A Trial to Evaluate the Safety of Once Weekly Dosing of Somapacitan (NNC0195-0092) and Daily Norditropin® FlexPro® for 52 Weeks in Previously Human Growth Hormone Treated Japanese Adults With Growth Hormone Deficiency
Primary Purpose
Growth Hormone Disorder, Adult Growth Hormone Deficiency
Status
Completed
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
somapacitan
Norditropin
Sponsored by
About this trial
This is an interventional treatment trial for Growth Hormone Disorder
Eligibility Criteria
Inclusion Criteria: - Male or female of at least 18 years of age and not more than 79 years of age at the time of signing informed consent - GHD diagnosed for at least 6 months (defined as 180 days) prior to screening - Treatment with hGH for at least 6 consecutive months (defined as 180 days) at screening - 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 Exclusion Criteria: - Active malignant disease or history of malignancy. Exceptions to this exclusion criterion:1/ Resected in situ carcinoma of the cervix and squamous cell or basal cell carcinoma of the skin with complete local excision 2/ 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 medical records - For subjects with surgical removal or debulking of pituitary adenoma or other benign intracranial tumour within the last 5 years:Evidence of growth of pituitary adenoma or other benign intracranial tumour within the last 12 months (defined as below or equal to 365 days) before randomisation. Absence of growth must be documented by two post-surgery magnetic resonance imaging (MRI) scans or CT scans. The most recent MRI or CT scan must be performed below or equal to 9 months (defined as below or equal to 270 days) prior to randomisation
Sites / Locations
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Somapacitan
Norditropin
Arm Description
Outcomes
Primary Outcome Measures
Incidence of Adverse Events, Including Injection Site Reactions
An adverse event (AE) was any untoward medical occurrence in a participant administered a medicinal product, and which did not necessarily have a causal relationship with the treatment. Rate of AEs per 100 patient years at risk with onset after the first administration of trial product and up until end of the trial (53 weeks) or 14 days after last trial drug administration, whichever came first, are presented.
Secondary Outcome Measures
Change in Cross-sectional Total Adipose Tissue Compartments
Cross-sectional total adipose tissue compartments (TAT) were determined by quantitative computed tomography (CT) scans. Change from baseline (week 0) to end of treatment period (52 weeks) in cross-sectional TAT compartments is presented.
Change in Subcutaneous Adipose Tissue Compartments
Subcutaneous adipose tissue compartments (SAT) was determined by quantitative CT scans. Change from baseline (week 0) to end of treatment period (52 weeks) in SAT compartments is presented.
Change in Intra-abdominal or Visceral Adipose Tissue Compartments
Intra-abdominal or visceral adipose tissue (VAT) compartments was determined by quantitative CT scans. Change from baseline (week 0) to end of treatment period (52 weeks) in VAT compartments is presented.
Change in Treatment Satisfaction Questionnaire for Medication (TSQM-9) Scores
The Treatment Satisfaction Questionnaire for Medication - 9 items (TSQM-9) is a generic questionnaire that measures a patients' satisfaction with medication. Items are rated on a 5-point or 7-point scale according to patients' experience with the medication. The items covered are satisfaction with the effectiveness of the medication, convenience and global satisfaction of treatment. Each domain is based on 3 questions. The score is calculated in a range from 0 to 100, where a higher score reflects a better outcome. Scores have been summed and then scaled to 0-100. Change in TSQM-9 scores from baseline (week 0) to week 52 are presented.
Change in Physical Examination
Physical examination parameters were evaluated for head, ears, eyes, nose, throat, neck; respiratory system; cardiovascular system, gastrointestinal system, incl. mouth; musculoskeletal system; nervous system (central and peripheral); skin; and lymph node palpation. The investigator evaluated the findings from the physical examination and classifies them as normal, abnormal not clinically significant (NCS) and abnormal clinically significant (CS). Results are presented for week 0 and week 52.
Change in Body Weight
Change from baseline (week -3) in body weight at week 52 is presented.
Change in SBP and DBP
Change from baseline (week 0) in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at week 52 is presented.
Change in Pulse
Change from baseline (week 0) in pulse at week 52 is presented.
Change in ECG
The ECG was assessed by the investigator at baseline (week -3) and week 52 and categorised as normal, abnormal NCS or abnormal CS. Number of participants in each ECG category at week -3 and week 52 are presented.
Change in Haematology: Haemoglobin
Change from baseline (week -3) in haemoglobin at week 52 is presented.
Change in Haematology: Haematocrit
Change from baseline (week -3) in haematocrit at week 52 is presented.
Change in Haematology: Thrombocytes, Leucocytes
Change from baseline (week -3) in thrombocytes and leucocytes at week 52 is presented.
Change in Haematology: Erythrocytes
Change from baseline (week -3) in erythrocytes at week 52 is presented.
Change in Haematology: Mean Corpuscular Volume
Change from baseline (week -3) in mean corpuscular volume at week 52 is presented.
Change in Haematology: Mean Corpuscular Haemoglobin Concentration
Change from baseline (week -3) in mean corpuscular haemoglobin concentration at week 52 is presented.
Change in Biochemistry: Creatinine, Uric Acid, and Bilirubin (Total)
Change from baseline (week -3) in creatinine, uric acid, and bilirubin (total) at week 52 is presented.
Change in Biochemistry: Creatinine Kinase, ALT, AST, ALP and GGT
Change from baseline (week -3) in creatinine kinase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) at week 52 is presented.
Change in Biochemistry: Urea, Sodium, Potassium, Chloride, Phosphate (Inorganic), Calcium (Total)
Change from baseline (week -3) in urea, sodium, potassium, chloride, phosphate (inorganic), calcium (total) (mmol/L) at week 52 is presented.
Change in Biochemistry: Total Protein and Albumin
Change from baseline (week -3) in total protein and albumin at week 52 is presented.
Change in Biochemistry: eGFR Creatinine
Estimated glomerular filtration rate (eGFR) creatinine (measured in milliliters per minute per 1.73 square meters [mL/min/1.73m^2]) was evaluated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. Change from baseline (week -3) in eGFR at week 52 is presented.
Change in HbA1c
Change from baseline (week -3) in glycosylated haemoglobin (HbA1c) at week 52 is presented.
Change in FPG
Change from baseline (week -3) in fasting plasma glucose (FPG) (mmol/L) at week 52 is presented.
Change in Fasting Insulin
Change from baseline (week -3) in fasting insulin at week 52 is presented.
Change in Steady State Beta Cell Function
Change from baseline (week -3) in steady state beta cell function (%B) at week 52 is presented.
Change in Insulin Resistance
Change from baseline (week -3) in insulin resistance (IR) (Homeostatic model assessment (HOMA) estimates) at week 52 is presented.
Occurrence of Anti-somapacitan Antibodies
Number of participants with anti-somapacitan antibodies at baseline (week 0) and week 53 are presented. This outcome measure is applicable only for the treatment arm "Somapacitan".
Occurrence of Anti-hGH Antibodies
Number of participants with anti-human growth hormone (hGH) antibodies at baseline (week 0) and week 53 are presented.
Incidence of Clinical Technical Complaints
A technical complaint was any written, electronic, or oral communication that alleged product (medicine or device) defects. Number of partipants who reported technical complaints during the course of the trial are presented.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03075644
Brief Title
A Trial to Evaluate the Safety of Once Weekly Dosing of Somapacitan (NNC0195-0092) and Daily Norditropin® FlexPro® for 52 Weeks in Previously Human Growth Hormone Treated Japanese Adults With Growth Hormone Deficiency
Official Title
A Multicentre, Randomised, Open-labelled, Parallel-group, Activecontrolled Trial to Evaluate the Safety of Once Weekly Dosing of Somapacitan (NNC0195-0092) and Daily Norditropin® FlexPro® for 52 Weeks in Previously Human Growth Hormone Treated Japanese Adults With Growth Hormone Deficiency
Study Type
Interventional
2. Study Status
Record Verification Date
November 2020
Overall Recruitment Status
Completed
Study Start Date
March 3, 2017 (Actual)
Primary Completion Date
October 4, 2018 (Actual)
Study Completion Date
October 4, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novo Nordisk A/S
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This trial is conducted in Asia. The aim of this trial is to evaluate the safety of once weekly dosing of somapacitan (NNC0195-0092) and daily Norditropin® FlexPro® for 52 weeks in previously human growth hormone treated Japanese adults with growth hormone deficiency.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Growth Hormone Disorder, Adult Growth Hormone Deficiency
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
62 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Somapacitan
Arm Type
Experimental
Arm Title
Norditropin
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
somapacitan
Intervention Description
Once weekly subcutaneous injections (s.c., under the skin)
Intervention Type
Drug
Intervention Name(s)
Norditropin
Intervention Description
Daily subcutaneous injections (s.c., under the skin)
Primary Outcome Measure Information:
Title
Incidence of Adverse Events, Including Injection Site Reactions
Description
An adverse event (AE) was any untoward medical occurrence in a participant administered a medicinal product, and which did not necessarily have a causal relationship with the treatment. Rate of AEs per 100 patient years at risk with onset after the first administration of trial product and up until end of the trial (53 weeks) or 14 days after last trial drug administration, whichever came first, are presented.
Time Frame
Weeks 0-53
Secondary Outcome Measure Information:
Title
Change in Cross-sectional Total Adipose Tissue Compartments
Description
Cross-sectional total adipose tissue compartments (TAT) were determined by quantitative computed tomography (CT) scans. Change from baseline (week 0) to end of treatment period (52 weeks) in cross-sectional TAT compartments is presented.
Time Frame
Week 0, week 52
Title
Change in Subcutaneous Adipose Tissue Compartments
Description
Subcutaneous adipose tissue compartments (SAT) was determined by quantitative CT scans. Change from baseline (week 0) to end of treatment period (52 weeks) in SAT compartments is presented.
Time Frame
Week 0, week 52
Title
Change in Intra-abdominal or Visceral Adipose Tissue Compartments
Description
Intra-abdominal or visceral adipose tissue (VAT) compartments was determined by quantitative CT scans. Change from baseline (week 0) to end of treatment period (52 weeks) in VAT compartments is presented.
Time Frame
Week 0, week 52
Title
Change in Treatment Satisfaction Questionnaire for Medication (TSQM-9) Scores
Description
The Treatment Satisfaction Questionnaire for Medication - 9 items (TSQM-9) is a generic questionnaire that measures a patients' satisfaction with medication. Items are rated on a 5-point or 7-point scale according to patients' experience with the medication. The items covered are satisfaction with the effectiveness of the medication, convenience and global satisfaction of treatment. Each domain is based on 3 questions. The score is calculated in a range from 0 to 100, where a higher score reflects a better outcome. Scores have been summed and then scaled to 0-100. Change in TSQM-9 scores from baseline (week 0) to week 52 are presented.
Time Frame
Week 0, week 52
Title
Change in Physical Examination
Description
Physical examination parameters were evaluated for head, ears, eyes, nose, throat, neck; respiratory system; cardiovascular system, gastrointestinal system, incl. mouth; musculoskeletal system; nervous system (central and peripheral); skin; and lymph node palpation. The investigator evaluated the findings from the physical examination and classifies them as normal, abnormal not clinically significant (NCS) and abnormal clinically significant (CS). Results are presented for week 0 and week 52.
Time Frame
Week 0, week 52
Title
Change in Body Weight
Description
Change from baseline (week -3) in body weight at week 52 is presented.
Time Frame
Week -3, week 52
Title
Change in SBP and DBP
Description
Change from baseline (week 0) in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at week 52 is presented.
Time Frame
Week 0, week 52
Title
Change in Pulse
Description
Change from baseline (week 0) in pulse at week 52 is presented.
Time Frame
Week 0, week 52
Title
Change in ECG
Description
The ECG was assessed by the investigator at baseline (week -3) and week 52 and categorised as normal, abnormal NCS or abnormal CS. Number of participants in each ECG category at week -3 and week 52 are presented.
Time Frame
Week -3, week 52
Title
Change in Haematology: Haemoglobin
Description
Change from baseline (week -3) in haemoglobin at week 52 is presented.
Time Frame
Week -3, week 52
Title
Change in Haematology: Haematocrit
Description
Change from baseline (week -3) in haematocrit at week 52 is presented.
Time Frame
Week -3, week 52
Title
Change in Haematology: Thrombocytes, Leucocytes
Description
Change from baseline (week -3) in thrombocytes and leucocytes at week 52 is presented.
Time Frame
Week -3, week 52
Title
Change in Haematology: Erythrocytes
Description
Change from baseline (week -3) in erythrocytes at week 52 is presented.
Time Frame
Week -3, week 52
Title
Change in Haematology: Mean Corpuscular Volume
Description
Change from baseline (week -3) in mean corpuscular volume at week 52 is presented.
Time Frame
Week -3, week 52
Title
Change in Haematology: Mean Corpuscular Haemoglobin Concentration
Description
Change from baseline (week -3) in mean corpuscular haemoglobin concentration at week 52 is presented.
Time Frame
Week -3, week 52
Title
Change in Biochemistry: Creatinine, Uric Acid, and Bilirubin (Total)
Description
Change from baseline (week -3) in creatinine, uric acid, and bilirubin (total) at week 52 is presented.
Time Frame
Week -3, week 52
Title
Change in Biochemistry: Creatinine Kinase, ALT, AST, ALP and GGT
Description
Change from baseline (week -3) in creatinine kinase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) at week 52 is presented.
Time Frame
Week -3, week 52
Title
Change in Biochemistry: Urea, Sodium, Potassium, Chloride, Phosphate (Inorganic), Calcium (Total)
Description
Change from baseline (week -3) in urea, sodium, potassium, chloride, phosphate (inorganic), calcium (total) (mmol/L) at week 52 is presented.
Time Frame
Week -3, week 52
Title
Change in Biochemistry: Total Protein and Albumin
Description
Change from baseline (week -3) in total protein and albumin at week 52 is presented.
Time Frame
Week -3, week 52
Title
Change in Biochemistry: eGFR Creatinine
Description
Estimated glomerular filtration rate (eGFR) creatinine (measured in milliliters per minute per 1.73 square meters [mL/min/1.73m^2]) was evaluated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. Change from baseline (week -3) in eGFR at week 52 is presented.
Time Frame
Week -3, week 52
Title
Change in HbA1c
Description
Change from baseline (week -3) in glycosylated haemoglobin (HbA1c) at week 52 is presented.
Time Frame
Week -3, week 52
Title
Change in FPG
Description
Change from baseline (week -3) in fasting plasma glucose (FPG) (mmol/L) at week 52 is presented.
Time Frame
Week -3, week 52
Title
Change in Fasting Insulin
Description
Change from baseline (week -3) in fasting insulin at week 52 is presented.
Time Frame
Week -3, week 52
Title
Change in Steady State Beta Cell Function
Description
Change from baseline (week -3) in steady state beta cell function (%B) at week 52 is presented.
Time Frame
Week -3, week 52
Title
Change in Insulin Resistance
Description
Change from baseline (week -3) in insulin resistance (IR) (Homeostatic model assessment (HOMA) estimates) at week 52 is presented.
Time Frame
Week -3, week 52
Title
Occurrence of Anti-somapacitan Antibodies
Description
Number of participants with anti-somapacitan antibodies at baseline (week 0) and week 53 are presented. This outcome measure is applicable only for the treatment arm "Somapacitan".
Time Frame
Weeks 0 - 53
Title
Occurrence of Anti-hGH Antibodies
Description
Number of participants with anti-human growth hormone (hGH) antibodies at baseline (week 0) and week 53 are presented.
Time Frame
Weeks 0 - 53
Title
Incidence of Clinical Technical Complaints
Description
A technical complaint was any written, electronic, or oral communication that alleged product (medicine or device) defects. Number of partipants who reported technical complaints during the course of the trial are presented.
Time Frame
Weeks 0 - 53
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: - Male or female of at least 18 years of age and not more than 79 years of age at the time of signing informed consent - GHD diagnosed for at least 6 months (defined as 180 days) prior to screening - Treatment with hGH for at least 6 consecutive months (defined as 180 days) at screening - 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 Exclusion Criteria: - Active malignant disease or history of malignancy. Exceptions to this exclusion criterion:1/ Resected in situ carcinoma of the cervix and squamous cell or basal cell carcinoma of the skin with complete local excision 2/ 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 medical records - For subjects with surgical removal or debulking of pituitary adenoma or other benign intracranial tumour within the last 5 years:Evidence of growth of pituitary adenoma or other benign intracranial tumour within the last 12 months (defined as below or equal to 365 days) before randomisation. Absence of growth must be documented by two post-surgery magnetic resonance imaging (MRI) scans or CT scans. The most recent MRI or CT scan must be performed below or equal to 9 months (defined as below or equal to 270 days) prior to randomisation
Facility Information:
Facility Name
Novo Nordisk Investigational Site
City
Bunkyo-ku, Tokyo
ZIP/Postal Code
113-8603
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Chiba-shi, Chiba
ZIP/Postal Code
260-8677
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Fukuoka
ZIP/Postal Code
818 8502
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Kagoshima
ZIP/Postal Code
890-8520
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Kobe, Hyogo
ZIP/Postal Code
650-0017
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Kyoto-shi Kyoto
ZIP/Postal Code
612-8555
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Okayama, Okayama
ZIP/Postal Code
700-8558
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Osaka
ZIP/Postal Code
565-0871
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Sagamihara-shi, Kanagawa
ZIP/Postal Code
252-0375
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Tokyo
ZIP/Postal Code
134-0088
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Yamagata-shi, Yamagata
ZIP/Postal Code
990-9585
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Yokohama, Kanagawa
ZIP/Postal Code
222-0036
Country
Japan
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
Citations:
PubMed Identifier
32603494
Citation
Otsuka F, Takahashi Y, Tahara S, Ogawa Y, Hojby Rasmussen M, Takano K. Similar safety and efficacy in previously treated adults with growth hormone deficiency randomized to once-weekly somapacitan or daily growth hormone. Clin Endocrinol (Oxf). 2020 Nov;93(5):620-628. doi: 10.1111/cen.14273. Epub 2020 Aug 14.
Results Reference
result
PubMed Identifier
36380045
Citation
Takahashi Y, Biller BMK, Fukuoka H, Ho KKY, Rasmussen MH, Nedjatian N, Svaerke C, Yuen KCJ, Johannsson G. Weekly somapacitan had no adverse effects on glucose metabolism in adults with growth hormone deficiency. Pituitary. 2023 Feb;26(1):57-72. doi: 10.1007/s11102-022-01283-3. Epub 2022 Nov 15.
Results Reference
derived
Learn more about this trial
A Trial to Evaluate the Safety of Once Weekly Dosing of Somapacitan (NNC0195-0092) and Daily Norditropin® FlexPro® for 52 Weeks in Previously Human Growth Hormone Treated Japanese Adults With Growth Hormone Deficiency
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