[Edaily Reporter Kim Jinsoo ] Bio Solution Co.,Ltd.(086820)BioSolution is focusing its R&D efforts on clearly demonstrating the difference in efficacy between the treatment group and the placebo group in the clinical trial for “SperoCure,” its injectable disease-modifying osteoarthritis drug (DMOAD) candidate. This is in response to previous studies of other candidate compounds, in which the placebo group showed significantly high efficacy.

According to the pharmaceutical and biotech industry on the 25th, Bio Solution Co.,Ltd. has designed the domestic Phase 1/2a clinical trial for SperoCure—which it is developing as a next-generation growth engine—to enable a multi-layered analysis that covers not only symptoms and function but also structural changes and biomarkers. The company also plans to use these findings to finalize the design for subsequent confirmatory clinical trials.

SperoCure received approval for its Phase 1 and 2a clinical trial protocol from the Ministry of Food and Drug Safety last July. The company will recruit up to 18 participants for the Phase 1 trial and 41 to 68 participants for the Phase 2a trial, targeting patients with Kellgren-Lawrence (K&L) Grade 2–3 knee osteoarthritis. The Phase 2a trial will be a multicenter, randomized, double-blind, placebo-controlled study.

The primary endpoints—the most critical measures in the clinical trial—have been set as the change in the 100 mm VAS pain score and the change in the WOMAC functional score at the 24-week mark.

Examining the Effects of the Placebo Group in Osteoarthritis Injections

The variable that Bio Solution Co.,Ltd. is particularly focusing on is the “placebo response.” In clinical trials involving intra-articular injections for osteoarthritis, significant improvements in pain and function have been repeatedly reported even in control groups administered saline solution.

According to a meta-analysis of 50 randomized controlled trials, VAS pain scores improved by –17.7 points at 1 month, –17.9 points at 3 months, and –13.4 points at 6 months following intra-articular administration of saline. The response rate according to “OMERACT-OARSI,” the international standard for comprehensively evaluating the efficacy of osteoarthritis treatments, reached 48% at 3 months and 56% at 6 months, making clinical trial designs that account for placebo responses essential.

In fact, Kolon TissueGene, Inc.’s “TG-C” failed to demonstrate efficacy because it overlooked the placebo effect. Specifically, TG-C did not achieve statistical significance for either the VAS pain score or the WOMAC total score—both of which were co-primary endpoints at 12 months—and also failed to meet the key secondary endpoints. According to the disclosed topline results, the VAS score decreased by 38.6 points in the TG-C group but also decreased by 39.1 points in the control group. Similarly, the WOMAC total score decreased by 26.34 points in the TG-C group and by 27.57 points in the control group. In fact, the magnitude of improvement in the control group was numerically greater for both measures.

Similar cases have been reported overseas. In 2020, UNITY Biotechnology conducted a Phase 2 clinical trial of UBX0101—a treatment based on a mechanism for removing senescent cells—for knee osteoarthritis, enrolling 183 participants and dividing them into a placebo group and dose groups of 0.5 mg, 2 mg, and 4 mg. The change in WOMAC-A pain scores at 12 weeks was -1.017 points for the placebo group, -0.924 points for the 0.5 mg group, -1.052 points for the 2 mg group, and -1.019 points for the 4 mg group. The difference between the highest dose (4 mg) and the placebo group was virtually zero, with a p-value of 0.9870. Unity subsequently discontinued the UBX0101 clinical trial.

Verifying SperoCure’s Efficacy Through Rigorous Control of the Placebo Group

Bio Solution Co.,Ltd. has identified verifying

SperoCure

’s efficacy relative to

the placebo group

as a key clinical objective. The company plans to rigorously control the patient population, endpoints, evaluation timepoints, and clinical operations to ensure that SperoCure’s efficacy is demonstrated even in the face of the high placebo response that can inevitably occur with intra-articular injections for osteoarthritis.

In particular, taking into account potential failures due to the placebo effect, the company’s strategy is to utilize the initial SperoCure clinical trial as a “data accumulation phase” for designing subsequent trials. Rather than simply comparing average VAS and WOMAC scores, the company aims to identify the characteristics of patients who respond well to treatment and to examine the durability of the effect across different dosages and evaluation time points.

Specifically, during the patient enrollment phase, the team will meticulously manage baseline pain levels and recent history of intra-articular injection therapies—such as steroids, hyaluronic acid, and PRP—and will track the use of rescue medications (such as analgesics) and any additional treatments during the trial to minimize variables that could affect the evaluation of the drug’s efficacy.

The evaluation metrics will also be refined. Currently, Phases 1 and 2a use the 24-week VAS and WOMAC function scores as co-primary endpoints, while symptom and functional indicators such as KOOS and IKDC, as well as MRI, X-ray, biomarkers, and quality of life, are evaluated as secondary or exploratory endpoints.

Long-term evaluations to confirm structural improvement at the one-year mark are also planned. This is intended to identify patients who exhibit actual changes in joint structure and biological responses—rather than merely assessing whether “pain has decreased” in the early stages—for use in future confirmatory DMOAD clinical trials.

In subsequent clinical trials, the policy is to rigorously manage not only the mean change but also response rate measures such as OMERACT-OARSI, long-term sustained effects at 36–48 weeks, and patient subgroups at high risk of structural progression, as these can all be important design variables.

Additionally, for the multicenter trial, the company plans to reduce inter-center variability by standardizing evaluator training, imaging interpretation, and pain assessment procedures. Rather than calculating the sample size for the large-scale trial based solely on the effect size observed in the initial clinical trial, the company has adopted a strategy of making conservative assumptions regarding the degree of improvement in the control group and the dropout rate.

A representative of Bio Solution Co.,Ltd. stated, “As several existing studies have shown that placebos also demonstrate significant efficacy in clinical trials of osteoarthritis injections, we will design a clinical trial plan that surpasses these results and will thoroughly manage the placebo group.”