Background/Purpose: The current Phase 2 study was designed to evaluate safety, tolerability and preliminary efficacy of TPX-100 by IA administration in subjects with mild to moderate patellofemoral osteoarthritis (PFOA) involving both knees. TPX-100, a 23-amino acid peptide derived from Matrix Extracellular Phosphoglycoprotein (MEPE), has been shown to induce articular cartilage proliferation and improve healing after experimental injury in large and small animal models after IA administration. A unique feature of this clinical trial was the use of each subject as his/her own control, intended to minimize effects of age, sex, genetic factors, and activity levels that can complicate inter-subject comparisons. Knee-specific patient-reported outcomes (PROs) used in this study, including the Knee Osteoarthritis Outcome Score (KOOS), were recorded separately for left and right knees.

Methods: Adult men and women with bilateral PFOA (ICRS grade 1-3, confirmed by screening MRI) were enrolled at 15 sites. One knee was randomly assigned to receive TPX-100 for 4 weekly injections, while the contralateral knee (control) received identical placebo (saline) injections. Investigator, subject, site and sponsor were blinded as to treatment assignment. The study had two parts: in Part A, 4 dose cohorts (n=6-9 subjects/cohort; 20, 50, 100 and 200mg/injection) were enrolled. Safety/tolerability of each cohort was evaluated by a Safety Review Committee (SRC) before the next cohort was enrolled. There were no dose-limiting toxicities or safety concerns at any dose, and the 200 mg dose was selected dose for Part B of the study.

Results: A total of 118 subjects (236 knees) were enrolled, 29 in Part A and 89 in Part B. The study population was fairly representative of the knee OA population in the U.S. regarding age (median 60 years) and Body Mass Index (29.2). There were no drug-related SAEs and no dose-limiting toxicities across doses from 20-200 mg/injection. Common adverse events such as knee pain had virtually identical incidences in control and TPX-100-treated knees. Efficacy results were based on the “per-protocol” population of 93 subjects (186 knees) who received 4 weekly injections of 200mg TPX-100 (from Part A or Part B) in the knee randomly assigned to active drug and had at least one MRI after baseline. Quantitative MRI revealed no measurable between-knee differences in cartilage thickness or volume at 6 or 12 months. However, statistically significant (P<.05) and clinically meaningful differences, per literature criteria, in knee function were demonstrated in favor of TPX-100-treated knees compared with controls at 6 and 12 months, including activities of daily living, sports activities, and knee-related quality of life, and a significant reduction in pain going up or down stairs. Subjects’ use of analgesics, including non-steroidal anti-inflammatory medications, declined markedly during the study. Results will be provided in detail.

Conclusion: Improving the functional status of patients with knee OA is a central therapeutic goal of OA treatment. In the present proof-of-concept study, TPX-100, administered in 4 weekly intra-articular injections, was safe and associated with robust functional benefits for up to 12 months.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/significant-sustained-improvement-in-knee-function-after-intra-articular-tpx-100-a-double-blind-randomized-multi-center-placebo-controlled-phase-2-trial/