Contributions
Abstract: S130
Type: Oral Presentation
Presentation during EHA22: On Friday, June 23, 2017 from 12:00 - 12:15
Location: Room N105
Background
Aims
The primary objective of this study was to evaluate the results of DMB on lumbar spine (L1-L4) BMD in patients with TM and osteoporosis as compared to placebo at 12 months. Secondary endpoints included the evaluation of the effects of DMB on femoral neck (FN) and wrist (WR) BMD at 12 months, the safety profile of DMB as well as its effects on bone turnover.
Methods
This was a single-site, randomized, placebo-controlled, double blind phase 2b clinical trial. Main inclusion criteria included adult patients (>30 years of age) with TM and BMD T-score between -2.5 and - 4.0 in at least one of the examined sites (L1-L4, FN, WR). Main exclusion criteria included: impaired renal function (eGFR of ≤30 mL/min); elevated ALT and/or AST >2 fold the upper limit of normal (UNL), or elevated direct bilirubin >1.5xUNL; heart failure (NYHA above 2); administration of bisphosphonates within one year of study enrolment; presence of any other disorder that affects bone metabolism. Patients were assigned into two treatment groups: in group A, 60 mg DMB was administered sc, every 6 months for 12 months for a total of 2 doses (day 0 and day 180); in group B, placebo was administered sc, at the same time. All patients received calcium and vitamin D supplementation. Measurement of BMD with dual energy X-ray absorptiometry at three body sites (L1-L4, FN, WR) was performed during the screening period and at the end of the study.
Results
Sixty-three patients with TM and osteoporosis participated in the study (group A, n=31; group B, n=32). Patients of groups A and B showed no differences in BMD of all evaluated sites at baseline. Patients of group A (DMB arm) achieved an increase in both L1-L4 BMD (mean±SD: 0.811±0.105 g/cm2 vs. 0.772±0.098, p<0.001) and FN BMD (0.653±0.121 g/cm2 vs. 0.631±0.103, p=0.022), while there were no changes in WR BMD. Patients of group B (placebo arm) achieved a slight increase in their L1-L4 BMD (0.801±0.097 g/cm2 vs. 0.775±0.080, p=0.004) and a significant decrease in their WR BMD (0.520±0.099 g/cm2 vs. 0.549±0.098, p=0.008). The percentage increase of L1-L4 BMD was higher in DMB arm than in placebo arm (6.02±5.30 % vs. 3.11±5.46 %, respectively; p=0.03), while the advantage of DMB regarding WR BMD was much higher compared to placebo (-0.22±5.40 % vs. -4.15±8.58 %, respectively; p=0.02) as well as in FN BMD (p<0.001). No grade 3 or 4 toxicity was observed in this study.
Conclusion
This first analysis of our phase 2B study regarding the effects of DMB on BMD of different sites (the results of bone markers will be presented in the conference), suggests that DMB, given twice per year, increases the BMD of the L1-L4 more efficiently than placebo (in combination with vitamin D and calcium), after 12 months, in patients with TM and osteoporosis, with excellent safety profile. Furthermore, DMB increased the FN BMD, which was not increased in the placebo arm, while DMB has also a positive effect on WR BMD compared to placebo. These data support the use of DMB for the management of TM-induced osteoporosis.
Session topic: 26. Thalassemias
Keyword(s): Treatment, Thalassemia, Osteoporosis, Beta thalassemia
Abstract: S130
Type: Oral Presentation
Presentation during EHA22: On Friday, June 23, 2017 from 12:00 - 12:15
Location: Room N105
Background
Aims
The primary objective of this study was to evaluate the results of DMB on lumbar spine (L1-L4) BMD in patients with TM and osteoporosis as compared to placebo at 12 months. Secondary endpoints included the evaluation of the effects of DMB on femoral neck (FN) and wrist (WR) BMD at 12 months, the safety profile of DMB as well as its effects on bone turnover.
Methods
This was a single-site, randomized, placebo-controlled, double blind phase 2b clinical trial. Main inclusion criteria included adult patients (>30 years of age) with TM and BMD T-score between -2.5 and - 4.0 in at least one of the examined sites (L1-L4, FN, WR). Main exclusion criteria included: impaired renal function (eGFR of ≤30 mL/min); elevated ALT and/or AST >2 fold the upper limit of normal (UNL), or elevated direct bilirubin >1.5xUNL; heart failure (NYHA above 2); administration of bisphosphonates within one year of study enrolment; presence of any other disorder that affects bone metabolism. Patients were assigned into two treatment groups: in group A, 60 mg DMB was administered sc, every 6 months for 12 months for a total of 2 doses (day 0 and day 180); in group B, placebo was administered sc, at the same time. All patients received calcium and vitamin D supplementation. Measurement of BMD with dual energy X-ray absorptiometry at three body sites (L1-L4, FN, WR) was performed during the screening period and at the end of the study.
Results
Sixty-three patients with TM and osteoporosis participated in the study (group A, n=31; group B, n=32). Patients of groups A and B showed no differences in BMD of all evaluated sites at baseline. Patients of group A (DMB arm) achieved an increase in both L1-L4 BMD (mean±SD: 0.811±0.105 g/cm2 vs. 0.772±0.098, p<0.001) and FN BMD (0.653±0.121 g/cm2 vs. 0.631±0.103, p=0.022), while there were no changes in WR BMD. Patients of group B (placebo arm) achieved a slight increase in their L1-L4 BMD (0.801±0.097 g/cm2 vs. 0.775±0.080, p=0.004) and a significant decrease in their WR BMD (0.520±0.099 g/cm2 vs. 0.549±0.098, p=0.008). The percentage increase of L1-L4 BMD was higher in DMB arm than in placebo arm (6.02±5.30 % vs. 3.11±5.46 %, respectively; p=0.03), while the advantage of DMB regarding WR BMD was much higher compared to placebo (-0.22±5.40 % vs. -4.15±8.58 %, respectively; p=0.02) as well as in FN BMD (p<0.001). No grade 3 or 4 toxicity was observed in this study.
Conclusion
This first analysis of our phase 2B study regarding the effects of DMB on BMD of different sites (the results of bone markers will be presented in the conference), suggests that DMB, given twice per year, increases the BMD of the L1-L4 more efficiently than placebo (in combination with vitamin D and calcium), after 12 months, in patients with TM and osteoporosis, with excellent safety profile. Furthermore, DMB increased the FN BMD, which was not increased in the placebo arm, while DMB has also a positive effect on WR BMD compared to placebo. These data support the use of DMB for the management of TM-induced osteoporosis.
Session topic: 26. Thalassemias
Keyword(s): Treatment, Thalassemia, Osteoporosis, Beta thalassemia