FYI:OPKO at the October 3rd (ESPE 2015 Meeting) Barcelona
Oct 1, 2015 2:36:31 GMT
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Post by Uncle on Oct 1, 2015 2:36:31 GMT
Two Reports on hGH-CTP Pediatric Phase 2 Clinical Data Accepted for Oral Presentation at the 54th Annual Meeting of the European Society for Paediatric Endocrinology (ESPE conference)
MIAMI--(BUSINESS WIRE)-- OPKO Health, Inc. (NYSE:OPK), announced that additional data from OPKO's hGH-CTP pediatric Phase 2 clinical trials summarized in two abstracts entitled, "12 month Safety and efficacy of a weekly long-acting growth hormone (GH, MOD-4023) compared to daily recombinant human GH (rh)GH) therapy in pre-pubertal growth hormone deficient children; Phase 2 study - Study CP-4-004 Summary" and "Pharmacokinetic (PK) and Pharmacodynamics (PD) Modeling of MOD 4023 (a long-acting human growth hormone (hGH)) in Growth Hormone Deficient (GHD) Children" has been selected for oral presentation at the upcoming 54th Annual Meeting of the European Society for Paediatric Endocrinology taking place in Barcelona, Spain from October 1-3.
The data to be presented include results for 52 patients completing twelve months of weekly treatment with hGH-CTP. This phase 2 study was a one year, dose finding study administering hGH-CTP to growth hormone deficient children once a week using Genotropin® administered daily as a comparator arm. The twelve months data confirm comparable response of hGH-CTP to Genotropin® injected daily as reflected by the twelve months serum insulin-like growth factor-1 standard deviation score (IGF-1SDS) profile, annual height velocity (HV), height velocity standard deviation score (HV SDS) and safety profile. The data affirm the selection of an optimal dose that would be used to demonstrate non-inferiority compared to daily administered hGH in the upcoming phase 3 study.
OPKO oral presentations will be held at the Growth-promoting therapies session on Saturday, October 3, 2015 at 9:55 AM and 10:05 AM.
Opko Health at ESPE 2015 Barcelona
[/a]12-Month Safety and Efficacy of a Weekly Long-Acting GH (MOD-4023) Compared to Daily Recombinant Human GH Therapy in Pre-Pubertal GH-Deficient Children; Phase 2 Study: Study CP-4-004 Summary
[/ul]Rosenfeld Ron
12 month safety and efficacy of a weekly long-acting growth hormone (GH, MOD-4023) compared to daily recombinant human GH (rh)GH) therapy in pre-pubertal growth hormone deficient children; Phase 2 study – Study CP-4-004 Summary Free Communications 7 - Growth promoting therapies (3 October 2015, 09:15 - 10:15 , Hall 2)
Objective and hypotheses: To compare the PK/PD, safety, efficacy, and tolerability of three doses of once-weekly MOD-4023 to that of a daily recombinant human GH (rhGH) formulation in pre-pubertal children with growth failure due to GH deficiency (GHD).
Method: The randomised, controlled phase 2 study was conducted in 53 pre-pubertal, hGH-naïve GHD children randomised to receive one of three MOD-4023 doses as a once-weekly s.c. injection (0.25, 0.48, and 0.66 mg/kg per week) or daily rhGH (34 μg/kg per day) as a control arm. Annual height velocity (HV) was evaluated at 12 months, accompanied by assessment of safety, including metabolic profiles.
Results: Last subject, last visit is anticipated in June 2015. Data on 49/52 subjects who completed 12 months treatment indicated that baseline demographic and auxological characteristics were comparable among all groups. Twelve months PK/PD profile following administration of MOD-4023 in these subjects demonstrated a significantly extended half-life compared to daily rhGH. A dose-dependent PK/PD (IGF1) response was observed among MOD-4023 dose cohorts, reaching steady state with no accumulation or excessive levels by 10 weeks. All cohorts demonstrated expected ‘catch-up’ growth, with subjects on the two highest doses of MOD-4023, demonstrating HV comparable to those in the hGH arm and ranging from 10 to 12 cm/year. Sub-analysis of HV response based on baseline characteristics confirmed a comparable response in all sub-populations. The 12-month safety analysis indicates a safety profile comparable to daily rhGH, while IGF1 and metabolic parameters remained within the normal range.
Conclusion: Available data on the PK/PD, efficacy, and safety analysis of MOD-4023 administration to GHD children confirmed its long acting properties and affirmed that a single weekly injection of MOD-4023 has the potential to replace seven consecutive daily injections of rhGH in pediatric GHD patients. Further, final study data, anticipated in June 2015, will provide the basis for dose selection for phase 3.
Pharmacokinetic and Pharmacodynamics Modelling of MOD-4023 (a Long-Acting Human GH) in GH-Deficient Children
Background, objective, and hypotheses: OPKO Biologics has produced a long-acting human GH (hGH), MOD-4023, containing copies of a naturally-occurring C-terminal peptide (CTP) to markedly increase GH’s in vivo residence. We describe the construction and validation of a pharmacokinetic (PK)/pharmacodynamics (PD) model to characterise the relationship between MOD-4023 dose, MOD-4023 serum concentrations (Cserum), and IGF1 responses in healthy adults, GH-deficient (GHD) adults and GHD children. The model was used to characterise the PK and PD profile of MOD-4023 as part of the on-going paediatric GHD clinical studies.
Method: MOD-4023 PK and PD were studied following administration to healthy adults (n=18), GHD adults (n=46), and GHD children (3–11 years of age, n=53). In children, doses were 0.25, 0.48, or 0.66 mg/kg weekly; genotropin® (hGH 34 μg/kg daily) was the comparator. Data from healthy adults were used to develop PK and PD models; models were then applied to GHD adults and children. Serum concentrations were fit to a linear compartmental model with first-order absorption and an absorption lag. An indirect-response PD model was applied to IGF1 data. Covariates (age, body size, gender, and organ function) were entered into the PK and PD models if justified statistically.
Results: In adults and children, a two-compartment PK model fit Cserum data well. For PD modeling, the indirect response model generally fit IGF1 data well. Systemic parameters scaled allometrically; baseline IGF1 increased with age in GHD children.
Conclusion: We constructed and validated MOD-4023 PK and PD models which predict the relationship between administered dose, Cserum, and IGF1 response with various dosing regimens in paediatric GHD population. This model can assist in safety monitoring, including dose selection and dose modification in future clinical studies.
MIAMI--(BUSINESS WIRE)-- OPKO Health, Inc. (NYSE:OPK), announced that additional data from OPKO's hGH-CTP pediatric Phase 2 clinical trials summarized in two abstracts entitled, "12 month Safety and efficacy of a weekly long-acting growth hormone (GH, MOD-4023) compared to daily recombinant human GH (rh)GH) therapy in pre-pubertal growth hormone deficient children; Phase 2 study - Study CP-4-004 Summary" and "Pharmacokinetic (PK) and Pharmacodynamics (PD) Modeling of MOD 4023 (a long-acting human growth hormone (hGH)) in Growth Hormone Deficient (GHD) Children" has been selected for oral presentation at the upcoming 54th Annual Meeting of the European Society for Paediatric Endocrinology taking place in Barcelona, Spain from October 1-3.
The data to be presented include results for 52 patients completing twelve months of weekly treatment with hGH-CTP. This phase 2 study was a one year, dose finding study administering hGH-CTP to growth hormone deficient children once a week using Genotropin® administered daily as a comparator arm. The twelve months data confirm comparable response of hGH-CTP to Genotropin® injected daily as reflected by the twelve months serum insulin-like growth factor-1 standard deviation score (IGF-1SDS) profile, annual height velocity (HV), height velocity standard deviation score (HV SDS) and safety profile. The data affirm the selection of an optimal dose that would be used to demonstrate non-inferiority compared to daily administered hGH in the upcoming phase 3 study.
OPKO oral presentations will be held at the Growth-promoting therapies session on Saturday, October 3, 2015 at 9:55 AM and 10:05 AM.
Opko Health at ESPE 2015 Barcelona
[/a]12-Month Safety and Efficacy of a Weekly Long-Acting GH (MOD-4023) Compared to Daily Recombinant Human GH Therapy in Pre-Pubertal GH-Deficient Children; Phase 2 Study: Study CP-4-004 Summary
[/ul]Rosenfeld Ron
12 month safety and efficacy of a weekly long-acting growth hormone (GH, MOD-4023) compared to daily recombinant human GH (rh)GH) therapy in pre-pubertal growth hormone deficient children; Phase 2 study – Study CP-4-004 Summary Free Communications 7 - Growth promoting therapies (3 October 2015, 09:15 - 10:15 , Hall 2)
Objective and hypotheses: To compare the PK/PD, safety, efficacy, and tolerability of three doses of once-weekly MOD-4023 to that of a daily recombinant human GH (rhGH) formulation in pre-pubertal children with growth failure due to GH deficiency (GHD).
Method: The randomised, controlled phase 2 study was conducted in 53 pre-pubertal, hGH-naïve GHD children randomised to receive one of three MOD-4023 doses as a once-weekly s.c. injection (0.25, 0.48, and 0.66 mg/kg per week) or daily rhGH (34 μg/kg per day) as a control arm. Annual height velocity (HV) was evaluated at 12 months, accompanied by assessment of safety, including metabolic profiles.
Results: Last subject, last visit is anticipated in June 2015. Data on 49/52 subjects who completed 12 months treatment indicated that baseline demographic and auxological characteristics were comparable among all groups. Twelve months PK/PD profile following administration of MOD-4023 in these subjects demonstrated a significantly extended half-life compared to daily rhGH. A dose-dependent PK/PD (IGF1) response was observed among MOD-4023 dose cohorts, reaching steady state with no accumulation or excessive levels by 10 weeks. All cohorts demonstrated expected ‘catch-up’ growth, with subjects on the two highest doses of MOD-4023, demonstrating HV comparable to those in the hGH arm and ranging from 10 to 12 cm/year. Sub-analysis of HV response based on baseline characteristics confirmed a comparable response in all sub-populations. The 12-month safety analysis indicates a safety profile comparable to daily rhGH, while IGF1 and metabolic parameters remained within the normal range.
Conclusion: Available data on the PK/PD, efficacy, and safety analysis of MOD-4023 administration to GHD children confirmed its long acting properties and affirmed that a single weekly injection of MOD-4023 has the potential to replace seven consecutive daily injections of rhGH in pediatric GHD patients. Further, final study data, anticipated in June 2015, will provide the basis for dose selection for phase 3.
Pharmacokinetic and Pharmacodynamics Modelling of MOD-4023 (a Long-Acting Human GH) in GH-Deficient Children
Background, objective, and hypotheses: OPKO Biologics has produced a long-acting human GH (hGH), MOD-4023, containing copies of a naturally-occurring C-terminal peptide (CTP) to markedly increase GH’s in vivo residence. We describe the construction and validation of a pharmacokinetic (PK)/pharmacodynamics (PD) model to characterise the relationship between MOD-4023 dose, MOD-4023 serum concentrations (Cserum), and IGF1 responses in healthy adults, GH-deficient (GHD) adults and GHD children. The model was used to characterise the PK and PD profile of MOD-4023 as part of the on-going paediatric GHD clinical studies.
Method: MOD-4023 PK and PD were studied following administration to healthy adults (n=18), GHD adults (n=46), and GHD children (3–11 years of age, n=53). In children, doses were 0.25, 0.48, or 0.66 mg/kg weekly; genotropin® (hGH 34 μg/kg daily) was the comparator. Data from healthy adults were used to develop PK and PD models; models were then applied to GHD adults and children. Serum concentrations were fit to a linear compartmental model with first-order absorption and an absorption lag. An indirect-response PD model was applied to IGF1 data. Covariates (age, body size, gender, and organ function) were entered into the PK and PD models if justified statistically.
Results: In adults and children, a two-compartment PK model fit Cserum data well. For PD modeling, the indirect response model generally fit IGF1 data well. Systemic parameters scaled allometrically; baseline IGF1 increased with age in GHD children.
Conclusion: We constructed and validated MOD-4023 PK and PD models which predict the relationship between administered dose, Cserum, and IGF1 response with various dosing regimens in paediatric GHD population. This model can assist in safety monitoring, including dose selection and dose modification in future clinical studies.