Clinical Trials Register

Summary
EudraCT Number:	2012-002787-27
Sponsor's Protocol Code Number:	ACP-001_CT-004
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-12-19
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2012-002787-27

A.3

Full title of the trial

A multicenter, Phase 2, randomized, open label, active-controlled, parallel-group study investigating the safety, tolerability, and efficacy of different dose levels of ACP-001 administered once weekly versus standard daily rhGH replacement therapy in pre-pubertal children with Growth Hormone Deficiency (GHD)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A study of ACP-001, a long-acting human growth hormone product, for treatment of Growth Hormone Deficiency in pre-pubertal children

A.4.1

Sponsor's protocol code number

ACP-001_CT-004

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Ascendis Pharma A/S
B.1.3.4	Country	Denmark
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Ascendis Pharma A/S
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Accelsiors CRO and Consultancy Services Ltd
B.5.2	Functional name of contact point	Clinical Trials Info
B.5.3	Address:
B.5.3.1	Street Address	103 Haros Str.
B.5.3.2	Town/ city	Budapest
B.5.3.3	Post code	1222
B.5.3.4	Country	Hungary
B.5.4	Telephone number	+361299 00 91
B.5.5	Fax number	+361299 00 96
B.5.6	E-mail	clinicaltrials@accelsiors.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	ACP-001
D.3.2	Product code	ACP-001
D.3.4	Pharmaceutical form	Powder and solvent for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	somatropin
D.3.9.2	Current sponsor code	TransCon PEG hGH
D.3.9.3	Other descriptive name	Transiently PEGylated hGH prodrug
D.3.9.4	EV Substance Code	SUB20678
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10.0
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Genotropin
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Recombinant human Growth Hormone (rhGH)
D.3.2	Product code	n/a
D.3.4	Pharmaceutical form	Powder and solvent for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	SOMATROPIN
D.3.9.1	CAS number	12629-01-5
D.3.9.3	Other descriptive name	recombinant DNA-derived human growth hormone
D.3.9.4	EV Substance Code	SUB10584MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5.3
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Growth Hormone Deficiency (GHD) in pre-pubertal children

E.1.1.1

Medical condition in easily understood language

Lack of growth hormone in the body

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	17.1
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 compare the safety and PK/PD profile of three different ACP-001 doses to that of a commercially available standard daily rhGH formulation in pre-pubertal children with growth failure due to GHD.

E.2.2

Secondary objectives of the trial

1.To evaluate the 6-month growth pattern (height velocity)
2.To select a safe and efficacious dose for pivotal development

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Pre-pubertal children with GHD (either isolated or as part of a multiple pituitary hormone deficiency) in Tanner stage I aged:
a. Boys: 3 years ≤ boy’s age ≤ 12 years
b. Girls: 3 years ≤ girl’s age ≤ 11 years;
2. Diagnosis of GHD confirmed by two different GH provocation tests, defined as a peak GH level of ≤ 10 ng/mL, determined by a central laboratory using a validated assay. One well documented historical test (with properly recorded sampling times and results as well as euthyroid status of the patient) performed within 3 months prior to Screening can be accepted to replace one GH stimulation test analyzed by the central laboratory;
3. Bone age (BA) not greater than the chronological age;
4. Impaired height and height velocity defined as:
a. Height (HT) of at least 2.0 standard deviations (SD) below the mean height for chronological age and sex (HT SDS ≤ - 2.0) according to the CDC standards of 2000
b. Height velocity (HV) of at least 1 SD below the mean HV for chronological age and sex (HV SDS ≤ - 1.0) according to the standards of Prader et al. of 1989, whereas the time between 2 height measurements is not less than 6 months;
5. BMI within ±2 SD of the mean BMI for chronological age and sex according to the 2000 CDC standards;
6. Baseline IGF-I level of at least 1 SD below the mean IGF-I level standardized for age and sex (IGF-I SDS ≤ -1.0) according to the central laboratory reference values;
7. Normal fundoscopy at Screening (without signs/symptoms of intracranial hypertension);
8. Children with multiple hormonal deficiencies must be on stable replacement therapy (stable dose and normal blood hormone levels) for other hypothalamo-pituitary axes for at least 3 months. Thyroid replacement therapy for thyroid hormone deficiency must be instituted at least 6 months (and be stable for at least 3 months) prior to Screening. Temporary adjustment of glucocorticoid replacement therapy, as appropriate, is acceptable;
9. Normal 46 XX karyotype for girls;
10. Written informed consent of the parent or legal guardian of the patient and written assent of the patient (if the patient is able to read, understand, and sign).

E.4

Principal exclusion criteria

1. Children with a body weight below 11 kg;
2. Children with hematocrit at Screening below 34%;
3. Prior exposure to rhGH or IGF-I therapy;
4. Children with past or present intracranial tumor growth as confirmed
by a sellar MRI scan (with contrast) at Screening (if no MRI was
performed within the last 6 months prior to Screening);
5. Children born small for gestational age (SGA), i.e. birth weight and/or
birth length < -2 SD for gestational age;
6. Malnutrition, defined as:
a. Serum albumin level below the lower limit of normal (LLN) according
to the reference ranges of the central laboratory, and
b. Serum iron below the lower limit of normal (LLN) according to the
reference ranges of the central laboratory, and
c. BMI < -2 SD for age and sex;
7. Children with psychosocial dwarfism;
8. Children with idiopathic short stature;
9. Other causes of short stature such as coeliac disease (confirmed by
anti-transglutaminase antibodies test), hypothyroidism, or rickets;
10. Presence of anti-hGH binding antibodies at Screening;
11. History or presence of malignant disease; any evidence of present
tumor growth;
12. Any clinically significant abnormality likely to affect growth or the
ability to evaluate growth, e.g. chronic diseases like renal insufficiency,
spinal cord irradiation, etc.;
13. Patients with diabetes mellitus or impaired fasting sugar (based on
WHO standards);
14. Chromosomal abnormalities and medical syndromes (Turner
syndrome, Laron syndrome, Noonan syndrome, Prader-Willi syndrome,
Russell-Silver syndrome, SHOX mutations/deletions and skeletal
dysplasias) with the exception of septo-optic dysplasia;
15. Closed epiphyses;
16. Concomitant administration of other treatments that may have an
effect on growth such as anabolic steroids or methylphenidate for
attention deficit hyperactivity disorder (ADHD) with the exception of
hormone replacement therapies (thyroxine, hydrocortisone,
desmopressin);
17. Children requiring glucocorticoid therapy (e.g. asthma) 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;
18. Major medical conditions and/or presence of contraindication to rhGH treatment;
19. Known or suspected HIV-positive patient;
20. Known hypersensitivity to the components of the study medication;
21. The patient and/or the parent/legal guardian are likely to be
noncompliant in respect to study conduct;
22. Participation in any other trial of an investigational agent within 30
days prior to Screening.

E.5 End points

E.5.1

Primary end point(s)

Safety endpoints
•Incidence of AEs;
•Local tolerability (assessed by the patient and the investigator);
•Incidence of anti-hGH antibody and incidence of treatment-emergent anti-PEG antibody formation;
•IGF-I levels;
•Parameters of glucose metabolism (fasting glucose and insulin level, HbA1c) and lipid parameters;
•Hormone levels: thyroid status and cortisol levels;
•All other hematology and biochemistry blood parameters;
•Results of the physical examinations, vital sign measurements and ECG.

Efficacy endpoints
•The relationship between the dose of ACP-001 or daily rhGH and the annualized HV at 6 months;
•Relationship between delta HT SDS and ACP-001 dose or daily rhGH dose after 3 and 6 months of treatment;
•Annualized HV during treatment with ACP-001 at the end of 6 months, for each ACP-001 dose group and for the daily rhGH treatment group;
•Comparison of annualized height velocity between ACP-001 and the corresponding dose of daily rhGH;
•Change in HT SDS during treatment with ACP-001 at 3 and 6 months compared to baseline for each ACP-001 dose groups and for the daily rhGH treatment group;
•Change in serum IGF-I levels during treatment with ACP-001, from baseline to end of 6 months for each ACP-001 dose group, compared between the ACP-001 dose groups and to the daily rhGH group;
•IGF-I standard deviation scores (IGF-I SDS) and proportion of patients achieving normalization of serum IGF-I levels during treatment with ACP-001 (for each dose regimen) or daily rhGH, including comparisons between treatment groups;
•Change in hGH levels during treatment with ACP-001, from baseline to end of 6 months compared between the ACP-001 dose groups and to the daily rhGH group.

E.5.1.1

Timepoint(s) of evaluation of this end point

•The relationship between the dose of ACP-001 or daily rhGH and the annualized HV at 6 months;
•Relationship between delta HT SDS and ACP-001 dose or daily rhGH dose after 3 and 6 months of treatment;
•Annualized HV during treatment with ACP-001 at the end of 6 months;
•Change in HT SDS during treatment with ACP-001 at 3 and 6 months compared to baseline;
•Change in serum IGF-I levels during treatment with ACP-001, from baseline to end of 6 months for each ACP-001 dose group;
•IGF-I standard deviation scores (IGF-I SDS) and proportion of patients achieving normalization of serum IGF-I levels during treatment with ACP-001 (for each dose regimen) or daily rhGH;
•Change in hGH levels during treatment with ACP-001, from baseline to end of 6 months.

E.5.2

Secondary end point(s)

PK and PD endpoints
•PK profile of hGH from ACP-001 treated patients compared between ACP-001 dose groups and to the PK profile of hGH from the daily rhGH group during V1 and V3;
•PK profile of TransCon PEG hGH during V1 and V3 (ACP-001 treated patients only);
•PK profile of PEG during V1 and V3 (ACP-001 treated patients only);
•PD profile of IGF-I and IGFBP-3 during V1 and V3 compared between the ACP-001 dose groups and to the daily rhGH group.

E.5.2.1

Timepoint(s) of evaluation of this end point

All PK and PD endpoints will be evaluated during visits V1 and V3

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

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

Belarus

Bulgaria

Czech Republic

Egypt

France

Germany

Greece

Hungary

Poland

Romania

Russian Federation

Slovenia

Turkey

Ukraine

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

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Patients are between 3-12 years old and therefore not able to give legal consent. Parents or legal guardian will sign the informed consent. Patients will sign as well in case they are able to read, understand and sign.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Treatment after the trial period is at the discretion of the treating physician / investigator. Up to 6 months hGH from commercial and approved source will be provided in case treatment is otherwise not available.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2013-05-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-06-17

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-07-14

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials