Clinical Trials Register

Summary
EudraCT Number:	2009-014918-99
Sponsor's Protocol Code Number:	BKOS-02
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2009-11-17
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2009-014918-99

A.3

Full title of the trial

Intra-articular treatment with MEN16132 in patients with symptomatic primary osteoarthritis of the knee: A randomised, multicentre, double blind, placebo controlled, five parallel group, dose finding study

A.3.2

Name or abbreviated title of the trial where available

ALBATROSS - A Locally injected Bradykinin Antagonist for TReatment of OSteoarthritiS

A.4.1

Sponsor's protocol code number

BKOS-02

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

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	MENARINI RICERCHE S.P.A.
B.1.3.4	Country	Italy
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	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	MEN16132
D.3.2	Product code	MEN16132
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Intraarticular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	883969-00-4
D.3.9.2	Current sponsor code	MEN16132
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	125
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	No
D.3.11.8	Extractive medicinal product	No
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.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	MEN16132
D.3.2	Product code	MEN16132
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Intraarticular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	883969-00-4
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	250
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	No
D.3.11.8	Extractive medicinal product	No
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.IMP: 3
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	MEN16132
D.3.2	Product code	MEN16132
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Intraarticular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	883969-00-4
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	500
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	No
D.3.11.8	Extractive medicinal product	No
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Intraarticular use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Intraarticular use
D.8 Placebo: 3
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Intraarticular use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

symptomatic primary osteoarthritis of the knee

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	12.1
E.1.2	Level	LLT
E.1.2	Classification code	10031161
E.1.2	Term	Osteoarthritis

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 efficacy of MEN16132 given by intra-articular injections as four different doses/regimens versus placebo

E.2.2

Secondary objectives of the trial

To evaluate the dose-effect relationship of MEN16132 to support the choice of the dose/schedule to be studied in the subsequent clinical phase III study; the time to onset and the duration of effect; the safety and tolerability of MEN16132 given as 1 mL solution for intra-articular injection up to 0.5 mg dose for a cumulative dose up to 1.0 mg; the population pharmacokinetics of MEN16132 in patients

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written informed consent. 2. Male or female patients ≥40 years old. 3. Women of childbearing potential are eligible to participate in the study if their pregnancy test (serum �-hCG) is negative at screening, they are not nursing, and they use an effective method of contraception until all follow-up procedures are complete. Methods of contraception considered effective include oral, injectable or implanted hormonal contraceptive agents, hormone containing intra-uterine devices with failure rates <1% per year. 4. Symptomatic primary knee osteoarthritis (ACR criteria) since ≥6 months prior to screening, with documented minimal to moderate radiological severity (i.e. Kellgren Lawrence Grade 2 or 3) based on X-ray not older than 6 months, and representing an indication for intra-articular drug injection. 5. >50 mm VAS pain score assigned to the index knee at WOMAC VA 3.1-A1 (pain while walking on a flat surface). 6. >125 mm VAS pain score assigned to the index knee at WOMAC VA 3.1 A subscore (total pain). 7. Pain in the index knee on at least 50% of the days in the month preceding the screening. 8. Minimum flexion of 90 degrees in both knees. 9. Ability to perform the 15 m walk test without the support of crutches or other assistive devices. 10. Willingness to discontinue all pain or OA medication (e.g. NSAIDs, COX-2 inhibitors, analgesics) prior to randomisation and for the entire course of the study with a minimum wash-out of 1 or 2 weeks for drugs with short (i.e. < 5 hours) or longer half-life, respectively. NOTE: This does not include paracetamol, up to 1000 mg/day, as rescue medication and low dose aspirin for cardioprotection, up to 100 mg/day or other salicilates at equivalent doses. 11. Willingness to refrain from paracetamol use 48 hours prior to any study visit.

E.4

Principal exclusion criteria

1 Inability to personally provide written informed consent 2 Inability to understand or collaborate throughout the study 3 Subjects who participated in another clinical trial within 30 days prior randomisation 4 Patients with Kellgren & Lawrence Grade I or IV osteoarthritis of the knee 5 Knee condition representing an indication for surgery 6 Inflammatory or crystal arthropathies 7 Patients with acute fractures, severe loss of bone density, bone necrosis 8 Patients with isolated patella-femoral syndrome or chondromalacia 9 Patients with OA predominant in the lateral compartment or any significant valgus deformity 10 Patients with any other disease or condition interfering with the free use and evaluation of the index knee for the 3 month duration of the trial 11 Major injury or surgery to the index knee within the previous 12 months prior to screening 12 Severe hip osteoarthritis ipsilateral to index knee 13 Any pain >30 mm VAS that could interfere with the assessment of index knee pain 14 Any pharmacological or non-pharmacological treatment started or changed during 4 weeks prior to randomisation or likely to be changed during the duration of the study. Stable treatment for stable chronic disease is permitted as is the use of oral contraception or hormone replacement therapy IF patients are expected to remain on constant doses throughout the course of the study 15 Use of systemic or topical corticosteroids >10 mg prednisolone equivalent per day during 30 days prior to randomisation 16 Use of any pain or OA medication during 1 or 2 weeks prior to randomisation for drugs with short or longer half-life, respectively 17 Any acute or newly diagnosed disease/condition requiring treatment 18 Any chronic disease/condition requiring treatment modification 19 History of hypersensitivity/allergy to drugs including paracetamol 20 Patients with any clinically significant abnormal diagnostic test result that may represent a health risk, impact the study or affect the patient`s ability to complete the study 21 Patients with liver disease 22 Patients with severe renal insufficiency 23 Any sign of significant inflammation or infection 24 Any skin disorder or infection overlying the index knee 25 Previous infection of the index knee 26 Any intra-articular or local peri-articular punction, injection or surgery to the index knee during the 6 months prior to screening 27 Patients with bleeding diathesis or on therapy with anticoagulants 28 Significant peri-articular calcification 29 Previous ligament reconstruction at the index knee

E.5 End points

E.5.1

Primary end point(s)

The primary end-point to be tested on the intention to treat (ITT) population will be WOMAC VA 3.1 A subscore decrease over the 3 weeks after the first administration (Visits 3, 4 and 5) compared with baseline (Visit 2).

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

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

Yes

E.8.2.3

Other

E.8.2.3.1

Comparator description

- same IMP used at different dosage

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

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

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

ultima visita dell`ultimo soggetto inserito nella sperimentazione

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

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.1.3

Elderly (>=65 years)

Yes

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

Yes

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

100

F.4.2

For a multinational trial

F.4.2.1

In the EEA

400

F.4.2.2

In the whole clinical trial

400

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)

secondo pratica clinica

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

2010-01-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-11-05

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2011-03-02

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