, the following variables will be estimated | Day 0 (Visit 1) |
| (33) a Mean and median values of specific bioimpedance parameters at baseline | a) Total Skeletal Muscle Mass (SMM) (kg); | Day 0 (Visit 1) |
| (34) a Mean and median Rating of Perceived Exertion (RPE) score, based on Borg Scale, during the following specific tests at baseline (when the respective tests have been performed): | a) 6MWT; | Day 0 (Visit 1) |
| (35) Mean and median weekly physical activity duration, measured using the International Physical Activity Questionnaire (IPAQ) Diary, at baseline | In order to achieve the primary objectives, the following variables will be estimated | Day 0 (Visit 1) |
| (36) Mean and median Pediatric Quality of Life Inventory (PedsQL) score at baseline (only for children <18 years); | In order to achieve the primary objectives, the following variables will be estimated | Day 0 (Visit 1) |
| (37) Proportion of patients with different levels of European Quality of Life 5 Dimensions 3-Level (EQ-5D-3L) questionnaire for each of the following dimensions at baseline | (1 / 2 / 3): mobility, self-care, usual activities, pain/discomfort, and anxiety/depression (only for adults aged ≥ 18 years); | Day 0 (Visit 1) |
| (38) Mean and median EQ-5D-3L Visual Analogue Scale (VAS) score at baseline (only for adults aged ≥ 18 years); | In order to achieve the primary objectives, the following variables will be estimated | Day 0 (Visit 1) |
| (39) Proportion of patients with different Modified Ashworth Scale (MAS) scores (0, 1, 1+, 2, 3, or 4) for each specific muscle / muscle group at baseline: |
| Day 0 (Visit 1) |
| (40) Proportion of patients with clinically significant spasticity (MAS score ≥2 in at least one muscle / muscle group) at baseline; | In order to achieve the primary objectives, the following variables will be estimated | Day 0 (Visit 1) |
| (41) Mean and median dynamic component (D) measure based on the modified Tardieu Scale (MTS) on the for each specific muscle / muscle group at baseline (degrees): |
| Day 0 (Visit 1) |
| (42) Proportion of patients with different MTS Resistance scores (0, 1, 2, 3, 4, or 5) for each specific muscle / muscle group at baseline: |
| Day 0 (Visit 1) |
| (43) Proportion of patients with clonus (MTS Resistance score ≥3 in at least one muscle / muscle group) at baseline; | In order to achieve the primary objectives, the following variables will be estimated | Day 0 (Visit 1) |
| (44) Proportion of patients with previous hospitalizations due to HPP manifestations at baseline; | In order to achieve the primary objectives, the following variables will be estimated | Day 0 (Visit 1) |
| (45) Median number of previous hospitalizations due to HPP manifestations at baseline | In order to achieve the primary objectives, the following variables will be estimated | Day 0 (Visit 1) |
| (46) Annualized rate of hospitalizations due to HPP manifestations prior to baseline | In order to achieve the primary objectives, the following variables will be estimated | Day 0 (Visit 1) |
| (47) Mean and median duration of previous hospitalizations due to HPP manifestations at baseline | In order to achieve the primary objectives, the following variables will be estimated | Day 0 (Visit 1) |
| (48) Proportions of patients with different degrees of disability according to national criteria at baseline |
| Day 0 (Visit 1) |
| (49) Proportions of patients who had specific previous medical interventions & surgeries at baseline: |
| Day 0 (Visit 1) |
| (50) Proportions of patients who previously received specific treatments at baseline: |
| Day 0 (Visit 1) |
| (34) b Mean and median Rating of Perceived Exertion (RPE) score, based on Borg Scale, during the following specific tests at baseline (when the respective tests have been performed): | b) Chair-Rise Test; | Day 0 (Visit 1) |
| (34) c Mean and median Rating of Perceived Exertion (RPE) score, based on Borg Scale, during the following specific tests at baseline (when the respective tests have been performed): | c) TUG Test; | Day 0 (Visit 1) |
| (33) b Mean and median values of specific bioimpedance parameters at baseline | b) Lean Body Mass (LBM) (kg); | Day 0 (Visit 1) |
| (33) c Mean and median values of specific bioimpedance parameters at baseline | c. Phase angle (degrees) | Day 0 (Visit 1) |
| (25) b Mean and median values of specific laboratory findings at baseline: | b) Serum/plasma PLP (ng/ml) | Day 0 (Visit 1) |
| (25) c Mean and median values of specific laboratory findings at baseline: | c. Urine PEA (m mol/mol creatinine) | Day 0 (Visit 1) |
| (25) d Mean and median values of specific laboratory findings at baseline: | d. GFR (ml/min/1.73m2) | Day 0 (Visit 1) |
| (25) e Mean and median values of specific laboratory findings at baseline: | e. Serum calcium (mmol/L) | Day 0 (Visit 1) |
| (25) f Mean and median values of specific laboratory findings at baseline: | f. Urine calcium (mmol/24h) | Day 0 (Visit 1) |
| (25) g Mean and median values of specific laboratory findings at baseline: | g. Serum PTH (pmol/L) | Day 0 (Visit 1) |
| (25) h Mean and median values of specific laboratory findings at baseline: | h. Serum 25-hydroxyvitamin D (ng/ml) | Day 0 (Visit 1) |
| Recruiting |
| Moscow |
| Russia |
| Research Site | Recruiting | Rostov-on-Don | Russia |
| Research site | Recruiting | Saint Petersburg | Russia |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |