A research study to compare somapacitan once a week with Norditropin® once a day in children who need help to grow

• Register: EUCTR
• Last refreshed on: 12 August 2024
• Main ID: EUCTR2021-005607-13-SI
• Date of registration: 29/04/2022
• Prospective Registration: Yes
• Primary sponsor: Novo Nordisk A/S
• Public title: A research study to compare somapacitan once a week with Norditropin® once a day in children who need help to grow
• Scientific title: A study comparing the effect and safety of once weekly dosing of somapacitan with daily Norditropin® as well as evaluating long-term safety of somapacitan in a basket study design in children with short stature either born small for gestational age or with Turner syndrome, Noonan syndrome, or idiopathic short stature.
• Date of first enrolment: 20/06/2022
• Target sample size: 395
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-005607-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Brazil, Bulgaria, Canada, China, Croatia, European Union, Finland, Germany, Greece, India, Ireland, Israel, Italy, Japan, Korea, Republic of, Latvia, Lithuania, Malaysia, Mexico, Netherlands, Poland, Portugal, Russian Federation, Saudi Arabia, Serbia, Slovenia, South Africa, Spain, Switzerland, Thailand, United Kingdom, United States

Contacts

• Name: Clinical Transparency (2834)
• Affiliation: Novo Nordisk A/S

• Name: Clinical Transparency (2834)
• Affiliation: Novo Nordisk A/S

Key inclusion & exclusion criteria

Inclusion criteria:
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:
3. Born small for gestational age (birth length below -2 SDS OR birth weight below -2 SDS OR both) (according to national standards).
4. 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.
5. 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.
6. 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.
7. 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:
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 height for chronological age and sex at screening according to the standards of Centers for Disease 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 90 days prior to randomisation, if applicable.
Applicable to children with NS:
13. Clinical diagnosis of NS according to van der Burgt score list
14. 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.
15. 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.
16. Historical height measured 6–18 months prior to screening.
17. Thyroid hormone replacement therapy should be adequate and stable for at least 90 days prior to randomisation, if applicable.
Applicable to children with ISS:
18. 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.
19. Bone age:
a) Boys:
• Bone age below or equal to 12 years.
• Bone age not delayed or advanced more than 2 years compared to chronologica
Exclusion criteria:
1. 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.
4. 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 any malignancy, intracranial tumour, or intracranial cyst.
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.
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:
a. Known family history of skeletal dysplasia.
b. Significant spinal abnormalities including but not limited to scoliosis, kyphosis and spina bifida variants.
c. 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.
Applicable to children with SGA:
a. TS (including mosaicism).
b. NS.
c. Hormonal deficiencies.
d. 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.
e. 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:
a. NS.
b. Mosaicism below 10%.
c. TS with Y-chromosome mosaicism where gonadectomy has not been performed.
d. NYHA class II or above or requiring medication for any heart condition.
e. Coeliac disease where participant is not stable on gluten free diet for the previous 12 months prior to screening.
Applicable to children with NS:
a. TS (including mosaicism).
b. Noonan-related disorders: Noonan syndrome wi

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Hormonal diseases [C19]

Short stature born small for gestational age Turner syndrome Noonan syndrome Idiopathic short stature
MedDRA version: 20.0 Level: PT Classification code 10045181 Term: Turner's syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders
MedDRA version: 20.0 Level: PT Classification code 10029748 Term: Noonan syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders
MedDRA version: 23.0 Level: LLT Classification code 10066333 Term: Idiopathic short stature System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
MedDRA version: 21.1 Level: LLT Classification code 10041093 Term: Small for gestational age System Organ Class: 10036585 - Pregnancy, puerperium and perinatal conditions

Intervention(s)

Trade Name: Sogroya 10 mg/1.5 mL solution for injection in pre-filled pen
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: Somapacitan
Other descriptive name: Somapacitan
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 6.7-

Product Name: somapacitan 5 mg/1.5 mL PDS290
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: Somapacitan
Other descriptive name: Somapacitan
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 3.3-

Product Name: Somapacitan 15 mg/1.5 mL PDS290
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: Somapacitan
Other descriptive name: Somapacitan
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Trade Name: Norditropin FlexPro 10 mg/1.5 ml, solution for injection in pre-filled pen
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: Somatropin
Other descriptive name: Somatropin
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 6.7-

Primary Outcome(s)

Primary end point(s): Height velocity reported for each indication separately.

Timepoint(s) of evaluation of this end point: From baseline (week 0) to visit 7 (week 52)

Main Objective: To confirm non-inferiority of once-weekly somapacitan compared with once-daily
Norditropin® in terms of longitudinal growth measured by height velocity at week 52 in
children with each of the four indications: SGA, TS, NS or ISS.

Secondary Objective: 1.To evaluate once-weekly somapacitan compared with once-daily Norditropin® in terms of other aspects of longitudinal growth in children with each of the four indications: SGA, TS, NS or ISS.

2. To evaluate safety of once-weekly somapacitan compared with once-daily Norditropin® in terms of safety parameters measured by glucose metabolism in children with each of the four indications: SGA, TS, NS or ISS.

3. To evaluate the steady state pharmacokinetics of once-weekly somapacitan in children with
each of the four indications: SGA, TS, NS or ISS.

4. 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 ISS.

Secondary Outcome(s)

Secondary end point(s): 1.1 Change in Height SDS reported for each indication separately.
1.2 Change in Height Velocity SDS reported for each indication separately.
1.3 Change in bone age reported for each indication separately
1.4 Change in IGF-I SDS reported for each indication separately.
1.5 Change in IGFBP-3 SDS reported for each indication separately.

2.1 Change in fasting plasma glucose reported for each indication separately.
2.2 Change in homeostatic model assessment-B (HOMA-B) reported for each indication separately.
2.3 Change in homeostatic model assessment-IR (HOMAIR) reported for each indication separately.
2.4 Change in glycated haemoglobin (HbA1c) reported for each indication separately.

3.1 Weekly average somapacitan concentration (Cavg) based on population PK analysis.

4.1 Change in fasting plasma glucose reported for each indication separately.
4.2 Change in homeostatic model assessment-B (HOMA-B) reported for each indication separately.
4.3 Change in homeostatic model assessment-IR (HOMA-IR) reported for each indication
separately.
4.4 Change in glycated haemoglobin (HbA1c) reported for each indication separately.

Timepoint(s) of evaluation of this end point: 1.1 From baseline (week 0) to visit 7 (week 52).
1.2 From baseline (week 0) to visit 7 (week 52).
1.3 For SGA, TS and NS: From baseline (week 0) to visit 7 (week 52).
For ISS: From screening (visit 1) to visit 7 (week 52).
1.4 From baseline (week 0) to visit 7 (week 52).
1.5 From baseline (week 0) to visit 7 (week 52).


2.1 From screening (visit 1) to visit 7(week 52).
2.2 From screening (visit 1) to visit 7(week 52).
2.3 From screening (visit 1) to visit 7(week 52).
2.4 From screening (visit 1) to visit 7(week 52).

3.1 From visit 3 (week 4) to visit 7 (week 52).

4.1 From screening (visit 1) to visit 15 (week 156).
4.2 From screening (visit 1) to visit 15 (week 156).
4.3 From screening (visit 1) to visit 15 (week 156).
4.4 From screening (visit 1) to visit 15 (week 156).

Secondary ID(s)

2021-005607-13-IT

NN8640-4467

Source(s) of Monetary Support

Novo Nordisk A/S

Ethics review

Status: Approved
Approval date: 09/06/2022
Contact: