Clinical Trials Register

Summary
EudraCT Number:	2021-005029-26
Sponsor's Protocol Code Number:	KF7039-01
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-05-04
Trial 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

2021-005029-26

A.3

Full title of the trial

A randomized, double-blind, placebo-controlled, Phase III trial to evaluate the efficacy and safety of intra-articular injections of RTX-GRT7039 in adult subjects with pain associated with osteoarthritis of the knee

Sperimentazione di fase III, randomizzata, in doppio cieco, controllata con placebo per valutare l’efficacia e la sicurezza di iniezioni intra-articolari di RTX GRT7039 in soggetti adulti con dolore associato a osteoartrite del ginocchio

A.3.1

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

Comparison of RTX-GRT7039 and placebo injections for pain associated with osteoarthritis of the knee.

Confronto delle iniezioni di RTX-GRT7039 e di placebo per il dolore associato a osteoartrite del ginocchio

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

KF7039-01

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1268-7314

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	GRUNENTHAL 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	Grünenthal GmbH
B.5.2	Functional name of contact point	Grünenthal Trial Information Desk
B.5.3	Address:
B.5.3.1	Street Address	Zieglerstrasse 6
B.5.3.2	Town/ city	Aachen
B.5.3.3	Post code	52078
B.5.3.4	Country	Germany
B.5.4	Telephone number	00492415693223
B.5.5	Fax number	000000
B.5.6	E-mail	Clinical-Trials@grunenthal.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	NA
D.3.2	Product code	[RTX-GRT7039]
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	NA
D.3.9.3	Other descriptive name	RTX, GRT1076857
D.3.9.4	EV Substance Code	SUB189873
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	1
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
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	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.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	Yes
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	Ropivacaina
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	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	ROPIVACAINA
D.3.9.1	CAS number	84057-95-4
D.3.9.2	Current sponsor code	NA
D.3.9.4	EV Substance Code	SUB10382MIG
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
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
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	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

Moderate to severe pain associated with osteoarthritis of the knee

Dolore da moderato a grave associato a osteoartrite del ginocchio

E.1.1.1

Medical condition in easily understood language

Pain due to osteoarthritis of the knee

Dolore dovuto a osteoartrite del ginocchio

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.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Demonstrate the analgesic efficacy of intra-articular RTX-GRT7039 compared with placebo.

Dimostrare l’efficacia analgesica di RTX-GRT7039 intra-articolare rispetto al placebo.

E.2.2

Secondary objectives of the trial

• Demonstrate the analgesic efficacy of intra-articular RTX-GRT7039 compared with placebo.
• Demonstrate the efficacy of intra-articular RTX-GRT7039 on function compared with placebo.
• To assess the safety and tolerability of intra-articular RTX-GRT7039.

• Dimostrare l’efficacia analgesica di RTX-GRT7039 intra-articolare rispetto al placebo.
• Dimostrare l’efficacia di RTX-GRT7039 intra-articolare sulla funzionalità rispetto al placebo.
• Valutare la sicurezza e la tollerabilità di RTX-GRT7039 intra-articolare.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• > or = 18 years of age at the screening visit.
• Body Mass Index (BMI) < or = 40.0 kg/m2.
• Diagnosis of osteoarthritis of the knee based on American College of Rheumatology criteria and functional capacity class of I-III.
• Moderate to severe osteoarthritis at baseline.
• Documented history indicating that subject has insufficient pain relief with optimal standard of care (SoC).
• The investigator does not consider that any additional benefit can reasonably be expected from further adjustments to the patient's pain treatment.

• Età > o =18 anni alla visita di screening.
• Indice di massa corporea (IMC) < o =40,0 kg/m2.
• Diagnosi di osteoartrite del ginocchio in base ai criteri dell’American College of Reumatology e classe di capacità funzionale di I-III.
• Osteoartrite da moderata a grave al basale.
• Anamnesi documentata indicante che il soggetto ha un sollievo dal dolore insufficiente con lo standard di cura (SoC) ottimale.
• Lo sperimentatore ritiene che non si possa ragionevolmente prevedere alcun beneficio aggiuntivo da ulteriori modifiche del trattamento antidolorifico del paziente.

E.4

Principal exclusion criteria

• The subject had an intra-articular injection of either corticosteroid or intra-articular visco-supplementation (i.e., hyaluronic acid) into the index knee within 3 months.
• The subject had an injection of platelet-rich plasma into the index knee within 6 months.
• The subject applied topical capsaicin on the index knee within 3 months.
• Pre-existing rapidly progressing osteoarthritis (RPOA) Type I or Type II, osteonecrosis, subchondral insufficiency fracture, atrophic osteoarthritis, or the subject has knee pain attributable to disease other than osteoarthritis.
• Other conditions that could confound discrimination of pain assessment in the index knee.
• Clinically significant disease(s) or condition(s) that may affect efficacy or safety assessments, or any other reason which, in the investigator's opinion, may preclude the subject's participation in the full duration of the trial.
• History of severe allergic or anaphylactic reactions.
• History of significant trauma or surgery, or surgery planned during the trial period, related to the knee.

• Il soggetto è stato trattato con un’iniezione intra-articolare di corticosteroidi o viscosupplementazione intra-articolare (cioè, acido ialuronico) nel ginocchio indice entro 3 mesi.
• Il soggetto è stato trattato con un’iniezione di plasma ricco di piastrine nel ginocchio indice entro 6 mesi.
• Il soggetto ha applicato capsaicina topica sul ginocchio indice entro 3 mesi.
• Osteoartrite rapidamente progressiva pre-esistente (RPOA) di tipo I o II, osteonecrosi, frattura subcondrale da insufficienza, osteoartrite atrofica oppure il soggetto manifesta dolore al ginocchio attribuibile a una malattia diversa dall’osteoartrite.
• Altre condizioni che potrebbero confondere la differenziazione della valutazione del dolore nel ginocchio indice.
• Malattie o condizioni clinicamente significative che possano influire sulle valutazioni dell’efficacia o della sicurezza, oppure qualsiasi motivo che, secondo il parere dello sperimentatore, possa precludere la partecipazione del soggetto per l’intera durata della sperimentazione.
• Anamnesi di gravi reazioni allergiche o anafilattiche.
• Anamnesi di trauma o intervento chirurgico significativo, oppure intervento chirurgico pianificato durante il periodo della sperimentazione, relativamente al ginocchio.

E.5 End points

E.5.1

Primary end point(s)

1) Change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale score in the index knee.

1) Cambiamento nel punteggio della sottoscala del dolore del Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) nel ginocchio indice.

E.5.1.1

Timepoint(s) of evaluation of this end point

1) From baseline (assessment at Visit 2) to Visit 5.

1) Dal basale (valutazione alla Visita 2) alla Visita 5.

E.5.2

Secondary end point(s)

1) Change in WOMAC pain subscale score in the index knee based on the 11-point numeric rating scale (NRS).
2) Change in WOMAC physical function subscale score.
3) Incidence of treatment-emergent adverse events (TEAEs). Incidence of TEAEs leading to discontinuation in the Treatment and Follow-up Period after the first and after the second injection, respectively. Incidence of related TEAEs representing structural changes of the knee joint as visualized by the imaging methods (X-ray and/or magnetic resonance imaging [MRI]).

1) Cambiamento nel punteggio della sottoscala del dolore del WOMAC nel ginocchio indice sulla base della scala di valutazione numerica (NRS) a 11 punti.
2) Cambiamento nel punteggio della sottoscala della funzionalità fisica WOMAC.
3) Incidenza degli eventi avversi emergenti dal trattamento (TEAE). Incidenza di TEAE che portano ad interruzione nel periodo di trattamento e follow-up dopo la prima e dopo la seconda iniezione, rispettivamente. Incidenza di TEAE correlati che rappresentano i cambiamenti strutturali dell’articolazione del ginocchio come visualizzato dai metodi di acquisizione delle immagini (rx e/o risonanza magnetica [RM]).

E.5.2.1

Timepoint(s) of evaluation of this end point

1) From baseline (assessment at Visit 2) to Visit 6 to Visit 10.
2) From baseline (assessment at Visit 2) to Visit 5 to Visit 6 to Visit 10.
3) From baseline (assessment at Visit 2) to Visit 10. (end of trial).

1) Dal basale (valutazione alla Visita 2) alla Visita 6 alla Visita 10.
2) Dal basale (valutazione alla Visita 2) alla Visita 5 alla Visita 6 alla Visita 10.
3) Dal basale (valutazione alla Visita 2) alla Visita 10 (fine della sperimentazione).

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

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

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

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

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

Canada

Japan

Mexico

France

Poland

Netherlands

Czechia

Germany

Italy

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

Ultima visita dell'ultimo soggetto

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:

180

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

270

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

304

F.4.2.2

In the whole clinical trial

450

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

Nessuno

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

2022-08-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-05-31

P. End of Trial
P.	End of Trial Status	Ongoing

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