Clinical trial: Dose Finding Study of GX-H9 in Paeditaric Patients With Growth Hormone Deficiency (NCT03309891)

Eligibility criteria:
Inclusion Criteria:

          1. Pre-pubertal children with either isolated GHD, or GH insufficiency as part of
             multiple pituitary hormone insufficiency, idiopathic or organic GH insufficiency
             (e.g., due to pituitary tumor, pituitary or brain surgery):

               -  Boys: 3 years ≤ boy's age ≤ 11 years

               -  Girls: 3 years ≤ girl's age ≤ 10 years

          2. GHD confirmed by 2 different GH provocation tests with peak GH concentration below 10
             ng/mL as described in consensus guidelines. Well documented historical GH provocation
             tests can be used for study eligibility providing that the tests are performed as
             defined in Appendix 2 (e.g. the same sampling time points). Data of each historical GH
             stimulation test will be reviewed by Medical Monitor and Sponsor in order to assess
             acceptance for the study

          3. Without prior exposure to any rhGH therapy

          4. Bone age (BA) is not older than chronological age and should not be greater than 9
             years for girls and 10 years for boys

          5. Impaired height and height velocity defined as:

               -  Height (HT) of at least 2.0 standard deviations (SD) below the mean height for
                  chronological age (CA) and gender according to the standards from Prader et. al
                  1989, (HT SDS ≤ -2.0)

               -  Annualized height velocity (HV) of at least 1 SD below the mean HV for
                  chronological age and gender according to the standards of Prader et al (1989).
                  The interval between two height measurements should be at least 6 months (but not
                  longer than 18 months) before inclusion

          6. All subjects must have at least one cranial imaging study [magnetic resonance imaging
             (MRI) or computed tomography (CT)] prior to randomization:

               -  To exclude intracranial causes of GHD in subjects without history of pituitary
                  tumor [obtained within 6 months prior to informed consent signing, or

               -  Subjects with a previously treated pituitary tumor must have no tumor progression
                  for at least the past year [obtained within 3 months prior to informed consent
                  signing, compared with a previous MRI or CT performed at least 12 months earlier]

               -  If not performed within these specified time frames prior to informed consent
                  signing, may be performed as a part of the screening procedures

          7. Body mass Index (BMI) must be within ±2 SD of mean BMI for the chronological age and
             sex according to the 2000 CDC standards

          8. Baseline IGF-1 level of at least 1 SD below the mean IGF-1 level standardized for age
             and sex (IGF-1 SDS≤ -1.0) according to the central laboratory reference values. One
             IGF-1 retest is allowed during the Screening period if first results were not higher
             than

             -0.85 SDS and if GH stimulation tests results and auxology parameters met eligibility
             criteria

          9. Children with normal fundoscopy (ophthalmoscopy) at screening (without signs/symptoms
             of intracranial hypertension as assessed by fundoscopy) - it is highly recommended to
             take a photograph (if equipment is available at the study center)

         10. Children with multiple hormonal deficiencies must be on stable replacement therapies
             for other hypothalamo-pituitary-organ axes for at least 3 months and 6 months for
             thyroid replacement therapy prior to Screening. Temporary adjustment of glucocorticoid
             replacement therapy, as appropriate, is acceptable

         11. Normal 46 XX karyotype for girls

         12. Written informed consent of the parent or legal guardian of the subject and assent of
             the subject (if the subject can read)

         13. Parent or legal guardian who is capable and willing to administer the study drug

        Exclusion Criteria:

          1. History of radiation therapy or chemotherapy

          2. Malnourished children defined as:

               -  Serum albumin below the lower limit of normal (LLN) according to the reference
                  ranges of central laboratory; and

               -  Serum iron below the lower limit of normal (LLN) according to the reference
                  ranges of central laboratory; and

               -  BMI<-2 SD for age and sex

          3. Children with psychosocial dwarfism

          4. Children born small for gestational age (SGA-birth weight and/or birth length < -2 SD
             for gestational age according to the standards from Niklasson et al., 1991)

          5. Presence of anti-hGH antibodies at screening

          6. Any clinically significant abnormality likely to affect growth or the ability to
             evaluate growth, such as, but not limited to, chronic diseases like renal
             insufficiency, spinal cord irradiation, etc.

          7. Subjects with diabetes mellitus

          8. Subjects with impaired fasting sugar (based on WHO; fasting blood sugar > 110mg/dl or
             6.1 mmol/l) after repeated blood analysis

          9. Chromosomal abnormalities and medical syndromes (Turner's syndrome, Laron syndrome,
             Noonan syndrome, Prader-Willi syndrome, Russell-Silver Syndrome, SHOX
             mutations/deletions and skeletal dysplasias), with the exception of septo-optic
             dysplasia

         10. Evidence of closed epiphyses

         11. Concomitant administration of other treatments that may have an effect on growth such
             as anabolic steroids and methylphenidate for attention deficit hyperactivity disorder
             (ADHD), with the exception of hormone replacement therapies [thyroxine,
             hydrocortisone, desmopressin (DDAVP)]

         12. Children requiring glucocorticoid therapy, other than treated for
             hypothalamo-pituitary-adrenal insufficiency in replacement doses who are taking a dose
             of greater than 400 μg/d of inhaled budesonide or equivalents for longer than 1 month
             during a calendar year (e.g. asthma)

         13. Major medical conditions and/or presence of contraindication to rhGH treatment

         14. Has a history of positive serology results to HIV, HBV and/or HCV

         15. Subject who has a known or suspected hypersensitivity to rhGH

         16. Other causes of short stature such as coeliac disease, hypothyroidism and rickets

         17. The subject and/or the parent/legal guardian are likely to be non-compliant in respect
             to study conduct

         18. Subject who has received an investigational product, or has participated in a clinical
             study within 60 days before screening
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 3 Years old.
Subject must be at most 11 Years

Patient description (medical language): A 9-year-old girl is brought to the office for evaluation of short stature and overweight body habitus. The patient's mother and father are 170 cm and 181 cm tall, respectively.  On physical examination, the patient's height is in the 5th percentile of her age.  Other findings include low-set ears, a high arched palate, a webbed neck, and cubitus valgus.  Chromosomal analysis reveals a 45, XO karyotype.

Patient description (patient's own words): I took my 9-year-old daughter to the doctor because my mother-in-law kept saying she seemed small and overweight. My husband and I are 170 cm and 181 cm tall, respectively. The physical health highlighted that she is in the 5th percentile of her age. The doctor said that she has low-set ears, a high-arched palate, a webbed neck, and cubitus valgus. She also did a chromosomal analysis, which revealed a 45, XO karyotype.

Does the patient match the trial criteria? Contradiction