A multicentre, multinational, randomised, parallel-group, placebo-controlled (double blind) and active-controlled (open) trial to compare the efficacy and safety of once weekly dosing of NNC0195-0092 with once weekly dosing of placebo and daily Norditropin FlexPro in adults with growth hormone deficiency for 35 weeks, followed by a 53-week open-label extension period
Description
Detailed Description
Rationale: The aim of the project is to develop a long-acting once-weekly GH product which is a safe and efficacious but has greater convenience and thus potentially better compliance compared to standard once daily GH treatment.
Intervention: Subjects will receive subcutaneous injection of study drug ( NNC0195-0092, Norditropin FlexPro or placebo. ) and being monitored efficacy and safety with AE, MRI, DEXA scan, Vital signs, Hts and weights, Hematology, Biochemistry, thyroid function, Hormones ,ECG and Eye exams.
Objectives or purpose: The primary objective is to access the efficacy and the secondary objective is to evaluate the clinical safety.
Study population or sample characteristics: This study is aiming for subjects who is between age of 23-79 with diagnosis of GHD who has no history of or active malignant disease.
Study methodology: Two hundred and eighty will be randomized in a 2:2:1 (NNC0195-0092: Norditropin FlexPro: placebo) ratio. The trial will compare the efficacy and safety of once weekly dosing of NNC0195-0092 with once weekly dosing of placebo and daily dosing of Norditropin FlexPro in adults with GHDs during the 35-week period (8 week dose titration, 26 week fixed dose treatment followed by 1 week washout), with a 53-week extension period (8 week dose titration, 44 week fixed dose treatment followed by 1 week washout). After the main trial period placebo subjects will be switched to NNC0195-0092 treatment and Norditropin FlexPro subjects will be randomised 1:1 to NNC0195-0092 or Norditropin FlexPro.
Study endpoints or outcomes: The primary endpoint will be at week 34 for the main trial and the secondary endpoint will be at 86 weeks for the extension period of trial. The study is looking for the outcome of changing in truncal fat mass and truncal lean body mass after the treatment, as well as to evaluate the safety of this drug.
Follow-up: Follow up visit will be scheduled 2 weeks after last treatment.
Statistics and plans for analysis: For each of the complete data sets, the change from baseline to 34 weeks is analysed using an ANCOVA model with treatment, GHD onset type, sex, region, DM and sex by region by DMinteraction as factors and the baseline truncal fat value as a covariate. From the pooled estimates, the treatment difference at Week 34 between NNC0195-0092 and placebo willbe estimated and the corresponding 95% CI and p-value will be calculated.Superiority of NNC0195-0092 over placebo will be considered confirmed if the upper boundary of
the two-sided 95% CI of the treatment difference (NNC0195-0092 placebo) is below 0. Sensitivity analysis will also be completed. Two partial database locks are planned during the trial.
Phase
Phase 3 - a treatment has shown activity against a particular disease, where it is either added to existing treatment or compared to the standard treatment.Inclusion and Exclusion Criteria
- Male or female of at least 23 years of age and not more than 79 years of age at the time of signing informed consent
- Human growth hormone (hGH) treatment naïve or no exposure to hGH or growth hormone (GH) secretagogues for at least 180 days prior to randomisation with any registered or investigational hGH or GH secretagogue product (if only used in connection with stimulation tests for diagnosis of growth hormone deficiency (GHD), subjects can be included)
- If applicable, hormone replacement therapies for any other hormone deficiencies, adequate and stable for at least 90 days prior to randomisation as judged by the investigator
- FOR ALL COUNTRIES EXCEPT JAPAN: Confirmed diagnosis of adult growth hormone deficiency (if a subject satisfies at least one of the following criteria):
- a. Insulin tolerance test (ITT) or glucagon test: a peak GH response of less than 3 ng/mL (3 mcg/L)
- b. Growth hormone releasing hormone (GHRH) + arginine test according to body mass index (BMI): i) BMI less than 25 kg/m^2, a peak GH less than 11 ng/mL (mcg/L), ii) BMI 25-30 kg/m^2, a peak GH less than 8 ng/mL (8 mcg/L), iii) BMI greater than 30 kg/m^2, a peak GH less than 4 ng/mL (4 mcg/L)
- c. Three or more pituitary hormone deficiencies at screening and insulin like growth factor
- I standard deviation score (IGF-I SDS) less than -2.0
- FOR JAPAN ONLY: Confirmed diagnosis of adult growth hormone deficiency (subjects with adult onset adult growth hormone deficiency (AGHD) need to satisfy at least one of the following criteria, subjects with a history of childhood GHD need to satisfy at least 2 of the following criteria):
- a. ITT test: a peak GH of less than or equal to 1.8 ng/mL (assay using recombinant GH standard)
- b. glucagon test: a peak GH of less than or equal to 1.8 ng/mL (assay using recombinant GH standard)
- c. growth hormone releasing peptide 2 (GHRP-2) tolerance test: a peak GH of less than or equal to 9 ng/mL (assay using recombinant GH standard)
- Active malignant disease or history of malignancy. Exceptions to this exclusion criterion:
- Resected in situ carcinoma of the cervix and squamous cell or basal cell carcinoma of the skin with complete local excision
- Subjects with GHD attributed to treatment of intracranial malignant tumours or leukaemia, provided that a recurrence-free survival period of at least 5 years is documented in the subject's file
Sites
Please contact Monica Chiu to learn more about where you can participate in this trial. Please use the contact form on the right side.
Powered by
SC CTSI