A Safety, Tolerability and Efficacy Study of TransCon hGH in Children With Growth Hormone Deficiency

• Sponsor: Ascendis Pharma Endocrinology Division A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03305016
• Collaborator: (none)
• Enrollment: 146
• Locations: 24
• Arm: 1
• Actual Duration (Months): 16.1
• Patients Per Site: 6.1
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

A 26 week trial of TransCon hGH, a long-acting growth hormone product, administered once-a-week. Approximately 150 children (males and females) with growth hormone deficiency (GHD) will be included. All study participants will receive TransCon hGH. This is a global trial that will be conducted in, but not limited to, the United States, Canada, Australia, and New Zealand.

Condition or Disease	Intervention/Treatment	Phase
Growth Hormone Deficiency, Pediatric; Endocrine System Diseases; Hormone Deficiency; Pituitary Diseases	Drug: TransCon hGH	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 146 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: All study participants will receive TransCon hGHAll study participants will receive TransCon hGH
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: fliGHt: A Multicenter, Phase 3, Open-Label, 26-Week Trial Investigating the Safety, Tolerability and Efficacy of TransCon hGH Administered Once Weekly in Children With GHD
• Actual Study Start Date: Nov 13, 2017
• Actual Primary Completion Date: Mar 19, 2019
• Actual Study Completion Date: Mar 19, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TransCon hGH Once weekly subcutaneous injection of TransCon hGH	Drug: TransCon hGH; Once weekly subcutaneous injection at a starting dose of 0.24 mg/kg/week

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] [26 weeks]

   Safety and tolerability of weekly lonapegsomatropin (TransCon hGH) treatment

Secondary Outcome Measures

1. Annualized Height Velocity (AHV) at 26 Weeks of Weekly Lonapegsomatropin Treatment [26 weeks]

   Annualized height velocity (AHV) at 26 weeks of weekly lonapegsomatropin (TransCon hGH) treatment. The AHV at each visit was modeled using ANCOVA adjusting for baseline age, peak GH levels (log transformed) at diagnosis, delta average-parental height SDS, prior GH dose level (log transformed), and prior GH dose duration (log transformed) as covariates and gender as a factor. Subjects who did not take prior GH treatment were not included in the model.

2. Number of Subjects With IGF-1 Standard Deviation Score (SDS) in the Range of 0.0 to +2.0 at 26 Weeks of Weekly Lonapegsomatropin Treatment [26 weeks]

   IGF-1 Standard Deviation Score (SDS) is the number of standard deviations above or below the mean Insulin-like Growth Factor 1 (IGF-1) level for age and sex. IGF-1 SDS was derived using the LMS method as ((IGF-1/M)^L)-1)/(L x S), where M = median, S = generalized coefficient of variation, and L = power in the Box-Cox transformation, the M, S, L values were obtained from Bidlingmaier et al. (2014). A Standard Deviation Score of 0 represents the population mean.

3. Change in Height Standard Deviation Scores (SDS) at 26 Weeks of Weekly Lonapegsomatropin Treatment [Baseline and 26 weeks]

   Height Standard Deviation Score (SDS) is the number of standard deviations above or below the mean height for age and sex. Height SDS was derived using the LMS method as ((Height/M)^L)-1)/(L x S), where M = median, S = generalized coefficient of variation, and L = power in the Box-Cox transformation, the M, S, L values were obtained from 2000 CDC growth charts for the United States. A Standard Deviation Score of 0 represents the population mean. A higher change from baseline in Height SDS indicates a better outcome. The height SDS change from baseline at each visit was modeled using ANCOVA adjusting for baseline age, peak GH levels (log transformed) at diagnosis, delta average-parental height SDS, prior GH dose level (log transformed), and prior GH dose duration (log transformed) as covariates and gender as a factor. Subjects who did not take prior GH treatment were not included in the model.

4. Number of Participants With Treatment Emergent Anti-hGH Binding Antibody Formation [26 weeks]

   Number of participants with treatment emergent anti-hGH antibodies over 26 weeks of weekly lonapegsomatropin (TransCon hGH) treatment. All samples were negative for anti-hGH neutralizing antibodies.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Months to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Investigator-determined GHD diagnosis prior to the historical initiation of daily hGH therapy.

2. 6 months to 17 years old, inclusive, at Visit 1

3. If 3 to 17 years old, are taking daily hGH at a dose of ≥ 0.20 mg hGH/kg/week for at least 13 weeks but no more than 130 weeks prior to Visit 1

4. If ≥ 6 months but < 3 years old, are either hGH treatment-naïve or are taking daily hGH at a dose of ≥ 0.20mg hGH/kg/week for no more than 130 weeks prior to Visit 1

5. Tanner stage < 5 at Visit 1

6. Open epiphyses (bone age ≤14.0 years for females or ≤16.0 years for males)

7. Written, signed, informed consent of the parent or legal guardian of the subject and written assent of the subject as required by the IRB/HREC/IEC

Exclusion Criteria:

1. Weight of < 5.5 kg or > 80 kg at Visit 1

2. Females of child-bearing potential

3. History of malignant disease

4. Any clinically significant abnormality likely to affect growth or the ability to evaluate growth (eg, chronic diseases or conditions such as renal insufficiency, spinal cord irradiation, hypothyroidism, active celiac disease, malnutrition or psychosocial dwarfism)

5. Poorly-controlled diabetes mellitus (HbA1c >8.0%) or diabetic complications

6. Known neutralizing antibodies against hGH

7. Major medical conditions, unless approved by Medical Monitor

8. Pregnancy

9. Presence of contraindications to hGH treatment

10. Likely to be non-compliant with respect to trial conduct (in regards to the subject and/or the parent/legal guardian/caregiver)

11. Participation in any other trial of an investigational agent within 30 days prior to Visit 1

12. Prior exposure to investigational hGH

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama	Birmingham	Alabama	United States	35233
2	Neufeld Medical Group Inc.	Los Angeles	California	United States	90048
3	Center of Excellence in Diabetes and Endocrinology	Sacramento	California	United States	95821
4	Rocky Mountain Pediatric Endocrinology	Centennial	Colorado	United States	80112
5	Nemours Children's Health System	Jacksonville	Florida	United States	32207
6	Orlando Health Inc.	Orlando	Florida	United States	32806
7	Tallahassee Memorial Hospital	Tallahassee	Florida	United States	32308
8	University of Iowa	Iowa City	Iowa	United States	52242
9	Children's Minnesota	Saint Paul	Minnesota	United States	55102
10	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
11	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
12	NYU Winthrop Hospital	Mineola	New York	United States	11501
13	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
14	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
15	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
16	Children's Diabetes and Endocrine Center	Portland	Oregon	United States	97227
17	Oregon Health & Science University	Portland	Oregon	United States	97239
18	Children's Medical Center	Dallas	Texas	United States	75235
19	Cook Children's Medical Center	Fort Worth	Texas	United States	76104
20	University of Virginia Children's Hospital	Charlottesville	Virginia	United States	22903
21	Children's Hospital of The King's Daughters	Norfolk	Virginia	United States	23507
22	Monash Children's Hospital	Clayton	Victoria	Australia	3168
23	Stollery Children's Hospital	Edmonton	Alberta	Canada	T6G 2B7
24	The Liggins Institute, The University of Auckland	Grafton	Auckland	New Zealand	1023

Sponsors and Collaborators

• Ascendis Pharma Endocrinology Division A/S

Investigators

• Study Director: Aimee D Shu, MD, Ascendis Pharma, Inc.
• Study Director: David B Karpf, MD, Ascendis Pharma, Inc.

Study Documents (Full-Text)

• Study Protocol - Aug 29, 2017
• Statistical Analysis Plan - Mar 14, 2019

More Information

Publications

None provided.

• Responsible Party: Ascendis Pharma Endocrinology Division A/S
• ClinicalTrials.gov Identifier: NCT03305016
• Other Study ID Numbers: TransCon hGH CT-302; U1111-1199-8218
• First Posted: Oct 9, 2017
• Last Update Posted: Jan 4, 2022
• Last Verified: Dec 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Ascendis Pharma Endocrinology Division A/S: Human Growth Hormone; hGH; GHD; rhGH; Pediatric Growth Hormone Deficiency; Long Acting Growth Hormone; Somatropin; Prodrug; Growth Failure; Growth Hormone Replacement Therapy; Sustained Release Growth Hormone; Growth Hormone Deficiency; TransCon GH
• Additional relevant MeSH terms: Dwarfism, Pituitary; Pituitary Diseases; Endocrine System Diseases

Study Results

Participant Flow

Pre-assignment Detail	A total of 162 subjects were screened for entry into this trial; of these, 16 subjects did not meet eligibility criteria and were considered screen failures.

Arm/Group Title	Lonapegsomatropin
Arm/Group Description	Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH) at a starting dose of 0.24 mg/kg/week
Period Title: Overall Study
STARTED	146
COMPLETED	144
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Lonapegsomatropin
Arm/Group Description	Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH) at a starting dose of 0.24 mg/kg/week
Overall Participants	146
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	10.6 (3.9)
Age, Customized (Count of Participants)
<3 years	4 2.7%
≥3 and <6 years	20 13.7%
≥6 to <11 years (girls) or ≥6 to <12 years (boys)	55 37.7%
≥11 years (girls) or ≥12 years (boys)	67 45.9%
Sex: Female, Male (Count of Participants)
Female	36 24.7%
Male	110 75.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	10 6.8%
Not Hispanic or Latino	124 84.9%
Unknown or Not Reported	12 8.2%
Race/Ethnicity, Customized (Count of Participants)
Asian	6 4.1%
Black or African American	3 2.1%
Native Hawaiian or Other Pacific Islander	2 1.4%
White	124 84.9%
More than one race	2 1.4%
Unknown	9 6.2%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	132.4 (22.5)
Height SDS (standard deviation score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [standard deviation score]	-1.42 (0.84)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	32.3 (14.2)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	17.5 (3.0)
IGF-1 SDS (standard deviation score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [standard deviation score]	0.85 (1.29)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability]
Description	Safety and tolerability of weekly lonapegsomatropin (TransCon hGH) treatment
Time Frame	26 weeks

Outcome Measure Data

Analysis Population Description

The Full Analysis Set included all subjects who received at least 1 dose of trial drug during the trial and who had any follow-up data.

Arm/Group Title	Lonapegsomatropin
Arm/Group Description	Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH) at a starting dose of 0.24 mg/kg/week
Measure Participants	146
TEAE	83 56.8%
Related TEAE	6 4.1%
Serious TEAE	1 0.7%
Related Serious TEAE	0 0%

2. Secondary Outcome

Title	Annualized Height Velocity (AHV) at 26 Weeks of Weekly Lonapegsomatropin Treatment
Description	Annualized height velocity (AHV) at 26 weeks of weekly lonapegsomatropin (TransCon hGH) treatment. The AHV at each visit was modeled using ANCOVA adjusting for baseline age, peak GH levels (log transformed) at diagnosis, delta average-parental height SDS, prior GH dose level (log transformed), and prior GH dose duration (log transformed) as covariates and gender as a factor. Subjects who did not take prior GH treatment were not included in the model.
Time Frame	26 weeks

Outcome Measure Data

Analysis Population Description

The Full Analysis Set included all subjects who received at least 1 dose of trial drug during the trial and who had any follow-up data.

Arm/Group Title	Lonapegsomatropin
Arm/Group Description	Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH) at a starting dose of 0.24 mg/kg/week
Measure Participants	144
Least Squares Mean (Standard Error) [cm/year]	8.72 (0.24)

3. Secondary Outcome

Title	Number of Subjects With IGF-1 Standard Deviation Score (SDS) in the Range of 0.0 to +2.0 at 26 Weeks of Weekly Lonapegsomatropin Treatment
Description	IGF-1 Standard Deviation Score (SDS) is the number of standard deviations above or below the mean Insulin-like Growth Factor 1 (IGF-1) level for age and sex. IGF-1 SDS was derived using the LMS method as ((IGF-1/M)^L)-1)/(L x S), where M = median, S = generalized coefficient of variation, and L = power in the Box-Cox transformation, the M, S, L values were obtained from Bidlingmaier et al. (2014). A Standard Deviation Score of 0 represents the population mean.
Time Frame	26 weeks

Outcome Measure Data

Analysis Population Description

The Full Analysis Set included all subjects who received at least 1 dose of trial drug during the trial and who had any follow-up data.

Arm/Group Title	Lonapegsomatropin
Arm/Group Description	Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH) at a starting dose of 0.24 mg/kg/week
Measure Participants	142
Count of Participants [Participants]	74 50.7%

4. Secondary Outcome

Title	Change in Height Standard Deviation Scores (SDS) at 26 Weeks of Weekly Lonapegsomatropin Treatment
Description	Height Standard Deviation Score (SDS) is the number of standard deviations above or below the mean height for age and sex. Height SDS was derived using the LMS method as ((Height/M)^L)-1)/(L x S), where M = median, S = generalized coefficient of variation, and L = power in the Box-Cox transformation, the M, S, L values were obtained from 2000 CDC growth charts for the United States. A Standard Deviation Score of 0 represents the population mean. A higher change from baseline in Height SDS indicates a better outcome. The height SDS change from baseline at each visit was modeled using ANCOVA adjusting for baseline age, peak GH levels (log transformed) at diagnosis, delta average-parental height SDS, prior GH dose level (log transformed), and prior GH dose duration (log transformed) as covariates and gender as a factor. Subjects who did not take prior GH treatment were not included in the model.
Time Frame	Baseline and 26 weeks

Outcome Measure Data

Analysis Population Description

The Full Analysis Set included all subjects who received at least 1 dose of trial drug during the trial and who had any follow-up data.

Arm/Group Title	Lonapegsomatropin
Arm/Group Description	Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH) at a starting dose of 0.24 mg/kg/week
Measure Participants	144
Least Squares Mean (Standard Error) [standard deviation score]	0.25 (0.02)

5. Secondary Outcome

Title	Number of Participants With Treatment Emergent Anti-hGH Binding Antibody Formation
Description	Number of participants with treatment emergent anti-hGH antibodies over 26 weeks of weekly lonapegsomatropin (TransCon hGH) treatment. All samples were negative for anti-hGH neutralizing antibodies.
Time Frame	26 weeks

Outcome Measure Data

Analysis Population Description

The Full Analysis Set included all subjects who received at least 1 dose of trial drug during the trial and who had any follow-up data.

Arm/Group Title	Lonapegsomatropin
Arm/Group Description	Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH) at a starting dose of 0.24 mg/kg/week
Measure Participants	145
Count of Participants [Participants]	4 2.7%

Adverse Events

Time Frame	26 weeks
Arm/Group Title	Lonapegsomatropin
Arm/Group Description	Once weekly subcutaneous injection of lonapegsomatropin (TransCon hGH) at a starting dose of 0.24 mg/kg/week
All Cause Mortality
	Lonapegsomatropin
	Affected / at Risk (%)	# Events
Total	0/146 (0%)
Serious Adverse Events
	Lonapegsomatropin
	Affected / at Risk (%)	# Events
Total	1/146 (0.7%)
Cardiac disorders
Atrioventricular block	1/146 (0.7%)	1
General disorders
Chest pain	1/146 (0.7%)	1
Other (Not Including Serious) Adverse Events
	Lonapegsomatropin
	Affected / at Risk (%)	# Events
Total	65/146 (44.5%)
General disorders
Pyrexia	17/146 (11.6%)
Infections and infestations
Nasopharyngitis	14/146 (9.6%)
Upper respiratory tract infection	14/146 (9.6%)
Nervous system disorders
Headache	12/146 (8.2%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	8/146 (5.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT 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.