A Research Study Looking at How Safe Somapacitan is and How Well it Works in Children Who Need Help to Grow - REAL 9 (REAL 9)

A Study Evaluating the Safety and Efficacy of Once-weekly Dosing of Somapacitan in a Basket Study Design in Paediatric Participants With Short Stature Either Born Small for Gestational Age or With Turner Syndrome, Noonan Syndrome or Idiopathic Short Stature

The purpose of this study is to find out if somapacitan is safe and how well somapacitan works in children either born small for gestational age or with Turner syndrome, Noonan syndrome or idiopathic short stature. Somapacitan is a new growth hormone medicine for treatment of low level of growth hormone. The study will last for about 3 years. During the study, the participants will be treated with somapacitan once a week. Somapacitan can be injected anytime during the day. The study doctor or nurse will show how to inject somapacitan, so that the participant knows how to do it at home.

Study Overview

• Status: Recruiting
• Conditions: Turner Syndrome; Noonan Syndrome; SGA; ISS
• Intervention / Treatment: Drug: Somapacitan

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Novo Nordisk; Phone Number: (+1) 866-867-7178; Email: clinicaltrials@novonordisk.com

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 05505
    • Recruiting
    • Asan Medical Center
  • Seoul, Korea, Republic of, 05505
    • Not yet recruiting
    • Asan Medical Center
  • Yangsan, Korea, Republic of, 50612
    • Recruiting
    • Pusan National University Yangsan Hospital
  • Yangsan, Korea, Republic of, 50612
    • Not yet recruiting
    • Pusan National University Yangsan Hospital
• Malaysia
  • Bandar Puncak Alam Selangor Darul Ehsan, Malaysia, 42300
    • Recruiting
    • University Technology MARA (UiTM) - Puncak Alam
  • Wilayah Persekutuan Kuala Lumpur
    • Kuala Lumpur, Wilayah Persekutuan Kuala Lumpur, Malaysia, 59100
      • Recruiting
      • University Malaya Medical Centre
• Netherlands
  • Rotterdam, Netherlands, 3015 GD
    • Not yet recruiting
    • Erasmus MC
  • Rotterdam, Netherlands, 3015 GD
    • Withdrawn
    • Erasmus MC
• Poland
  • Gdansk, Poland, 80-952
    • Recruiting
    • UCK, Klinika Pediatrii, Diabetologii i Endokrynologii,
  • Lodz, Poland, 93-338
    • Recruiting
    • Instytut Centrum Zdrowia Matki Polki
  • Zabrze, Poland, 41-800
    • Recruiting
    • Klinika Pediatrii SUM, SPSK nr 1 im. prof.S.Szyszko w Zabrzu_LOC#1
  • Podkarpackie Voivodeship
    • Rzeszow, Podkarpackie Voivodeship, Poland, 35-301
      • Recruiting
      • Kliniczny Szpital Wojewódzki Nr 2 Im. Św. Jadwigi Królowej W Rzeszowie
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Vall d'Hebron
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • Univ of AL at Birmingham_BRM
  • California
    • Sacramento, California, United States, 95821
      • Recruiting
      • Ctr of Exclnce in Diab and Endo
  • Colorado
    • Centennial, Colorado, United States, 80112
      • Recruiting
      • Rocky Mt Ped and Endo
  • District of Columbia
    • Washington, District of Columbia, United States, 20010-2978
      • Not yet recruiting
      • Childrens National Medical Ctr
  • Idaho
    • Idaho Falls, Idaho, United States, 83404-7596
      • Recruiting
      • Rocky Mt Clin Res, LLC
  • Minnesota
    • Saint Paul, Minnesota, United States, 55102
      • Recruiting
      • Children's Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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).

• Age:

  - Male participants: Age equal to or above 11.0 years and below 18.0 years at screening.

  - Female participants: Age equal to or above 10.0 years and below 18.0 years at screening.

• Open epiphyses; defined as bone age less than (<) 14 years for females and bone age < 16 years for males.
• For Growth Hormone (GH) treatment naïve participants: 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.

Applicable to children with TS:

• Diagnosis of TS according to local clinical practice.

• Age:

  - Female participants: Age equal to or above 10.0 years and below 18.0 years at screening.

• Open epiphyses; defined as bone age < 14 years for females and bone age < 16 years for males.
• For GH treatment naïve participants: Impaired height defined as at least 2.0 standard deviation below the mean height for chronological age and sex at screening according to the standards of Centers for Disease Control and Prevention.
• For GH treatment naïve participants: Confirmed diagnosis of TS by 30-cell (or more) lymphocyte chromosomal analysis or confirmation of TS and TS mosaicism using comparative genomic hybridization (CGH)-array.

Applicable to children with NS:

• Diagnosis of NS according to local clinical practice.

• Age:

  • Male participants: Age equal to or above 11.0 years and below 18.0 years at screening.
  • Female participants: Age equal to or above 10.0 years and below 18.0 years at screening.
• Open epiphyses; defined as bone age < 14 years for females and bone age < 16 years for males.
• For GH treatment naïve participants: Clinical diagnosis of NS according to van der Burgt score list and genetic test result or confirmed mutation in any of the genes associated with NS before allocation.

Applicable to children with ISS:

• Age:

  - Male participants: Age equal to or above 11.0 years and below 18.0 years at screening.

  - Female participants: Age equal to or above 10.0 years and below 18.0 years at screening.

• Open epiphyses; defined as bone age < 14 years for females and bone age < 16 years for males.
• For GH treatment naïve participants: Impaired height defined as at least 2.5 standard deviations below the mean height for chronological age and sex at screening
• For GH treatment naïve participants: Normal GH secretion (GH peak above 7 ng/mL) during GH stimulation test performed within 18 months prior to screening.
• For GH treatment naïve participants: Bone age not delayed more than 2 years compared to chronological age at screening.

Exclusion Criteria:

• Children with suspected or confirmed growth hormone deficiency according to local practice.
• Children diagnosed with diabetes mellitus or screening values from the central laboratory.
• Fasting plasma glucose above or equal to 126 milligrams per deciliter (mg/dL) [7.0 millimoles per litre (mmol/L)] or
• Glycated hemoglobin (HbA1c) above or equal to 6.5%.
• Current inflammatory diseases requiring systemic corticosteroid treatment for longer than 2 consecutive weeks within the last 3 months prior to screening.
• Children requiring inhaled glucocorticoid therapy at a dose greater than 400 micrograms per day (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.
• History or known presence of malignancy including intracranial tumours.

Applicable to children with SGA:

• Any known or suspected clinically significant abnormality likely to affect growth or the ability to evaluate growth with height, such as, but not limited to:

• Poorly controlled or uncontrolled hormonal deficiencies.
• 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 short stature homeobox (SHOX) gene analysis or absence of GH receptors.

Applicable to children with TS:

• Any known or suspected clinically significant abnormality likely to affect growth or the ability to evaluate growth with height, such as, but not limited to:

• Known family history of skeletal dysplasia.
• Significant spinal abnormalities including but not limited to scoliosis, kyphosis and spina bifida variants.
• Any other disorder that can cause short stature such as, but not limited to nutritional disorders, chronic systemic illness and chronic renal disease.
• Mosaicism below 10%.
• TS with Y-chromosome mosaicism where gonadectomy has not been performed.
• New York Heart Association (NYHA) class II or above or requiring medication for any heart condition.

Applicable to children with NS:

• Any known or suspected clinically significant abnormality likely to affect growth or the ability to evaluate growth with height, such as, but not limited to:

• Known family history of skeletal dysplasia.
• Significant spinal abnormalities including but not limited to scoliosis, kyphosis and spina bifida variants.
• Any other disorder that can cause short stature such as, but not limited to nutritional disorders, chronic systemic illness and chronic renal disease.
• Noonan-related disorders including but not limited to: Noonan syndrome with multiple lentigines (formerly called 'LEOPARD' syndrome), Noonan syndrome with loose anagen hair, cardiofaciocutaneous syndrome (CFC), Costello syndrome, neurofibromatosis type 1 (NF1) and Legius syndrome.

Applicable to children with ISS:

• Any known or suspected clinically significant abnormality likely to affect growth or the ability to evaluate growth with height, such as, but not limited to:

• Known family history of skeletal dysplasia.
• Significant spinal abnormalities including but not limited to scoliosis, kyphosis and spina bifida variants.
• Any other disorder that can cause short stature such as, but not limited to nutritional disorders, chronic systemic illness and chronic renal disease.
• Poorly controlled or uncontrolled hormonal deficiencies.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Somapacitan; Participants will receive Somapacitan for 26-week main phase followed by 130-week extension phase.	Drug: Somapacitan; Somapacitan 0.24 milligrams per kilograms per week (mg/kg/week) will be administered subcutaneously (s.c.) using PDS290 pen-injector.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of adverse events (AEs) reported separately for small for gestational age (SGA), Turner syndrome (TS), Noonan syndrome (NS) and idiopathic short stature (ISS)	Measured as number of events.	From baseline (week 0) to week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of adverse events (AEs) possibly or probably related to somapacitan reported separately for SGA, TS, NS and ISS	Measured as number of events.	From baseline (week 0) to week 26
Number of adverse events (AEs) reported separately for SGA, TS, NS and ISS	Measured as number of events.	From baseline (week 0) to week 156
Height Velocity reported separately for SGA, TS, NS and ISS	Measured in centimeters per year (cm/year).	From baseline (week 0) to week 26
Change in Height standard deviation scores (SDS) reported separately for SGA, TS, NS and ISS	Measured in score. Positive score indicates that the value is closer to or above the reference population compared to baseline.	From baseline (week 0) to week 26
Change in Height Velocity SDS reported separately for SGA, TS, NS and ISS	Measured in score. Positive score indicates that the value is closer to or above the reference population compared to baseline.	From baseline (week 0) to week 26
Change in insulin-like growth factor 1 (IGF-1) SDS reported separately for SGA, TS, NS and ISS	Measured in score. Positive score indicates that the value is closer to or above the reference population compared to baseline.	From baseline (week 0) to week 26
Change in insulin-like growth factor binding protein-3 (IGFBP-3) SDS reported separately for SGA, TS, NS and ISS	Measured as score. Positive score indicates that the value is closer to or above the reference population compared to baseline.	From baseline (week 0) to week 26
Weekly average somapacitan concentration (Cavg) based on population pharmacokinetic (PK) analysis	Measured in nanograms per milliliter (ng/mL).	From baseline (week 0) to week 26

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Transparency (dept. 2834), Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2023
• Primary Completion (Estimated): November 15, 2024
• Study Completion (Estimated): June 21, 2027

Study Registration Dates

• First Submitted: January 29, 2023
• First Submitted That Met QC Criteria: January 29, 2023
• First Posted (Actual): February 13, 2023

Study Record Updates

• Last Update Posted (Actual): April 1, 2024
• Last Update Submitted That Met QC Criteria: March 29, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Endocrine System Diseases; Disease; Gonadal Disorders; Disorders of Sex Development; Urogenital Abnormalities; Congenital Abnormalities; Genetic Diseases, Inborn; Musculoskeletal Diseases; Connective Tissue Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Chromosome Disorders; Sex Chromosome Disorders; Sex Chromosome Disorders of Sex Development; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Syndrome; Turner Syndrome; Gonadal Dysgenesis; Noonan Syndrome
• Other Study ID Numbers: NN8640-4469; U1111-1277-9765 (Other Identifier: World Health Organization (WHO)); 2022-501055-87 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No