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Clinical Trial Results:
A randomized, double-blind, placebo-controlled, Phase III trial to evaluate the efficacy and safety of a single intra-articular injection of RTX-GRT7039 in adult subjects with pain associated with osteoarthritis of the knee.

Summary
EudraCT number	2021-005020-38
Trial protocol	ES DK PT BG
Global end of trial date	15 Aug 2024

Results information
Results version number	v1(current)
This version publication date	27 Jun 2025
First version publication date	27 Jun 2025
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

KF7039-02

ISRCTN number

US NCT number

NCT05449132

WHO universal trial number (UTN)

U1111-1268-7267

Sponsor organisation name

Grünenthal GmbH

Sponsor organisation address

Zieglerstr. 6, Aachen, Germany, 52099

Public contact

Grünenthal Trial Information Desk, Grünenthal GmbH, Clinical-Trials@grunenthal.com

Scientific contact

Grünenthal Trial Information Desk, Grünenthal GmbH, Clinical-Trials@grunenthal.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

15 Aug 2024

Is this the analysis of the primary completion data?

Yes

Primary completion date

15 Aug 2024

Global end of trial reached?

Yes

Global end of trial date

15 Aug 2024

Was the trial ended prematurely?

Main objective of the trial

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

Protection of trial subjects

The trial was conducted according to Good Clinical Practice guidelines, the ethical principles that have their origin in the Declaration of Helsinki, and the applicable local laws and regulations. The applicable regulatory authorities approved the trial as required by national regulations, and the trial activities were only started when approval from the relevant independent ethics committee was available.

Background therapy

Evidence for comparator

Actual start date of recruitment

26 Aug 2022

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United Kingdom: 60

Country: Number of subjects enrolled

United States: 306

Country: Number of subjects enrolled

Spain: 91

Country: Number of subjects enrolled

Denmark: 9

Worldwide total number of subjects

466

EEA total number of subjects

100

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

207

From 65 to 84 years

257

85 years and over

Subject disposition

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Recruitment details

This study was conducted in 4 countries (including Denmark, Spain, United Kingdom, and United States) between 26 Aug 2022 (first-subject-in) and 15 August 2024 (last-subject-out).

Screening details

A total of 1302 subjects were screened in the study, of which 466 subjects were randomized and treated. Results reporting groups (Full Analysis Set and Safety Analysis Set) correspond to all subjects that received investigational medicinal product (IMP)

Period 1 title

Overall study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor

Are arms mutually exclusive

Yes

RTX-GRT7039

Arm description

Intra-articular RTX-GRT7039 400 ng injection. Full Analysis Set: 231 RTX-GRT7039; Safety Analysis Set: 231 RTX-GRT7039.

Arm type

Experimental

Investigational medicinal product name

RTX-GRT7039

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Injection

Dosage and administration details

Fifteen minutes following intra-articular injection of 5 mL ropivacaine 0.5% as local anesthetic, 5 mL (400 ng) RTX-GRT7039 were injected into the joint of the index knee.

Placebo

Arm description

Intra-articular injection of matching placebo. Full Analysis Set: 235 placebo; Safety Analysis Set: 235 placebo.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Injection

Dosage and administration details

Fifteen minutes following intra articular injection of 5 mL ropivacaine 0.5% as local anesthetic, 5 mL of matching placebo were injected into the joint of the index knee.

Number of subjects in period 1	RTX-GRT7039	Placebo
Started	231	235
Completed	207	200
Not completed	24	35
Consent withdrawn by subject	7	13
Physician decision	1	2
Adverse event, non-fatal	2	6
Not specified	1	3
Lost to follow-up	9	7
Lack of efficacy	4	4

Baseline characteristics

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Reporting group title

Overall study (overall period)

Reporting group description

Reporting group values	Overall study (overall period)	Total
Number of subjects	466	466
Age categorical
Units: Subjects
18 - 35	0	0
36 - 64	207	207
≥65	259	259
Gender categorical
Units: Subjects
Female	307	307
Male	159	159

End points

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Reporting group title

RTX-GRT7039

Reporting group description

Intra-articular RTX-GRT7039 400 ng injection. Full Analysis Set: 231 RTX-GRT7039; Safety Analysis Set: 231 RTX-GRT7039.

Reporting group title

Placebo

Reporting group description

Intra-articular injection of matching placebo. Full Analysis Set: 235 placebo; Safety Analysis Set: 235 placebo.

Primary: LS-mean (standard error [SE]) change from baseline in WOMAC pain subscale score at Week 12

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End point title

LS-mean (standard error [SE]) change from baseline in WOMAC pain subscale score at Week 12

End point description

Difference in mean change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale score at Week 12 in the index knee using an 11-point (0-10) numeric rating scale (NRS) between RTX-GRT7039 and placebo.

End point type

Primary

End point timeframe

At Week 12

End point values	RTX-GRT7039	Placebo
Number of subjects analysed	231	235
Units: LS-mean change
least squares mean (standard error)	-3.25 ( 0.16 )	-2.99 ( 0.17 )

Mixed model repeated measures (MMRM) analysis

Comparison groups

RTX-GRT7039 v Placebo

Number of subjects included in analysis

466

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.25

Method

MMRM

Confidence interval

Secondary: LS-mean (SE) change from baseline in WOMAC pain subscale score at Week 26

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End point title

LS-mean (SE) change from baseline in WOMAC pain subscale score at Week 26

End point description

Difference in mean change from baseline in WOMAC pain subscale score at Week 26 in the index knee using an 11-point (0-10) numeric rating scale (NRS) between RTX-GRT7039 and placebo.

End point type

Secondary

End point timeframe

At Week 26

End point values	RTX-GRT7039	Placebo
Number of subjects analysed	231	235
Units: LS-mean change
least squares mean (standard error)
Week 26	-3.27 ( 0.17 )	-2.82 ( 0.17 )

No statistical analyses for this end point

Secondary: LS-mean change from baseline in WOMAC physical function subscale score at Week 12 and Week 26

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End point title

LS-mean change from baseline in WOMAC physical function subscale score at Week 12 and Week 26

End point description

Difference in mean change from baseline in WOMAC physical function subscale score at Week 12 and at Week 26 in the index knee using an 11-point (0-10) numeric rating scale (NRS) between RTX-GRT7039 and placebo

End point type

Secondary

End point timeframe

at Week 12, Week 26

End point values	RTX-GRT7039	Placebo
Number of subjects analysed	231	235
Units: LS mean change
least squares mean (standard error)
Week 12	-3.17 ( 0.16 )	-2.86 ( 0.16 )
Week 26	-3.16 ( 0.16 )	-2.65 ( 0.16 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Adverse events were documented from the time of enrollment (i.e., the time the informed consent form is signed) up to the time of the last protocol scheduled contact.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

27.0

Reporting group title

RTX-GRT7039

Reporting group description

Intra-articular RTX-GRT7039 400 ng injection. Full Analysis Set: 231 RTX-GRT7039; Safety Analysis Set: 231 RTX-GRT7039.

Reporting group title

Placebo

Reporting group description

Intra-articular injection of matching placebo. Full Analysis Set: 235 placebo; Safety Analysis Set: 235 placebo.

Serious adverse events	RTX-GRT7039	Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	11 / 231 (4.76%)	15 / 235 (6.38%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Clear cell renal cell carcinoma
subjects affected / exposed	0 / 231 (0.00%)	1 / 235 (0.43%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Joint injury
subjects affected / exposed	1 / 231 (0.43%)	0 / 235 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular disorders
Aortic aneurysm
subjects affected / exposed	0 / 231 (0.00%)	1 / 235 (0.43%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Deep vein thrombosis
subjects affected / exposed	0 / 231 (0.00%)	1 / 235 (0.43%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Acute coronary syndrome
subjects affected / exposed	1 / 231 (0.43%)	0 / 235 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Acute myocardial infarction
subjects affected / exposed	0 / 231 (0.00%)	1 / 235 (0.43%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Aortic valve stenosis
subjects affected / exposed	0 / 231 (0.00%)	1 / 235 (0.43%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Atrioventricular block
subjects affected / exposed	0 / 231 (0.00%)	1 / 235 (0.43%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Amyotrophic lateral sclerosis
subjects affected / exposed	1 / 231 (0.43%)	0 / 235 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cerebral ischaemia
subjects affected / exposed	1 / 231 (0.43%)	0 / 235 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cerebrovascular accident
subjects affected / exposed	0 / 231 (0.00%)	1 / 235 (0.43%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	1 / 231 (0.43%)	0 / 235 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatobiliary disorders
Portal vein thrombosis
subjects affected / exposed	0 / 231 (0.00%)	1 / 235 (0.43%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Osteoarthritis
subjects affected / exposed	5 / 231 (2.16%)	7 / 235 (2.98%)
occurrences causally related to treatment / all	0 / 5	0 / 10
deaths causally related to treatment / all	0 / 0	0 / 0
Arthralgia
subjects affected / exposed	0 / 231 (0.00%)	2 / 235 (0.85%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Osteonecrosis
subjects affected / exposed	1 / 231 (0.43%)	0 / 235 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Liver abscess
subjects affected / exposed	0 / 231 (0.00%)	1 / 235 (0.43%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 231 (0.00%)	1 / 235 (0.43%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 231 (0.00%)	1 / 235 (0.43%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	RTX-GRT7039	Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	41 / 231 (17.75%)	35 / 235 (14.89%)
Injury, poisoning and procedural complications
Procedural pain
subjects affected / exposed	28 / 231 (12.12%)	13 / 235 (5.53%)
occurrences all number	29	14
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	13 / 231 (5.63%)	22 / 235 (9.36%)
occurrences all number	14	28

More information

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Were there any global substantial amendments to the protocol? Yes

14 Sep 2022

This global amendment incorporates changes that have been implemented as requested by the health authorities during their review of the clinical trial application, including update on IMP administration, exclusion criteria, concomitant treatments, imputation methods, adjustment trial discontinuation criteria, storage conditions, documentation requirements, contraception method definitions, and editorial adjustments.

01 Dec 2022

This amendment incorporates changes that have been implemented in order to enhance trial feasibility and recruitment, including correction and clarifications on safety endpoint, eligibility criteria, X-ray procedures, clarifications to the reporting of procedural pain as AE, addition of re-screening procedures, addition of definition for important medical events, updates to durability of effect analysis, and editorial changes.

01 Feb 2023

This amendment incorporates an update on the qualification of the person administering IMP.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

The study failed to meet its primary endpoint and is not intended to contribute to the evaluation of product effectiveness.

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Clinical trials

Clinical Trial Results:
A randomized, double-blind, placebo-controlled, Phase III trial to evaluate the efficacy and safety of a single intra-articular injection of RTX-GRT7039 in adult subjects with pain associated with osteoarthritis of the knee.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: LS-mean (standard error [SE]) change from baseline in WOMAC pain subscale score at Week 12

Primary: LS-mean (standard error [SE]) change from baseline in WOMAC pain subscale score at Week 12

Secondary: LS-mean (SE) change from baseline in WOMAC pain subscale score at Week 26

Secondary: LS-mean (SE) change from baseline in WOMAC pain subscale score at Week 26

Secondary: LS-mean change from baseline in WOMAC physical function subscale score at Week 12 and Week 26

Secondary: LS-mean change from baseline in WOMAC physical function subscale score at Week 12 and Week 26

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

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Outside EU/EEA

Clinical trials

Clinical Trial Results: A randomized, double-blind, placebo-controlled, Phase III trial to evaluate the efficacy and safety of a single intra-articular injection of RTX-GRT7039 in adult subjects with pain associated with osteoarthritis of the knee.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: LS-mean (standard error [SE]) change from baseline in WOMAC pain subscale score at Week 12

Primary: LS-mean (standard error [SE]) change from baseline in WOMAC pain subscale score at Week 12

Secondary: LS-mean (SE) change from baseline in WOMAC pain subscale score at Week 26

Secondary: LS-mean (SE) change from baseline in WOMAC pain subscale score at Week 26

Secondary: LS-mean change from baseline in WOMAC physical function subscale score at Week 12 and Week 26

Secondary: LS-mean change from baseline in WOMAC physical function subscale score at Week 12 and Week 26

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A randomized, double-blind, placebo-controlled, Phase III trial to evaluate the efficacy and safety of a single intra-articular injection of RTX-GRT7039 in adult subjects with pain associated with osteoarthritis of the knee.