Six months’ treatment with MIV-711, a novel Cathepsin K inhibitor induces osteoarthritis structure modification: results from a randomized double-blind placebo-controlled phase IIA trial

Abstract

and exercise). The primary outcome measure was hip-related quality of life using the patient-reported International Hip Outcome Tool (iHOT-33) at 12 months (score 0-100, higher scores indicate better quality of life, and the minimal clinical important difference is 6.1). Secondary outcomes included generic health-related quality of life (EQ5D5L, SF12), adverse events, and cost-effectiveness. Primary analysis compared the differences in iHOT-33 scores at 12 months between groups, by intention to treat. Cost-effectiveness analysis took an NHS and personal social services perspective. Results: Of 6028 patients attending hip clinics at participating sites, 648 patients were eligible and 348 were randomised (171 to HA; 177 to PHT). There were no important differences between the groups in baseline characteristics. The average time to surgery was 132 days (SD 71) versus 47 days (SD 52) to PHT. 92.5% were followed-up for the primary outcome at 12 months. Baseline mean and standard deviation in iHOT-33 scores were 39.2 (SD 21) and 35.6 (SD 18) in the surgery and PHT groups, and 58.8 (SD 27) and 49.7 (SD 25) at 12 months, respectively. On average, patients in both groups improved over 12 months, and the mean iHOT-33 score increased more in those allocated to HA than to PHT, with a mean difference of 6.8 points (95% CI 1.7,12.0 p ¼ 0.009) in favour of surgery. Muscle soreness was common in both groups; one HA patient developed an infection requiring further surgery. Mean overall costs were £3713 for HA and £1283 for PHT. Conclusions: Treatment of patients with FAI syndrome with a strategy of either physiotherapy-led best conservative care or arthroscopic hip surgery led to improved hip-related quality of life. At 12 month followup that improvement was significantly greater in those allocated to surgery than in those allocated to conservative care. Hip arthroscopy was safe, but is associated with higher overall cost than conservative care over 12 months.

Chondroprotective Factors in Osteoarthritis: a Joint Affair

“… Cathepsin K inhibitor MIV-711 MIV-711 was well tolerated in a phase I study in healthy subjects [ 26 ]. Phase IIa trial showed significant reductions in bone and cartilage disease progression in the femur [ 27 ]. No further studies registered to date.…”

“…Phase I clinical trial of multiple ascending doses of anti-ADAMTS-5 nanobody in knee OA, due for completion in May 2019 (NCT03583346).Anti-proteaseAlpha-2-macroglobulinPhase I trial to look at the reduction of pro-inflammatory synovial fluid biomarkers in OA due for completion in 2019 (NCT03656575).Cathepsin K inhibitorMIV-711MIV-711 was well tolerated in a phase I study in healthy subjects [26]. Phase IIa trial showed significant reductions in bone and cartilage disease progression in the femur [27]. No further studies registered to date.Promotion of cartilage building factorsFibroblast growth factor (FGF)Sprifermin (rhFGF-18)After positive results in pre-clinical trials [28, 29], the results from the first-in-human clinical trial were cautiously optimistic [30].…”

Accuracy and longitudinal reproducibility of quantitative femorotibial cartilage measures derived from automated U-Net-based segmentation of two different MRI contrasts: data from the osteoarthritis initiative healthy reference cohort

“…While radiography was previously used to assess the structural progression of OA, quantitative measurement of articular cartilage based on serial magnetic resonance images (MRI) is now the method of choice and provides the high test-retest precision and sensitivity to longitudinal change required for clinical trials [3][4][5]. The use of quantitative MRI also has revolutionized the conduct of clinical trials on structure or disease modifying OA drugs (S/DMOADs) [5][6][7][8], by having recently been scaled up from exploratory to secondary or even primary endpoints for submission for potential regulatory approval [6,9].…”

Update on novel pharmacological therapies for osteoarthritis

“…A 6-month, multicentre, randomized, placebo-controlled, double-blind, three-arm parallel, phase IIa study evaluating the efficacy, safety and tolerability of MIV-711 in patients with knee OA was completed in 2017 and preliminary results presented. 88 Patients with knee OA received MIV-711 100 mg, 200 mg or matched placebo four times daily for 26 weeks. A significant reduction in pain and QoL scores was not detected, although there was a trend towards a reduction in pain scores with 100 mg and 200 mg doses at 26 weeks.…”