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LIVERPOOL, ENGLAND – The investigational cathepsin K inhibitor MIV-711 had positive effects on both bone and cartilage at 6 months in patients with knee osteoarthritis (OA) in a phase 2a study.
The MRI measures of the “area of bone in the medial femur region” and “average cartilage thickness” showed reduced progression with MIV-711 versus placebo.
MIV-711 also produced rapid and sustained reductions in the bone biomarkers CTX-I and CTX-II, study investigator Philip Conaghan, MBBS, PhD, reported at the World Congress on Osteoarthritis.
The primary endpoint of the trial – the change in average knee pain over 26 weeks assessed using an 11-point numerical rating scale (NRS) – was not met, however, with no differences between MIV-711 treatment and placebo.
While there were also no statistical differences in Western Ontario and McMaster Universities Osteoarthritis Index pain scores, one of several secondary endpoints assessed, there was a trend for less pain with MIV-711 than with placebo.
“The lack of symptom benefits may reflect that the study duration was not sufficient to see symptom reduction following structure modification,” Dr. Conaghan and his coauthors stated in their abstract.
“That’s something we’re seeing with all the drugs that are trying to get DMOAD [disease modifying osteoarthritis drug] licenses at present,“ Dr. Conaghan said at the Congress, sponsored by the Osteoarthritis Research Society International.
Dr. Conaghan, who is professor of musculoskeletal medicine and director of the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine, noted: “Cathepsin K is a cysteine protease that degrades the collagen matrix and stops bone resorption, so it’s got a number of potential actions,” in the development of OA.
MIV-711 is a potent, selective, and reversible inhibitor of cathepsin K, he added, which has previously been shown to have bone structure–modifying properties in preclinical models. It also has been shown to reduce CTX-I and CTX-II in healthy volunteers.
The current randomized, double-blind, placebo-controlled phase 2a study included two active treatment (100 mg and 200 mg, once daily) arms and one placebo arm. For inclusion, patients had to have knee pain rated as 4 or higher on an 11-point NRS and Kellgren-Lawrence grade 2 or 3 knee OA.
Patients also were allowed to remain on any analgesic medication they were currently taking, provided this was stable. “That enables recruitment as a trialist, and it’s more like my usual practice as it’s unlikely I’d stop an analgesic before starting a new one,” Dr. Conaghan said.
In all, 240 patients were enrolled at six European sites. They had a mean age of 62 years, a body mass index of 32 kg/m2, and 77% were women. MRIs were assessed at baseline and at week 26, with additional clinic visits scheduled at 2, 4, 8, 14, and 20 weeks.
“Overall, there are not any great safety signals,” Dr. Conaghan said. The placebo, 100-mg, and 200-mg MIV-117 arms had similar rates of any adverse event (55%, 54.9%, and 52.4%) or treatment-related adverse events (21.2%, 20.7%, and 24.4%). There were more serious adverse events in the 100-mg and 200-mg MIV-711 treatment arms (3.7% and 2.4%) than in the placebo arm (1.3%), and more discontinuations (7.3%, 4.9%, and 3.8%).
“The primary endpoint of knee pain was not met, but there was a consistent trend, and it looks like there’s a benefit, but the statistically endpoint was not achieved,” Dr. Conaghan summarized.
“MRI measures do show structural modification in terms of bone shape and probably an effect on cartilage,” although the study was not powered to show an effect on the latter, Dr. Conaghan noted.
“The overall data, and from what we’ve seen regarding structural effects, do warrant this drug moving forward into further trials,” he added.
The study was sponsored by Medivir. Dr. Conaghan disclosed being a member of the speaker’s bureau for Kolon TissueGene and Samumed and on advisory boards for AbbVie, Centrexion, Flexion Therapeutics, Medivir, Novartis, and ONO Pharmaceutical.
SOURCE: Conaghan P et al. Osteoarthritis Cartilage. 2018 Apr 16:26(1):S25-26. Abstract 29.
LIVERPOOL, ENGLAND – The investigational cathepsin K inhibitor MIV-711 had positive effects on both bone and cartilage at 6 months in patients with knee osteoarthritis (OA) in a phase 2a study.
The MRI measures of the “area of bone in the medial femur region” and “average cartilage thickness” showed reduced progression with MIV-711 versus placebo.
MIV-711 also produced rapid and sustained reductions in the bone biomarkers CTX-I and CTX-II, study investigator Philip Conaghan, MBBS, PhD, reported at the World Congress on Osteoarthritis.
The primary endpoint of the trial – the change in average knee pain over 26 weeks assessed using an 11-point numerical rating scale (NRS) – was not met, however, with no differences between MIV-711 treatment and placebo.
While there were also no statistical differences in Western Ontario and McMaster Universities Osteoarthritis Index pain scores, one of several secondary endpoints assessed, there was a trend for less pain with MIV-711 than with placebo.
“The lack of symptom benefits may reflect that the study duration was not sufficient to see symptom reduction following structure modification,” Dr. Conaghan and his coauthors stated in their abstract.
“That’s something we’re seeing with all the drugs that are trying to get DMOAD [disease modifying osteoarthritis drug] licenses at present,“ Dr. Conaghan said at the Congress, sponsored by the Osteoarthritis Research Society International.
Dr. Conaghan, who is professor of musculoskeletal medicine and director of the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine, noted: “Cathepsin K is a cysteine protease that degrades the collagen matrix and stops bone resorption, so it’s got a number of potential actions,” in the development of OA.
MIV-711 is a potent, selective, and reversible inhibitor of cathepsin K, he added, which has previously been shown to have bone structure–modifying properties in preclinical models. It also has been shown to reduce CTX-I and CTX-II in healthy volunteers.
The current randomized, double-blind, placebo-controlled phase 2a study included two active treatment (100 mg and 200 mg, once daily) arms and one placebo arm. For inclusion, patients had to have knee pain rated as 4 or higher on an 11-point NRS and Kellgren-Lawrence grade 2 or 3 knee OA.
Patients also were allowed to remain on any analgesic medication they were currently taking, provided this was stable. “That enables recruitment as a trialist, and it’s more like my usual practice as it’s unlikely I’d stop an analgesic before starting a new one,” Dr. Conaghan said.
In all, 240 patients were enrolled at six European sites. They had a mean age of 62 years, a body mass index of 32 kg/m2, and 77% were women. MRIs were assessed at baseline and at week 26, with additional clinic visits scheduled at 2, 4, 8, 14, and 20 weeks.
“Overall, there are not any great safety signals,” Dr. Conaghan said. The placebo, 100-mg, and 200-mg MIV-117 arms had similar rates of any adverse event (55%, 54.9%, and 52.4%) or treatment-related adverse events (21.2%, 20.7%, and 24.4%). There were more serious adverse events in the 100-mg and 200-mg MIV-711 treatment arms (3.7% and 2.4%) than in the placebo arm (1.3%), and more discontinuations (7.3%, 4.9%, and 3.8%).
“The primary endpoint of knee pain was not met, but there was a consistent trend, and it looks like there’s a benefit, but the statistically endpoint was not achieved,” Dr. Conaghan summarized.
“MRI measures do show structural modification in terms of bone shape and probably an effect on cartilage,” although the study was not powered to show an effect on the latter, Dr. Conaghan noted.
“The overall data, and from what we’ve seen regarding structural effects, do warrant this drug moving forward into further trials,” he added.
The study was sponsored by Medivir. Dr. Conaghan disclosed being a member of the speaker’s bureau for Kolon TissueGene and Samumed and on advisory boards for AbbVie, Centrexion, Flexion Therapeutics, Medivir, Novartis, and ONO Pharmaceutical.
SOURCE: Conaghan P et al. Osteoarthritis Cartilage. 2018 Apr 16:26(1):S25-26. Abstract 29.
LIVERPOOL, ENGLAND – The investigational cathepsin K inhibitor MIV-711 had positive effects on both bone and cartilage at 6 months in patients with knee osteoarthritis (OA) in a phase 2a study.
The MRI measures of the “area of bone in the medial femur region” and “average cartilage thickness” showed reduced progression with MIV-711 versus placebo.
MIV-711 also produced rapid and sustained reductions in the bone biomarkers CTX-I and CTX-II, study investigator Philip Conaghan, MBBS, PhD, reported at the World Congress on Osteoarthritis.
The primary endpoint of the trial – the change in average knee pain over 26 weeks assessed using an 11-point numerical rating scale (NRS) – was not met, however, with no differences between MIV-711 treatment and placebo.
While there were also no statistical differences in Western Ontario and McMaster Universities Osteoarthritis Index pain scores, one of several secondary endpoints assessed, there was a trend for less pain with MIV-711 than with placebo.
“The lack of symptom benefits may reflect that the study duration was not sufficient to see symptom reduction following structure modification,” Dr. Conaghan and his coauthors stated in their abstract.
“That’s something we’re seeing with all the drugs that are trying to get DMOAD [disease modifying osteoarthritis drug] licenses at present,“ Dr. Conaghan said at the Congress, sponsored by the Osteoarthritis Research Society International.
Dr. Conaghan, who is professor of musculoskeletal medicine and director of the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine, noted: “Cathepsin K is a cysteine protease that degrades the collagen matrix and stops bone resorption, so it’s got a number of potential actions,” in the development of OA.
MIV-711 is a potent, selective, and reversible inhibitor of cathepsin K, he added, which has previously been shown to have bone structure–modifying properties in preclinical models. It also has been shown to reduce CTX-I and CTX-II in healthy volunteers.
The current randomized, double-blind, placebo-controlled phase 2a study included two active treatment (100 mg and 200 mg, once daily) arms and one placebo arm. For inclusion, patients had to have knee pain rated as 4 or higher on an 11-point NRS and Kellgren-Lawrence grade 2 or 3 knee OA.
Patients also were allowed to remain on any analgesic medication they were currently taking, provided this was stable. “That enables recruitment as a trialist, and it’s more like my usual practice as it’s unlikely I’d stop an analgesic before starting a new one,” Dr. Conaghan said.
In all, 240 patients were enrolled at six European sites. They had a mean age of 62 years, a body mass index of 32 kg/m2, and 77% were women. MRIs were assessed at baseline and at week 26, with additional clinic visits scheduled at 2, 4, 8, 14, and 20 weeks.
“Overall, there are not any great safety signals,” Dr. Conaghan said. The placebo, 100-mg, and 200-mg MIV-117 arms had similar rates of any adverse event (55%, 54.9%, and 52.4%) or treatment-related adverse events (21.2%, 20.7%, and 24.4%). There were more serious adverse events in the 100-mg and 200-mg MIV-711 treatment arms (3.7% and 2.4%) than in the placebo arm (1.3%), and more discontinuations (7.3%, 4.9%, and 3.8%).
“The primary endpoint of knee pain was not met, but there was a consistent trend, and it looks like there’s a benefit, but the statistically endpoint was not achieved,” Dr. Conaghan summarized.
“MRI measures do show structural modification in terms of bone shape and probably an effect on cartilage,” although the study was not powered to show an effect on the latter, Dr. Conaghan noted.
“The overall data, and from what we’ve seen regarding structural effects, do warrant this drug moving forward into further trials,” he added.
The study was sponsored by Medivir. Dr. Conaghan disclosed being a member of the speaker’s bureau for Kolon TissueGene and Samumed and on advisory boards for AbbVie, Centrexion, Flexion Therapeutics, Medivir, Novartis, and ONO Pharmaceutical.
SOURCE: Conaghan P et al. Osteoarthritis Cartilage. 2018 Apr 16:26(1):S25-26. Abstract 29.
REPORTING FROM OARSI 2018
Key clinical point:
Major finding: A 63%-66% reduction in the medial femur bone area was observed with MIV-711, compared with placebo.
Study details: Randomized, double-blind, placebo-controlled phase 2a study of 240 patients with osteoarthritis knee pain.
Disclosures: The study was sponsored by Medivir. Dr. Conaghan disclosed being a member of the speakers bureau for Kolon TissueGene and Samumed and on advisory boards for AbbVie, Centrexion, Flexion Therapeutics, Medivir, Novartis, and ONO Pharmaceutical.
Source: Conaghan P et al. Osteoarthritis Cartilage. 2018 Apr 16:26(1):S25-26. Abstract 29.