A Research Study to Compare Somapacitan Once a Week With Norditropin® Once a Day in Children Who Need Help to Grow

Inclusion criteria:

1. Informed consent of parent or legally acceptable representative of participant andchild assent, as age appropriate must be obtained before any study-relatedactivities. Study-related activities are any procedures that are carried out as partof the study, including activities to determine suitability for the study.

2. No prior exposure to growth promoting therapy, including but not limited to growthhormone, IGF-I and ghrelin analogues. Applicable to children with SGA:

3. Born small for gestational age (birth length below -2 SDS OR birth weight below -2SDS OR both) (according to national standards).

4. Prepubertal children:

5. Boys:

• Age above or equal to 2 years and 26 weeks and below 11.0 years atscreening.
• Testis volume below 4 mL

2. Girls:

• Age above or equal to 2 years and 26 weeks and below 10.0 years atscreening.
• Tanner stage 1 for breast development: No palpable glandular breasttissue)

5. Impaired height defined as at least 2.5 standard deviations below the mean heightfor chronological age and sex at screening according to the standards of Centers forDisease Control and Prevention.

6. Impaired height velocity defined as annualized height velocity below the 50thpercentile for chronological age and sex according to the standards of Pradercalculated over a time span of minimum 6 months and maximum 18 months prior toscreening.

7. Body Mass Index below the 95th percentile according to Centers for Disease Controland Prevention, Body Mass Index-for-age growth charts. Applicable to girls with TS:

8. Confirmed diagnosis of TS by 30-cell (or more) lymphocyte chromosomal analysis.*

9. 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)

10. Impaired height defined as at least 2.0 standard deviations below the mean heightfor chronological age and sex at screening according to the standards of Centers forDisease Control and Prevention.

11. Historical height measured 6-18 months prior to screening.

12. Thyroid hormone replacement therapy should be adequate and stable for at least 90days prior to randomization, if applicable. Applicable to children with NS:

13. Clinical diagnosis of NS according to van der Burgt score list

14. Prepubertal children:

15. Boys:

• Age above or equal to 2 years and 26 weeks and below 11.0 years atscreening.
• Testis volume below 4 mL

2. Girls:

• Age above or equal to 2 years and 26 weeks and below 10.0 years atscreening.
• Tanner stage 1 for breast development: No palpable glandular breasttissue)

15. Impaired height defined as at least 2.0 standard deviations below the mean heightfor chronological age and sex at screening according to the standards of Centers forDisease Control and Prevention.

16. Historical height measured 6-18 months prior to screening.

17. Thyroid hormone replacement therapy should be adequate and stable for at least 90days prior to randomization, if applicable. Applicable to children with ISS:

18. Prepubertal children:

19. Boys:

• Age above or equal to 2 years and 26 weeks and below 11.0 years atscreening.
• Testis volume below 4 mL

2. Girls:

• Age above or equal to 2 years and 26 weeks and below 10.0 years atscreening.
• Tanner stage 1 for breast development: No palpable glandular breasttissue)

19. Bone age:

20. Boys:

• Bone age below or equal to 12 years.
• Bone age not delayed or advanced more than 2 years compared tochronological age.

2. Girls:

• Bone age below or equal to 11 years.
• Bone age not delayed or advanced more than 2 years compared tochronological age.

20. Impaired height defined as at least 2.5 standard deviations below the mean heightfor chronological age and sex at screening according to the standards of Centers forDisease Control and Prevention.

21. Historical height measured 6-18 months prior to screening.

22. One normal GH secretion (GH peak above 7 ng/mL) during GH stimulation test performedwithin 18 months prior to screening or if such a test is not available for childrenwith ISS, a test should be performed as part of the screening assessments and theresult must be available prior to randomization.

• If a 30-cell count is not available for patients with TS, a test should bedone, and results must be available prior to randomization.

Exclusion criteria:

1. Known or suspected hypersensitivity to study intervention(s) or related products.

2. Previous randomization into same sub-study in this study.

3. Receipt of any investigational medicinal product within 3 months before screening orparticipation in another clinical study at the time of randomization.

4. Children with suspected or confirmed growth hormone deficiency according to localpractice.

5. laboratory of

6. fasting plasma glucose above or equal to 126 mg/dL (7.0 mmol/L) or

7. HbA1c above or equal to 6.5%.

8. Current inflammatory diseases requiring systemic corticosteroid treatment for longerthan 2 consecutive weeks within the last 3 months prior to screening.

9. Children requiring inhaled glucocorticoid therapy at a dose greater than 400 µg/dayof 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.

10. Concomitant administration of other treatments that may have an effect on growth,e.g., but not limited to methylphenidate for treatment of attention deficithyperactivity disorder (ADHD).

11. Diagnosis of attention deficit hyperactivity disorder (ADHD).

12. History or known presence of any malignancy, intracranial tumour, or intracranialcyst.

13. History or known presence of active Hepatitis B or Hepatitis C (exceptions to thisexclusion criterion is the presence of antibodies due to vaccination againstHepatitis B).

14. Any disorder, which in the investigator's opinion, might jeopardize participant'ssafety or compliance with the protocol.

15. The participant or the parent/legally acceptable representative is likely to benon-compliant in respect to study conduct, as judged by the investigator.

16. Current treatment with sex hormones or aromatase inhibitors.

17. Any known or suspected clinically significant abnormality likely to affect growth orthe ability to evaluate growth with standing height measurements, such as, but notlimited to:

18. Known family history of skeletal dysplasia.

19. Significant spinal abnormalities including but not limited to scoliosis,kyphosis and spina bifida variants.

20. Any other disorder/condition that can cause short stature such as, but notlimited to, psychosocial deprivation, nutritional disorders, chronic systemicillness and chronic renal disease.

Applicable to children with SGA:

1. TS (including mosaicism).

2. NS.

3. Hormonal deficiencies.

4. Children who are small due to malnutrition defined as -2 standard deviationsaccording to standards. 0¬-5 years: weight for height on World Health OrganizationMulticentre Growth Reference Study 2006. Above 5 years: World Health Organization 2007 Body Mass Index.

5. 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 SHOXgene analysis or absence of GH receptors.

Applicable to children with TS:

1. NS.

2. Mosaicism below 10%.

3. TS with Y-chromosome mosaicism where gonadectomy has not been performed.

4. NYHA class II or above or requiring medication for any heart condition.

5. Coeliac disease where participant is not stable on gluten free diet for the previous 12 months prior to screening.

Applicable to children with NS:

1. TS (including mosaicism).

2. Noonan-related disorders: Noonan syndrome with multiple lentigines (formerly called 'LEOPARD' syndrome), Noonan syndrome with loose anagen hair, cardiofaciocutaneoussyndrome (CFC), Costello syndrome, neurofibromatosis type 1 (NF1) and Legiussyndrome. Molecular genetic panel testing results must be available prior torandomisation to exclude these.

3. Coeliac disease where participant is not stable on gluten free diet for the previous 12 months prior to screening.

Applicable to children with ISS:

1. TS (including mosaicism).

2. NS.

3. Hormonal deficiencies.

4. Born small for gestational age (defined as birth length below -2 SDS OR birth weightbelow -2 SDS OR both) (according to national standards).

5. 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 SHOXgene analysis or absence of GH receptors.