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

NCT ID: NCT03223025

Last Updated: 2023-08-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-03-09

Study Completion Date

2017-02-04

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.

Conditions

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Idiopathic Growth Hormone Deficiency

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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CinnaTropin®, Then Nordilet®

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.

Group Type EXPERIMENTAL

CinnaTropin®

Intervention Type DRUG

0.03 mg/kg daily subcutaneous injections

Nordilet®

Intervention Type DRUG

0.03 mg/kg daily subcutaneous injections

Nordilet®, Then CinnaTropin®

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.

Group Type ACTIVE_COMPARATOR

CinnaTropin®

Intervention Type DRUG

0.03 mg/kg daily subcutaneous injections

Nordilet®

Intervention Type DRUG

0.03 mg/kg daily subcutaneous injections

Interventions

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CinnaTropin®

0.03 mg/kg daily subcutaneous injections

Intervention Type DRUG

Nordilet®

0.03 mg/kg daily subcutaneous injections

Intervention Type DRUG

Other Intervention Names

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recombinant human growth hormone (CinnaTropin®) recombinant human growth hormone (Nordilet®)

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
Minimum Eligible Age

4 Years

Maximum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cinnagen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

References

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Kato Y, Murakami Y, Sohmiya M, Nishiki M. Regulation of human growth hormone secretion and its disorders. Intern Med. 2002 Jan;41(1):7-13. doi: 10.2169/internalmedicine.41.7.

Reference Type BACKGROUND
PMID: 11838603 (View on PubMed)

Henwood MJ, Grimberg A, Moshang T Jr. Expanded spectrum of recombinant human growth hormone therapy. Curr Opin Pediatr. 2002 Aug;14(4):437-42. doi: 10.1097/00008480-200208000-00015.

Reference Type BACKGROUND
PMID: 12130909 (View on PubMed)

Frindik JP, Kemp SF, Sy JP. Effects of recombinant human growth hormone on height and skeletal maturation in growth hormone-deficient children with and without severe pretreatment bone age delay. Horm Res. 1999;51(1):15-9. doi: 10.1159/000023307.

Reference Type BACKGROUND
PMID: 10095164 (View on PubMed)

Lanes R. Growth velocity, final height and bone mineral metabolism of short children treated long term with growth hormone. Curr Pharm Biotechnol. 2000 Jul;1(1):33-46. doi: 10.2174/1389201003378997.

Reference Type BACKGROUND
PMID: 11467359 (View on PubMed)

Shulman DI, Root AW, Diamond FB, Bercu BB, Martinez R, Boucek RJ Jr. Effects of one year of recombinant human growth hormone (GH) therapy on cardiac mass and function in children with classical GH deficiency. J Clin Endocrinol Metab. 2003 Sep;88(9):4095-9. doi: 10.1210/jc.2003-030030.

Reference Type BACKGROUND
PMID: 12970269 (View on PubMed)

Bernasconi S, Arrigo T, Wasniewsk M, Ghizzoni L, Ruggeri C, Di Pasquale G, Vottero A, De Luca F. Long-term results with growth hormone therapy in idiopathic hypopituitarism. Horm Res. 2000;53 Suppl 1:55-9. doi: 10.1159/000053206.

Reference Type BACKGROUND
PMID: 10895044 (View on PubMed)

Gasperi M, Aimaretti G, Scarcello G, Corneli G, Cosci C, Arvat E, Martino E, Ghigo E. Low dose hexarelin and growth hormone (GH)-releasing hormone as a diagnostic tool for the diagnosis of GH deficiency in adults: comparison with insulin-induced hypoglycemia test. J Clin Endocrinol Metab. 1999 Aug;84(8):2633-7. doi: 10.1210/jcem.84.8.5904.

Reference Type BACKGROUND
PMID: 10443652 (View on PubMed)

Biller BM, Vance ML, Kleinberg DL, Cook DM, Gordon T. Clinical and reimbursement issues in growth hormone use in adults. Am J Manag Care. 2000 Sep;6(15 Suppl):S817-27.

Reference Type BACKGROUND
PMID: 11184423 (View on PubMed)

Bright GM, Julius JR, Lima J, Blethen SL. Growth hormone stimulation test results as predictors of recombinant human growth hormone treatment outcomes: preliminary analysis of the national cooperative growth study database. Pediatrics. 1999 Oct;104(4 Pt 2):1028-31.

Reference Type BACKGROUND
PMID: 10506258 (View on PubMed)

Janssen YJ, Frolich M, Roelfsema F. The absorption profile and availability of a physiological subcutaneously administered dose of recombinant human growth hormone (GH) in adults with GH deficiency. Br J Clin Pharmacol. 1999 Mar;47(3):273-8. doi: 10.1046/j.1365-2125.1999.00892.x.

Reference Type BACKGROUND
PMID: 10215751 (View on PubMed)

Drake WM, Howell SJ, Monson JP, Shalet SM. Optimizing gh therapy in adults and children. Endocr Rev. 2001 Aug;22(4):425-50. doi: 10.1210/edrv.22.4.0438.

Reference Type BACKGROUND
PMID: 11493578 (View on PubMed)

De Muinck Keizer-Schrama S, Rikken B, Hokken-Koelega A, Wit JM, Drop S. Comparative effect of two doses of growth hormone for growth hormone deficiency. The Dutch Growth Hormone Working Group. Arch Dis Child. 1994 Jul;71(1):12-8. doi: 10.1136/adc.71.1.12.

Reference Type BACKGROUND
PMID: 8067786 (View on PubMed)

Soliman AT, abdul Khadir MM. Growth parameters and predictors of growth in short children with and without growth hormone (GH) deficiency treated with human GH: a randomized controlled study. J Trop Pediatr. 1996 Oct;42(5):281-6. doi: 10.1093/tropej/42.5.281.

Reference Type BACKGROUND
PMID: 8936959 (View on PubMed)

Rikken B, van Doorn J, Ringeling A, Van den Brande JL, Massa G, Wit JM. Plasma levels of insulin-like growth factor (IGF)-I, IGF-II and IGF-binding protein-3 in the evaluation of childhood growth hormone deficiency. Horm Res. 1998 Sep;50(3):166-76. doi: 10.1159/000023268.

Reference Type BACKGROUND
PMID: 9762006 (View on PubMed)

Other Identifiers

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IRCT201409064920N5

Identifier Type: REGISTRY

Identifier Source: secondary_id

GH.CIN.MR93

Identifier Type: -

Identifier Source: org_study_id

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