Study to know the safety and efficacy of once once weekly dosing of somapacitan with daily Norditropin in children with short stature either born small for gestational age or with Turner syndrome, Noonan syndrome, or idiopathic short stature
- Conditions
- Health Condition 1: E368- Other intraoperative complicationsof endocrine system
- Registration Number
- CTRI/2023/03/050330
- Lead Sponsor
- ovo Nordisk AS
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- Not specified
- Target Recruitment
- 0
1.Informed consent of parent or legally acceptable representative of participant and child assent, as age appropriate must be obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study.
2.No prior exposure to growth promoting therapy, including but not limited to growth hormone, IGF-I and ghrelin analogues.
Applicable to children with SGA:
Born small for gestational age (birth length below -2 SDS OR birth weight below -2 SDS OR both) (according to national standards).
3.Prepubertal children:
a)Boys:
•Age above or equal to 2 years and 26 weeks and below 11.0 years at screening.
•Testis volume below 4 mL
b)Girls:
•Age above or equal to 2 years and 26 weeks and below 10.0 years at screening.
•Tanner stage 1 for breast development: No palpable glandular breast tissue)
Impaired height defined as at least 2.5 standard deviations below the mean height for chronological age and sex at screening according to the standards of Centers for Disease Control and Prevention
Impaired height velocity defined as annualised height velocity below the 50th percentile for chronological age and sex according to the standards of Prader calculated over a time span of minimum 6 months and maximum 18 months prior to screening.
Body Mass Index below the 95th percentile according to Centers for Disease Control and Prevention, Body Mass Index-for-age growth charts
Applicable to girls with TS:
Confirmed diagnosis of TS by 30-cell (or more) lymphocyte chromosomal analysis
Prepubertal girls:
•Age above or equal to 2 years and 26 weeks and below 10.0 years at screening.
•Tanner stage 1 for breast development: No palpable glandular breast tissue)
Impaired height defined as at least 2.0 standard deviations below the mean height for chronological age and sex at screening according to the standards of Centers for Disease Control and Prevention
Historical height measured 6–18 months prior to screening.
Thyroid hormone replacement therapy should be adequate and stable for at least 90 days prior to randomisation, if applicable.
Applicable to children with NS:
Clinical diagnosis of NS according to van der Burgt score list Prepubertal children:
c)Boys:
•Age above or equal to 2 years and 26 weeks and below 11.0 years at screening.
•Testis volume below 4 mL
d)Girls:
•Age above or equal to 2 years and 26 weeks and below 10.0 years at screening.
•Tanner stage 1 for breast development: No palpable glandular breast tissue)
Impaired height defined as at least 2.0 standard deviations below the mean height for chronological age and sex at screening according to the standards of Centers for Disease Control and Prevention
Historical height measured 6–18 months prior to screening.
Thyroid hormone replacement therapy should be adequate and stable for at least 90 days prior to randomisation, if applicable.
Applicable to children with ISS:
Prepubertal children:
e)Boys:
•Age above or equal to 2 years and 26 weeks and below 11.0 years at screening.
•Testis volume below 4 mL
f)Girls:
•Age above or equal to 2 years and 26 weeks and below 10.0 y
Known or suspected hypersensitivity to study intervention(s) or related products.
2. Previous randomisation into same sub-study in this study.
3. Receipt of any investigational medicinal product within 3 months before screening or participation in another clinical study at the time of randomisation
Children with suspected or confirmed growth hormone deficiency according to local practice.
5. Children diagnosed with diabetes mellitus or screening values from the central laboratory of
a. fasting plasma glucose above or equal to 126 mg/dL (7.0 mmol/L) or
b. HbA1c above or equal to 6.5%.
6. Current inflammatory diseases requiring systemic corticosteroid treatment for longer than 2 consecutive weeks within the last 3 months prior to screening.
7. Children requiring inhaled glucocorticoid therapy at a dose greater than 400 µg/day of inhaled budesonide or equivalent (i.e., 250 µg/day for fluticasone propionate) for longer than 4 consecutive weeks within the last 12 months prior to screening.
8. Concomitant administration of other treatments that may have an effect on growth, e.g., but not limited to methylphenidate for treatment of attention deficit hyperactivity disorder (ADHD).
9. Diagnosis of attention deficit hyperactivity disorder (ADHD).
10. History or known presence of malignancy including intracranial tumours.
11. History or known presence of active Hepatitis B or Hepatitis C (exceptions to this exclusion criterion is the presence of antibodies due to vaccination against Hepatitis B).
12. Any disorder, which in the investigator’s opinion, might jeopardise participant’s safety or compliance with the protocol.
13. The participant or the parent/legally acceptable representative is likely to be non-compliant in respect to study conduct, as judged by the investigator.
14. Current treatment with sex hormones or aromatase inhibitors.
Applicable to children with SGA:
15. Any known or suspected clinically significant abnormality likely to affect growth or the ability to evaluate growth with standing height measurements, such as, but not limited to: India: Please see local requirements in Appendix 11 (Section 10.11).
a. Known family history of skeletal dysplasia.
b. Significant spinal abnormalities including but not limited to scoliosis, kyphosis and spina bifida variants.
Any other disorder/condition that can cause short stature such as, but not limited to, psychosocial deprivation, nutritional disorders, chronic systemic illness and chronic renal disease.
d. TS (including mosaicism). India: Please see local requirements in Appendix 11 (Section 10.11).
e. NS.
f. Hormonal deficiencies.
g. Children who are small due to malnutrition defined as -2 standard deviations according to standards. 0–5 years: weight for height on World Health Organisation Multicentre Growth Reference Study 2006. Above 5 years: World Health Organisation 2007 Body Mass Index. India: Please see local requirements in Appendix 11 (Section 10.11).
h. Known chromosomal aneuploidy or significant gene mutations causing medical ‘syndromes’ with short stature, including but not limited to Laron syndrome, Prader-Willi syndrome, Russell-Silver Syndrome, skeletal dysplasias, abnormal SHOX gene analysis or absence of GH receptors.
Applicable to children with TS:
16. Any known or suspected clinically si
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To confirm non-inferiority of <br/ ><br>once-weekly somapacitan <br/ ><br>compared with once-daily <br/ ><br>Norditropin® in terms of <br/ ><br>longitudinal growth measured by height velocity at week 52 in children with each of the four indications: SGA, TS, NS or ISSTimepoint: From baseline (week 0) to visit 7 (week 52).
- Secondary Outcome Measures
Name Time Method To evaluate long-term safety of once-weekly somapacitan in terms of safety parameters measured by glucose metabolism in children with each of the four indications: SGA, TS, NS or ISSTimepoint: From screening (visit 1) to visit 15 (week 156).;To evaluate once-weekly somapacitan compared with <br/ ><br>once-daily Norditropin® in terms of other aspects of longitudinal growth in children with each of <br/ ><br>the four indications: SGA, TS, <br/ ><br>NS or ISS.Timepoint: From baseline (week <br/ ><br>0) to visit 7 (week <br/ ><br>52);To evaluate safety of onceweekly somapacitan compared with once-daily Norditropin® in terms of safety parameters measured by glucose metabolism <br/ ><br>in children with each of the four indications: SGA, TS, NS or ISSTimepoint: From screening <br/ ><br>(visit 1) to visit 7 <br/ ><br>(week 52);To evaluate the steady state pharmacokinetics of once-weekly somapacitan in children with each of the four indications: SGA, TS, NS or ISSTimepoint: From visit 3 (week 4) to visit 7 (week 52).