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Trial · Interventional

CompletedPhase 3Results postedRegistry data

A Research Study in Children With a Low Level of Hormone to Grow. Treatment is Somapacitan Once a Week Compared to Norditropin® Once a Day (REAL4)

Short name REAL4

NCTNCT03811535 (opens ClinicalTrials.gov in a new tab)Other idNN8640-4263Other idU1111-1207-9691Other id2018-000231-27Other idJapicCTI-194773
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 3
Enrollment
200 participants (actual)
Sponsor
Novo Nordisk A/S · Industry
Design
Randomized · Open label (no masking)
Countries
26 countries

United States, Algeria, Austria, Canada, Denmark, Estonia, France, Germany, Hungary, India, Ireland, Israel, Italy, Japan, Latvia, Norway, Poland, Russia, Serbia, Slovenia, South Korea, Spain, Switzerland, Thailand, Ukraine, United Kingdom

Start
20 May 2019
Primary completion
10 Nov 2021
Completion
30 Sept 2025
First posted
22 Jan 2019
Last update posted
22 Oct 2026
Conditions
Growth Hormone Deficiency in Children

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2020202220242026
  1. Ph 3

    REAL4

    NCT03811535

    20 May 2019 to 30 Sept 2025

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

The study compares 2 medicines for children who do not have enough hormone to grow: somapacitan given once a week (a new medicine) and Norditropin® given once a day (the medicine doctors can already prescribe). Researchers will test to see how well somapacitan works. The study will also test if somapacitan is safe. Participants will either get somapacitan or Norditropin® - which treatment participants get, is decided by chance. Both participants and the study doctor will know which treatment participants get. The study will last for 4 years. Participants will attend 19 clinic visits and have 1 phone call with the study doctor.

Interventions

  • SomapacitanDrug
  • Norditropin®Drug

Arms2

  • Experimental

    Somapacitan weekly

    Participants will receive somapacitan weekly for 52 weeks (main trial period). Participants completing the main trial period in both the treatment arms ('Somapacitan weekly' and 'Norditropin® daily') will receive somapacitan weekly for 3 years (extension trial period).

  • Active comparator

    Norditropin® daily

    Participants will receive Norditropin® daily for 52 weeks (main trial period).

Primary outcomes2

Outcomes the sponsor listed as primary.

  1. Height Velocity: In-trial Observation Period

    Time frame · From baseline (week 0) to visit 7 (week 52)

    Registry description

    Height velocity (HV) was derived from height measurements taken at baseline and Week 52 visit as: HV = (height at 52 weeks visit - height at baseline)/(time from baseline to 52 weeks visit in years). Data is reported for 'in-trial' observation period. In-trial observation period: from first administration and up until visit 7 or last trial contact, whichever comes first.

  2. Height Velocity: On-treatment Observation Period

    Time frame · From baseline (week 0) to visit 7 (week 52)

    Registry description

    Height velocity was derived from height measurements taken at baseline and Week 52 visit as: HV = (height at 52 weeks visit - height at baseline)/(time from baseline to 52 weeks visit in years). Data is reported for 'on-treatment' observation period. On-treatment observation period: from first administration and up until last trial contact, visit 7 or 14 days after last administration, whichever comes first.

Secondary outcomes(20)

  1. Change in Bone Age

    Time frame · Baseline (week -2), week 52

    Registry description

    Change from baseline (week -2) in bone age at week 52 is presented. X-ray images of left hand and wrist for bone age assessment according to the Greulich and Pyle atlas were taken. In-trial observation period: from first administration and up until visit 7 or last trial contact, whichever comes first.

  2. Change in Height Standard Deviation Score (HSDS)

    Time frame · Baseline (week 0), week 52

    Registry description

    Change from baseline (week 0) in HSDS at week 52 is presented. HSDS was derived using Centre for Disease Control and Prevention (CDC) standards. The range for HSDS was -10 to +10. Negative scores indicated a height below the mean height for a child with the same age and gender, whereas positive scores indicated a height above the mean height for a child with the same age and gender. Positive value in change from baseline in HSDS indicated that HSDS was better than baseline HSDS. In-trial observation period: from first administration and up until visit 7 or last trial contact, whichever comes first.

  3. Change in Height Velocity Standard Deviation Score (HV SDS)

    Time frame · Baseline (week 0), week 52

    Registry description

    Change from baseline (week 0) in HV SDS at week 52 is presented. HV SDS was calculated using the formula: HV SDS = (height velocity - mean)/standard deviation (SD), where height velocity was the height velocity variable measured, mean and SD of height velocity by gender and age for the reference population. The range for HV SDS was -10 to +10. Negative scores indicated a height velocity below the mean height velocity for a child with the same age and gender, whereas positive scores indicated a height velocity above the mean height velocity for a child with the same age and gender. Positive value in change from baseline in HV SDS indicated that HV SDS was better than baseline HV SDS. In-trial observation period: from first administration and up until visit 7 or last trial contact, whichever comes first.

  4. Change in Fasting Plasma Glucose (FPG) at Week 52

    Time frame · Baseline (week -2), week 52

    Registry description

    Change from baseline (week -2) in FPG at week 52 is presented.

  5. Change in FPG at Week 104

    Time frame · Baseline (week -2), week 104

    Registry description

    Change from baseline (week -2) in FPG at week 104 is presented.

  6. Change in FPG at Week 156

    Time frame · Baseline (week -2), week 156

    Registry description

    Change from baseline (week -2) in FPG at week 156 is presented.

  7. Change in FPG at Week 208

    Time frame · Baseline (week -2), week 208

    Registry description

    Change from baseline (week -2) in FPG at week 208 is presented.

  8. Change in Homeostatic Model Assessment Steady State Beta Cell Function (HOMA-B) at Week 52

    Time frame · Baseline (week -2), week 52

    Registry description

    Change from baseline (week -2) in HOMA-B at week 52 is presented. HOMA-B is a measure of the beta cell function and was calculated as follows: HOMA-B = (20 \* fasting insulin (picomoles per liter \[pmol/L\]) \* 1/6(microunit per milliliter \[µU/mL\]))/ FPG(mmol/L)-3.5). Negative change from baseline in HOMA-B indicated a worse outcome.

  9. Change in HOMA-B at Week 104

    Time frame · Baseline (week -2), week 104

    Registry description

    Change from baseline (week -2) in HOMA-B at week 104 is presented. HOMA-B is a measure of the beta cell function and was calculated as follows: HOMA-B = (20 \* fasting insulin \[pmol/L\]) \* 1/6 (\[µU/mL\] / FPG (mmol/L)-3.5). Negative change from baseline in HOMA-B indicated a worse outcome.

  10. Change in HOMA-B at Week 156

    Time frame · Baseline (week -2), week 156

    Registry description

    Change from baseline (week -2) in HOMA-B at week 156 is presented. HOMA-B is a measure of the beta cell function and was calculated as follows: HOMA-B = (20 \* fasting insulin \[pmol/L\]) \* 1/6 (\[µU/mL\] / FPG (mmol/L)-3.5). Negative change from baseline in HOMA-B indicated a worse outcome.

  11. Change in HOMA-B at Week 208

    Time frame · Baseline (week -2), week 208

    Registry description

    Change from baseline (week -2) in HOMA-B at week 208 is presented. HOMA-B is a measure of the beta cell function and was calculated as follows: HOMA-B = (20 \* fasting insulin \[pmol/L\]) \* 1/6 (\[µU/mL\] / FPG (mmol/L)-3.5). Negative change from baseline in HOMA-B indicated a worse outcome.

  12. Change in Homeostatic Model Assessment Insulin Resistance (HOMA-IR) at Week 52

    Time frame · Baseline (week -2), week 52

    Registry description

    Change from baseline (week -2) in HOMA-IR at week 52 is presented. HOMA-IR is an evaluation of the insulin resistance and was calculated as HOMA-IR = fasting insulin (pmol/L) \* 1/6(µU/mL) \* FPG(mmol/L) / 22.5. Positive change from baseline in HOMA-IR indicated a worse outcome.

  13. Change in HOMA-IR at Week 104

    Time frame · Baseline (week -2), week 104

    Registry description

    Change from baseline (week -2) in HOMA-IR at week 104 is presented. HOMA-IR is an evaluation of the insulin resistance and was calculated as HOMA-IR = fasting insulin (pmol/L) \* 1/6(µU/mL) \* FPG (mmol/L) / 22.5. Positive change from baseline in HOMA-IR indicated a worse outcome.

  14. Change in HOMA-IR at Week 156

    Time frame · Baseline (week -2), week 156

    Registry description

    Change from baseline (week -2) in HOMA-IR at week 156 is presented. HOMA-IR is an evaluation of the insulin resistance and was calculated as HOMA-IR = fasting insulin (pmol/L) \* 1/6(µU/mL) \* FPG (mmol/L) / 22.5. Positive change from baseline in HOMA-IR indicated a worse outcome.

  15. Change in HOMA-IR at Week 208

    Time frame · Baseline (week -2), week 208

    Registry description

    Change from baseline (week -2) in HOMA-IR at week 208 is presented. HOMA-IR is an evaluation of the insulin resistance and was calculated as HOMA-IR = fasting insulin (pmol/L) \* 1/6(µU/mL) \* FPG (mmol/L) / 22.5. Positive change from baseline in HOMA-IR indicated a worse outcome.

  16. Change in Glycated Haemoglobin (HbA1c) at Week 52

    Time frame · Baseline (week -2), week 52

    Registry description

    Change from baseline (week -2) in HbA1c at week 52 is presented.

  17. Change in HbA1c at Week 104

    Time frame · Baseline (week -2), week 104

    Registry description

    Change from baseline (week -2) in HbA1c at week 104 is presented.

  18. Change in HbA1c at Week 156

    Time frame · Baseline (week -2), week 156

    Registry description

    Change from baseline (week -2) in HbA1c at week 156 is presented.

  19. Change in HbA1c at Week 208

    Time frame · Baseline (week -2), week 208

    Registry description

    Change from baseline (week -2) in HbA1c at week 208 is presented.

  20. Change in Insulin-like Growth Factor I (IGF-I) Standard Deviation Score (SDS) at Week 52

    Time frame · Baseline (week 0), week 52

    Registry description

    Change from baseline (week 0) in IGF-I SDS at week 52 is presented. The range for IGF-I SDS was from -10 to +10. Negative scores indicated a IGF-I below the mean IGF-I for a child with the same age and gender, whereas positive scores indicated a IGF-I above the mean IGF-I for a child with the same age and gender. For participants with low IGF-I SDS at baseline, a positive change from baseline in IGF-I SDS indicated a better outcome. Data is reported for 'in-trial' observation period. In-trial observation period: from first administration and up until visit 7 or last trial contact, whichever comes first.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· From baseline (week 0) to visit 7 (week 52)

Height Velocity: In-trial Observation Period

GroupValue (centimeters per year (cm/year))Spread
Norditropin11.82.9
Somapacitan11.22.5
Primary outcomeMean· From baseline (week 0) to visit 7 (week 52)

Height Velocity: On-treatment Observation Period

GroupValue (cm/year)Spread
Norditropin11.82.9
Somapacitan11.22.5
Secondary and other outcome results(6)
Secondary outcomeMean· Baseline (week -2), week 52

Change in Bone Age

GroupValue (Years)Spread
Norditropin1.280.76
Somapacitan1.130.78
Secondary outcomeMean· Baseline (week 0), week 52

Change in Height Standard Deviation Score (HSDS)

GroupValue (Score on a scale)Spread
Norditropin1.370.69
Somapacitan1.210.54
Secondary outcomeMean· Baseline (week 0), week 52

Change in Height Velocity Standard Deviation Score (HV SDS)

GroupValue (Score on a scale)Spread
Norditropin8.974.38
Somapacitan7.973.36
Secondary outcomeMean· Baseline (week -2), week 52

Change in Fasting Plasma Glucose (FPG) at Week 52

GroupValue (Millimoles per liter (mmol/L))Spread
Norditropin0.2550.8
Somapacitan0.0830.6
Secondary outcomeMean· Baseline (week -2), week 104

Change in FPG at Week 104

GroupValue (mmol/L)Spread
Norditropin0.1080.9
Somapacitan0.0680.5
Secondary outcomeMean· Baseline (week -2), week 156

Change in FPG at Week 156

GroupValue (mmol/L)Spread
Norditropin0.0330.8
Somapacitan0.1110.6

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Somapacitan Week 0-52Participants received somapacitan 0.16 mg/kg s.c. once weekly by PDS290 pen-injector for 52 weeks (main trial period).0 / 1327 / 13263 / 132
Norditropin Week 0-52Participants received norditropin 0.034 mg/kg subcutaneously (s.c.; under the skin) by FlexPro pen-injector once daily for 52 weeks (main trial period).0 / 682 / 6832 / 68
Somapacitan/Somapacitan Week 52-208Participants who received somapacitan in main trial period continued somapacitan 0.16 mg/kg once weekly until 208 weeks during safety extension period.0 / 13111 / 13192 / 131
Norditropin/Somapacitan Week 52-208Participants who received Norditropin in main trial period switched to Somapacitan 0.16 mg/kg once weekly and continued until 208 weeks during safety extension period.0 / 684 / 6846 / 68
Norditropin/Somapacitan Week > 208After completion of the safety extension (week 208) during additional extension period, participants in countries where somapacitan was not available for prescription were offered to continue the trial and received somapacitan 0.16 mg/kg until it became available for prescription in their respective country or until September 2025 at the latest.0 / 351 / 3514 / 35
Somapacitan/Somapacitan Week > 208After completion of the safety extension (week 208) during additional extension period, participants in countries where somapacitan was not available for prescription were offered to continue the trial and received somapacitan 0.16 mg/kg until it became available for prescription in their respective country or until September 2025 at the latest.0 / 684 / 6827 / 68

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies5

Studies that cite this trial.

Studies with results

3 studies on this page

Indexing hint: Randomized controlled trial · 2025

8 results

Efficacy, safety, and insulin-like growth factor I of weekly somapacitan in children with growth hormone deficiency: 3-year results from REAL4.

Miller et al. 2025European journal of endocrinologycited by 7

PMID 40400262DOI 10.1093/ejendo/lvaf096PUB-40400262

Full text at the publisher8 results
Publisher pageSee results (8)

Indexing hint: Randomized controlled trial · 2024

Gene Expression Signatures Predict First-Year Response to Somapacitan Treatment in Children With Growth Hormone Deficiency.

Garner et al. 2024The Journal of clinical endocrinology and metabolismcited by 8

PMID 38066644PMC11031233DOI 10.1210/clinem/dgad717PUB-38066644

CC BY
Download PDF

Indexing hint: Randomized controlled trial · 2024

7 results

Effective growth hormone replacement with once-weekly somapacitan in Japanese children with growth hormone deficiency: Results from REAL4, a phase 3 clinical trial.

Mori et al. 2024Clinical endocrinologycited by 16

PMID 38368603DOI 10.1111/cen.15025PUB-38368603

Full text at the publisher7 results
Publisher pageSee results (7)

Indexing hint: Randomized controlled trial · 2022

10 results

Weekly Somapacitan is Effective and Well Tolerated in Children With GH Deficiency: The Randomized Phase 3 REAL4 Trial.

Miller et al. 2022The Journal of clinical endocrinology and metabolismcited by 65

PMID 36062966PMC9693810DOI 10.1210/clinem/dgac513PUB-36062966

Free to read · publisher termsCC BY-NC-ND10 results
Read at sourceSee results (10)

More studies

1 study on this page

Indexing hint: Randomized controlled trial · 2023

Corrected

Effective GH Replacement With Somapacitan in Children With GHD: REAL4 2-year Results and After Switch From Daily GH.

Miller et al. 2023The Journal of clinical endocrinology and metabolismcited by 26

PMID 37406251PMC10655534DOI 10.1210/clinem/dgad394PUB-37406251

Free to read · publisher termsCC BY-NC-ND
Read at sourceRead the notice

Eligibility

Who could join, as posted.

Sex
All
Age
up to 11 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: * Prepubertal children: a) Boys: Age more than or equal to 2 years and 26 weeks and less than 11.0 years at screening. Testis volume less than 4 ml. b) Girls: Age more than or equal to 2 years and 26 weeks and less than 10.0 years at screening. Tanner stage 1 for breast development (no palpable glandular breast tissue) * Confirmed diagnosis of growth hormone deficiency determined by two different growth hormone stimulation tests performed within 12 months prior to randomisation, defined as a peak growth hormone level of less than or equal to 10.0 ng/ml using the World Health Organisation (WHO) International Somatropin 98/574 standard * Impaired height defined as at least 2.0 standard deviations below the mean height for chronological age and gender at screening according to the standards of Center for Disease Control and Prevention * Impaired height velocity, defined as annualised height velocity below the 25th percentile for chronological age and gender according to the standards of Prader calculated over a time span of minimum 6 months and maximum 18 months prior to screening * Insulin-like Growth Factor-I (IGF-I) less than -1.0 SDS at screening, compared to age and gender normalized range measured at central laboratory * No prior exposure to growth hormone therapy or IGF-I treatment Exclusion Criteria: * Any known or suspected clinically significant abnormality likely to affect growth or the ability to evaluate growth with standing height measurements * 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 of greater than 400 μg/day of inhaled budesonide or equivalents for longer than 4 consecutive weeks within the last 12 months prior to screening * Diagnosis of attention deficit hyperactivity disorder * 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 * Prior history or presence of malignancy including intracranial tumours

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