Trial Outcomes & Findings for Optimization of the Dosage Regimen of Growth Hormone Therapy in Children Born Small for Gestational Age (NCT NCT00249821)

Results Overview

Height Velocity (HV) is the change in height since the previous year´s measurement and more precisely: HV = {(h-hp)/(d-dp)} \* 365.25 \[centimeter (cm)/year\] where h is current height in cm, hp is previous height in cm, closest to 1 year previous, d is the current date and dp is the date of measurement of previous height, closest to 1 year previous. Additionally, d and dp have to be within 0.6 years and 1.5 years. HV is the mean height velocity over the interval between d and dp but is displayed as HV at d.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

22 participants

Primary outcome timeframe

Month 12

Results posted on

2017-09-26

Participant Flow

Participant milestones

Participant milestones
Measure	Saizen® 0.057 mg/kg/Day Saizen® (recombinant human growth hormone, r-hGH) subcutaneously administered at the daily dose of 0.057 milligram/kilogram (mg/kg) or 0.40 mg/kg/week for duration of 12 months.	Saizen® 0.035 mg/kg/Day Saizen® (r-hGH) subcutaneously administered at the daily dose of 0.035 mg/kg or 0.24 mg/kg/week for duration of 12 months.
Overall Study STARTED	10	12
Overall Study COMPLETED	10	11
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Saizen® 0.057 mg/kg/Day Saizen® (recombinant human growth hormone, r-hGH) subcutaneously administered at the daily dose of 0.057 milligram/kilogram (mg/kg) or 0.40 mg/kg/week for duration of 12 months.	Saizen® 0.035 mg/kg/Day Saizen® (r-hGH) subcutaneously administered at the daily dose of 0.035 mg/kg or 0.24 mg/kg/week for duration of 12 months.
Overall Study Technical problem	0	1

Baseline Characteristics

Optimization of the Dosage Regimen of Growth Hormone Therapy in Children Born Small for Gestational Age

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Saizen® 0.057 mg/kg/Day n=10 Participants Saizen® (recombinant human growth hormone, r-hGH) subcutaneously administered at the daily dose of 0.057 milligram/kilogram (mg/kg) or 0.40 mg/kg/week for duration of 12 months.	Saizen® 0.035 mg/kg/Day n=12 Participants Saizen® (r-hGH) subcutaneously administered at the daily dose of 0.035 mg/kg or 0.24 mg/kg/week for duration of 12 months.	Total n=22 Participants Total of all reporting groups
Age, Continuous	8.00 years STANDARD_DEVIATION 1.49 • n=5 Participants	7.90 years STANDARD_DEVIATION 0.90 • n=7 Participants	8.00 years STANDARD_DEVIATION 1.17 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	8 Participants n=7 Participants	14 Participants n=5 Participants

PRIMARY outcome

Timeframe: Month 12

Population: Full Analysis (FA) set included all the participants who received at least 1 dose of study medication and had at least 1 height evaluation post randomization. Last observation carried forward (LOCF) was used to impute missing values.

Height Velocity (HV) is the change in height since the previous year´s measurement and more precisely: HV = {(h-hp)/(d-dp)} \* 365.25 \[centimeter (cm)/year\] where h is current height in cm, hp is previous height in cm, closest to 1 year previous, d is the current date and dp is the date of measurement of previous height, closest to 1 year previous. Additionally, d and dp have to be within 0.6 years and 1.5 years. HV is the mean height velocity over the interval between d and dp but is displayed as HV at d.

Outcome measures

Outcome measures
Measure	Saizen® 0.057 mg/kg/Day n=10 Participants Saizen® (recombinant human growth hormone, r-hGH) subcutaneously administered at the daily dose of 0.057 milligram/kilogram (mg/kg) or 0.40 mg/kg/week for duration of 12 months.	Saizen® 0.035 mg/kg/Day n=12 Participants Saizen® (r-hGH) subcutaneously administered at the daily dose of 0.035 mg/kg or 0.24 mg/kg/week for duration of 12 months.
Height Velocity	6.40 centimeter (cm)/year Standard Deviation 1.35	4.40 centimeter (cm)/year Standard Deviation 1.15

SECONDARY outcome

Timeframe: Baseline (randomization), Month 6 and Month 12

Population: FA set included all the participants who received at least 1 dose of study medication and had at least 1 height evaluation post randomization. LOCF was used to impute missing values.

Height-Standard Deviation Score (H-SDS) was calculated as height minus mean (age-and sex-matched reference) divided by standard deviation (SD) \[age and sex-matched reference\]. Greater H-SDS indicates greater height.

Outcome measures

Outcome measures
Measure	Saizen® 0.057 mg/kg/Day n=10 Participants Saizen® (recombinant human growth hormone, r-hGH) subcutaneously administered at the daily dose of 0.057 milligram/kilogram (mg/kg) or 0.40 mg/kg/week for duration of 12 months.	Saizen® 0.035 mg/kg/Day n=12 Participants Saizen® (r-hGH) subcutaneously administered at the daily dose of 0.035 mg/kg or 0.24 mg/kg/week for duration of 12 months.
Change From Baseline in Height-Standard Deviation Score (H-SDS) at Month 6 and Month 12 Baseline (randomization)	-1.30 standard deviation score Standard Deviation 0.42	-1.50 standard deviation score Standard Deviation 0.37
Change From Baseline in Height-Standard Deviation Score (H-SDS) at Month 6 and Month 12 Change at Month 6	0.30 standard deviation score Standard Deviation 0.22	0.10 standard deviation score Standard Deviation 0.10
Change From Baseline in Height-Standard Deviation Score (H-SDS) at Month 6 and Month 12 Change at Month 12	0.30 standard deviation score Standard Deviation 0.30	-0.10 standard deviation score Standard Deviation 0.24

SECONDARY outcome

Timeframe: Month 6 and Month 12

Population: FA set included all the participants who received at least 1 dose of study medication and had at least 1 height evaluation post randomization. Here "n" signifies number of participants analyzed at that particular time point for each arm group respectively. LOCF was used to impute missing values.

Height Velocity-Standard Deviation Score (HV-SDS) was calculated as height velocity minus reference mean height velocity divided by SD of the reference mean height velocity. Greater HV-SDS indicates greater height velocity.

Outcome measures

Outcome measures
Measure	Saizen® 0.057 mg/kg/Day n=10 Participants Saizen® (recombinant human growth hormone, r-hGH) subcutaneously administered at the daily dose of 0.057 milligram/kilogram (mg/kg) or 0.40 mg/kg/week for duration of 12 months.	Saizen® 0.035 mg/kg/Day n=12 Participants Saizen® (r-hGH) subcutaneously administered at the daily dose of 0.035 mg/kg or 0.24 mg/kg/week for duration of 12 months.
Height Velocity-Standard Deviation Score (HV-SDS) Month 6 (n= 10,11)	0.60 standard deviation score Standard Deviation 0.44	0.10 standard deviation score Standard Deviation 0.22
Height Velocity-Standard Deviation Score (HV-SDS) Month 12 (n=10,12)	0.30 standard deviation score Standard Deviation 0.29	-0.10 standard deviation score Standard Deviation 0.24

SECONDARY outcome

Timeframe: Baseline (randomization) and Month 6

Population: FA set included all the participants who received at least 1 dose of study medication and had at least 1 height evaluation post randomization. LOCF was used to impute missing values.

Outcome measures

Outcome measures
Measure	Saizen® 0.057 mg/kg/Day n=10 Participants Saizen® (recombinant human growth hormone, r-hGH) subcutaneously administered at the daily dose of 0.057 milligram/kilogram (mg/kg) or 0.40 mg/kg/week for duration of 12 months.	Saizen® 0.035 mg/kg/Day n=12 Participants Saizen® (r-hGH) subcutaneously administered at the daily dose of 0.035 mg/kg or 0.24 mg/kg/week for duration of 12 months.
Change From Baseline in Height at Month 6 Baseline (randomization)	121.10 cm Standard Deviation 7.99	119.20 cm Standard Deviation 5.29
Change From Baseline in Height at Month 6 Change at Month 6	3.60 cm Standard Deviation 1.31	2.50 cm Standard Deviation 0.99

SECONDARY outcome

Timeframe: Baseline (randomization) and Month 12

Population: FA set included all participants who received at least 1 dose of study medication and had at least 1 height evaluation post randomization. 'N' (Number of participants analyzed) signified those participants who were evaluable for this measure and "n" = number of participants analyzed at that particular time point for each arm group respectively.

Bone age was assessed by a left wrist X-Ray and evaluated by the investigator according to the Greulich and Pyle method.

Outcome measures

Outcome measures
Measure	Saizen® 0.057 mg/kg/Day n=9 Participants Saizen® (recombinant human growth hormone, r-hGH) subcutaneously administered at the daily dose of 0.057 milligram/kilogram (mg/kg) or 0.40 mg/kg/week for duration of 12 months.	Saizen® 0.035 mg/kg/Day n=10 Participants Saizen® (r-hGH) subcutaneously administered at the daily dose of 0.035 mg/kg or 0.24 mg/kg/week for duration of 12 months.
Change From Baseline in Bone Age at Month 12 Baseline (randomization) (n = 9,10)	7.50 years Standard Deviation 0.82	7.00 years Standard Deviation 1.85
Change From Baseline in Bone Age at Month 12 Change at Month 12 (n=9,7)	1.40 years Standard Deviation 0.79	1.40 years Standard Deviation 0.89

SECONDARY outcome

Timeframe: Baseline (randomization), Month 6 and Month 12

Population: FA set included all participants who received at least 1 dose of study medication and had at least 1 height evaluation post randomization. 'N' (Number of participants analyzed) signified those participants who were evaluable for this measure and "n" = number of participants analyzed at that particular time point for each arm group respectively.

Outcome measures

Outcome measures
Measure	Saizen® 0.057 mg/kg/Day n=10 Participants Saizen® (recombinant human growth hormone, r-hGH) subcutaneously administered at the daily dose of 0.057 milligram/kilogram (mg/kg) or 0.40 mg/kg/week for duration of 12 months.	Saizen® 0.035 mg/kg/Day n=11 Participants Saizen® (r-hGH) subcutaneously administered at the daily dose of 0.035 mg/kg or 0.24 mg/kg/week for duration of 12 months.
Insulin Like Growth Factor-1 (IGF-1) Levels Baseline (randomization) (n= 10,11)	319.60 microgram/liter (mcg/L) Standard Deviation 146.27	275.40 microgram/liter (mcg/L) Standard Deviation 98.82
Insulin Like Growth Factor-1 (IGF-1) Levels Month 6 (n= 9,7)	369.30 microgram/liter (mcg/L) Standard Deviation 120.13	262.40 microgram/liter (mcg/L) Standard Deviation 65.52
Insulin Like Growth Factor-1 (IGF-1) Levels Month 12 (n=10,10)	414.30 microgram/liter (mcg/L) Standard Deviation 176.70	263.00 microgram/liter (mcg/L) Standard Deviation 120.70

SECONDARY outcome

Timeframe: Baseline (randomization), Month 6 and Month 12

Population: FA set included all participants who received at least 1 dose of study medication and had at least 1 height evaluation post randomization. 'N' (Number of participants analyzed) signified those participants who were evaluable for this measure and "n" = number of participants analyzed at that particular time point for each arm group respectively.

Outcome measures

Outcome measures
Measure	Saizen® 0.057 mg/kg/Day n=10 Participants Saizen® (recombinant human growth hormone, r-hGH) subcutaneously administered at the daily dose of 0.057 milligram/kilogram (mg/kg) or 0.40 mg/kg/week for duration of 12 months.	Saizen® 0.035 mg/kg/Day n=10 Participants Saizen® (r-hGH) subcutaneously administered at the daily dose of 0.035 mg/kg or 0.24 mg/kg/week for duration of 12 months.
Insulin Like Growth Factor Binding Protein-3 (IGFBP-3) Levels Baseline (randomization) (n= 10,10)	3.40 milligram/L (mg/L) Standard Deviation 0.70	3.40 milligram/L (mg/L) Standard Deviation 0.60
Insulin Like Growth Factor Binding Protein-3 (IGFBP-3) Levels Month 6 (n= 9,7)	3.00 milligram/L (mg/L) Standard Deviation 0.84	3.30 milligram/L (mg/L) Standard Deviation 0.81
Insulin Like Growth Factor Binding Protein-3 (IGFBP-3) Levels Month 12 (n= 9,10)	3.60 milligram/L (mg/L) Standard Deviation 1.02	3.50 milligram/L (mg/L) Standard Deviation 0.77

SECONDARY outcome

Timeframe: Baseline (randomization) until Month 12

Population: The safety population included all the participants who received at least 1 dose of study medication.

Adverse Events (AEs): Any untoward medical occurrence in the form of signs, clinically significant abnormalities in laboratory findings, diseases, symptoms, or worsening of complications. TEAEs: AEs that occur during treatment with the Investigational Medicinal Product (IMP).

Outcome measures

Outcome measures
Measure	Saizen® 0.057 mg/kg/Day n=10 Participants Saizen® (recombinant human growth hormone, r-hGH) subcutaneously administered at the daily dose of 0.057 milligram/kilogram (mg/kg) or 0.40 mg/kg/week for duration of 12 months.	Saizen® 0.035 mg/kg/Day n=12 Participants Saizen® (r-hGH) subcutaneously administered at the daily dose of 0.035 mg/kg or 0.24 mg/kg/week for duration of 12 months.
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	2 participants	1 participants

Adverse Events

Saizen® 0.057 mg/kg/Day

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Saizen® 0.035 mg/kg/Day

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Saizen® 0.057 mg/kg/Day n=10 participants at risk Saizen® (recombinant human growth hormone, r-hGH) subcutaneously administered at the daily dose of 0.057 milligram/kilogram (mg/kg) or 0.40 mg/kg/week for duration of 12 months.	Saizen® 0.035 mg/kg/Day n=12 participants at risk Saizen® (r-hGH) subcutaneously administered at the daily dose of 0.035 mg/kg or 0.24 mg/kg/week for duration of 12 months.
Immune system disorders Asthma	0.00% 0/10 • Adverse Events (AEs) are collected on an ongoing basis from day of written informed consent. All new AEs must be recorded until 4 weeks post drug administration. AEs are classified as pre-treatment, treatment-emergent and post-treatment. Pre-Treatment:Medical conditions present at initial study visit that did not worsen in severity or frequency during study;Treatment-Emergent: If onset date of AE was on or after the first dose date of the study medication; Post-Treatment: If the onset date of AE was post 4 weeks after drug administration for participants who completed the study.	8.3% 1/12 • Number of events 1 • Adverse Events (AEs) are collected on an ongoing basis from day of written informed consent. All new AEs must be recorded until 4 weeks post drug administration. AEs are classified as pre-treatment, treatment-emergent and post-treatment. Pre-Treatment:Medical conditions present at initial study visit that did not worsen in severity or frequency during study;Treatment-Emergent: If onset date of AE was on or after the first dose date of the study medication; Post-Treatment: If the onset date of AE was post 4 weeks after drug administration for participants who completed the study.
Infections and infestations Bronchitis	10.0% 1/10 • Number of events 1 • Adverse Events (AEs) are collected on an ongoing basis from day of written informed consent. All new AEs must be recorded until 4 weeks post drug administration. AEs are classified as pre-treatment, treatment-emergent and post-treatment. Pre-Treatment:Medical conditions present at initial study visit that did not worsen in severity or frequency during study;Treatment-Emergent: If onset date of AE was on or after the first dose date of the study medication; Post-Treatment: If the onset date of AE was post 4 weeks after drug administration for participants who completed the study.	0.00% 0/12 • Adverse Events (AEs) are collected on an ongoing basis from day of written informed consent. All new AEs must be recorded until 4 weeks post drug administration. AEs are classified as pre-treatment, treatment-emergent and post-treatment. Pre-Treatment:Medical conditions present at initial study visit that did not worsen in severity or frequency during study;Treatment-Emergent: If onset date of AE was on or after the first dose date of the study medication; Post-Treatment: If the onset date of AE was post 4 weeks after drug administration for participants who completed the study.
Infections and infestations Ear infection	10.0% 1/10 • Number of events 2 • Adverse Events (AEs) are collected on an ongoing basis from day of written informed consent. All new AEs must be recorded until 4 weeks post drug administration. AEs are classified as pre-treatment, treatment-emergent and post-treatment. Pre-Treatment:Medical conditions present at initial study visit that did not worsen in severity or frequency during study;Treatment-Emergent: If onset date of AE was on or after the first dose date of the study medication; Post-Treatment: If the onset date of AE was post 4 weeks after drug administration for participants who completed the study.	0.00% 0/12 • Adverse Events (AEs) are collected on an ongoing basis from day of written informed consent. All new AEs must be recorded until 4 weeks post drug administration. AEs are classified as pre-treatment, treatment-emergent and post-treatment. Pre-Treatment:Medical conditions present at initial study visit that did not worsen in severity or frequency during study;Treatment-Emergent: If onset date of AE was on or after the first dose date of the study medication; Post-Treatment: If the onset date of AE was post 4 weeks after drug administration for participants who completed the study.
Investigations Insulin-like growth factor increased	10.0% 1/10 • Number of events 1 • Adverse Events (AEs) are collected on an ongoing basis from day of written informed consent. All new AEs must be recorded until 4 weeks post drug administration. AEs are classified as pre-treatment, treatment-emergent and post-treatment. Pre-Treatment:Medical conditions present at initial study visit that did not worsen in severity or frequency during study;Treatment-Emergent: If onset date of AE was on or after the first dose date of the study medication; Post-Treatment: If the onset date of AE was post 4 weeks after drug administration for participants who completed the study.	0.00% 0/12 • Adverse Events (AEs) are collected on an ongoing basis from day of written informed consent. All new AEs must be recorded until 4 weeks post drug administration. AEs are classified as pre-treatment, treatment-emergent and post-treatment. Pre-Treatment:Medical conditions present at initial study visit that did not worsen in severity or frequency during study;Treatment-Emergent: If onset date of AE was on or after the first dose date of the study medication; Post-Treatment: If the onset date of AE was post 4 weeks after drug administration for participants who completed the study.

Additional Information

Merck KGaA Communication Center

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Phone: +49-6151-72-5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER