Study design of a phase 2 clinical trial with a disease-modifying Osteoarthritis drug candidate GLPG1972/S201086: The roccella trial

The Development of Disease-Modifying Therapies for Osteoarthritis (DMOADs): The Evidence to Date

“…35 Phase-1 clinical studies revealed favorable pharmacokinetics as well as a strong and consistent target engagement in both healthy subjects and OA patients (n=171). 36 In a phase-2 study (Roccella study) which investigated the efficacy and safety profile of three different once-daily oral doses of GLPG1972/S201086 (n=932), the change in 37 Another ADAMTS5targeting agent, M6495 an anti-ADAMTS5 Nanobody (Ablynx), showed an acceptable safety profile and dosedependent effects in a phase-1 study. 38…”

“… 35 Phase-1 clinical studies revealed favorable pharmacokinetics as well as a strong and consistent target engagement in both healthy subjects and OA patients (n=171). 36 In a phase-2 study (Roccella study) which investigated the efficacy and safety profile of three different once-daily oral doses of GLPG1972/S201086 (n=932), the change in cartilage thickness [in mm (SD)] of central medial tibiofemoral compartment of the target knee via quantitative MRI was −0.116 (0.27) for the placebo group and −0.068 (0.20), −0.097 (0.27) and 0.085 (0.22), for the low, medium and high dose, respectively. There was no statistically significant difference versus placebo in both MRI and clinical outcome measures.…”

Repurposed and investigational disease-modifying drugs in osteoarthritis (DMOADs)

“…143 Neither symptomatic nor disease-modifying benefits detected by MRI were found in a phase II study (Roccella study) for knee OA (n = 932) 117 despite the fact that the study design was optimized for capturing cartilage changes. 144 Phase I studies for an ADAMTS-5 nanobody (M6495) showed overall acceptable safety at single doses up to 300 mg for further clinical development. 145 Fibroblast growth factor 18.…”

Designing polymers for cartilage uptake: effects of architecture and molar mass

“…9 As articular cartilage loss is one of the hallmarks of OA progression, cartilage has been an important therapeutic target. For example, inhibitors of matrix metalloproteinases 10 and aggrecanases, 11,12 which degrade collagen and aggrecan in cartilage respectively, are being studied. Recombinant human fibroblast growth factor 18 is also being investigated as a promoter of cartilage repair.…”

“…13 However, the potential therapeutics that have undergone clinical trials thus far have not yet succeeded due in part to issues such as adverse effects and poor therapeutic efficacy. [10][11][12]14 Intra-articular delivery is a promising approach to mitigate the side effects associated with systemic administration and enhance efficacy by delivering the correct dose of a drug to the target tissue. [15][16][17] However, the rapid clearance of drugs from the joint space, 18,19 combined with the avascular nature of cartilage and its dense anionic network of collagen and aggrecan proteoglycans makes it difficult for therapeutics to reach targets, such as chondrocytes embedded within cartilage.…”