Session: LBSU 0377-0378-Growth Hormone Signaling
Poster Board LBSU-0377
The trial was a randomised, open-labelled, active-controlled, multiple dose, dose-escalating, sequential dose group trial investigating the safety, tolerability, pharmacokinetic (PK) and PD of weekly NNC0195-0092 compared to once daily rhGH. Four (4) cohorts of 8 adults with GHD in each cohort were investigated (in total, 32 AGHD subjects). The subjects enrolled into the trial were on stable GH replacement therapy, either male or female with a BMI between 18.0 to 35.0 kg/m2, age 20 to 70 years, Fourteen days before being randomized the AGHD subjects discontinued their GH replacement therapy. Four escalating doses of NNC0195-0092 were tested; 0.02, 0.04, 0.08 and 0.12 mg kg/week and in each dose-group 8 AGHD subjects were dosed with a subcutaneous administration of NNC0195-0092 (n=6) or daily rhGH (n=2). After 1st and 4th dosing at each dose level the pharmacokinetics and PD (IGF-I, IGFBP-3) were evaluated.
Multiple doses of NNC0195-0092 administered sc. to AGHD subjects were well tolerated at all doses investigated, with no serious safety issues identified. No positive test results for anti NNC0195-0092 antibodies, anti hGH antibodies, or local tolerability issues were observed at any dose level tested. A significant dose-dependent IGF-I response was induced, with elevated IGF-I levels at all dose levels of NNC0195-0092 investigated (0.02, 0.04, 0.08, 0.12 mg/kg). The IGF-I and IGFBP-3 levels were significantly greater for the 0.12mg/kg dose compared to rhGH and 0.02−0.08 mg/kg doses based on comparison of AUC0-168h and Cmax. A clinically relevant IGF-I response was induced by doses up to 0.08 mg/kg.
In conclusion, multiple dosing of NNC0195-0092 administered sc. to adult patients with GHD was well tolerated at all doses investigated. No antibodies or local tolerability issues were observed at any dose level tested. A clear dose-dependent PD response was observed with elevated IGF-I levels at all dose levels. The IGF-I profiles indicate that NNC0195-0092 possesses a very promising sustained once-weekly treatment profile in AGHD.
Disclosure: MHR: Employee, Novo Nordisk. JJ: Researcher, Novo Nordisk. LFN: Employee, Novo Nordisk. CH: Coinvestigator, Novo Nordisk. MA: Coinvestigator, Novo Nordisk. UF: Principal Investigator, Novo Nordisk, Principal Investigator, Novartis Pharmaceuticals, Speaker, Pfizer, Inc., Speaker, Novo Nordisk, Speaker, Ipsen, Speaker, Novartis Pharmaceuticals, Advisory Group Member, Pfizer, Inc.. JSC: Research Funding, Novo Nordisk, Board Member, Novo Nordisk, Board Member, The name is Merck Serono, lectures, Novo Nordisk, lectures, Pfizer, Inc., fees, Eli Lilly & Company. Nothing to Disclose: MCK, DM, MHT
*Please take note of The Endocrine Society's News Embargo Policy at https://www.endocrine.org/news-room/endo-annual-meeting