E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of osteoporosis in a paediatric population (aged 5 to 17 years old) treated with systemic glucocorticoids (i.v. or oral) |
|
E.1.1.1 | Medical condition in easily understood language |
Disease of bones that leads to an increase risk of fracture |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10028395 |
E.1.2 | Term | Musculoskeletal and connective tissue disorders |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is to demonstrate that zoledronic acid
administered every 6 months 0.05 mg/kg (max 5 mg) is superior to
placebo for the change in lumbar spine (LS) bone mineral density (BMD)
Z-score at Month 12 relative to baseline. |
|
E.2.2 | Secondary objectives of the trial |
▪ To evaluate between-treatment differences for the change in LS-BMD Zscore
▪ To evaluate between-treatment differences for the change in LS and
total body BMC
▪ To evaluate between-treatment differences for the change in serum
P1NP, BSAP, NTX, and TRAP-5b
▪ To evaluate between-treatment differences for the proportion of
patients with new vertebral fractures
▪ To evaluate the between-treatment differences for change in vertebral
morphometry
▪ To evaluate the between-treatment differences for change in pain using
the Faces Pain Scale-Revised (FPS-R)
▪ To evaluate the between-treatment differences for change in 2nd
metacarpal cortical width
▪ To measure urinary concentration of zoledronic acid
▪ The safety objective is to demonstrate that zoledronic acid is safe for
the treatment of osteoporotic children treated with glucocorticoids
through the monitoring of relevant clinical and laboratory safety
parameters. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
▪ Written informed consent must be obtained before any assessment is
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performed. An assent needs to be provided in accordance with ICH and
local regulations.
▪ Children, male or female, between 5 and 17 years of age
▪ Confirmed diagnosis of non-malignant conditions requiring treatment
with systemic glucocorticoids (including but not limited to chronic
rheumatologic conditions or, inflammatory bowel disease or Duchenne
muscular dystrophy) requiring treatment with systemic glucocorticoids
(i.v. or oral) within 12 months prior to screening
▪ Lumbar Spine BMD Z-score of -0.5 or worse confirmed by the central
imaging vendor
▪ Evidence of at least 1 vertebral compression fracture of Genant Grade 1
or higher or radiographic signs of vertebral compression fracture seen in
X-ray within 1 month of or at screening visit, confirmed by central
reading. Radiographic signs of fracture include loss of endplate
parallelism, vertebral buckling and endplate interruption.
OR
One or more, low-trauma*, lower extremity long-bone fracture which
occurred sometime within the 2 years preceding enrollment in the study,
confirmed by radiological report
OR
Two or more, low-trauma*, upper extremity long-bone fractures which
occurred sometime within the 2 years preceding enrollment in the study,
confirmed by radiological report
*Low trauma fracture is defined as falling from standing height or less.
Other protocol-defined inclusion criteria may apply |
|
E.4 | Principal exclusion criteria |
Patients/subjects fulfilling any of the following criteria are not eligible
for inclusion in this study. No additional exclusions may be applied by
the investigator, in order to ensure that the study population will be
representative of all eligible patients.
▪ History of primary bone disease (osteogenesis imperfecta, idiopathic
juvenile osteoporosis, rickets/osteomalacia).
▪ Any prior use bisphosphonates, or high dose sodium fluoride (i.e.
dental use is permitted)
▪ Any medical condition that might interfere with the evaluation of LSBMD,
such as severe scoliosis or spinal fusion
▪ As per Investigator's judgment, patient is anticipated to have surgery
within subsequent year.
▪ Hypocalcemia and hypophosphatemia: any value (age-matched) below
the normal range at screening
▪ Serum 25-hydroxy vitamin D concentrations of < 20 ng/mL or < 50
nmol/L at screening
▪ Renal impairment defined as an estimated glomerular filtration rate
(GFR) < 60ml/min/1.73 m2 at screening based on the Schwartz formula
at screening.
▪ A serum creatinine increase between Visit 1 and Visit 2 greater than 0.5
mg/dL (44.2mmol/L)
▪ Uncontrolled symptoms of cardiac failure or arrhythmia.
▪ History of hyperparathyroidism or hyperthyroidism within 1 year of
screening
▪ History of hypothyroidism unless on a stable treatment regimen for > 6
months, with at least one documented normal TSH and FT4 levels during
this 6 month period
▪ History of sarcoidosis
▪ Diagnosis of active uveitis (symptomatic or asymptomatic) at the time
of enrollment in the study
▪ History of hypersensitivity to any of the study drugs or its excipients orto drugs of similar chemical classes
▪ Female patients of child bearing potential are eligible only if they are:
(1) not pregnant/ non-lactating;
(2) are sexually abstinent or are surgically sterile
(3) if sexually active, must be practicing a medically acceptable form of
birth control for greater than 2 months prior to screening visit. Females
of child bearing potential who are sexually active must agree to continue
to practice their birth control during the trial and at least 1 year after
completing the trial and must consent to a pregnancy test prior to every
dose administration and at the End of Study (EOS) Visit.
▪ [For sites and/or regions where additional safeguards are required
e.g. UK, Italy, Germany, Sweden & etc.: Female patients of child bearing
potential are eligible only if they are not pregnant/non-lactating.
Females of child bearing potential must be practicing a medically
acceptable form of birth control for greater than 2 months prior to
screening visit. At least one and preferably two complementary forms of
contraception including a barrier method should be used and be
continued throughout the trial and for at least 1 year after completing
the trial. They must also consent to a
pregnancy test prior to every dose administration and at the EOS Visit.
An additional supervised urine pregnancy test will be assessed at Week
12
▪ History of malignancy of any organ system (other than localized basal
cell carcinoma of the skin or in-situ cervical cancer), treated or
untreated, within the past 5 years, regardless of whether there is
evidence of local recurrence or metastases.
Other protocol-defined exclusion criteria may apply |
|
E.5 End points |
E.5.1 | Primary end point(s) |
LS areal BMD Z-score measurement.
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
At screening and month 12.
|
|
E.5.2 | Secondary end point(s) |
Secondary efficacy assessments:
a. LS areal BMD Z-score.
b. LS and total body BMC.
c. Serum P1NP and BSAP.
d. Serum NTx and TRAP5b.
e. new vertebral fractures based on a lateral thoracolumbar spine x-ray.
f. vertebral morphometry, based on a lateral thoracolumbar spine x-ray.
g. Pain using the Faces Pain Scale-Revised (FPS-R).
h. Metacarpal cortical width.
I. measurement of urinary concentration |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary efficacy assessments:
a. at Month 6 (visit 5).
b. at 6 and 12 months (visits 5 and 8/EOS).
c. at months 6 and 12 (visits 5 and 8/EOS).
d. at months 6 and 12 (visits 5 and 8/EOS).
e. at month 12 relative to baseline (visit 8/EOS).
f. at month 12 relative to baseline (visit 8/EOS).
g. at months 3, 6, 9 and 12 relative to baseline (visit 4,5,7 and 8/EOS)
h. at month 12 relative to baseline (visit 8/EOS).
I. at Month 12 (Visit 8) |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Belgium |
Brazil |
Canada |
Finland |
Germany |
Hungary |
Italy |
New Zealand |
Poland |
Romania |
Russian Federation |
South Africa |
Sweden |
Turkey |
Ukraine |
United Kingdom |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
last visit of the last subject |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |