Efficacy and Safety of RTX-GRT7039 in Adult Subjects With Knee Osteoarthritis

Osteoarthritis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05248386
• Other study ID #: KF7039-01
• Secondary ID: 2021-005029-26U1
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: August 26, 2022
• Est. completion date: February 2024

Study information

• Verified date: February 2024
• Source: Grünenthal GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A double-blind, randomized, placebo-controlled, parallel-group, multi-site, clinical trial to confirm the efficacy and safety of repeated injections of RTX-GRT7039 versus placebo in patients who have pain associated with osteoarthritis of the knee despite standard of care.

Description:

This trial comprises a total observation period of up to 52 weeks.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 450
• Est. completion date: February 2024
• Est. primary completion date: February 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• The participant has given written informed consent to participate.

• The participant is 18 years of age or older at the Screening Visit.

• The participant has a diagnosis of osteoarthritis of the knee based on American College of Rheumatology criteria and functional capacity class of I to III.

• There is a documented history indicating that participant has insufficient pain relief with previous Standard of Care.

Exclusion Criteria:

• The participant has past joint replacement surgery of the index knee.

• The participant has a history of significant trauma or surgery (e.g., open or arthroscopic) to the index knee within 12 months of Screening.

• The participant has periarticular pain from any cause other than osteoarthritis, including referred pain, bursitis, or tendonitis.

• The participant has clinical hip osteoarthritis on the side of the index knee.

• The participant has pre-existing osteonecrosis, subchondral insufficiency fracture, atrophic osteoarthritis, severe bone on bone osteoarthritis, knee pain attributable to disease other than osteoarthritis, or the participant has rapidly progressing osteoarthritis (RPOA) Type I or Type II.

• The participant has significant malalignment of anatomical axis (medial angle formed by the femur and tibia) of the target knee (varus >10, valgus >10) by X-ray as assessed by independent Central Readers at Screening Visit.

• The participant has other conditions that could affect trial endpoint assessments of the index knee.

• The participant has current 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 participant's participation for the full duration of the trial.

• The participant has a history of hypersensitivity to resiniferatoxin (RTX) or any similar component (capsaicin, chili peppers).

• The participant is currently participating or was participating in another investigational drug trial within 3 months prior to the Screening Visit.

• The participant is an employee of the investigator or trial site, with direct involvement in the proposed trial or other trials under the direction of that investigator or trial site or is a family member of the employees or the investigator.

Related Conditions & MeSH terms

• Osteoarthritis

Intervention

Drug:
• RTX-GRT7039
RTX-GRT7039 intra-articular injection.
• Placebo
Placebo matching RTX-GRT7039 intra-articular injection.

Locations

Country	Name	City	State
Canada	Aggarwal and Associates Limited	Brampton	Ontario
Canada	Malton Medical Research	Mississauga	Ontario
Canada	GRMO (Groupe de Recherche en Rhumatologie et Maladies Osseuses) Inc.	Sainte-Foy	Quebec
Canada	Diex Research Sherbrooke Inc.	Sherbrooke	Quebec
Canada	Cook Street Medical Clinic	Victoria	British Columbia
Canada	Dr. M. B. Jones	Victoria	British Columbia
Canada	Diex Recherche Victoriaville Inc.	Victoriaville	Quebec
Czechia	Interni A Revmatologicka Ambulance	Breclav
Czechia	Revmatologie s.r.o.	Brno
Czechia	Revmatologicka Ambulance	Ostrava
Czechia	Vesalion s.r.o.	Ostrava
Czechia	Lekarna U Svate Anny	Pisek	Czech Republic
Czechia	Ortopedicko-traumatologicka ambulance	Pisek
Czechia	Revmatologicka ambulance	Prague 4
Czechia	CCBR Czech Prague, s.r.o	Praha 3
Czechia	CCR Prague, s.r.o	Praha 3
Czechia	Fakultni Thomayerova nemocnice s poliklinikou	Praha 4
Czechia	Revmatologicka ambulance	Praha 4
Czechia	Thomayerova Nemocnice (TN)	Praha 4
Czechia	EUC Klinika	Praha 5
Czechia	PV-MEDICAL s.r.o. Revmatologicka ambulance	Zlin
France	Centre Hospitalier Universitaire d'Amiens-Picardie - Site Sud	Amiens
France	CHU Amiens Nord	Amiens Cedex 1
France	Hopital Edouard Herriot	Lyon
France	CHU Nimes Cedex	Nîmes
France	Cochin Hospital-Paris Descartes University	Paris
France	Hopital Lariboisiere,Hospitalier Universitaire Nord	Paris
France	Hopital Saint antoine	Paris
France	Hopitaux de Paris (AP-HP) - Groupe Hospitalier Cochin -Assistance Publique	Paris
Germany	Praxis Dr. med. Stephan Grunert	Eichstätt
Germany	Medizentrum Essen Borbeck	Essen
Germany	HRF Hamburger Rheuma Forschungszentrum	Hamburg
Germany	AmBeNet, Practice Dr. Dr. med. Hans-Detlev Stahl	Leipzig
Germany	Velocity Clinical Research Leipzig GmbH	Leipzig
Germany	Centrum fuer Diagnostik und Gesundheit (CDG)	Muenchen
Germany	Praxis-Reinfeld-Mitte	Reinfeld
Italy	AOU-Careggi	Firenze
Italy	AOU-Careggi	Firenze
Japan	KKR Tohoku Kosai Hospital	Aoba-ku	Sendai-shi
Japan	Juntendo University Graduate School of Medicine	Bunkyo-ku	Tokyo
Japan	Juntendo University Hospital	Bunkyo-Ku	Tokyo
Japan	Hamanomachi Hospital	Fukuoka-shi	Fukuoka-ken
Japan	Souseikai Fukuoka Mirai Hospital	Fukuoka-shi	Fukuoka-Ken
Japan	Funabashi Municipal Medical Center	Funabashi-shi	Chiba
Japan	Hakodate Central General Hospital	Hakodate	Hokkaido
Japan	Japanese Red Cross Hamamatsu Hospital	Hamamatsu-shi	Shizuoka-ken
Japan	Seiwa-kai medical corporation Hiroshima clinic	Hiroshima-shi	Hiroshima
Japan	Shimane University Hospital	Izumo	Shimane
Japan	Shimane University Hospital	Izumo	Shimane
Japan	Marunouchi Hospital	Matsumoto	Nagano
Japan	Kosei General Hospital	Mihara	Hiroshima-ken
Japan	Kosei General Hospital	Mihara-shi	Hiroshima-ken
Japan	Kitasato University Kitasato Institute Hospital	Minato-ku	Tokyo
Japan	Social Medical Care Corporation Hosei-kai Marunouchi Hospital	Nagano	Matsumoto-shi Nagano
Japan	Shirahama Hamayu Hospital	Nishimuro-gun	Wakayama-ken
Japan	Otsu City Hospital	Otsu	Shiga
Japan	KKR Sapporo Medical Center	Sapporo	Hokkaido
Japan	Sapporo kotoni Orthopedies	Sapporo	Hokkaido
Japan	Sapporo Maruyama Orthopedic Hospital	Sapporo-shi	Hokkaido
Japan	Nakajo Orthopedic Clinic	Sendai	Miyagi
Japan	KKR Tohoku Kosai Hospital	Sendai-shi	Miyagi
Japan	Kinashi Obayashi Hospital	Takamatsu-shi	Kagawa
Japan	Juntendo University Hospital	Tokyo
Japan	Medical Corporation Teda Ooimachi Orthopaedic Surgery and Surgery Clinic	Tokyo
Japan	Yokohoma Rosai Hospital	Yokohama	Kanagawa
Japan	Japan Organization of Occupational Health and Safety Yokohama Rosai Hospital	Yokohama-city	Kanagawa
Mexico	Investigacion y Biomedicina de Chihuahua	Chihuahua
Mexico	Clinstile, S.A. de C.V	Cuauhtemoc	Ciudad De Mexico
Mexico	Dr. Miguel Cortes Hernandez MD, Office of	Cuernavaca	Morelos
Mexico	Centro de Investigacion de Tratamientos Innovadores de Sinaloa S.C.	Culiacan	Sinaloa
Mexico	Centro Integral en Reumatologia, SA de CV	Guadalajara	Jalisco
Mexico	Consultorio de Reumatologia	Gustavo A. Madero	Distrito Federal
Mexico	Morales Vargas Centro de Investigacion SC	León	Guanajuato
Mexico	CINTRE, Centro de Investigacion y Tratamiento Reumatologico S.C.	Mexico	Distrito Federal
Netherlands	Medisch Spectrum Twente (MST) - Enschede Haaksbergerstraat	Enschede	KZ
Netherlands	Spaarne Gasthuis (Kennemer Gasthuis)	Hoofddorp
Poland	Synexus Polska Sp. z o.o. Oddzial w Gdansku	Gdansk	Pomorskie
Poland	Synexus Gdynia	Gdynia
Poland	Mazowieckie Centrum Badan Klinicznych	Grodzisk Mazowiecki
Poland	Centrum Medyczne Pratia Katowice	Katowice
Poland	Synexus Katowice Medical Center	Katowice
Poland	Malopolskie Centrum Kliniczne	Krakow
Poland	Pratia MCM Krakow	Krakow	Malopolskie
Poland	St Centrum Medyczne Plejady	Krakow
Poland	Synexus Polska Sp. z o.o. Oddzial w Lodzi	Lodz
Poland	KO-MED Centra Kliniczne Lublin II	Lublin
Poland	Reumed Spolka z o.o. Zespol poradni Specjalistycznych Filia Nr 1 Wallenroda	Lublin	Lubelskie
Poland	Makmed Nzoz	Nadarzyn	Mazowieckie
Poland	NZOZ Lecznica MAK-MED S.C.	Nadarzyn	Mazowieckie
Poland	Synexus Poznan Medical Center	Poznan	Wielkopolskie
Poland	Synexus Polska Spolka z ograniczona odpowiedzialnoscia Oddzial we Wroclawiu	Wroclaw
Poland	Centrum Medyczne Kuba-Med Zamosc	Zamosc
Poland	KO-MED Centra Kliniczne Lublin II	Zamosc	Lubelskie

Sponsors (1)

Lead Sponsor	Collaborator
Grünenthal GmbH

Countries where clinical trial is conducted

Canada,  Czechia,  France,  Germany,  Italy,  Japan,  Mexico,  Netherlands,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score	The WOMAC pain subscale will be assessed using an 11-point numeric rating scale (NRS), where 0= no pain and 10=worst pain imaginable.	Baseline up to Week 12
Secondary	Change from Baseline in WOMAC Pain Subscale Score	The WOMAC pain subscale will be assessed using an 11-point NRS, where 0= no pain and 10=worst pain imaginable.	From Baseline up to Week 52
Secondary	Change from Baseline in WOMAC Physical Function Subscale Score	The WOMAC physical function subscale will be assessed using 11-point NRS, where 0= no pain and 10=worst pain imaginable.	From Baseline up to Week 52
Secondary	Number of Participants With Treatment Emergent Adverse Events (TEAEs)		From Baseline up to Week 52
Secondary	Change from Baseline in WOMAC Stiffness Subscale Score	The WOMAC stiffness subscale will be assessed using an 11-point NRS, where 0= no pain and 10=worst pain imaginable.	From Baseline up to Week 52
Secondary	Change from Baseline in WOMAC Total Score	The WOMAC total score will be calculated as the sum of pain subscale score, stiffness subscale score and physical function subscale score. It will be calculated by averaging all of the scores available for the questions and assessed using an 11-point NRS, where 0= no pain and 10=worst pain imaginable.	From Baseline up to Week 52
Secondary	Change from Baseline in WOMAC A1 (Walking Pain) Subscale Score	The WOMAC A1 subscale will be assessed using an 11-point NRS, where 0= no pain and 10=worst pain imaginable.	From Baseline up to Week 52
Secondary	Percentage of Participants With at Least 30% and 50% Reduction From Baseline in WOMAC Pain Subscale Score	The WOMAC pain subscale will be assessed using an 11-point NRS, where 0= no pain and 10=worst pain imaginable.	From Baseline up to Week 52
Secondary	Percentage of Participants With at Least 30% and 50% Reduction From Baseline in WOMAC A1 (Walking Pain) Subscale Score	The WOMAC A1 subscale will be assessed using an 11-point NRS, where 0= no pain and 10=worst pain imaginable.	From Baseline up to Week 52
Secondary	Percentage of Participants With Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Response	OMERACT-OARSI response: A high improvement of >=50% (percentage change) and >=2 (absolute change) in either the WOMAC pain subscale score or WOMAC physical function subscale score, OR An improvement in at least 2 of the following 3: Improvement of >=20% (percentage change) and >=1 (absolute change) in the WOMAC pain subscale score.; Improvement of >=20% (percentage change) and >=1 (absolute change) in the WOMAC physical function subscale score.; Improvement of >=20% (percentage change) and >=10 (absolute change) in Patient Global Assessment (PGA) of osteoarthritis. Absolute values will be normalized to the 0 (no pain) to 100 scale (higher pain/difficulty).	From Baseline up to Week 52
Secondary	Percentage of Participants Categorized by Each Patient Global Impression of Change (PGIC) Score	The 7-point PGIC is a complementary assessment of analgesic efficacy on a 7-point scale where 1 = "Very much improved" and 7 = "Very much worse".	From Baseline up to Week 52
Secondary	Change From Baseline in EuroQol-5 Dimension Health Questionnaire 5 Levels (EQ-5D-5L) Score	EQ-5D consists of EQ-5D descriptive system (Index score) and EQ visual analogue scale (VAS). EQ-5D-5L Index Score ranges from 0 to 1, with 0 representing death and 1.0 representing perfect health. EQ-5D-5L-VAS records participant's self-rated health on a vertical VAS that range from where 0 (worst imaginable) to 100 (best imaginable).	From Baseline up to Week 52
Secondary	Change From Baseline in 36-Item Short-Form (SF-36) Domain Scores	The SF-36 domain scores ranged from 0 (worst value) to 100 (best value), with higher scores reflecting better health status.	From Baseline up to Week 52