Clinical Trials Register

Summary
EudraCT Number:	2018-000818-37
Sponsor's Protocol Code Number:	MTX-071-P03
National Competent Authority:	Slovakia - SIDC (Slovak)
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2019-02-15
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

Slovakia - SIDC (Slovak)

A.2

EudraCT number

2018-000818-37

A.3

Full title of the trial

A randomized, double-blind, placebo-controlled, single dose phase IIb exploratory study to document the clinical effects and safety of intra-articular injections of Lopain (MTX-071) in patients with chronic osteoarthritic knee joint pain (Part 1 and Part 3) with exploratory pharmacokinetics (Part 3) and of higher doses or consecutive administrations with local anesthetics with exploratory pharmacokinetics (Part 2)

Randomizovaná, dvojito zaslepená, placebom kontrolovaná, prieskumná štúdia s jednorazovou dávkou, fáza II.b, zameraná na dokumentáciu klinických účinkov a bezpečnosť intraartikulárnych injekcií Lopainu (MTX-071) u pacientov s chronickou osteoartritickou bolesťou kolenného kĺbu (Časť 1 a Časť 3) s prieskumnou farmakokinetikou (časť 3) a vyššie dávky alebo následné podávanie s lokálnym anestetikom s prieskumnou farmakokinetikou (Časť 2)

A.3.1

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

The pain reduction effects of different doses and modes of administration of Lopain (MTX-071) relative to placebo are evaluated in patients with chronic osteoarthritic knee joint pain.

Porovnávanie efektu zníženia bolesti pri rôznych dávkach a spôsoboch podania Lopainu (MTX-071) oproti placebu hodnoteného u pacientov s chronickou osteoartritídou kolenného kĺbu.

A.4.1

Sponsor's protocol code number

MTX-071-P03

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	Grünenthal GmbH
B.1.3.4	Country	Germany
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	Grünenthal GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	QPS Austria GmbH
B.5.2	Functional name of contact point	Clinical Trials Information
B.5.3	Address:
B.5.3.1	Street Address	Parkring 12
B.5.3.2	Town/ city	Grambach
B.5.3.3	Post code	8074
B.5.3.4	Country	Austria
B.5.4	Telephone number	+43316258111332
B.5.5	Fax number	+43316258111300
B.5.6	E-mail	office-austria@qps.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	Lopain
D.3.2	Product code	MTX-071
D.3.4	Pharmaceutical form	Concentrate for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intraarticular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	resiniferatoxin
D.3.9.1	CAS number	57444-62-9
D.3.9.2	Current sponsor code	RTX
D.3.9.3	Other descriptive name	RESINIFERATOXIN
D.3.9.4	EV Substance Code	SUB178982
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	6.4
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)	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	No
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	Concentrate for 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

chronic osteoarthritic knee joint pain

E.1.1.1

Medical condition in easily understood language

pain due to degenerative lesions of the knee joint

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10023476
E.1.2	Term	Knee osteoarthritis
E.1.2	System Organ Class	100000004859

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10003244
E.1.2	Term	Arthritic pains
E.1.2	System Organ Class	100000004859

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10064238
E.1.2	Term	Gonalgia
E.1.2	System Organ Class	100000004859

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Part 1, 2, 3
The primary exploratory objectives are to compare the pain reduction
effects (absolute and relative) at 3 months and 6 months of intraarticular
injections of different dose levels of MTX-071 (Lopain) relative
to placebo in patients with chronic osteoarthritic knee joint pain
Specific to Part 3:
Same primary objectives as in Part 1 but in a narrowed patients
population having insufficient pain relief and was unsatisfied with
optimized Standard of Care (including corticosteroids, hyaluronic acid,
NSAIDs, opioids, non-pharmacological treatment).

E.2.2

Secondary objectives of the trial

•Pain-relieving effect
-To compare the pain-relieving effects (expressed as percentages of
patient with ≥ 50 % or ≥ 70 % reduction in VAS score relative to Baseline)
at 3months and 6months of intra-articular injections of different dose
levels of MTX-071 relative to placebo
-To compare the improvements on pain, stiffness, and physical function
at 3 months and 6 months of intra-articular injections of different dose
levels of MTX-071 relative to placebo
•Safety
To document the safety of different dose levels of MTX-071 and placebo
To compare the pain at injection of different dose levels of MTX-071
relative to placebo
Specific Part 3
Documentation of efficacy assessments: patient global impression of
change(PGIC) and patient specific functional scale(PSFS)
Comparison of the pain-relieving effects after a second injection (MTX-
071 ) to those after the first injection in patients having less than
25% reduction of their baseline VAS score on motion after the 6month
time point

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

•Written informed consent
•Otherwise healthy (or with stable medical conditions) men or women
with knee osteoarthritis aged between 40 and 80 years (extremes
included).
•At least 40 mm on motion on the 100 mm-VAS (Visual Analog Scale) for
average osteoarthritic joint pain in the target knee during the last 2
days, with or without pain medication.
• Only for Part 3: Documented history indicating that subject had
insufficient pain relief and was unsatisfied with optimized Standard of
Care, i.e.
a. non-pharmacological treatment, and
b. treatment with oral or topical NSAIDS, and
c. intra-articular treatment with corticosteroids,
d. and where appropriate intra-articular treatment with hyaluronic acid
and/or opioids in combination or as monotherapies,
or subject is unable to take Standard of Care due to contraindication or
intolerability. If this refers only to one of the Standard of Care
treatments the criterion above applies for the other treatment options.
•Previous assessment (e.g. radiography, MRI or arthroscopy, not older
than 3 years) showing a Kellgren Lawrence Grade of 2 – 4.
•Female patients are only eligible for the study if they are either
surgically sterile or at least 2 years postmenopausal.
•Sexually active male patients must agree to use a reliable contraceptive
method for at least one month after the injection of MTX-071/Placebo.
•Patient is highly likely to comply with the protocol and complete the
study.

E.4

Principal exclusion criteria

•Previous exposure to the study drug of the target knee.
•Any contra-indication as per summary of product characteristics for the
premedication used.
•Surgery of the target knee within 6 months before study start or
planned surgery for any time during the next 6 months.
•Any injection into the target knee within the previous month or trauma
to the knee not yet healed.
• Only for Part 3: The subject is not able to clearly identify the target
knee (i.e. the more painful knee)
•History of uncontrolled (at the discretion of the investigator)
cardiovascular, renal, and/or other disease or malignancy.
•History of severe allergic or anaphylactic reactions.
•Male patients whose partner is planning to receive a child
•Major bleeding disorder encompassing, but not limited to coagulopathy
and any current antithrombotic and anticoagulant events. Low dose
acetylsalicylic acid for cardiovascular prevention can be allowed in
consultation with the medical monitor.
•Clinically significant (at the discretion of the investigator) deviation
from the normal laboratory values.
•Clinically significant (at the discretion of the investigator) abnormal
ECG.
•History of drug/chemical/substance/alcohol abuse within the past 2
years prior to Screening.
•Significant (at the discretion of the investigator) symptomatic, viral,
bacterial (including upper respiratory infection), or fungal (noncutaneous)
infection within the past 2 weeks prior to study medication administration.
•Patients positive for human immunodeficiency virus (HIV) antibody,
hepatitis C antibody, or for hepatitis B virus surface antigen (HBsAg).
• Patients who had a corticosteroid or hyaluronic acid injection in the
target knee within 3 months prior to Baseline or are planned to get a
corticosteroid injection within 6 months (Part 1, Part 2 and Part 3), any
other such injection within 3 months (Part 1 and Part 2 only) following
the injection of MTX-071/placebo or any other such injection within 6
months (Part 3 only) following the first injection of MTX-071/placebo.
•Systemic (except inhaled) immunosuppressant agent within 6 months
prior to study medication administration.
•Experimental agent within 30 days or ten half-lives, whichever is
longer, prior to study medication administration.
•Any other condition, which in the opinion of the investigator precludes
the patient's participation in the trial.
•Patients who are dependent on the sponsor or investigator

E.5 End points

E.5.1

Primary end point(s)

-Absolute reduction of the Visual Analog Scale (VAS) scores for pain on motion as average of the last two days in the target knee joint between Baseline and at 3 months and 6 months.

-Percentage of reduction of the Visual Analog Scale (VAS) scores for pain on motion as average of the last two days in the target knee joint between Baseline and at 3 months and 6 months.

E.5.1.1

Timepoint(s) of evaluation of this end point

after 3 and 6 months after injection

E.5.2

Secondary end point(s)

•Pain relieving effect
-Percentage of patients with ≥ 50% and ≥ 70% decrease in VAS scores
for pain on motion in the target knee joint as average of the last two
days between Baseline and at 3 months and 6 months.
-Percentage of decrease of the WOMAC scores (pain, stiffness, and
physical function) between Baseline and at 3 months and 6 months.
Specific to Part 3
- WOMAC score is changed from 5-point Likert scale to NRS 0-10
version.
- Percentage of evolution of the patient global impression of change
(PGIC) and patient specific functional scale (PSFS) scores.
•Safety
-Changes in safety parameters between Baseline and at 3 months and 6
months.
-Incidence, nature and severity of AES/SAEs potentially causally related
with the study medication.
-Maximal VAS (current pain) scores relative to Baseline (-0.5h) during
the Day 1 assessments period.
Specific to Part 3
- Documentation of the injection site pain and wrong injections

E.5.2.1

Timepoint(s) of evaluation of this end point

after 3 and 6 months of injection

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

Yes

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

Yes

E.6.13.1

Other scope of the trial description

tolerability

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.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the 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

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

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

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:

104

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

111

F.4.2.2

In the whole clinical trial

156

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)

None

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

2019-04-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-03-12

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-01-26

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