臨床研究等提出・公開システム

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.

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

93

This trial enrolled subjects who had moderate to severe pain associated with osteoarthritis of the knee despite receiving continued treatment with optimal standard of care or who were unable to receive standard of care treatment due to contraindications or intolerability. Eligible subjects 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. Subjects were required to have a baseline WOMAC pain subscale score of >=5 and =<9 using the 11-point (0-10) NRS for the index knee at Screening and baseline and pain in the index knee for at least 6 months prior to the Screening Visit. In addition, subjects had to have a Kellgren Lawrence (K-L) grade of 2 to 4 in the index knee and a documented history of insufficient pain relief with optimal standard of care. The demographics and baseline disease characteristics of the subjects enrolled in this trial were similar across treatment groups.

Of the 902 subjects screened, 469 subjects were randomized: 234 allocated to RTX-GRT7039 and 235 allocated to placebo treatment groups. In the RTX-GRT7039 group, all 234 (100%) subjects received the first Investigational medicinal product (IMP) injection. In the placebo group, 232 (98.7%) subjects received the first IMP injection (3 subjects randomized but not exposed to the IMP). In the RTX-GRT7039 and placebo groups, 39 (16.7%) and 31 (13.2%) subjects discontinued the treatment, respectively. Overall, 406 (86.6%) subjects completed the trial; 202 (86.3%) subjects in the RTX-GRT7039 group and 204 (86.8%) subjects in the placebo group. Thirty-two (13.7%) subjects in the RTX-GRT7039 group and 31 (13.2%) subjects in the placebo group withdrew early from the trial.

In the overall population, a higher incidence of adverse events (AEs) was observed in the RTX-GRT7039 group compared to the placebo group (62.8% versus 48.3%, respectively). This was primarily driven by procedural pain AEs in the RTX-GRT7039 group. No trends or patterns were identified in the analyses of clinical laboratory tests, vital signs, ECG results, or imaging data. Four AEs representing structural changes of the knee joint as visualized by imaging methods were reported for 4 subjects, evenly distributed between RTX-GRT7039 and placebo treated subjects. No deaths and no pregnancies occurred in this study.

The primary endpoint was the change from baseline in the WOMAC pain subscale score in the index knee at Week 12. Compared to baseline, both the RTX-GRT7039 and placebo group showed a substantial reduction from baseline at Week 12; however, the difference in the change from baseline between the 2 groups was not statistically significant (p = 0.569). For the key secondary efficacy endpoints ; the change from baseline in WOMAC pain subscale score in the index knee at Week 26 and 52, and the change from baseline in WOMAC physical function subscale score at Week 12, 26, and 52 ; the treatment difference was not statistically significant at any timepoint.

In terms of efficacy, both the IMP and placebo group showed a substantial reduction of the WOMAC pain subscale score from baseline at Week 12; however, the difference in the change from baseline between the 2 groups was small and not statistically significant. Therefore, this study did not meet its primary endpoint. Based on the observed safety data in this study, the intra-articular administration of a 400 ng dose of the IMP, including 1 repeat dose administered in this trial, was safe and well tolerated.

https://www.clinicaltrialsregister.eu/ctr-search/search?query=KF7039-01

Yes

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. LINK:https://www.grunenthal.com/en/science/clinical-trials/data-sharing-clinical-trials

https://jrct.mhlw.go.jp/latest-detail/jRCT2031220354

Lange Bernd, MD, MSc, Medical Lead

Grunenthal GmbH

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

Japan-Chiken@iconplc.com

Clinical trial contact

ICON Clinical Research GK

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

+81-6-4560-2001

Japan-Chiken@iconplc.com

Complete

Oct. 01, 2022

Interventional

randomized controlled trial

double blind

placebo control

parallel 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 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.

- 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.

Both

Moderate to severe pain associated with osteoarthritis of the knee

RTX-GRT7039 intra-articular injection.

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

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 treatment discontinuation after the first injection.
Incidence of TEAEs representing structural changes of the knee joint as visualized by the imaging methods (X-ray and/or magnetic resonance imaging [MRI]).

+81-42-648-5551

June. 17, 2022

Canada/Czech Republic/France/Germany/Italy/Mexico/Netherland/Poland