| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Adult or childhood onset growth hormone deficiency (GHD) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Adult or childhood onset growth hormone deficiency (GHD) |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10056438 |
| E.1.2 | Term | Growth hormone deficiency |
| E.1.2 | System Organ Class | 10014698 - Endocrine disorders |
|
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To demonstrate a clinical superiority of MOD-4023 over placebo in terms of decrease in Fat Mass (FM) in adult subjects with GHD |
|
| E.2.2 | Secondary objectives of the trial |
•To determine the efficacy of MOD-4023 over placebo in other body composition variables (such as lean body mass and waist-to-hip ratio)
•To evaluate the safety and tolerability of MOD-4023 over placebo in adult subjects with GHD
•To determine the IGF-I and IGFBP-3 serum levels
• To monitor long-term safety and efficacy of MOD-4023 in adult
subjects with GHD who completed Treatment Periods I and II of this
study |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Men and women between the age of 23 to 70 years old at screening,
inclusive
2. GHD subjects as defined in the Consensus guidelines for the diagnosis
and treatment of adults with GH deficiency II (2007). The following
cutoff values for the diagnosis of GHD will be used
• Insulin tolerance test or glucagon test, the validated cutoff for GHD in
adults is a peak GH response ≤ 3 μg/L
• Growth-hormone-releasing hormone (GHRH) + arginine : for those
with a body mass index:
- BMI <25 kg/m2, a peak GH ≤11 μg/L;
- BMI 25–30 kg/m2 (included), a peak GH≤8 μg/L;
- BMI >30 kg/m2, a peak GH≤4 μg/L.
3. Subjects using hormonal replacement therapy(s) for deficiencies of
other hypothalamo-pituitary axes must be on an optimized and stable
treatment regimen (hormone levels within normal ranges on screening)
for at least three months prior to screening:
• Temporary adjustment of glucocorticoid replacement therapy, as
appropriate, is acceptable.
• Peripheral thyroid hormones (FT4) within the normal range of the
central or local lab .
• Adrenal insufficiency – documented adrenal status (subjects that are
sufficient with documented test in last 6 months or insufficient and on
stable replacement.
4. Subjects with Diabetes Insipidus should be on stable treatment for at
least 6 months
5. No r-hGH replacement therapy or use of GH secretagogues for at least
9 months with any registered or investigational r-hGH or GH
secretagogue product.
6. The IGF-I level at screening ≤-1 SDS of the age and sex normal
ranges according to the central laboratory measurements.
7. For patients treated for Cushing's, at least two years elapsed since
pituitary surgery and in biochemical remission without current medical
therapy for the condition, documented within 6 months of study entry
8. Body Mass Index (BMI, kg/m2) of 23.0 to 35.0 kg/m2, both inclusive
9. Confirmed to be negative for anti r-hGH antibodies at the time of
screening.
10. Women of childbearing potential and fertile men must agree to use
appropriate contraceptive methods during the study until one month
after the last study visit. For the purposes of this protocol, a history of
tubal ligation, bilateral oophorectomy or hysterectomy, or postmenopausal
women constitutes non-fertility. Fertile men must agree to
use a barrier contraceptive (condom). Vasectomy older than 6 months is
also acceptable.
11. Women of childbearing potential must have a negative serum
pregnancy test at inclusion.
12. Subjects who are on a stable diet and exercise regime and do not
have plans to modify their diet or exercise for at least 12 months.
13. Subject had a DXA screening and the results are interpretable
according to the study plan.
14. Willing and able to provide written informed consent prior to
performing any study procedures.
Inclusion into Treatment Period III (LT-OLE):
1. Completion of Treatment Periods I and II of study CP-4-005
2. Signing consent form for Treatment Period III
3. Investigator's approval of the patient anticipated compliance and
safety
4.Agreement to continue with use of contraception in women of child
bearing potential and fertile men
|
|
| E.4 | Principal exclusion criteria |
1. Women who are pregnant or breast-feeding (at least 6 months delay
from childbirth or lactation)
2. Evidence of growth benign intracranial tumor within the last 12
months (determined by comparing a previous MRI to a new one
obtained no more than 6 months prior to study entry to clarify dynamics of growth).
3. Suspected or diagnosed ongoing cancer or history of any cancer.
Exceptions to this exclusion criterion include resected in situ carcinoma
of the cervix and squamous cell or basal cell carcinoma of the skin with
complete local excision. Patients with GHD attributed to treatment of
intracranial malignant lesions in childhood or adulthood (or, tumors) or
leukemia may also be enrolled into the study provided that a recurrencefree
survival period of at least 5 years is well documented in the study record.
4. Signs of intracranial hypertension at screening
5. Heart insufficiency, NYHA class > 2 (Appendix C)
6. History of overt diabetes mellitus (including currently treated, wellcontrolled
DM) defined according to the American Diabetes Association
(ADA) Criteria , including ongoing administration of anti-diabetic
medications/agents. A history of gestational diabetes, resolved after childbirth, is not exclusionary.
7. Impaired liver function defined as:
a. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST)
greater than three times the upper limit of normal (ULN) at Screening
visit in a patient without prior history of elevated LFTs (non-alcoholic
fatty liver disease is not excluded, but requires etiological clarification
prior to eligibility confirmation) OR
b. Total bilirubin greater than 2 times the ULN at Screening
8. Subjects with severe renal failure at the Screening visit (defined by
GFR < 30 mL/min using MDRD Study Equation)
9. History of Acromegaly
10. For patients treated for Cushing's, biochemical, documented
evidence of possible recurrence within 2 months of study entry
according to 2008 Endocrine Society Guideline
11. Active Carpal tunnel syndrome suspected on a recent history (last 6
months) or ongoing symptoms such as: Numbness, or tingling in hand
and/or finger, pain in the arm, palm or forearm, both occurring also at
night and with intensive use of the hand; trouble gripping objects and
weakness in the thumb.
12. Systemic corticosteroids other than in replacement doses within the
3 months before study entry (temporary adjustment of glucocorticoids,
as appropriate, is acceptable)
13. Anabolic therapy or supplements (subject to Medical Monitor's
decision) other than gonadal steroid replacement therapy within 2
months before study entry
14. History of non-compliance with medications, un-cooperativeness or
drug abuse
15. Subjects who, based on the investigator's judgment, have a clinically
significant or unstable medical or surgical condition that may preclude
safe and complete study participation. Conditions may include
cardiovascular, peripheral vascular, pulmonary, hepatic, renal, or
neurological disease, as determined by medical history, physical
examination, laboratory tests or ECG.
16. Subjects who participated in any study and had administration of an
investigational medicinal product (IMP) within the last 2 months.
Subjects with previous participation in investigational studies must have
recovered from all adverse effects.
17. Subjects who participated within the last 12 months in any clinical
trial involving the use of medicinal products (investigational or
approved) that impact insulin levels, or that included specific dietary or
physical activity requirements are excluded
18. History of positive serology to HBC, HBV and HIV (patients that have
been previously vaccinated and therefore have positive serology are not
excluded)
19. Subjects with genetic causes of familial lipodystrophy.
20. Subjects who are confined to an institution by official directives or
court order.
Specific Exclusion for Treatment Period III (LT-OLE)
1. Unresolved drug related SAE from previous treatment periods
2. Clinical or imaging evidence of pituitary tumor growth
3. Diagnosis of ongoing cancer
4. Duration longer than 3 months since the last dose in Treatment Period
II of study CP-4-005, except if the cause for delay is due to study
logistics (i.e.: extended approval timelines or lack of clinical supplies)
The Medical Monitor may exempt this exclusion and approve participation in LT-OLE following evaluation of patient condition.
5. Uncontrolled diabetes mellitus (HbA1C ≥ 8.5%)
6. Subjects who, based on the investigator's judgment, have a clinically
significant or unstable medical or surgical condition that may preclude
safe and complete study participation. Conditions may include
cardiovascular, peripheral vascular, pulmonary, hepatic, renal, or
neurological disease, as determined by physical examination, laboratory
tests or ECG.
7. Participation in any other clinical trial, other than CP-4-005, in the
past 90 days
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Change in trunk fat mass (FM), expressed in kilograms measured with
DXA, from baseline to 26 weeks |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Changes in body composition:
• Change in total FM, expressed in kilograms, measured with DXA, from
baseline to 26 and 52 weeks
• Change in lean body mass, expressed in kilograms measured with DXA,
from baseline to 26 and 52 weeks
• Change in trunk FM, expressed in kilograms measured with DXA, from
baseline to 52 weeks
• Change in trunk FM, expressed as % change from baseline, measured
with DXA, from baseline to 26 and 52 weeks
Change in Biochemical markers:
• Change of IGF-I and IGF-I SDS levels across study visits
• Change of IGFBP-3 levels across study visits
• Proportion of subjects achieving normalization of IGF-I levels during
and at the end of each treatment period (week 26,week 52 and end-ofstudy).
Additional Measurements:
• Change in QoL from baseline across study visits
• Change in Waist-to-hip ratio from baseline across study visits
• Change in bone density from baseline on a yearly basis during
Treatment Period III
• Change in fat and lean body mass from baseline on a yearly basis
during Treatment Period III
• Change in lipid profile: fasting HDL cholesterol, LDL cholesterol,
triglycerides, Lp(a) from baseline on a six-monthly basis
Safety and Tolerability
• AEs and local tolerability (injection site reaction)
• Parameters of glucose metabolism:
- Fasting insulin level
- Fasting glucose levels
- HbA1c levels
• Immunogenicity
- Anti MOD-4023 Neutralizing Antibody occurrence
• IGF-I levels
• MOD-4023 levels
• Status of other hormonal axes
- Thyroid hormones (Free T4, T3 and TSH)
- Morning cortisol levels
• Other safety laboratory parameters, including serum chemistry profile, liver enzymes, hematology and urinalysis
• Vital signs including body mass index (BMI)
• ECG (screening, 6 months, 12 months and yearly thereafter)
• Fundoscopy for the occurrence of increased intracranial pressure (if PI
feels it is required) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Changes in body composition from baseline to 26 and 52 weeks
Change in Biochemical markers across the visits
Additional Measurements
Safety and Tolerability
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| Open-label for Treatment Period II and III |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 28 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| Austria |
| France |
| Georgia |
| Germany |
| Greece |
| Hungary |
| Israel |
| Korea, Republic of |
| Poland |
| Romania |
| Russian Federation |
| Serbia |
| Slovakia |
| Spain |
| Taiwan |
| Ukraine |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
This study is expected to end when the last subject has completed the
OLE portion of the study and database lock has been achieved for both
study periods.
Note, after completion of the DBPC period by all subjects, there will be
an interim analysis.
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 4 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
