An efficacy and safety study of weekly mod-4023 compared to daily genotropin® therapy in pre-pubertal children with growth hormone deficiency
- Conditions
- Growth hormone deficiency in pre-pubertal childrenMedDRA version: 20.0 Level: PT Classification code 10056438 Term: Growth hormone deficiency System Organ Class: 10014698 - Endocrine disordersTherapeutic area: Diseases [C] - Hormonal diseases [C19]
- Registration Number
- EUCTR2016-003874-42-GR
- Lead Sponsor
- OPKO Biologics Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 220
1. Pre-pubertal children aged =3 yrs old 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 deficiencies.
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 (if done prior to signing the ICF) or central laboratory using a validated assay. Prior local laboratory results will be accepted subject to pre-approval by Sponsor Global Medical Monitor and if the tests were conducted according to one of the protocols in Appendix B.
3. Bone age (BA) is not older than chronological age and should be less than 10 for females and less than 11 for males.
4. Without prior exposure to any r-hGH therapy.
5. Impaired height and height velocity defined as:
- Annualized height velocity (HV) below the 25th percentile for CA (HV < -0.7 SDS) and gender according to OPKO HV (Tanner, Prader and Hermanussen) calculator provided.
- The interval between two height measurements should be at least 6 months, but should not exceed 18 months prior to inclusion.
6. Baseline IGF-I level of at least 1 SD below the mean IGF-I level standardized for age and sex (IGF-I SDS = -1) 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.
7. Normal calculated GFR based on updated bedside” Schwartz formula for pediatric patients (recommended calculation is provided below):
CrCL (mL/min/1.73 m2) =0.413 * Ht / Scr
Ht: height in cm;
Scr: serum creatinine in mg/dL;
8. 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 ICF signing
9. Normal 46XX karyotype for girls.
10. 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).
Inclusion into the LT-OLE:
11. Completion of the main study (12 months of treatment) with adequate compliance.
12. 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).
13. Agreement to refrain from sexual activity during the LT-OLE i.e. observe complete sexual abstinence as the only acceptable contraceptive measure during the LT-OLE (for pubertal and post-pubertal patients).
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
1. Children with prior history of leukemia, lymphoma, sarcoma or any other form 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 Ab at screening
7. Any CS 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. T2 and T1 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 of the protocol.
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/day of inhaled budesonide or equivalent as described in Appendix J of the protocol.
12. Major medical conditions and/or presence of contraindication to r-hGH treatment
13. More than 1 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 study of an investigational agent within 30 days prior to ICF signature (including administration of investigational agent)
20. Study enrollment requirements have been met or the study has been closed by the Sponsor prior to the completion of screening process
Exclusion during the LT-OLE:
21. Concomitant administration of other treatments that may have an effect on growth such as anabolic steroids, or sex steroids (other than for hormonal replacement), with the exception of ADHD drugs or hormone replacement therapies (thyroxin, hydrocortisone, testosterone, estrogen/progesterone, desmopressin [DDAVP®])
22. Change in medical condition during the treatment period (such as, but not limited to, development of a serious inter-current critical illness, a severe adverse drug reaction, etc.)
23. Positive pregnancy test. 24. Unresolved drug related (MOD-4023 or Genotropin®) SAE from the treatment period as per MM judgement
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To demonstrate that weekly MOD-4023 administration is non-inferior to daily Genotropin administration;<br> Secondary Objective: To evaluate the safety and tolerability of weekly MOD-4023 administration.<br> To demonstrate LT safety and efficacy of MOD-4023 in an OLE<br> ;Primary end point(s): Annual (HV) in cm/year after 12 months of treatment. ;Timepoint(s) of evaluation of this end point: Baseline and after 12 months of treatment
- Secondary Outcome Measures
Name Time Method