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CompletedNCT03223025Updated Aug 31, 2023

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

A Phase 3 interventional study of CinnaTropin® and Nordilet® in Idiopathic Growth Hormone Deficiency, sponsored by Cinnagen. Completed. Open to participants aged 4 Years to 16 Years. Per ClinicalTrials.gov, last updated 2023-08-31.

Sponsored by Cinnagen · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
30
Allocation
Randomized
Ages
4 Years to 16 Years
Sex
All
01

Study summary

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®.

Read the detailed description

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.

02

Conditions studied

  • Idiopathic Growth Hormone Deficiency

Keywords

  • IGHD
  • somatropin
03

Who can participate

Ages eligible
4 Years to 16 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
None (open label)
Enrollment
30 participants (actual)

Study arms

  • Experimental
    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.

    Drug: CinnaTropin® · Drug: Nordilet®

  • Active comparator
    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.

    Drug: CinnaTropin® · Drug: Nordilet®

Interventions

  • DrugCinnaTropin®

    0.03 mg/kg daily subcutaneous injections

    Also known as: recombinant human growth hormone (CinnaTropin®)

  • DrugNordilet®

    0.03 mg/kg daily subcutaneous injections

    Also known as: recombinant human growth hormone (Nordilet®)

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: three months

Secondary outcomes

  1. Height

    Changes in height is measured in both treatment arms.

    Time frame: three months

  2. Weight

    Changes in height is measured in both treatment arms.

    Time frame: three months

  3. Bone Age

    Bone age is determined by wrist x-ray radiography in both treatment arms

    Time frame: six months

  4. HSDS

    Height standard deviation score is calculated to compare height based on reference population.

    Time frame: three months

  5. HVSDS

    Height velocity standard deviation score (HVSDS) is calculated to assess height velocity based on reference population.

    Time frame: three months

  6. 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.

    Time frame: three months; From receiving the first dose of each recombinant human growth hormone product until the last dose;

06

Study locations

No study locations are listed for this record.

07

References and documents

Publications

  • 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. PubMed 11838603 ↗
  • 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. PubMed 12130909 ↗
  • 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. PubMed 10095164 ↗
  • 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. PubMed 11467359 ↗
  • 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. PubMed 12970269 ↗
  • 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. PubMed 10895044 ↗
  • 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. PubMed 10443652 ↗
  • 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. PubMed 11184423 ↗
  • 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. PubMed 10506258 ↗
  • 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. PubMed 10215751 ↗
  • 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. PubMed 11493578 ↗
  • 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. PubMed 8067786 ↗
  • 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. PubMed 8936959 ↗
  • 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. PubMed 9762006 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03223025
Lead sponsor
Cinnagen
Responsible party
Sponsor
First posted
Jul 19, 2017
Start date
Mar 9, 2016
Primary completion
Feb 4, 2017
Completion
Feb 4, 2017
Last update
Aug 31, 2023

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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