Trial Outcomes & Findings for Saizen in Intra-uterine Growth Retardation (NCT NCT01400698)

Last Updated: 2013-09-18

Results Overview

Final height was defined as the height reached 1 year after height velocity (HV) was less than 2 centimeter/year (cm/year). Height velocity was the change in height since the previous year's measurement. Height was measured with a wall-mounted stadiometer (or in supine position if the participant's age was less than 3 years) and the measurement was repeated thrice by the same observer. The mean of the values obtained in the repeated measurements was taken for the analysis.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

91 participants

Primary outcome timeframe

One year after final height was attained up to 10.6 years

Results posted on

2013-09-18

Participant Flow

Participants who completed 3 or 2 years treatment and at least 1 year post treatment observation in Sponsor Studies GF 4001 (Safety and Efficacy of Saizen in the Treatment of Young Children Born with Severe IUGR) or GF 6283 (Effect of Intermittent versus Continuous Saizen Therapy in Young Children Born with Severe IUGR), respectively were enrolled.

Participant milestones

Participant milestones
Measure	Saizen® Continuous (A1) Participants with bone age less than or equal to (\<=) 12 years for girls or 14 years for boys and height \<=-2 standard deviation (SD) received continuous treatment with recombinant human Growth Hormone (r-hGH) 0.067 milligram/kilogram/day (mg/kg/day) subcutaneously (sc) until they reached final height for a maximum duration of 10.6 years.	Saizen® Intermittent (A2) Participants with bone age \<=12 years for girls or 14 years for boys and height \<=-2 SD received intermittent treatment with r-hGH 0.067 mg/kg/day sc until they reached final height for a maximum duration of 10.6 years. Intermittent treatment was given on an individual basis depending on the height achieved during the study.	Observed, Not Randomized (B0) Participants with bone age \<=12 years for girls or 14 years for boys and height greater than (\>) -2 SD were observed until first signs of puberty but not randomized.	Observed Then Randomized to Saizen® (B1) Participants with bone age \<=12 years for girls or 14 years for boys and height \>-2 SD were observed until first signs of puberty and if remained at a height \>-2 SD, were randomized to receive continuous treatment with r-hGH 0.067 mg/kg/day sc until they reached final height for a maximum duration of 10.6 years. Participants whose height fell to \<=-2 SD before the first sign of puberty, were randomized to either Saizen® Continuous (A1) or Saizen® Intermittent (A2) treatment group.	Observed Then Randomized to Observation (B2) Participants with bone age \<=12 years for girls or 14 years for boys and height \>-2 SD were observed until first signs of puberty and if remained at a height \>-2 SD, were randomized to observation group with no treatment until they reached final height for a maximum duration of 10.6 years. Participants whose height fell to \<=-2 SD before the first sign of puberty, were randomized to either Saizen® Continuous (A1) or Saizen® Intermittent (A2) treatment group.	Observation (C) Participants with bone age \>12 years for girls or 14 years for boys or refused to be treated in any of the above groups were followed without treatment until they reached final height for a maximum duration of 10.6 years.
Overall Study STARTED	23	23	2	14	14	15
Overall Study COMPLETED	8	12	0	6	7	9
Overall Study NOT COMPLETED	15	11	2	8	7	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Saizen® Continuous (A1) Participants with bone age less than or equal to (\<=) 12 years for girls or 14 years for boys and height \<=-2 standard deviation (SD) received continuous treatment with recombinant human Growth Hormone (r-hGH) 0.067 milligram/kilogram/day (mg/kg/day) subcutaneously (sc) until they reached final height for a maximum duration of 10.6 years.	Saizen® Intermittent (A2) Participants with bone age \<=12 years for girls or 14 years for boys and height \<=-2 SD received intermittent treatment with r-hGH 0.067 mg/kg/day sc until they reached final height for a maximum duration of 10.6 years. Intermittent treatment was given on an individual basis depending on the height achieved during the study.	Observed, Not Randomized (B0) Participants with bone age \<=12 years for girls or 14 years for boys and height greater than (\>) -2 SD were observed until first signs of puberty but not randomized.	Observed Then Randomized to Saizen® (B1) Participants with bone age \<=12 years for girls or 14 years for boys and height \>-2 SD were observed until first signs of puberty and if remained at a height \>-2 SD, were randomized to receive continuous treatment with r-hGH 0.067 mg/kg/day sc until they reached final height for a maximum duration of 10.6 years. Participants whose height fell to \<=-2 SD before the first sign of puberty, were randomized to either Saizen® Continuous (A1) or Saizen® Intermittent (A2) treatment group.	Observed Then Randomized to Observation (B2) Participants with bone age \<=12 years for girls or 14 years for boys and height \>-2 SD were observed until first signs of puberty and if remained at a height \>-2 SD, were randomized to observation group with no treatment until they reached final height for a maximum duration of 10.6 years. Participants whose height fell to \<=-2 SD before the first sign of puberty, were randomized to either Saizen® Continuous (A1) or Saizen® Intermittent (A2) treatment group.	Observation (C) Participants with bone age \>12 years for girls or 14 years for boys or refused to be treated in any of the above groups were followed without treatment until they reached final height for a maximum duration of 10.6 years.
Overall Study Lost to Follow-up	2	5	2	1	4	3
Overall Study Withdrawal by Subject	8	2	0	4	1	3
Overall Study Protocol Violation	0	1	0	0	1	0
Overall Study Non-compliance	0	1	0	1	0	0
Overall Study Adverse Event	1	0	0	0	0	0
Overall Study Other	4	2	0	2	1	0

Baseline Characteristics

Saizen in Intra-uterine Growth Retardation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Non-Final Height: Not Treated n=10 Participants Includes all participants who did not achieve the final height during the study period and did not receive r-hGH 0.067 mg/kg/day sc either continuously or intermittently.	Non-Final Height: Treated n=13 Participants Includes all participants who did not achieve the final height during the study period and received r-hGH 0.067 mg/kg/day sc either continuously or intermittently.	Final Height: Not Treated n=22 Participants Includes all participants who achieved the final height during the study period and did not receive r-hGH 0.067 mg/kg/day sc either continuously or intermittently.	Final Height: Treated n=46 Participants Includes all participants who achieved the final height during the study period and received r-hGH 0.067 mg/kg/day sc either continuously or intermittently.	Total n=91 Participants Total of all reporting groups
Age Continuous	10.6 years STANDARD_DEVIATION 3.0 • n=5 Participants	9.2 years STANDARD_DEVIATION 2.4 • n=7 Participants	12.5 years STANDARD_DEVIATION 3.1 • n=5 Participants	9.5 years STANDARD_DEVIATION 2.6 • n=4 Participants	10.3 years STANDARD_DEVIATION 3.0 • n=21 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants	21 Participants n=4 Participants	41 Participants n=21 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	8 Participants n=7 Participants	12 Participants n=5 Participants	25 Participants n=4 Participants	50 Participants n=21 Participants
Race/Ethnicity, Customized Asian	2 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	2 participants n=21 Participants
Race/Ethnicity, Customized Black	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants	1 participants n=21 Participants
Race/Ethnicity, Customized White	8 participants n=5 Participants	13 participants n=7 Participants	22 participants n=5 Participants	45 participants n=4 Participants	88 participants n=21 Participants
Original Study GF4001	6 participants n=5 Participants	6 participants n=7 Participants	18 participants n=5 Participants	22 participants n=4 Participants	52 participants n=21 Participants
Original Study GF6283	4 participants n=5 Participants	7 participants n=7 Participants	4 participants n=5 Participants	24 participants n=4 Participants	39 participants n=21 Participants
Birth Height	41.8 cm STANDARD_DEVIATION 4.3 • n=5 Participants	42.2 cm STANDARD_DEVIATION 3.5 • n=7 Participants	44.8 cm STANDARD_DEVIATION 3.4 • n=5 Participants	42.3 cm STANDARD_DEVIATION 3.5 • n=4 Participants	42.8 cm STANDARD_DEVIATION 3.7 • n=21 Participants
Birth Weight	1848 g STANDARD_DEVIATION 601.2 • n=5 Participants	2076.9 g STANDARD_DEVIATION 520.9 • n=7 Participants	2312 g STANDARD_DEVIATION 451.1 • n=5 Participants	2030.9 g STANDARD_DEVIATION 573.4 • n=4 Participants	2085.3 g STANDARD_DEVIATION 551.8 • n=21 Participants
Length of Gestation	37 weeks STANDARD_DEVIATION 2.9 • n=5 Participants	37.3 weeks STANDARD_DEVIATION 2.6 • n=7 Participants	38.9 weeks STANDARD_DEVIATION 1.5 • n=5 Participants	37.9 weeks STANDARD_DEVIATION 2.8 • n=4 Participants	37.9 weeks STANDARD_DEVIATION 2.6 • n=21 Participants

PRIMARY outcome

Timeframe: One year after final height was attained up to 10.6 years

Population: Intention-to-treat (ITT) population included all participants enrolled in this study. Safety population was identical in this study.

Outcome measures

Outcome measures
Measure	Non-Final Height: Not Treated n=10 Participants Includes all participants who did not achieve the final height during the study period and did not receive r-hGH 0.067 mg/kg/day sc either continuously or intermittently.	Non-Final Height: Treated n=13 Participants Includes all participants who did not achieve the final height during the study period and received r-hGH 0.067 mg/kg/day sc either continuously or intermittently.	Final Height: Not Treated n=22 Participants Includes all participants who achieved the final height during the study period and did not receive r-hGH 0.067 mg/kg/day sc either continuously or intermittently.	Final Height: Treated n=46 Participants Includes all participants who achieved the final height during the study period and received r-hGH 0.067 mg/kg/day sc either continuously or intermittently.
Final Height	145.90 cm Standard Deviation 16.08	150.06 cm Standard Deviation 12.89	153.27 cm Standard Deviation 8.71	155.59 cm Standard Deviation 8.38

PRIMARY outcome

Timeframe: One year after final height was attained up to 10.6 years

Population: ITT population included all participants enrolled in this study. Safety population was identical in this study.

HSDS was calculated as height minus reference mean height divided by SD of the reference mean height, both given by the reference growth table (Sempe) for the corresponding chronological age at the height measurement. Greater HSDS indicate greater height. (Sempe M et al., 1979)

Outcome measures

Outcome measures
Measure	Non-Final Height: Not Treated n=10 Participants Includes all participants who did not achieve the final height during the study period and did not receive r-hGH 0.067 mg/kg/day sc either continuously or intermittently.	Non-Final Height: Treated n=13 Participants Includes all participants who did not achieve the final height during the study period and received r-hGH 0.067 mg/kg/day sc either continuously or intermittently.	Final Height: Not Treated n=22 Participants Includes all participants who achieved the final height during the study period and did not receive r-hGH 0.067 mg/kg/day sc either continuously or intermittently.	Final Height: Treated n=46 Participants Includes all participants who achieved the final height during the study period and received r-hGH 0.067 mg/kg/day sc either continuously or intermittently.
Height Standard Deviation Score (HSDS)	-1.45 standard deviation score Standard Deviation 0.76	-1.90 standard deviation score Standard Deviation 1.73	-2.33 standard deviation score Standard Deviation 1.01	-1.99 standard deviation score Standard Deviation 0.88

SECONDARY outcome

Timeframe: One year after final height was attained up to 10.6 years

Population: ITT population included all participants enrolled in this study. Safety population was identical in this study.

PAHSDS is the distance between the participant's current and target heights, expressed in units of SD of the height distribution of the reference population. Target height is a measure of the height which the participant could hypothetically reach based only on his parents' heights. Target height standard deviation score (THSDS) was calculated as target height minus mean adult height of the reference population divided by SD of the mean adult height of the reference population.

Outcome measures

Outcome measures
Measure	Non-Final Height: Not Treated n=10 Participants Includes all participants who did not achieve the final height during the study period and did not receive r-hGH 0.067 mg/kg/day sc either continuously or intermittently.	Non-Final Height: Treated n=13 Participants Includes all participants who did not achieve the final height during the study period and received r-hGH 0.067 mg/kg/day sc either continuously or intermittently.	Final Height: Not Treated n=22 Participants Includes all participants who achieved the final height during the study period and did not receive r-hGH 0.067 mg/kg/day sc either continuously or intermittently.	Final Height: Treated n=46 Participants Includes all participants who achieved the final height during the study period and received r-hGH 0.067 mg/kg/day sc either continuously or intermittently.
Parental Adjusted Height Standard Deviation Score (PAHSDS)	-0.82 standard deviation score Standard Deviation 0.59	-1.52 standard deviation score Standard Deviation 1.92	-1.64 standard deviation score Standard Deviation 1.61	-1.24 standard deviation score Standard Deviation 1.39

POST_HOC outcome

Timeframe: Up to 10.6 years

Population: ITT population included all participants enrolled in this study. Safety population was identical in this study. Here, 'N' (number of participants analyzed) signifies those participants who were treated and hence, were evaluated for this measure.

Outcome measures

Outcome measures
Measure	Non-Final Height: Not Treated n=13 Participants Includes all participants who did not achieve the final height during the study period and did not receive r-hGH 0.067 mg/kg/day sc either continuously or intermittently.	Non-Final Height: Treated n=46 Participants Includes all participants who did not achieve the final height during the study period and received r-hGH 0.067 mg/kg/day sc either continuously or intermittently.	Final Height: Not Treated Includes all participants who achieved the final height during the study period and did not receive r-hGH 0.067 mg/kg/day sc either continuously or intermittently.	Final Height: Treated Includes all participants who achieved the final height during the study period and received r-hGH 0.067 mg/kg/day sc either continuously or intermittently.
Duration of Treatment	4.09 years Standard Deviation 2.92	4.51 years Standard Deviation 2.20	—	—

POST_HOC outcome

Timeframe: Up to 10.6 years

Outcome measures

Outcome measures
Measure	Non-Final Height: Not Treated n=9 Participants Includes all participants who did not achieve the final height during the study period and did not receive r-hGH 0.067 mg/kg/day sc either continuously or intermittently.	Non-Final Height: Treated n=13 Participants Includes all participants who did not achieve the final height during the study period and received r-hGH 0.067 mg/kg/day sc either continuously or intermittently.	Final Height: Not Treated n=22 Participants Includes all participants who achieved the final height during the study period and did not receive r-hGH 0.067 mg/kg/day sc either continuously or intermittently.	Final Height: Treated n=46 Participants Includes all participants who achieved the final height during the study period and received r-hGH 0.067 mg/kg/day sc either continuously or intermittently.
Duration of Participation in the Study	2.08 years Standard Deviation 2.27	5.29 years Standard Deviation 2.89	4.10 years Standard Deviation 2.87	7.02 years Standard Deviation 2.06

Adverse Events

Not Treated

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

Treated

Serious events: 13 serious events

Other events: 52 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Not Treated n=32 participants at risk Included all participants who did not receive r-hGH 0.067 mg/kg/day sc either continuously or intermittently.	Treated n=59 participants at risk Included all participants who received r-hGH 0.067 mg/kg/day sc either continuously or intermittently.
Infections and infestations Pharyngitis	15.6% 5/32 • Number of events 6 • Baseline up to Day 30 after end of study An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.	15.3% 9/59 • Number of events 14 • Baseline up to Day 30 after end of study An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Infections and infestations Bronchitis	9.4% 3/32 • Number of events 6 • Baseline up to Day 30 after end of study An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.	13.6% 8/59 • Number of events 11 • Baseline up to Day 30 after end of study An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Infections and infestations Gastroenteritis	9.4% 3/32 • Number of events 3 • Baseline up to Day 30 after end of study An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.	11.9% 7/59 • Number of events 8 • Baseline up to Day 30 after end of study An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Infections and infestations Nasopharyngitis	0.00% 0/32 • Baseline up to Day 30 after end of study An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.	10.2% 6/59 • Number of events 11 • Baseline up to Day 30 after end of study An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Infections and infestations Influenza	0.00% 0/32 • Baseline up to Day 30 after end of study An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.	10.2% 6/59 • Number of events 8 • Baseline up to Day 30 after end of study An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Infections and infestations Ear infection	6.2% 2/32 • Number of events 3 • Baseline up to Day 30 after end of study An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.	6.8% 4/59 • Number of events 4 • Baseline up to Day 30 after end of study An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Infections and infestations Rhinitis	3.1% 1/32 • Number of events 1 • Baseline up to Day 30 after end of study An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.	6.8% 4/59 • Number of events 4 • Baseline up to Day 30 after end of study An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/32 • Baseline up to Day 30 after end of study An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.	11.9% 7/59 • Number of events 8 • Baseline up to Day 30 after end of study An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Skin and subcutaneous tissue disorders Acne	3.1% 1/32 • Number of events 2 • Baseline up to Day 30 after end of study An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.	10.2% 6/59 • Number of events 7 • Baseline up to Day 30 after end of study An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Skin and subcutaneous tissue disorders Eczema	3.1% 1/32 • Number of events 2 • Baseline up to Day 30 after end of study An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.	6.8% 4/59 • Number of events 4 • Baseline up to Day 30 after end of study An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Nervous system disorders Headache	3.1% 1/32 • Number of events 2 • Baseline up to Day 30 after end of study An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.	16.9% 10/59 • Number of events 14 • Baseline up to Day 30 after end of study An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.

Additional Information

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Principal investigator is a sponsor employee
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