A randomized, two-armed, parallel, active-controlled clinical trial to compare equivalent efficacy along with safety, and immunogenicity of CinnaTropin® (CinnaGen, Iran) to Norditropin® NordiLet® (Novo Nordisk, Denmark) in pre-pubertal children with growth hormone deficiency (GHD)
This study aims to compare equivalent efficacy along with safety, and immunogenicity of CinnaTropin® to Norditropin® NordiLet® in children with growth hormone deficiency.
Design
This phase III study is a randomized, two-armed, parallel, and active-controlled clinical trial to compare equivalent efficacy along with safety, and immunogenicity of CinnaTropin® to Norditropin® NordiLet® in pre-pubertal children with growth hormone deficiency.
Settings and conduct
This study will be conducted in 17 cities and 33 centers in Iran. In this phase 3 study, after providing informed consent, 102 pre-pubertal patients with growth hormone deficiency will be evaluated regarding inclusion and exclusion criteria. After fulfilling the criteria patients will receive a randomization code, and be randomly assigned to one of the arms of CinnaTropin or Norditropin NordiLet. Patients will receive the treatments for 12 months.
Participants/Inclusion and exclusion criteria
Inclusion Criteria:GH-naïve; Prepubertal; male children aged 3-10 and female children 3-8 years; Isolated idiopathic growth hormone(GH) deficiency diagnosed; Peak GH<10.0µg/l following two recommended GH stimulation tests; Height Standard Deviation Score(HSDS)≤-2.0 and Height Velocity SDS≤-1.0; or HSDS ≤ -3.0; bone age to chronological age ratio<0.9; Full-term birth weight>2500g; Euthyroid. Exclusion Criteria: Chronic systemic disease; Evidence of active tumor; Chromosomal or skeletal abnormalities; Signs of idiopathic intracranial hypertension; Closed epiphyses; Chronic use of oral or parenteral glucocorticoid in the last three years; Using methylphenidate in the last 14 days
Intervention groups
Daily injection of 0.03 mg/kg of CinnaTropin
Daily injection of 0.03 mg/kg of Norditropin NordiLet
Main outcome variables
Change in height velocity (cm/year)
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20150303021315N12
Registration date:2019-04-07, 1398/01/18
Registration timing:registered_while_recruiting
Last update:2019-04-07, 1398/01/18
Update count:0
Registration date
2019-04-07, 1398/01/18
Registrant information
Name
Nassim Anjidani
Name of organization / entity
Orchid Pharmed
Country
Iran (Islamic Republic of)
Phone
+98 21 4347 3000
Email address
amini@orchidpharmed.com
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2018-12-14, 1397/09/23
Expected recruitment end date
2020-11-21, 1399/09/01
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
A randomized, two-armed, parallel, active-controlled clinical trial to compare equivalent efficacy along with safety, and immunogenicity of CinnaTropin® (CinnaGen, Iran) to Norditropin® NordiLet® (Novo Nordisk, Denmark) in pre-pubertal children with growth hormone deficiency (GHD)
Public title
Comparing CinnaTropin® with Norditropin® NordiLet® in pre-pubertal children with growth hormone deficiency
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
GH-naïve
Prepubertal (Tanner stage I)
3 to 10 years of age for male children and 3 to 8 years of age for female children
Isolated idiopathic growth hormone deficiency diagnosed
Peak growth hormone value of <10.0 µg/l following two recommended growth hormone stimulation tests
Height Standard Deviation Score (HSDS) ≤ -2.0 and Height Velocity Standard Deviation Score (HVSDS) ≤-1.0; or HSDS ≤ -3.0
The ratio of bone age to chronological age < 0.9
Full-term birth weight above 2500 g
Euthyroid state
Exclusion criteria:
Chronic systemic disease, such as diabetes mellitus or renal disease
Evidence of active tumor
Chromosomal or skeletal abnormalities
Signs of idiopathic intracranial hypertension
Closed epiphyses
Chronic use of oral or parenteral glucocorticoid in the past three months
Using methylphenidate in the last 14 days
Age
From 3 years old to 10 years old
Gender
Both
Phase
3
Groups that have been masked
No information
Sample size
Target sample size:
102
Randomization (investigator's opinion)
Randomized
Randomization description
The randomization plan of the patients will be carried out centrally using an R-CRAN software version 3.2.3. Blocks (with the size 2 or 4) will be made using permuted block randomization for a total of 102 patients (1:1 allocation ratio). After the randomization procedure, a code will be allocated to each patient that will be used as a patient-identifier throughout the study. The assigned code will be denoted by 4 initials (corresponding to the first two letters of the first name, first two letters of surname) and 3 numbers (center code). Moreover, the code described is followed by the study unique identification code consisting of first three letters of the name of the investigational product (which is CIN-) and three numbers (corresponding to the randomization number), e.g. ABCD001CIN-001. The randomization number will be assigned in a consecutive way.
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Research Ethics Committee of Tehran University of Medical Sciences
Street address
Sixth floor, Research Deputy of Tehran University of Medical Sciences, Ghods Street, Keshavarz Boulvard
City
Tehran
Province
Tehran
Postal code
1417653761
Approval date
2018-08-25, 1397/06/03
Ethics committee reference number
IR.TUMS.VCR.REC.1397.363
Health conditions studied
1
Description of health condition studied
Isolated idiopathic growth hormone deficiency
ICD-10 code
E23.0
ICD-10 code description
Hypopituitarism
Primary outcomes
1
Description
Change in height velocity
Timepoint
Prior to intervention and 12 months after the first intervention
Method of measurement
wall-mounted stadiometer
Secondary outcomes
1
Description
Change in height
Timepoint
Prior to intervention and 12 months after the first intervention
Method of measurement
wall-mounted stadiometer
2
Description
Change in weight
Timepoint
Prior to intervention and 12 months after the first intervention
Method of measurement
Weight measuring device
3
Description
Change in Height Standard Deviation Score (HSDS)
Timepoint
Prior to intervention and 12 months after the first intervention
Method of measurement
Centers for Disease Control and Prevention clinical growth data
4
Description
Safety
Timepoint
At screening visit, first intervention, and 3, 6, 9, and 12 months after the first intervention
Method of measurement
Patient’s history, physical examination, and laboratory data
5
Description
Immunogenicity
Timepoint
Prior to first intervention and at 3, 6, 9, and 12 months after the first intervention
Method of measurement
Evaluation of the presence and titre of anti-drug antibody in the blood sample
Intervention groups
1
Description
Control group: CinnaTropin® pen-injector (5 mg/1.5 mL, CinnaGen, Iran), SC injection of 0.03 mg/kg for one year
Category
Treatment - Drugs
2
Description
Control group: Norditropin® NordiLet® pen (5 mg/1.5 mL, Novo Nordisk, Denmark), SC injection of 0.03 mg/kg for one year
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
Children's Medical Center
Full name of responsible person
Dr. Ali Rabbani
Street address
Children's Medical Center, Dr. Mohammad Gharib St.,Tehran