Clinical Trials Register

Summary
EudraCT Number:	2004-001666-40
Sponsor's Protocol Code Number:	CZOL446H2202E1
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2005-05-13
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

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2004-001666-40

A.3

Full title of the trial

An international, multicenter, randomized, open-label, safety and
efficacy trial of intravenous zoledronic acid administered either
once or twice yearly in children with severe osteogenesis
imperfecta, a 1-year extension to CZOL446H2202

A.3.2

Name or abbreviated title of the trial where available

2202E

A.4.1

Sponsor's protocol code number

CZOL446H2202E1

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Novartis Pharma AG
B.1.3.4	Country	Switzerland
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	Information not present in EudraCT
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	zoledronic acid
D.3.2	Product code	ZOL446
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.8	Extractive medicinal product	Information not present in EudraCT
D.3.11.9	Recombinant medicinal product	Information not present in EudraCT
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

Osteogenesis Imperfecta

MedDRA Classification

E.1.3

Condition being studied is a rare disease

Information not present in EudraCT

E.2 Objective of the trial

E.2.1

Main objective of the trial

to examine the long-term safety of two different dosage regiments of zoledronic acid over an additional 12 months in pediatric patients who have completed one-year of treatment of zoledronic acid in the core CZOL446H2202 study, with focus on general safety and renal safety.

E.2.2

Secondary objectives of the trial

to assess continued efficacy, compared to baseline (visit 1 of core) :
• % change in lumbar spine bone mineral density at mo 18 & 24
• change in Z score of lumbar spine at mo18 & 24
• # clinical fractures per patient over 12-mo ext & 24-mo total
• change in bone resorption / formation markers at mo15, 18, 21 & 24
• change in supine length/height at mo 15, 18, 21 & 24
• change in bone pain
• change in bone mineral content of total body at mo 18 & 24
• change in cortical bone thickness at mo 24
• change in vertebral spine length at mo 24
• change in grip strength at mo 15, 18, 21 & 24
• % of patients need treatment before scheduled dosing visits during the extension

E.2.3

Trial contains a sub-study

Information not present in EudraCT

E.3

Principal inclusion criteria

• Children, male or female, between 1 year and 17 years of age at visit 1 of the extension, all inclusive, who have completed 1 year treatment of zoledronic acid or pamidronate in CZOL446H2202 trial.

E.4

Principal exclusion criteria

• Any disease or planned therapy which will interfere with the procedures or data collection of this trial.
• Any disease or abnormality that would prevent accurate bone-mineral density measurements of the lumbar spine (e.g., intra-abdominal calcification that may prohibit accurate data collection/interpretation; severe scoliosis, kyphosis, or metal implants, etc.)
• Any surgical bone-lengthening procedure, e.g. Ilizarov procedure planned/scheduled to occur during the trial.
• Female patients of child-bearing potential are eligible only if they are: not pregnant (serum β-hCG pregnancy-test negative)/non-lactating; are sexually abstinent or are surgically sterile (tubal ligation or hysterectomy): and if sexually active, must be practicing a medically acceptable form of birth control, defined as the use of an IUD, a barrier method with spermicide, condoms, subdermal implant or oral contraceptives. Females of child-bearing potential who are sexually active must agree to continue to practice their birth control during the trial and at least 1 year after completing the trial and must consent to a pregnancy test prior to every dose administration.
• Renal abnormality (please see section 7.5.1): defined as a serum-creatinine value above the upper limit of normal (age- and sex-matched) or a urine dipstick greater than 2 + protein.
• Hypocalcemia: any value (age-matched) below the normal range.
• History or evidence of an intestinal malabsorption syndrome.
• Patients with a significant drug-related adverse event in the original protocol.
• Patients who discontinued treatment in the original protocol ZOL446H2202.

E.5 End points

E.5.1

Primary end point(s)

• Bone-mineral density (BMD) measurements (lumbar spine and total body) by dual energy absorptiometry (DEXA)
• X-rays of the vertebral spine and the left hand: to determine vertebral spine length, bone cortical thickness and number of clinical fractures.
• Specialized serum tests to evaluate bone resorption and formation will be performed for C-telopeptide (CTX), N-terminal propeptide of type I collagen (P1NP), parathyroid hormone (PTH) and bone specific alkaline phosphatase (SAP).
• Bone Pain Assessment using the pediatric Wong-Baker FACES Pain Rating Scale.
• Grip Strength using dynamometry
• Clinical fractures
• Height using stadiometer
• Incidence of patients who need treatment before scheduled dosing visit.

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

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Information not present in EudraCT

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

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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)

E.8.2.2

Placebo

E.8.2.3

Other

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.8.5

The trial involves multiple Member States

Yes

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

Information not present in EudraCT

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

E.8.7

Trial has a data monitoring committee

Information not present in EudraCT

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

if the trial is endangering the safety of the patients

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

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)

Yes

F.1.1.5

Children (2-11years)

Yes

F.1.1.6

Adolescents (12-17 years)

Yes

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

Information not present in EudraCT

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Information not present in EudraCT

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

Pediatric patients

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

130

G. Investigator Networks to be involved in the Trial

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2005-06-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2005-06-07

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2007-05-01

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