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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Osteoarthritis
• Intervention / Treatment: Drug: RTX-GRT7039; Drug: Placebo

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 450
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Victoria, British Columbia, Canada, V8V 4A1
      • Cook Street Medical Clinic
    • Victoria, British Columbia, Canada, V9V 4A1
      • Dr. M. B. Jones
  • Ontario
    • Brampton, Ontario, Canada, L6T 0G1
      • Aggarwal and Associates Limited
    • Mississauga, Ontario, Canada, L4V 1P1
      • Malton Medical Research
  • Quebec
    • Sainte-Foy, Quebec, Canada, G1V 3M7
      • GRMO (Groupe de Recherche en Rhumatologie et Maladies Osseuses) Inc.
    • Sherbrooke, Quebec, Canada, J1L 0H8
      • Diex Research Sherbrooke Inc.
    • Victoriaville, Quebec, Canada, G6P 6P6
      • Diex Recherche Victoriaville Inc.
• Czechia
  • Breclav, Czechia, 690 02
    • Interni A Revmatologicka Ambulance
  • Brno, Czechia, 63800
    • Revmatologie s.r.o.
  • Ostrava, Czechia, 702 00
    • Vesalion s.r.o.
  • Ostrava, Czechia, 70200
    • Revmatologicka ambulance
  • Pisek, Czechia, 397 01
    • Ortopedicko-traumatologicka ambulance
  • Prague 4, Czechia, 14000
    • Revmatologicka ambulance
  • Praha 3, Czechia, 130 00
    • CCBR Czech Prague, s.r.o
  • Praha 3, Czechia, 130 00
    • CCR Prague, s.r.o
  • Praha 4, Czechia, 140 00
    • Revmatologicka ambulance
  • Praha 4, Czechia, 140 59
    • Fakultni Thomayerova nemocnice s poliklinikou
  • Praha 4, Czechia, 140 00
    • Thomayerova Nemocnice (TN)
  • Praha 5, Czechia, 15000
    • EUC Klinika
  • Zlin, Czechia, 760 01
    • PV-MEDICAL s.r.o. Revmatologicka ambulance
  • Czech Republic
    • Pisek, Czech Republic, Czechia, 397 01
      • Lekarna U Svate Anny
• France
  • Amiens, France, 80000
    • Centre Hospitalier Universitaire d'Amiens-Picardie - Site Sud
  • Amiens Cedex 1, France, 80054
    • CHU Amiens Nord
  • Lyon, France, 69437
    • Hôpital Edouard Herriot
  • Nîmes, France, 30029
    • CHU Nimes Cedex
  • Paris, France, 75012
    • Hôpital Saint Antoine
  • Paris, France, 75014
    • Cochin Hospital-Paris Descartes University
  • Paris, France, 75014
    • Hopitaux de Paris (AP-HP) - Groupe Hospitalier Cochin -Assistance Publique
  • Paris, France, 75475
    • Hopital Lariboisiere,Hospitalier Universitaire Nord
• Germany
  • Eichstätt, Germany, 85072
    • Praxis Dr. med. Stephan Grunert
  • Essen, Germany, 45355
    • Medizentrum Essen Borbeck
  • Hamburg, Germany, 20095
    • HRF Hamburger Rheuma Forschungszentrum
  • Leipzig, Germany, 04103
    • Velocity Clinical Research Leipzig GmbH
  • Leipzig, Germany, 04107
    • AmBeNet, Practice Dr. Dr. med. Hans-Detlev Stahl
  • Muenchen, Germany, 80809
    • Centrum fuer Diagnostik und Gesundheit (CDG)
  • Reinfeld, Germany, 23858
    • Praxis-Reinfeld-Mitte
• Italy
  • Firenze, Italy, 50134
    • AOU-Careggi
  • Firenze, Italy, 50139
    • AOU-Careggi
• Japan
  • Tokyo, Japan, 113-8431
    • Juntendo University Hospital
  • Tokyo, Japan, 140-0014
    • Medical Corporation Teda Ooimachi Orthopaedic Surgery and Surgery Clinic
  • Chiba
    • Funabashi-shi, Chiba, Japan, 273-8588
      • Funabashi Municipal Medical Center
  • Fukuoka-Ken
    • Fukuoka-shi, Fukuoka-Ken, Japan, 813-0017
      • Souseikai Fukuoka Mirai Hospital
  • Fukuoka-ken
    • Fukuoka-shi, Fukuoka-ken, Japan, 810-8539
      • Hamanomachi Hospital
  • Hiroshima
    • Hiroshima-shi, Hiroshima, Japan, 733-0032
      • Seiwa-kai medical corporation Hiroshima clinic
  • Hiroshima-ken
    • Mihara, Hiroshima-ken, Japan, 370-0115
      • Kosei General Hospital
    • Mihara-shi, Hiroshima-ken, Japan, 723-8686
      • Kosei General Hospital
  • Hokkaido
    • Hakodate, Hokkaido, Japan, 040-8585
      • Hakodate Central General Hospital
    • Sapporo, Hokkaido, Japan, 062-0931
      • KKR Sapporo Medical Center
    • Sapporo, Hokkaido, Japan, 0630814
      • Sapporo kotoni Orthopedies
    • Sapporo-shi, Hokkaido, Japan, 060-0007
      • Sapporo Maruyama Orthopedic Hospital
  • Kagawa
    • Takamatsu-shi, Kagawa, Japan, 761-8024
      • Kinashi Obayashi Hospital
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 222-0036
      • Yokohoma Rosai Hospital
    • Yokohama-city, Kanagawa, Japan, 222-0036
      • Japan Organization of Occupational Health and Safety Yokohama Rosai Hospital
  • Matsumoto-shi Nagano
    • Nagano, Matsumoto-shi Nagano, Japan, 390-8601
      • Social Medical Care Corporation Hosei-kai Marunouchi Hospital
  • Miyagi
    • Sendai, Miyagi, Japan, 983-0862
      • Nakajo Orthopedic Clinic
    • Sendai-shi, Miyagi, Japan, 980-0803
      • KKR Tohoku Kosai Hospital
  • Nagano
    • Matsumoto, Nagano, Japan, 390-0841
      • Marunouchi Hospital
  • Sendai-shi
    • Aoba-ku, Sendai-shi, Japan, 980-0803
      • KKR Tohoku Kosai Hospital
  • Shiga
    • Otsu, Shiga, Japan, 520-0804
      • Otsu City Hospital
  • Shimane
    • Izumo, Shimane, Japan, 693-8501
      • Shimane University Hospital
    • Izumo, Shimane, Japan, 693-0021
      • Shimane University Hospital
  • Shizuoka-ken
    • Hamamatsu-shi, Shizuoka-ken, Japan, 434-8533
      • Japanese Red Cross Hamamatsu Hospital
  • Tokyo
    • Bunkyo-Ku, Tokyo, Japan, 113-0033
      • Juntendo University Hospital
    • Bunkyo-ku, Tokyo, Japan, 113-0034
      • Juntendo University Graduate School of Medicine
    • Minato-ku, Tokyo, Japan, 108-8642
      • Kitasato University Kitasato Institute Hospital
  • Wakayama-ken
    • Nishimuro-gun, Wakayama-ken, Japan, 649-2211
      • Shirahama Hamayu Hospital
• Mexico
  • Chihuahua, Mexico, 31000
    • Investigacion y Biomedicina de Chihuahua
  • Ciudad De Mexico
    • Cuauhtemoc, Ciudad De Mexico, Mexico, 06700
      • Clinstile, S.A. de C.V
  • Distrito Federal
    • Gustavo A. Madero, Distrito Federal, Mexico, 07760
      • Consultorio de Reumatologia
    • Mexico, Distrito Federal, Mexico, 11850
      • CINTRE, Centro de Investigacion y Tratamiento Reumatologico S.C.
  • Guanajuato
    • León, Guanajuato, Mexico, 37000
      • Morales Vargas Centro de Investigacion SC
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44160
      • Centro Integral en Reumatologia, SA de CV
  • Morelos
    • Cuernavaca, Morelos, Mexico, 62448
      • Dr. Miguel Cortes Hernandez MD, Office of
  • Sinaloa
    • Culiacan, Sinaloa, Mexico, 80000
      • Centro de Investigacion de Tratamientos Innovadores de Sinaloa S.C.
• Netherlands
  • Hoofddorp, Netherlands, 2134 TM
    • Spaarne Gasthuis (Kennemer Gasthuis)
  • KZ
    • Enschede, KZ, Netherlands, 7512 KZ
      • Medisch Spectrum Twente (MST) - Enschede Haaksbergerstraat
• Poland
  • Gdynia, Poland, 81-537
    • Synexus Gdynia
  • Grodzisk Mazowiecki, Poland, 05-825
    • Mazowieckie Centrum Badan Klinicznych
  • Katowice, Poland, 40-081
    • Centrum Medyczne Pratia Katowice
  • Katowice, Poland, 40-040
    • Synexus Katowice Medical Center
  • Krakow, Poland, 30-149
    • Malopolskie Centrum Kliniczne
  • Krakow, Poland, 30-363
    • St Centrum Medyczne Plejady
  • Lodz, Poland, 90-127
    • Synexus Polska Sp. z o.o. Oddzial w Lodzi
  • Lublin, Poland, 20-362
    • KO-MED Centra Kliniczne Lublin II
  • Wroclaw, Poland, 50-381
    • Synexus Polska Spolka z ograniczona odpowiedzialnoscia Oddzial we Wroclawiu
  • Zamosc, Poland, 22400
    • Centrum Medyczne Kuba-Med Zamosc
  • Lubelskie
    • Lublin, Lubelskie, Poland, 20-607
      • Reumed Spolka z o.o. Zespol poradni Specjalistycznych Filia Nr 1 Wallenroda
    • Zamosc, Lubelskie, Poland, 20-362
      • KO-MED Centra Kliniczne Lublin II
  • Malopolskie
    • Krakow, Malopolskie, Poland, 30-727
      • Pratia MCM Krakow
  • Mazowieckie
    • Nadarzyn, Mazowieckie, Poland, 05-830
      • NZOZ Lecznica MAK-MED s.c.
    • Nadarzyn, Mazowieckie, Poland, 05-830
      • Makmed Nzoz
  • Pomorskie
    • Gdansk, Pomorskie, Poland, 80-382
      • Synexus Polska Sp. z o.o. Oddzial w Gdansku
  • Wielkopolskie
    • Poznan, Wielkopolskie, Poland, 60-702
      • Synexus Poznan Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RTX-GRT7039; Participants will receive 2 intra-articular injections of RTX-GRT7039 during the 52-week double-blind treatment period.	Drug: RTX-GRT7039; RTX-GRT7039 intra-articular injection.
Placebo Comparator: Placebo; Participants will receive 2 intra-articular injections of placebo matching to RTX-GRT7039 during the 52-week double-blind treatment period.	Drug: Placebo; Placebo matching RTX-GRT7039 intra-articular injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Number of Participants With Treatment Emergent Adverse Events (TEAEs)		From Baseline up to Week 52
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
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Grünenthal GmbH

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2022
• Primary Completion (Estimated): February 1, 2024
• Study Completion (Estimated): February 1, 2024

Study Registration Dates

• First Submitted: February 10, 2022
• First Submitted That Met QC Criteria: February 10, 2022
• First Posted (Actual): February 21, 2022

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: osteoarthritis; pain assessment; Knee,
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis
• Other Study ID Numbers: KF7039-01; 2021-005029-26 (EudraCT Number); U1111-1268-7314 (Other Identifier: Universal Trial Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Information available on the Grünenthal Group Web Site (see URL below for details); according to the European Federation of Pharmaceutical Industries and Associations (EFPIA) Data Sharing Principles.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No