A Research Study in Children Born Small and Who Stayed Small. Treatment is Somapacitan Once a Week Compared to Norditropin® Once a Day

Phase 2Active Not RecruitingNCT03878446

Novo Nordisk A/S62 enrolled

Overview

The study compares 2 medicines used for the treatment of children who are born small and who stayed small: somapacitan given once a week (a new medicine) and Norditropin® given once a day (the medicine doctors can already prescribe). Participants will either get somapacitan or Norditropin® - which treatment is decided by chance. Both participants and the study doctor will know which treatment the participants get. The study will last for 5 years. Participants will take either an injection once every week or once every day.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Short Stature Children Born Small for Gestational Age (SGA)

Interventions

Eligibility

Sex: ALLMin age: 2 YearsMax age: 11 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Pre-pubertal children, boys: 1. age between 2.5 and 11.0 years at screening. 2. testes volume below 4 ml. * Pre-pubertal children, girls: 1. age between 2.5 and 10.0 years at screening. 2. Tanner stage 1 for breast development (no palpable glandular breast tissue). * Born small for gestational age (birth length and/or weight below -2 standard deviation scores) (according to national standards). * Impaired height defined as at least 2.5 standard deviations below the mean height for chronological age and gender at screening according to the standards of Centers for Disease Control and Prevention at screening. * Impaired height velocity defined as annualized height velocity below the 50th 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. * No prior exposure to growth hormone therapy or Insulin-like Growth Factor-I (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. * Children with hormonal deficiencies including suspected or confirmed growth hormone deficiency according to local practise. * 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. * 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. * Diagnosis of attention deficit hyperactivity disorder. * Prior history or presence of malignancy including intracranial tumours.

Locations (92)

Univ of AL at Birmingham_BRM

Birmingham, Alabama, United States

Children's Hosp Of Orange

Orange, California, United States

St. Luke's Children's Endo

Boise, Idaho, United States

Univ of Minnesota M.C.H.

Minneapolis, Minnesota, United States

Children's Minnesota

Saint Paul, Minnesota, United States

Outcomes

Primary Outcomes

Height Velocity

Height velocity (HV) was derived from height measurements taken at baseline (week 0) and week 26 visit as: HV = (height at 26 weeks visit - height at baseline)/(time from baseline to 26 weeks visit in years). The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: from first administration and up until week 26 or last trial contact, whichever came first.

Time frame: Baseline (week 0); week 26

Secondary Outcomes

Change in Ratio of Bone Age Versus Chronological Age

Change in ratio of bone age (years) versus chronological age (years) from baseline (week 0) to week 52 is presented. X-rays of left hand and wrist for bone age assessment according to the Greulich and Pyle atlas were taken. X-ray images were sent to a central imaging laboratory for evaluation. Chronological Age (years) was calculated as: (Date minus Date of Birth) divided by 365.25. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: from first administration and up until week 52 or last trial contact, whichever came first.

Time frame: Baseline (week 0); week 52

Change in Height Standard Deviation Score (HSDS)

Change in HSDS from baseline (week 0) to week 26 is presented. HSDS was derived using Centre for Disease Control and Prevention (CDC) standards. HSDS = \[(height/population median)\^skewness - 1\]/(skewness \* population standard deviation) where skewness, median and standard deviation is given by a reference growth table for the corresponding chronological age. 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 week 26 or last trial contact, whichever came first.

Time frame: Baseline (week 0); week 26

Change in Height Velocity Standard Deviation Score (HVSDS)

Change in HVSDS from baseline (week 0) to week 26 is presented. HVSDS was derived using Prader standards. 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 HVSDS 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 HVSDS indicated that HVSDS was better than baseline HVSDS. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: from first administration and up until week 26 or last trial contact, whichever came first.

Time frame: Baseline (week 0); week 26

Change in Fasting Plasma Glucose

Change in fasting plasma glucose from baseline (week 0) to week 26 is presented. The outcome measure was evaluated based on the data from on-treatment observation period. On-treatment observation period: from first administration and up until last trial contact, week 26 or 14 days after last administration, whichever came first.

Time frame: Baseline (week 0); week 26

Change in Homeostatic Model Assessment for Steady State Beta Cell Function (HOMA-B)

Change in HOMA-B from baseline (week 0) to week 26 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). HOMA-beta score ranges from minus infinity to infinity (no limits). Higher score means better beta-cell function for HOMA-beta. Negative change from baseline (week 0) in HOMA-B indicated a worse outcome. The outcome measure was evaluated based on the data from on-treatment observation period. On-treatment observation period: from first administration and up until last trial contact, week 26 or 14 days after last administration, whichever came first.

Time frame: Baseline (week 0); week 26

Change in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)

Change in HOMA-IR from baseline (week 0) to week 26 is presented. Insulin resistance is a condition in which cells fail to respond to normal actions of hormone in body. HOMA-IR is calculated using a participant's fasting plasma insulin and glucose levels. HOMA-IR = fasting serum insulin (micro international units per milliliter (μU/ml)) × fasting plasma glucose (millimoles per liter (mmol/l)) / 22.5. HOMA-IR scores are classified as follows: less than 1.0: considered insulin sensitive, 0.5-1.4: considered healthy, above 1.8: considered early insulin resistance; above 2.7 is considered significant insulin resistance. HOMA-IR score ranges from 0-infinity (no upper limit). Higher the score, higher the level of insulin resistance. The outcome measure was evaluated based on the data from on-treatment observation period. On-treatment observation period: from first administration and up until last trial contact, week 26 or 14 days after last administration, whichever came first.

Time frame: Baseline (week 0); week 26

Change in Glycated Haemoglobin (HbA1c)

Change in HbA1c from baseline (week 0) to week 26 is presented. The outcome measure was evaluated based on the data from on-treatment observation period. On-treatment observation period: from first administration and up until last trial contact, week 26 or 14 days after last administration, whichever came first.

Time frame: Baseline (week 0); week 26

Change in Insulin-like Growth Factor I (IGF-I) Standard Deviation Score (SDS)

Change in IGF-I SDS from baseline (week 0) to week 26 is presented. IGF-I SDS was provided by the central laboratory; its calculation is based on the actual value of IGF-1 minus mean reference value of IGF-1 divided by reference standard deviation of IGF-1. 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. Positive value in change from baseline in IGF-I SDS indicated that IGF-I SDS was higher than baseline IGF-I SDS. The outcome measure was evaluated based on the data from on-treatment observation period. On-treatment observation period: from first administration and up until last trial contact, week 26 or 14 days after last administration, whichever came first.

Time frame: Baseline (week 0); week 26

Change in Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) SDS

Change in IGFBP-3 SDS from baseline (week 0) to week 26 is presented. The range for IGFBP-3 SDS was from -10 to +10. Negative scores indicated a IGFBP-3 below the mean IGFBP-3 for a child with the same age and gender, whereas positive scores indicated a IGFBP-3 above the mean IGFBP-3 for a child with the same age and gender. Positive value in change from baseline in IGFBP-3 SDS indicated that IGFBP-3 SDS was higher than baseline IGFBP-3 SDS. The outcome measure was evaluated based on the data from on-treatment observation period. On-treatment observation period: from first administration and up until last trial contact, week 26 or 14 days after last administration, whichever came first.

Time frame: Baseline (week 0); week 26