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A Trial to Compare the Safety of Once Weekly Dosing of Somapacitan With Daily Norditropin® FlexPro® for 26 Weeks in Previously Human Growth Hormone Treated Adults With Growth Hormone Deficiency (REAL 2)

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ClinicalTrials.gov Identifier: NCT02382939
Recruitment Status : Completed
First Posted : March 9, 2015
Results First Posted : June 16, 2020
Last Update Posted : July 9, 2020
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Adult Growth Hormone Deficiency
Growth Hormone Disorder
Interventions Drug: somapacitan
Drug: somatropin
Enrollment 92
Recruitment Details The trial was conducted at 26 sites in 6 countries. All 26 sites screened and randomised/ assigned patients to treatment. Denmark: 3 sites; France: 5 sites; Germany: 3 sites; Sweden: 3 sites; United Kingdom: 5 sites; Japan: 7 sites.
Pre-assignment Details Participants, who were diagnosed with adults with growth hormone deficiency ≥ 6 months (defined as 180 days) prior to screening and receiving treatment with human growth hormone at least 6 months (defined as 180 days) at screening, were enrolled.
Arm/Group Title Norditropin Somapacitan
Hide Arm/Group Description

Participants received subcutaneous (s.c.) injections of Norditropin daily for 26 weeks (8 weeks dose titration followed by 18 weeks fixed dose treatment) followed by 1 week washout. The starting dose of Norditropin was 0.2 mg/day (except females on oral oestrogen: 0.3 mg/day; participants older than 60 years: 0.1 mg/day). An individualised dose titration regimen was used. Adjustment of dose was performed at weeks 2, 4, 6 and 8 based on insulin-like growth factor-I standard deviation score (IGF-I SDS) values:

IGF-I SDS > 3: dose reduction by 0.1 mg/day 2 < IGF-I SDS ≤ 3: dose reduction by 0.05 mg/day 0 < IGF-I SDS ≤ 2: No need of dose adjustment

  • 2 < IGF-I SDS ≤ 0: Dose increment by 0.1 mg/day IGF-I SDS ≤ -2: Dose increment by 0.2 mg/day After the last dose adjustment (if any) at week 8, the individual dose level was fixed. The minimum and maximum daily dose was set to 0.05 mg and 1.1 mg (Japan: maximum daily dose was 1.0 mg).

Participants received s.c. injections of somapacitan once-weekly for 26 weeks (8 weeks dose titration followed by 18 weeks fixed dose treatment) followed by 1 week washout. The starting dose of somapacitan was 1.5 mg/week (except females on oral oestrogen 2.0 mg/week; participants older than 60 years 1.0 mg/week). An individualised dose titration regimen was used. Adjustment of dose was performed at weeks 2, 4, 6 and 8 based on IGF-I SDS values:

IGF-I SDS > 3: dose reduction by 1 mg 2 < IGF-I SDS ≤ 3: dose reduction by 0.5 mg 0 < IGF-I SDS ≤ 2: No need for dose adjustment

  • 2 < IGF-I SDS ≤ 0: Dose Increment by 0.7 mg IGF-I SDS ≤ -2: Dose Increment by 1.5 mg After the last dose adjustment (if any) at week 8, the individual dose level was fixed. The minimum and maximum weekly dose was set to 0.1 mg and 8 mg.
Period Title: Overall Study
Started 31 61
Exposed 31 61
Completed 28 58
Not Completed 3 3
Reason Not Completed
Adverse Event             1             1
Withdrawal by Subject             2             2
Arm/Group Title Norditropin Somapacitan Total
Hide Arm/Group Description

Participants received s.c. injections of Norditropin daily for 26 weeks (8 weeks dose titration followed by 18 weeks fixed dose treatment) followed by 1 week washout. The starting dose of Norditropin was 0.2 mg/day (except females on oral oestrogen: 0.3 mg/day; participants older than 60 years: 0.1 mg/day). An individualised dose titration regimen was used. Adjustment of dose was performed at weeks 2, 4, 6 and 8 based on IGF-I SDS values:

IGF-I SDS > 3: dose reduction by 0.1 mg/day 2 < IGF-I SDS ≤ 3: dose reduction by 0.05 mg/day 0 < IGF-I SDS ≤ 2: No need of dose adjustment

  • 2 < IGF-I SDS ≤ 0: Dose increment by 0.1 mg/day IGF-I SDS ≤ -2: Dose increment by 0.2 mg/day After the last dose adjustment (if any) at week 8, the individual dose level was fixed. The minimum and maximum daily dose was set to 0.05 mg and 1.1 mg (Japan: maximum daily dose was 1.0 mg).

Participants received s.c. injections of somapacitan once-weekly for 26 weeks (8 weeks dose titration followed by 18 weeks fixed dose treatment) followed by 1 week washout. The starting dose of somapacitan was 1.5 mg/week (except females on oral oestrogen 2.0 mg/week; participants older than 60 years 1.0 mg/week). An individualised dose titration regimen was used. Adjustment of dose was performed at weeks 2, 4, 6 and 8 based on IGF-I SDS values:

IGF-I SDS > 3: dose reduction by 1 mg 2 < IGF-I SDS ≤ 3: dose reduction by 0.5 mg 0 < IGF-I SDS ≤ 2: No need for dose adjustment

  • 2 < IGF-I SDS ≤ 0: Dose Increment by 0.7 mg IGF-I SDS ≤ -2: Dose Increment by 1.5 mg After the last dose adjustment (if any) at week 8, the individual dose level was fixed. The minimum and maximum weekly dose was set to 0.1 mg and 8 mg.
Total of all reporting groups
Overall Number of Baseline Participants 31 61 92
Hide Baseline Analysis Population Description
Full analysis set (FAS): all randomised participants that received at least one dose of randomised treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 31 participants 61 participants 92 participants
51.7  (17.1) 48.1  (16.2) 49.3  (16.5)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 31 participants 61 participants 92 participants
18-64 years
23
  74.2%
50
  82.0%
73
  79.3%
≥65 years
8
  25.8%
11
  18.0%
19
  20.7%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 31 participants 61 participants 92 participants
Female
14
  45.2%
28
  45.9%
42
  45.7%
Male
17
  54.8%
33
  54.1%
50
  54.3%
1.Primary Outcome
Title Incidence of Adverse Events
Hide Description An adverse event can be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. Presented results are event rate per 100 patient years of exposure.
Time Frame Weeks 0 - 26
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set: all randomised participants that received at least one dose of randomised treatment.
Arm/Group Title Norditropin Somapacitan
Hide Arm/Group Description:

Participants received s.c. injections of Norditropin daily for 26 weeks (8 weeks dose titration followed by 18 weeks fixed dose treatment) followed by 1 week washout. The starting dose of Norditropin was 0.2 mg/day (except females on oral oestrogen: 0.3 mg/day; participants older than 60 years: 0.1 mg/day). An individualised dose titration regimen was used. Adjustment of dose was performed at weeks 2, 4, 6 and 8 based on IGF-I SDS values:

IGF-I SDS > 3: dose reduction by 0.1 mg/day 2 < IGF-I SDS ≤ 3: dose reduction by 0.05 mg/day 0 < IGF-I SDS ≤ 2: No need of dose adjustment

  • 2 < IGF-I SDS ≤ 0: Dose increment by 0.1 mg/day IGF-I SDS ≤ -2: Dose increment by 0.2 mg/day After the last dose adjustment (if any) at week 8, the individual dose level was fixed. The minimum and maximum daily dose was set to 0.05 mg and 1.1 mg (Japan: maximum daily dose was 1.0 mg).

Participants received s.c. injections of somapacitan once-weekly for 26 weeks (8 weeks dose titration followed by 18 weeks fixed dose treatment) followed by 1 week washout. The starting dose of somapacitan was 1.5 mg/week (except females on oral oestrogen 2.0 mg/week; participants older than 60 years 1.0 mg/week). An individualised dose titration regimen was used. Adjustment of dose was performed at weeks 2, 4, 6 and 8 based on IGF-I SDS values:

IGF-I SDS > 3: dose reduction by 1 mg 2 < IGF-I SDS ≤ 3: dose reduction by 0.5 mg 0 < IGF-I SDS ≤ 2: No need for dose adjustment

  • 2 < IGF-I SDS ≤ 0: Dose Increment by 0.7 mg IGF-I SDS ≤ -2: Dose Increment by 1.5 mg After the last dose adjustment (if any) at week 8, the individual dose level was fixed. The minimum and maximum weekly dose was set to 0.1 mg and 8 mg.
Overall Number of Participants Analyzed 31 61
Measure Type: Number
Unit of Measure: Events per 100 patient years
530.8 514.2
2.Primary Outcome
Title Incidence of Injection Site Reactions
Hide Description Presented results are event (injection site reaction) rate per 100 patient years of exposure.
Time Frame Weeks 0- 26
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set: all randomised participants that received at least one dose of randomised treatment.
Arm/Group Title Norditropin Somapacitan
Hide Arm/Group Description:

Participants received s.c. injections of Norditropin daily for 26 weeks (8 weeks dose titration followed by 18 weeks fixed dose treatment) followed by 1 week washout. The starting dose of Norditropin was 0.2 mg/day (except females on oral oestrogen: 0.3 mg/day; participants older than 60 years: 0.1 mg/day). An individualised dose titration regimen was used. Adjustment of dose was performed at weeks 2, 4, 6 and 8 based on IGF-I SDS values:

IGF-I SDS > 3: dose reduction by 0.1 mg/day 2 < IGF-I SDS ≤ 3: dose reduction by 0.05 mg/day 0 < IGF-I SDS ≤ 2: No need of dose adjustment

  • 2 < IGF-I SDS ≤ 0: Dose increment by 0.1 mg/day IGF-I SDS ≤ -2: Dose increment by 0.2 mg/day After the last dose adjustment (if any) at week 8, the individual dose level was fixed. The minimum and maximum daily dose was set to 0.05 mg and 1.1 mg (Japan: maximum daily dose was 1.0 mg).

Participants received s.c. injections of somapacitan once-weekly for 26 weeks (8 weeks dose titration followed by 18 weeks fixed dose treatment) followed by 1 week washout. The starting dose of somapacitan was 1.5 mg/week (except females on oral oestrogen 2.0 mg/week; participants older than 60 years 1.0 mg/week). An individualised dose titration regimen was used. Adjustment of dose was performed at weeks 2, 4, 6 and 8 based on IGF-I SDS values:

IGF-I SDS > 3: dose reduction by 1 mg 2 < IGF-I SDS ≤ 3: dose reduction by 0.5 mg 0 < IGF-I SDS ≤ 2: No need for dose adjustment

  • 2 < IGF-I SDS ≤ 0: Dose Increment by 0.7 mg IGF-I SDS ≤ -2: Dose Increment by 1.5 mg After the last dose adjustment (if any) at week 8, the individual dose level was fixed. The minimum and maximum weekly dose was set to 0.1 mg and 8 mg.
Overall Number of Participants Analyzed 31 61
Measure Type: Number
Unit of Measure: Events per 100 patient years
0 6.5
3.Secondary Outcome
Title Occurrence of Anti-NNC0195-0092 Antibodies
Hide Description Number of participants with anti-somapacitan (NNC0195-0092) antibodies are presented.
Time Frame At week 0 (baseline), and at week 2, 4, 8, 16, 25 and 27
Hide Outcome Measure Data
Hide Analysis Population Description
Overall Number of Participants Analyzed = safety analysis set which included all randomised participants that received at least one dose of randomised treatment. Number Analyzed = number of participants with available data. This outcome measure is applicable only for the somapacitan treatment arm.
Arm/Group Title Somapacitan
Hide Arm/Group Description:

Participants received s.c. injections of somapacitan once-weekly for 26 weeks (8 weeks dose titration followed by 18 weeks fixed dose treatment) followed by 1 week washout. The starting dose of somapacitan was 1.5 mg/week (except females on oral oestrogen 2.0 mg/week; participants older than 60 years 1.0 mg/week). An individualised dose titration regimen was used. Adjustment of dose was performed at weeks 2, 4, 6 and 8 based on IGF-I SDS values:

IGF-I SDS > 3: dose reduction by 1 mg 2 < IGF-I SDS ≤ 3: dose reduction by 0.5 mg 0 < IGF-I SDS ≤ 2: No need for dose adjustment

  • 2 < IGF-I SDS ≤ 0: Dose Increment by 0.7 mg IGF-I SDS ≤ -2: Dose Increment by 1.5 mg After the last dose adjustment (if any) at week 8, the individual dose level was fixed. The minimum and maximum weekly dose was set to 0.1 mg and 8 mg.
Overall Number of Participants Analyzed 61
Measure Type: Count of Participants
Unit of Measure: Participants
Week 0: Number Analyzed 60 participants
0
   0.0%
Week 2: Number Analyzed 60 participants
0
   0.0%
Week 4: Number Analyzed 60 participants
0
   0.0%
Week 8: Number Analyzed 58 participants
0
   0.0%
Week 16: Number Analyzed 57 participants
0
   0.0%
Week 25: Number Analyzed 60 participants
0
   0.0%
Week 27: Number Analyzed 60 participants
0
   0.0%
4.Secondary Outcome
Title Change in Treatment Satisfaction Questionnaire for Medication (TSQM) Scores (Effectiveness,Convenience, and Global Satisfaction Scores)
Hide Description The Treatment Satisfaction Questionnaire for Medication (TSQM-9) is a psychometric measure of a patient's satisfaction with medication. It consists of 3 subscales: effectiveness, convenience and global satisfaction. Items are rated on a 5 or 7-point scale according to participants' experience with the medication. Each domain score can vary from 0 to 100 with higher scores indicating higher effectiveness of treatment, more convenient use of medication and overall greater satisfaction with the treatment.
Time Frame Baseline (week 0), week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Overall Number of Participants Analyzed = full analysis set which included all randomised participants that received at least one dose of randomised treatment. Number Analyzed = number of participants with available data.
Arm/Group Title Norditropin Somapacitan
Hide Arm/Group Description:

Participants received s.c. injections of Norditropin daily for 26 weeks (8 weeks dose titration followed by 18 weeks fixed dose treatment) followed by 1 week washout. The starting dose of Norditropin was 0.2 mg/day (except females on oral oestrogen: 0.3 mg/day; participants older than 60 years: 0.1 mg/day). An individualised dose titration regimen was used. Adjustment of dose was performed at weeks 2, 4, 6 and 8 based on IGF-I SDS values:

IGF-I SDS > 3: dose reduction by 0.1 mg/day 2 < IGF-I SDS ≤ 3: dose reduction by 0.05 mg/day 0 < IGF-I SDS ≤ 2: No need of dose adjustment

  • 2 < IGF-I SDS ≤ 0: Dose increment by 0.1 mg/day IGF-I SDS ≤ -2: Dose increment by 0.2 mg/day After the last dose adjustment (if any) at week 8, the individual dose level was fixed. The minimum and maximum daily dose was set to 0.05 mg and 1.1 mg (Japan: maximum daily dose was 1.0 mg).

Participants received s.c. injections of somapacitan once-weekly for 26 weeks (8 weeks dose titration followed by 18 weeks fixed dose treatment) followed by 1 week washout. The starting dose of somapacitan was 1.5 mg/week (except females on oral oestrogen 2.0 mg/week; participants older than 60 years 1.0 mg/week). An individualised dose titration regimen was used. Adjustment of dose was performed at weeks 2, 4, 6 and 8 based on IGF-I SDS values:

IGF-I SDS > 3: dose reduction by 1 mg 2 < IGF-I SDS ≤ 3: dose reduction by 0.5 mg 0 < IGF-I SDS ≤ 2: No need for dose adjustment

  • 2 < IGF-I SDS ≤ 0: Dose Increment by 0.7 mg IGF-I SDS ≤ -2: Dose Increment by 1.5 mg After the last dose adjustment (if any) at week 8, the individual dose level was fixed. The minimum and maximum weekly dose was set to 0.1 mg and 8 mg.
Overall Number of Participants Analyzed 31 61
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Effectiveness Number Analyzed 28 participants 53 participants
3.8  (27.4) 9.7  (18.1)
Convenience Number Analyzed 28 participants 55 participants
3.0  (16.5) 15.3  (20.9)
Global satisfaction Number Analyzed 28 participants 54 participants
-1.2  (15.2) 5.4  (21.0)
Time Frame Baseline (week 0) to week 26.
Adverse Event Reporting Description Participants in the safety analysis set contributed to the evaluation of adverse events.
 
Arm/Group Title Norditropin Somapacitan
Hide Arm/Group Description

Participants received s.c. injections of Norditropin daily for 26 weeks (8 weeks dose titration followed by 18 weeks fixed dose treatment) followed by 1 week washout. The starting dose of Norditropin was 0.2 mg/day (except females on oral oestrogen: 0.3 mg/day; participants older than 60 years: 0.1 mg/day). An individualised dose titration regimen was used. Adjustment of dose was performed at weeks 2, 4, 6 and 8 based on IGF-I SDS values:

IGF-I SDS > 3: dose reduction by 0.1 mg/day 2 < IGF-I SDS ≤ 3: dose reduction by 0.05 mg/day 0 < IGF-I SDS ≤ 2: No need of dose adjustment

  • 2 < IGF-I SDS ≤ 0: Dose increment by 0.1 mg/day IGF-I SDS ≤ -2: Dose increment by 0.2 mg/day After the last dose adjustment (if any) at week 8, the individual dose level was fixed.

Participants received s.c. injections of somapacitan once-weekly for 26 weeks (8 weeks dose titration followed by 18 weeks fixed dose treatment) followed by 1 week washout. The starting dose of somapacitan was 1.5 mg/week (except females on oral oestrogen 2.0 mg/week; participants older than 60 years 1.0 mg/week). An individualised dose titration regimen was used. Adjustment of dose was performed at weeks 2, 4, 6 and 8 based on IGF-I SDS values:

IGF-I SDS > 3: dose reduction by 1 mg 2 < IGF-I SDS ≤ 3: dose reduction by 0.5 mg 0 < IGF-I SDS ≤ 2: No need for dose adjustment

  • 2 < IGF-I SDS ≤ 0: Dose Increment by 0.7 mg IGF-I SDS ≤ -2: Dose Increment by 1.5 mg After the last dose adjustment (if any) at week 8, the individual dose level was fixed. The minimum and maximum weekly dose was set to 0.1 mg and 8 mg.
All-Cause Mortality
Norditropin Somapacitan
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Norditropin Somapacitan
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/31 (6.45%)      4/61 (6.56%)    
Gastrointestinal disorders     
Intestinal ischaemia  1  1/31 (3.23%)  1 0/61 (0.00%)  0
Short-bowel syndrome  1  1/31 (3.23%)  1 0/61 (0.00%)  0
Hepatobiliary disorders     
Cholelithiasis  1  0/31 (0.00%)  0 1/61 (1.64%)  1
Injury, poisoning and procedural complications     
Patella fracture  1  0/31 (0.00%)  0 1/61 (1.64%)  1
Procedural complication  1  0/31 (0.00%)  0 1/61 (1.64%)  1
Renal and urinary disorders     
Nephrolithiasis  1  1/31 (3.23%)  1 0/61 (0.00%)  0
Surgical and medical procedures     
Mammoplasty  1  0/31 (0.00%)  0 1/61 (1.64%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Norditropin Somapacitan
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   18/31 (58.06%)      30/61 (49.18%)    
Endocrine disorders     
Hypothyroidism  1  2/31 (6.45%)  2 1/61 (1.64%)  1
Gastrointestinal disorders     
Abdominal pain  1  0/31 (0.00%)  0 4/61 (6.56%)  4
General disorders     
Asthenia  1  1/31 (3.23%)  1 4/61 (6.56%)  5
Fatigue  1  5/31 (16.13%)  5 6/61 (9.84%)  7
Infections and infestations     
Nasopharyngitis  1  8/31 (25.81%)  11 12/61 (19.67%)  13
Investigations     
Gamma-glutamyltransferase increased  1  2/31 (6.45%)  2 0/61 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Arthralgia  1  2/31 (6.45%)  2 5/61 (8.20%)  5
Nervous system disorders     
Dizziness  1  3/31 (9.68%)  3 1/61 (1.64%)  1
Headache  1  6/31 (19.35%)  10 7/61 (11.48%)  11
Sciatica  1  0/31 (0.00%)  0 4/61 (6.56%)  4
Psychiatric disorders     
Depression  1  2/31 (6.45%)  2 0/61 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
At the end of the trial, one or more manuscripts for publication will be prepared collaboratively between Investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for less than 60 days to protect intellectual property.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Global Clinical Registry (GCR, 1452)
Organization: Novo Nordisk A/S
EMail: clinicaltrials@novonordisk.com
Layout table for additonal information
Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT02382939    
Other Study ID Numbers: NN8640-4043
2014-000290-39 ( EudraCT Number )
U1111-1152-3664 ( Other Identifier: WHO )
JapicCTI-152850 ( Other Identifier: JAPIC )
First Submitted: February 10, 2015
First Posted: March 9, 2015
Results First Submitted: May 1, 2020
Results First Posted: June 16, 2020
Last Update Posted: July 9, 2020