Comparing Efficacy and Safety of CinnaGen Biosimilar Growth Hormone (CinnaTropin®) Versus Nordilet in Children With Idiopathic Growth Hormone Deficiency

Study Overview
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Brief Summary
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This randomized, active-controlled, two-armed, open-label, and cross-over trial was designed to compare efficacy and safety of 0.03 mg/kg/day subcutaneous injections of either CinnaTropin® or Novo Nordisk growth hormone product in 30 children with Idiopathic Growth Hormone Deficiency. Patients were randomized to receive one of the products for three months. After that, each patient crossed over to the other arm to receive the other product for another three months. The primary objective of this study was to compare the efficacy of CinnaGen growth hormone (GH) with Nordilet. The secondary objectives of this study were further comparison and evaluation of efficacy along with safety between CinnaTropin® and Nordilet®.

Detailed Description
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This study was a national, single center, randomized, active-controlled, two-arm, cross-over clinical trial to compare efficacy and safety of CinnaTropin® with Novo Nordisk growth hormone product in children with Idiopathic Growth Hormone Deficiency (IGHD). After signing the written informed consent, patients were randomized to receive daily subcutaneous injections of CinnaTropin® or reference product (0.03mg/kg/day). Patients were admitted to receive the medication based on planned treatment. After three months patients were switched to receive the other product for another three months. Treatment visits were monthly for both groups. The primary objective of this study is to compare the efficacy of CinnaTropin® with Novo Nordisk growth hormone product. The secondary objectives of this study are to further evaluation efficacy and safety. During the trial, if patients bone age reached 14 and the improvement in their height was less than 2.5 cm than last year or, they did not reach the desired height appropriate for their age and gender or, if the growth plates were closed and they couldn't reach appropriate adulthood height, treatment will be discontinued. The clinical trial was according to procedures that incorporate the ethical principles of GCP. Accurate and reliable data collection was assured by verification and cross-check of the CRFs against the patient's records by clinical monitors (source document verification was performed), and the maintenance of a drug-dispensing log by the center. A comprehensive validation check program was used to verify the data, and discrepancy reports were generated accordingly for resolution by the investigator. Determination of sample size was based on the mean growth velocity of 9.7±1.3 following treatment with growth hormone and under consideration of 80% power, a sample size of 6 patient in each group was calculated. By considering patient loss and in order to increase the statistical power of the study a sample size of 15 patients in each group was determined.

Official Title
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Efficacy and Safety of CinnaGen Recombinant Human Growth Hormone (CinnaTropin®) in Comparison With Novo Nordisk Growth Hormone (Nordilet®) Product in Pre-Pubertal Children With Idiopathic Growth Hormone Deficiency (IGHD)

Conditions
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Idiopathic Growth Hormone Deficiency

Intervention / Treatment
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* Drug: CinnaTropin®
* Drug: Nordilet®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Pre-pubertal boys and girls between 4-16 years (Tanner's stage 1) Height Standard Deviation Score (HSDS) ≤ -2 SD for chronological age (Brandt/Reinken) Approved GH Deficiency following clonidine GH stimulation test (150 µg/ m2, up to a maximum of 0.2 mg), and determining GH levels at 0, 30, 60, 90, and 120 minutes. This test is performed by overnight fasting and considered positive if GH ≥ 10 ng/ml, otherwise GHD is relevant. Ruling out of other causes of short stature (hypothyroidism, Celiac disease, and etc.) Documented Pituitary or hypothalamic hormone deficiency and below normal serum IGF-1 at the time of diagnosis In case of the deficiency in other pituitary hormones, the patient can only be included, if the replacement of other pituitary hormones was done, and this is determined by the replacement of glucocorticoids provided that no symptoms of Cushing's syndrome be present, and the replacement of thyroxine and reaching to normal levels of free T4 and free T3. Exclusion Criteria: • Any Illness that prevent the proper conduct of the trial, such as seizure, acute or systemic infectious disease in the past 6 months, chronic pulmonary infection, AIDS, chronic liver disease (verified disease of the hepatic cells or 2-fold or more increase in liver enzymes) Any active malignancy (such as leukemia, etc.), Contraindications of the administration of growth hormone (sleep apnea syndrome) Turner syndrome. Short stature due to chronic renal failure, other causes of GHD, such as craniopharyngioma History of diabetes in patient or his/her first-degree relatives Concomitant use of steroids

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CinnaTropin®, Then Nordilet®<br>CinnaTropin® was administered with 0.03 mg/kg daily subcutaneous injections for three months. After that, the participants received 0.03 mg/kg daily subcutaneous injections of Nordilet® for three months. | Drug: CinnaTropin®<br>* 0.03 mg/kg daily subcutaneous injections<br>* Other names: recombinant human growth hormone (CinnaTropin®);Drug: Nordilet®<br>* 0.03 mg/kg daily subcutaneous injections<br>* Other names: recombinant human growth hormone (Nordilet®);|
| Active Comparator: Nordilet®, Then CinnaTropin®<br>Nordilet® was administered with 0.03 mg/kg daily subcutaneous injections for three months. After that, the participants received 0.03 mg/kg daily subcutaneous injections of CinnaTropin® for three months. | Drug: CinnaTropin®<br>* 0.03 mg/kg daily subcutaneous injections<br>* Other names: recombinant human growth hormone (CinnaTropin®);Drug: Nordilet®<br>* 0.03 mg/kg daily subcutaneous injections<br>* Other names: recombinant human growth hormone (Nordilet®);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Height velocity | The primary outcome of this study is to compare height velocity of patients in each treatment arm. Height velocity is reported in terms of centimeters per year. | three months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Height | Changes in height is measured in both treatment arms. | three months | 
| Weight | Changes in height is measured in both treatment arms. | three months | 
| Bone Age | Bone age is determined by wrist x-ray radiography in both treatment arms | six months | 
| HSDS | Height standard deviation score is calculated to compare height based on reference population. | three months | 
| HVSDS | Height velocity standard deviation score (HVSDS) is calculated to assess height velocity based on reference population. | three months | 
| The incidence of Adverse Events | The incidence of adverse events at each visit is recorded based on patients' reports, vital signs, physical examinations, and laboratory tests for systemic safety, including liver function, renal function, complete blood count and clinical chemistries, urinalysis, and hematologic testing. | three months; From receiving the first dose of each recombinant human growth hormone product until the last dose; | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IGHD, somatropin