Clinical Trials Register

Summary
EudraCT Number:	2017-003512-40
Sponsor's Protocol Code Number:	20150120
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2018-01-15
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

Poland - Office for Medicinal Products

A.2

EudraCT number

2017-003512-40

A.3

Full title of the trial

A Randomized, Multicenter, Open-label, Parallel Group Study in Postmenopausal Women With Osteoporosis to Evaluate the Noninferiority of Subject-administered Romosozumab via Autoinjector/Pen vs Healthcare Provider-administered Romosozumab via Prefilled Syringe

A.3.1

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

A Comparison of Subject-administered Romosozumab with Healthcare Provider-administered Romosozumab for Osteoporosis

A.4.1

Sponsor's protocol code number

20150120

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	Amgen Inc.
B.1.3.4	Country	United States
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	Amgen Inc
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Amgen (Europe) GmbH
B.5.2	Functional name of contact point	IHQ-Medical Info - Clinical Trials
B.5.3	Address:
B.5.3.1	Street Address	Dammstrasse 23, P.O Box 1557
B.5.3.2	Town/ city	Zug
B.5.3.3	Post code	CH-6300
B.5.3.4	Country	Switzerland
B.5.6	E-mail	medinfointernational@amgen.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	romosozumab
D.3.2	Product code	AMG785
D.3.4	Pharmaceutical form	Solution for injection in pre-filled pen
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	romosozumab
D.3.9.2	Current sponsor code	AMG785
D.3.9.3	Other descriptive name	ROMOSOZUMAB
D.3.9.4	EV Substance Code	SUB31075
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	90
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	Yes
D.3.11.13.1	Other medicinal product type	Monoclonal antibody
D.IMP: 2
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	romosozumab
D.3.2	Product code	AMG785
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
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	romosozumab
D.3.9.2	Current sponsor code	AMG785
D.3.9.3	Other descriptive name	ROMOSOZUMAB
D.3.9.4	EV Substance Code	SUB31075
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	90
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	Yes
D.3.11.13.1	Other medicinal product type	Monoclonal antibody

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

Postmenopausal osteoporosis

E.1.1.1

Medical condition in easily understood language

Osteoporosis

E.1.1.2

Therapeutic area

Body processes [G] - Bones and nerves physological processes [G11]

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	10031285
E.1.2	Term	Osteoporosis postmenopausal
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

• To evaluate the noninferiority of a 6-month treatment with 210 mg romosozumab at 90 mg/mL administered subcutaneously (SC) once a month (QM) in postmenopausal women with osteoporosis either by healthcare provider (HCP) administration with prefilled syringe (PFS) or by subject self-administration with autoinjector/pen (AI/Pen)

E.2.2

Secondary objectives of the trial

Efficacy
• To evaluate the efficacy of a 6-month treatment with 210 mg romosozumab at 90 mg/mL SC M in postmenopausal women with osteoporosis either by HCP administration with PFS or by subject self-administration with AI/Pen
Safety
• To evaluate the safety and tolerability of a 6-month treatment with 210 mg romosozumab at 90 mg/mL SC QM by HCP administration with PFS or by subject self-administration with AI/Pen
Exploratory
• To describe the effect of 6 months of treatment with HCP-administered romosozumab with PFS versus subject self-administered romosozumab with AI/Pen SC QM in postmenopausal women with osteoporosis on bone turnover markers (BTMs)
• To evaluate serum concentration changes of romosozumab at Months 1, 3, and 6 after SC QM administration of romosozumab

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Subject has provided informed consent/assent prior to initiation of any study specific activities/procedures, or subject’s legally acceptable representative has provided informed consent prior to any study-specific activities/procedures being initiated when the subject has any kind of condition that, in the opinion of the Investigator, may compromise the ability of the subject to give written informed consent.
• Postmenopausal female (postmenopausal status is defined as no vaginal bleeding or spotting for 12 consecutive months prior to screening).
• ≥ 55 to ≤ 90 years of age at the time of informed consent
• Ambulatory
• BMD T-score ≤ -2.50 at the lumbar spine, total hip, or femoral neck, as assessed by the central imaging vendor at the time of screening, based on DXA scans
• Subject has at least 2 vertebrae in the L1-L4 region evaluable by DXA, as assessed by the principal investigator or designee
• Subject has at least 1 hip evaluable by DXA, as assessed by the principal investigator or designee
• Subject has history of fragility (ie, osteoporosis-related fracture) or subject meets at least 2 of the following clinical risk factors for fracture:
- ≥ 70 years of age at the time of informed consent
- BMD T-score ≤ -3.00 at the lumbar spine, total hip, or femoral neck, as assessed by the central imaging vendor at the time of screening, based on DXA scans
- current smoker
- consumption of ≥ 3 glasses of alcohol a day
- parental history of fragility (ie, osteoporosis-related) fracture
- body weight ≤ 125 pounds/56 kilogram
• Ability to follow and understand instructions and the ability to self-inject, per investigator judgement

E.4

Principal exclusion criteria

Disease-Related
• History of ONJ and/or AFF
• History of metabolic or bone disease (except osteoporosis) that may interfere with the interpretation of the results, such as sclerosteosis, Paget’s disease, rheumatoid arthritis, osteomalacia, osteogenesis imperfecta, osteopetrosis, ankylosing spondylitis, Cushing’s disease, hyperprolactinemia, and malabsorption syndrome
• Subject with reported history of hearing loss associated with cranial nerve VIII compression due to excessive bone growth (eg, as seen in conditions such as Paget’s disease, sclerosteosis and osteopetrosis)
• Vitamin D insufficiency [defined as serum 25 (OH) vitamin D levels < 20 ng/mL], as determined by the central laboratory. Vitamin D repletion will be permitted and subjects may be rescreened.
• Current hyperthyroidism (unless well controlled on stable antithyroid therapy) by subject report or by chart review, per principal investigator evaluation
• Current clinical hypothyroidism (unless well controlled on stable thyroid replacement therapy) by subject report or by chart review, per principal investigator evaluation
• Current, uncontrolled hyper- or hypoparathyroidism, defined as PTH outside the normal range, per subject medical history. Uncontrolled hyperparathyroidism is defined as: parathyroid hormone (PTH) outside the normal range in subjects with concurrent hypercalcemia; or PTH values > 20% above the upper limit of normal (ULN) in normocalcemic subjects.
• Current hyper- or hypocalcemia, defined as albumin-adjusted serum calcium outside the normal range, as assessed by the central laboratory. Serum calcium levels may be retested once in case of an elevated serum calcium level within 1.1x the ULN as assessed by the central laboratory
Other Medical Conditions
• Malignancy, except non-melanoma skin cancers or cervical or breast ductal carcinoma in situ within the last 5 years
• Possible diagnosis of multiple myeloma or related lymphoproliferative disorder, as assessed by serum protein electrophoresis performed by the central laboratory and interpreted by the investigator
• Evidence of acute or chronic hepatitis B or hepatitis C virus. Hepatitis status will be evaluated by testing for hepatitis B surface antigen (HepBsAg), total hepatitis B core antibody (HepBcAb) and hepatitis C antibody by the central laboratory at initial screening. Polymerase chain reaction (PCR) should be performed to confirm active disease only if total HepBcAb is positive and HepBsAg is negative or if C antibody is positive.
• Positive for Human Immunodeficiency Virus, per subject report or chart review Prior/Concomitant Therapy
• Strontium ranelate or fluoride (for osteoporosis): more than 1 month of cumulative use within 5 years prior to randomization
• Intravenous (IV) bisphosphonates
Zoledronic acid:
− any dose received within 3 years prior to randomization
− more than 1 dose received within 5 years prior to randomization
IV ibandronate or IV pamidronate:
− any dose received within 12 months prior to randomization
− more than 3 years of cumulative use, unless last dose received ≥ 5 years prior to randomization
• Dose received within the past 18 months prior to randomization: denosumab or any cathepsin K inhibitor, such as odanacatib (MK-0822)
• Teriparatide or any PTH analogs
− any dose received within 3 months prior to randomization
− more than 1 month of cumulative use between 3 and 12 months prior to Randomization
• Oral bisphosphonates
− any dose received within 3 months prior to randomization
− more than 1 month of cumulative use between 3 and 12 months prior to randomization
− more than 3 years of cumulative use, unless last dose received ≥ 5 years
prior to randomization
• Dose received within the past 6 months prior to randomization: systemic oral or transdermal estrogen or SERMs (up to 1 month of cumulative use is allowed)
• More than 1 month of cumulative use of activated vitamin D3 or vitamin K2 within 6 months prior to randomization
• Dose received within the past 6 months prior to randomization: hormonal ablation therapy (up to 1 month of cumulative use is allowed)
• Dose received within the past 3 months prior to randomization: tibolone, calcitonin, or cinacalcet
• Dose received within the past 3 months prior to randomization: systemic glucocorticosteroids (≥ 5 mg prednisone equivalent per day for more than 14 days
• Subject has previously received a sclerostin antibody product within the past 12 months prior to randomization
Prior/Concurrent Clinical Study Experience
• Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(ies).
• Subject has previously entered this study
• Other investigational procedures while participating in this study are excluded
For Other Exclusions Criteria please see the Protocol dated !0 August 2017.

E.5 End points

E.5.1

Primary end point(s)

• Percent change from baseline in bone mineral density (BMD) at the lumbar spine, as assessed by dual-energy x-ray absorptiometry (DXA)

E.5.1.1

Timepoint(s) of evaluation of this end point

Month 6

E.5.2

Secondary end point(s)

Efficacy
• Percent changes from baseline in BMD at the total hip and femoral neck by DXA
Safety
• Incidence of treatment-emergent adverse events, serious adverse events, and adverse device effects
• Incidence of subjects developing anti-romosozumab antibodies
•Change from baseline in laboratory assessments and vital signs
Exploratory
• Percent change in bone turnover markers procollagen type 1 N telopeptide (P1NP) and bone resorption marker serum type I collagen C telopeptide (sCTX)
• Serum romosozumab concentration at Months 1, 3, and 6

E.5.2.1

Timepoint(s) of evaluation of this end point

Efficacy:
Month 6 (total hip and femoral neck)
Exploratory:
Months 1, 3, 6 (Serum romosozumab concentration)

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

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

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)

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

Poland

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

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

EoS: The date when the last subject across all sites is assessed or receives an intervention for evaluation in the study (ie., LSLV).
Primary Completion:
The date when the last subject is assessed or receives an intervention for the final collection of data for the primary endpoint, for the purposes of conducting the primary analysis, whether the study concluded as planned in the protocol or was terminated early;
The date when the LS has completed the assessments for the Month 6 visit.

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

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)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

173

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

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

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

170

F.4.2

For a multinational trial

F.4.2.1

In the EEA

186

F.4.2.2

In the whole clinical trial

260

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)

Normal treatment of the condition as per standard of care

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	Synexus Clinical Research Limited
G.4.3.4	Network Country	United Kingdom

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2018-02-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-01-04

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-01-08

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