An efficacy and safety study of weekly mod-4023 compared to daily genotropin® therapy in pre-pubertal children with growth hormone deficiency

Phase 1

• Conditions: Growth hormone deficiency in pre-pubertal children; MedDRA version: 19.1Level: PTClassification code 10056438Term: Growth hormone deficiencySystem Organ Class: 10014698 - Endocrine disorders; Therapeutic area: Diseases [C] - Hormonal diseases [C19]

• Registration Number: EUCTR2016-003874-42-ES
• Lead Sponsor: OPKO Biologics Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-03-14
• Last Update Posted: 3 July 2017

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 220

Inclusion Criteria

1. Pre-pubertal children aged =3 years , and not yet 11 years for girls (10 years
and 364 days) or not yet 12 years (11 years and 364 days) for boys, (on the
date of ICF signature), with either isolated GHD, or GH insufficiency as part
of multiple pituitary hormone deficiency.
2. Confirmed diagnosis of GHD by two different GH provocation tests defined
as a peak plasma GH level of =10 ng/mL, determined by local or central
laboratory using a validated assaya. Global Medical Monitor may accept
prior local laboratory results; subject to pre-approval and if the tests were
conducted as recommended in the protocol Appendix B.
3. Bone age (BA) is not older than chronological age and should be less than
10 for girls and less than 11 for boys.
4. Without prior exposure to any rhGH therapy (naïve patients).
5. Impaired height velocity defined as:
-Annualized height velocity (HV) below the 25th percentile for CA (HV < -
0.7 SDS) and gender according to Prader HV standard tables, Tanner HV
curves, or local primary care provider standard.
-The interval between two height measurements should be at least 6 months,
but should not exceed 18 months prior to inclusion.
6. BMI must be within ±2 SDS of mean BMI for the chronological age and
sex.
7. Baseline IGF-I level of at least 1 SD below the mean IGF-I level
standardized for age and sex (IGF-I SDS =-1)a according to the central
laboratory reference values. A single re-test will be allowed (subject to
discussion with medical monitor) if all other criteria are met.
8. Normal calculated GFR based on updated bedside” Schwartz formula for
pediatric patients (calculation is recommended below):
CrCL (mL/min/1.73 m2) =0.413 * Ht / Scr
Ht: height in cm;
Scr: serum creatinine in mg/dL;
9. Children with multiple hormonal deficiencies must be on stable replacement
therapies (no change in dose) for other hypothalamo-pituitary organ axes for
at least 3 months prior to ICF signing
10. Normal 46XX karyotype for girls.
11. Willing and able to provide written informed consent of the parent or legal
guardian of the patient and written assent from pediatric patients (where
applicable based on age and country regulation).
Are the trial subjects under 18? yes
Number of subjects for this age range: 220
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Children with prior history of leukemia, lymphoma, sarcoma or any other
forms of cancer.
2. History of radiation therapy or chemotherapy
3. Malnourished children defined as BMI < -2 SDS for age and sex
4. Children with psychosocial dwarfism
5. Children born small for gestational age (SGA – birth weight and/or birth
length <-2 SDS for gestational age)
6. Presence of anti-hGH antibodies at screening
7. 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.
8. Type 1 and type 2 diabetic patients who, in the opinion of the investigator, are
not receiving standard of care treatment, or are non-compliant with their
prescribed treatment or who are in poor metabolic control.(Criteria for
controlled diabetes are defined in Appendix F).
9. Chromosomal abnormalities including Turner’s syndrome, Laron syndrome,
Noonan syndrome, Prader-Willi syndrome, Russell-Silver syndrome, SHOX
mutations/deletions and skeletal dysplasias.
10. Concomitant administration of other treatments that may have an effect on
growth such as anabolic steroids, or sex steroids, with the exception of
ADHD drugs or hormone replacement therapies (thyroxin, hydrocortisone,
desmopressin [DDAVP])
11. Children requiring glucocorticoid therapy (e.g. for asthma) that are taking
chronically a dose greater than 400 µg/d of inhaled budesonide or equivalent
as provided in Appendix J.
12. Major medical conditions and/or presence of contraindication to r-hGH
treatment.
13. Closed epiphyses
14. Known or suspected HIV-positive patient, or patient with advanced diseases
such as AIDS or tuberculosis.
15. Drug, substance, or alcohol abuse.
16. Known hypersensitivity to the components of study medication.
17. Other causes of short stature such as celiac disease, uncontrolled primary
hypothyroidism and rickets.
18. The patient and/or the parent/legal guardian are likely to be non-compliant in
respect to study conduct.
19. Participation in any other trial of an investigational agent within 30 days prior
to ICF signature (including administration of investigational agent).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified