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A single-arm, open-label, Phase III trial to evaluate the safety and tolerability of intra-articular injections of RTX-GRT7039 in subjects with moderate to severe pain associated with osteoarthritis of the knee.

Open-label trial to check the safety and tolerability of RTX-GRT7039 injections for pain associated with osteoarthritis of the knee.

714

Eligible participants were males and females aged >=18 years with a diagnosis of osteoarthritis of the knee based on American College of Rheumatology criteria and a functional capacity class of I to III. Participants were required to have a baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale score of >=4 in one knee (eligible for mono-articular injection) or both knees (eligible for bilateral injections) at Screening and at baseline. Additionally, participants had to have a Kellgren Lawrence (K-L) grade of 2 to 4 in the index knee and the non-index knee in the case of bilateral injections, and a documented history of insufficient pain relief with optimal SoC. The demographics, baseline disease characteristics, general medical history, and medication use (prior and concomitant) of participants enrolled in this study were similar across treatment groups (unilaterally or bilaterally treated participants) and were typical of the target population of participants with osteoarthritis of the knee, though with an overall high proportion of radiographic K-L grade of 3 or 4 (74.5% of all treated knees). Participant demographic characteristics were overall well-balanced between the unilaterally treated and bilaterally treated groups. The median age was 66.0 years in both groups, and the majority of participants (84.7%) were below 75 years of age. Overall, most participants were female (548 [76.8%]), White (574 [80.4%]) with an average (+- SD) body mass index (BMI) of 31.6 (+- 4.5) kg/m^2.

Of 1130 participants screened overall, 403 were screen failed and a total of 714 participants received at least one injection of RTX-GRT7039 (420 participants were treated unilaterally and 294 were treated bilaterally). Thirteen participants did not receive IMP despite being eligible; for 12 participants this was due to withdrawal of consent and for one participant this was due to an adverse event.

Based on the data observed in KF7039-03, intra-articular administration of 400 ng RTX-GRT7039, including unilateral and bilateral repeat dosing (up to five injections per knee, administered at least 12 weeks apart) was considered safe and well tolerated.

Safety: - Overall, intra-articular administration of 400 ng RTX-GRT7039, including unilateral and bilateral multiple repeat doses (up to five injections, at least 12 weeks apart per knee) in this study was considered safe and well-tolerated - The overall incidence of TEAEs was similar in the unilaterally and bilaterally treated groups (55.0% and 55.4%). The majority of TEAEs were mild (19.3%) or moderate (26.6%) in intensity. - TEAEs leading to study discontinuation were rare (1.3%), occurred at similar rates in the unilaterally and bilaterally treated groups, and none were considered related to the IMP - The overall incidence of TEAEs related to IMP was 9.9% - The unilaterally versus bilaterally treated groups generally showed little difference in the incidence of common TEAE Preferred Terms. The most frequently reported (in >=5% participants in any treatment group) Preferred Terms in the unilaterally and bilaterally treated groups were Procedural pain (7.1% and 8.2%), Osteoarthritis (5.2% and 3.1%), and Arthralgia (4.0% and 5.1%). - Review of TEAEs starting on the day of and during the first week after IMP administration showed a decrease in the incidence of TEAEs reported over multiple injections - Subgroup analyses for age and baseline osteoarthritis severity according to K-L grade suggested that participants >=65 years of age and with a K-L grade of 3 and 4 may have had a slightly higher incidence of TEAEs - The incidence of treatment-emergent serious adverse events (SAEs) was slightly higher in the unilaterally than in the bilaterally treated groups (9.5% and 6.1%). Only one SAE (loss of consciousness, which resolved after 1 minute) was assessed as related to IMP by the Investigator (ie, 1 SUSAR), none were assessed by the investigators as related to local anesthetic or injection procedures. Five SAEs were assessed by the Sponsor as related to the injection procedure. - Four deaths, two in each treatment group were reported in this study. All of these were cardiac-related TEAEs, and none were considered related to the IMP. - No trends or patterns were identified in the analyses of clinical laboratory tests, vital signs, ECG results, or imaging data - Ten TEAEs representing structural changes of the knee joint as visualized by imaging methods were reported for seven participants, five in the bilaterally treated and two in the unilaterally treated group. One TEAE, RPOA type 1, was assessed by the Investigator as related to the IMP because a possible association could not be ruled out; however, it should be noted that the participant had a pre-existing meniscal tear, which is a risk factor for RPOA (Foreman et al., 2021). The remaining 9 TEAEs representing structural changes were not assessed as related to IMP. - No pregnancies occurred in this study - No new safety concerns were noted for RTX-GRT7039 from the analysis of SAEs, TEAEs leading to study discontinuation and the numbers of participants having total knee arthroplasty Efficacy: - The secondary endpoints of change from baseline in the WOMAC pain and WOMAC physical function subscale score for the index and non-index knee at Week 12 showed a substantial reduction in both subscale scores These changes from baseline were overall consistent with the observations in the earlier studies of this investigational product.

The overall incidence of TEAEs was 55.2%, and the majority were mild (19.3%) or moderate (26.6%) in intensity. TEAEs leading to discontinuation were rare (1.3%) and none were related to the IMP. The incidence of SAEs was 8.1%, with only 1 out of 70 events (Loss of consciousness) assessed by the Investigator as related to the IMP. No new safety concerns were identified from the analysis of TEAEs, SAEs, deaths, or structural changes of the knee joint. In terms of efficacy, compared to baseline, a substantial

Dec. 05, 2025

https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2024-515709-24-00

Yes

Information available on the Grunenthal Group Web Site (see URL below for details); according to the European Federation of Pharmaceutical Industries and Associations (EFPIA) Data Sharing Principles. LINK: https://www.grunenthal.com/en/science/clinical-trials/data-sharing-clinical-trials

https://jrct.mhlw.go.jp/latest-detail/jRCT2031230069

Lange Bernd, MD, MSc, Medical Lead

Grunenthal GmbH

4-1-3 Kyuutaromachi, Chuo-ku, Osaka City, Osaka

Japan-Chiken@iconplc.com

Clinical trial contact

ICON Clinical Research GK

4-1-3 Kyuutaromachi, Chuo-ku, Osaka City, Osaka

+81-6-4560-2001

Japan-Chiken@iconplc.com

Complete

May. 14, 2023

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

- >=18 years of age at the screening visit.
- Body Mass Index (BMI)=< 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 severepain due to osteoarthritis of the knee.
- 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.

- The subject had an intra-articular injection of either corticosteroid or intra-articular visco-supplementation (i.e., hyaluronic acid) into the index knee within one month.
- The subject had an injection of platelet-rich plasma into the index knee within one month.
- The subject applied topical capsaicin on the index knee within 3months.
- 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.

Both

Moderate to severe pain associated with osteoarthritis of the knee

RTX-GRT7039 intra-articular injection.

1) Incidence of treatment-emergent adverse events(TETAEs). Incidence of TETAEs leading to discontinuation. [Time Frame: From baseline (assessment at Visit 2) to Visit 8 or 9 (end of trial)]

1) Incidence of TEAEs representing structural changes of the knee joint as visualized by the imaging methods (X-ray and/or magnetic resonance imaging [MRI]. [Time frame: From baseline (assessment at Visit 2) to Visit 8 or 9 (end of trial)]
2) Change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical function and pain subscale score for the index and the non-index (where applicable) knee. [Time Frame: From baseline (assessment at Visit 2) to Visit 5]
3) Change in QoL as assessed by questionnaires EQ-5D-5L and SF-36. [Time Frame: From baseline (assessment at Visit 2) to Visit 5]

+81-42-648-5551

Nov. 15, 2022

United States/United Kingdom/South Africa/Poland/Romania/Bulgaria/Colombia