foresiGHt: A Trial to Compare the Efficacy and Safety of Once-weekly Lonapegsomatropin With Placebo and a Daily Somatropin Product in Adults With Growth Hormone Deficiency

• Sponsor: Ascendis Pharma Endocrinology Division A/S (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04615273
• Collaborator: (none)
• Enrollment: 240
• Locations: 64
• Arms: 3
• Anticipated Duration (Months): 47.9
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

A 38 week dosing trial of lonapegsomatropin, a long-acting growth hormone product, administered once-a-week versus placebo-control. A daily somatropin product arm is also included to assist clinical judgement on the trial results. Approximately 240 adults (males and females) with growth hormone deficiency will be included. Randomization will occur in a 1:1:1 ratio (lonapegsomatropin : placebo : daily somatropin product). This is a global trial that will be conducted in, but not limited to, the United States, Europe, and Asia.

Condition or Disease	Intervention/Treatment	Phase
Growth Hormone Deficiency; Endocrine System Diseases; Hormone Deficiency	Drug: Lonapegsomatropin; Other: Placebo; Drug: Somatropin	Phase 3

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 240 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Double-blind, placebo-controlled, parallel group with subjects randomized into 3 treatment groups (1:1:1); lonapegsomatropin once-weekly, placebo for lonapegsomatropin once-weekly, somatropin daily.Double-blind, placebo-controlled, parallel group with subjects randomized into 3 treatment groups (1:1:1); lonapegsomatropin once-weekly, placebo for lonapegsomatropin once-weekly, somatropin daily.
• Masking: Double (Participant, Investigator)
• Masking Description: Once-weekly lonapegsomatropin and once-weekly placebo treatment arms will be double-blinded, daily somatropin product will be open-label.
• Primary Purpose: Treatment
• Official Title: foresiGHt: A Multicenter, Randomized, Parallel-arm, Placebo-controlled (Double- Blind) and Active-controlled (Open-label) Trial to Compare the Efficacy and Safety of Once-weekly Lonapegsomatropin With Placebo and a Daily Somatropin Product in Adults With Growth Hormone Deficiency
• Actual Study Start Date: Dec 3, 2020
• Anticipated Primary Completion Date: Dec 1, 2023
• Anticipated Study Completion Date: Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lonapegsomatropin Lonapegsomatropin administered once-weekly by subcutaneous injection	Drug: Lonapegsomatropin; Due to the different hGH dose requirements, depending on subject's age and concomitant use of oral estrogen, this trial has 3 dosing groups per arm, followed by gradual increasing dose titration to a target maintenance dose.
Placebo Comparator: Placebo Placebo for Lonapegsomatropin administered once-weekly by subcutaneous injection	Other: Placebo; The placebo for lonapegsomatropin drug product will contain the same excipients as lonapegsomatropin drug product but does not contain lonapegsomatropin itself. The placebo solution will be administered by SC injection via syringe and needle. Due to the different hGH dose requirements, depending on subject's age and concomitant use of oral estrogen, this trial has 3 dosing groups and the placebo will receive the same dose volume as if they would have been randomized to once-weekly lonapegsomatropin.
Active Comparator: Somatropin Somatropin administered once-daily by subcutaneous injection	Drug: Somatropin; Somatropin solution is provided in a pre-filled pen intended for daily subcutaneous injection. Due to the different hGH dose requirements, depending on subject's age and concomitant use of oral estrogen, this trial has 3 dosing groups per arm, followed by gradual increasing dose titration to a target maintenance dose.

Outcome Measures

Primary Outcome Measures

1. Change from Baseline in Trunk Percent Fat [38 weeks]

   Change from baseline in trunk percent fat (as assessed by dual-energy x ray absorptiometry [DXA]) at Week 38

Secondary Outcome Measures

1. Incidence of Treatment-Emergent Adverse Events [38 weeks]

   To evaluate the safety and tolerability of once-weekly lonapegsomatropin in adults with GHD

2. Evaluate serum hGH, lonapegsomatropin, and mPEG levels [38 weeks]

   To evaluate the pharmacokinetics (PK) of once-weekly lonapegsomatropin in adults with GHD

3. Evaluate serum IGF-1 and IGFBP-3 and IGF-1 SDS and IGFBP-3 SDS [38 weeks]

   To evaluate the pharmacodynamics (PD) of once-weekly lonapegsomatropin in adults with GHD

4. Change from Baseline in Trunk Fat Mass [38 weeks]

   Change from baseline in trunk percent fat (as assessed by dual-energy x ray absorptiometry [DXA]) compared to daily Somatropin at Week 38

5. Change from Baseline in Total Body Lean Mass [38 weeks]

   Change from baseline in total body lean mass (as assessed by dual-energy x ray absorptiometry [DXA]) compared to daily Somatropin at Week 38

Eligibility Criteria

Criteria

• Ages Eligible for Study: 23 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

1. Age between 23 and 80 years, inclusive, at screening.

2. AGHD Diagnosis Criteria

For adult-onset AGHD: documented history of structural hypothalamic-pituitary disease, hypothalamic-pituitary surgery, cranial irradiation, 1-4 non-GH pituitary hormone deficiencies, a proven genetic cause of GHD, or traumatic brain injury (TBI).

1. For all countries except Japan: Subjects must satisfy at least one of the following criteria:

1. Insulin tolerance test: peak GH ≤5 ng/mL

2. Glucagon stimulation test according to body mass index (BMI)

• 1. BMI ≤30 kg/m2: peak GH ≤3 ng/mL
• 1. BMI >30 kg/m2: peak GH ≤1 ng/mL

1. Three or four pituitary axis deficiencies (i.e., adrenal, thyroid, gonadal, and/or vasopressin; not including GH) with IGF-1 SDS ≤ -2.0 at screening

2. Macimorelin test: peak GH ≤2.8 ng/mL

3. Growth hormone releasing hormone (GHRH) + arginine test according to BMI:

• 1. BMI <25 kg/m2, peak GH <11 ng/mL
• 1. BMI ≥25-≤30 kg/m2, peak GH <8 ng/mL
• 1. BMI >30 kg/m2, peak GH <4 ng/mL

1. For Japan only: Subjects with AGHD and deficiency of at least one non-GH pituitary hormones need to satisfy one of the following GH stimulation tests. Subjects with GHD and evidence of intracranial structure disorder need to satisfy at least 2 of the following stimulation tests:

1. Insulin tolerance test: peak GH ≤1.8 ng/mL

2. Glucagon test: peak GH ≤1.8 ng/mL

3. Growth Hormone Releasing Peptide-2 (GHRP-2) tolerance test: peak GH ≤9 ng/mL

4. IGF-1 SDS ≤ -1.0 at screening as measured by central laboratory.

5. hGH treatment naïve or no exposure to hGH therapy or GH secretagogue for at least 12 months prior to screening.

6. For subjects on hormone replacement therapies for any hormone deficiencies other than GH (e.g., adrenal, thyroid, estrogen, testosterone) must be on adequate and stable doses for ≥6 weeks prior to and throughout screening.

7. For subjects not on glucocorticoid replacement therapy, documentation of adequate adrenal function at screening defined.

8. For males not on testosterone replacement therapy: morning (6:00 - 10:00AM) total testosterone within normal limits for age.

9. On a stable diet and exercise regime at screening with no intention to modify diet or exercise pattern during the trial, i.e., no weight reduction program intended during the trial or within the last 90 days prior to or through screening.

10. No plans to undergo bariatric surgery during the trial.

11. Fundoscopy at screening without signs/symptoms of intracranial hypertension or diabetic retinopathy above stage 2 / moderate or above or any other retinal disease contraindicated to growth hormone therapy. For subjects with a diagnosis of diabetes mellitus at screening, this must be documented with a fundus photograph.

12. Able and willing to provide a written informed consent and authorization for protected health information (PHI) disclosure in accordance with Good Clinical Practice (GCP).

13. Serum fT4 in the normal range at screening as measured by central laboratory.

Exclusion Criteria

1. Known Prader-Willi Syndrome and/or other genetic diseases that may have an impact on an endpoint.

2. Diabetes mellitus at screening if any of the following criteria are met:

3. Poorly controlled diabetes, defined as HbA1c >7.5% at screening.

4. Diabetes mellitus (defined as HbA1c ≥6.5% and/or fasting plasma glucose ≥126 mg/dL and/or plasma glucose ≥200 mg/dL two hours after oral glucose tolerance test) diagnosed <26 weeks prior to screening

5. Change in diabetes regimen (includes dose adjustment) within <90 days prior and throughout screening

6. Use of any diabetes drugs other than metformin and/or DPP-4 inhibitors for a cumulative duration of greater than 4 weeks within 12 months prior to screening

7. Diabetes-related complications at screening (i.e., nephropathy as judged by the investigator, neuropathy requiring pharmacological treatment, retinopathy stage 2 / moderate and above within 90 days prior to screening or during screening)

8. Active malignant disease or history of malignancy. Exceptions to this exclusion criterion:

9. Resection of in situ carcinoma of the cervix uteri

10. Complete eradication of squamous cell or basal cell carcinoma of the skin

11. Subjects with GHD attributed to treatment of intracranial malignant tumors or leukemia, provided that a recurrence-free survival period of at least 5 years prior to screening is documented in the subject's file (based on a Magnetic Resonance Imaging (MRI) result for intracranial malignant tumors)

12. Evidence of growth of pituitary adenoma or other benign intracranial tumor within the last 12 months before screening.

13. Subjects with acromegaly without remission / with documented remission less than 24 months prior to screening.

14. Subjects with Cushing's disease without remission / with documented remission less than 24 months prior to screening.

15. Subjects with prior cranial irradiation or hypothalamic-pituitary surgery: the procedure took place less than 12 months prior to screening.

16. eGFR <60 mL/min/1.73m2 determined based on Modification of Diet in Renal Disease (MDRD) equation.

17. Hepatic transaminases (i.e., AST or ALT) >3 times the upper limit of normal.

18. Heart failure NYHA class 3 or greater (NYHA 1994).

19. QTcF ≥ 451 milliseconds on 12-lead ECG at screening.

20. Poorly controlled hypertension, defined as supine systolic blood pressure >159 mmHg and/or supine diastolic blood pressure >95 mmHg at screening.

21. Cerebrovascular accident within 5 years prior to screening.

22. Anabolic steroids (other than gonadal steroid replacement therapy) or oral/intravenous/intramuscular corticosteroids within 90 days prior to or throughout screening.

23. Currently using or have used within 26 weeks prior to screening any weight-loss or appetite-suppressive medications.

24. Known history of hypersensitivity and/or idiosyncrasy to any of the test compounds (somatropin) or excipients employed in this trial.

25. Known history of neutralizing anti-hGH antibodies.

26. Inability to undergo scanning by DXA or a non-interpretable DXA scan at screening.

27. Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential (i.e., fertile, following menarche and until becoming post-menopausal unless permanently sterile) and not using adequate contraceptive methods

28. Male subjects must use a condom, or his female partner of childbearing potential must use an effective form of contraception as described above, from the beginning of screening to the last trial visit.

29. Known substance abuse or known (or previous) eating disorders, including anorexia nervosa, bulimia and severe gastrointestinal disease affecting normal eating (as judged by the investigator).

30. Any disease or condition that, in the judgement of the investigator, may make the subject unlikely to comply with the requirements of the trial or any condition that presents undue risk from the investigational product or procedures.

31. Participation in another interventional clinical trial involving an investigational compound within 26 weeks prior to screening or in parallel to this trial.

32. Currently using or have used within the last 3 days prior to screening: biotin >0.03 mg/day from supplements

33. Known history of positive results of tests for human immunodeficiency virus (HIV) antibodies or hepatitis B and/or C (exceptions if vaccinated towards Hepatitis B virus and Hepatitis C virus).

34. Any of the following: acute critical illness, and complications following open heart surgery, abdominal surgery, multiple accidental traumas, acute respiratory failure, or similar conditions within 180 days prior to screening.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ascendis Pharma Investigational Site	Phoenix	Arizona	United States	85048
2	Ascendis Pharma Investigational Site	Fresno	California	United States	93720
3	Ascendis Pharma Investigational Site	Los Angeles	California	United States	90048
4	Ascendis Pharma Investigational Site	Los Angeles	California	United States	90095
5	Ascendis Pharma Investigational Site	Indianapolis	Indiana	United States	46202
6	Ascendis Pharma Investigational Site	Boston	Massachusetts	United States	02114
7	Ascendis Pharma Investigational Site	Dearborn	Michigan	United States	48126
8	Ascendis Pharma Investigational Site	Saint Louis	Missouri	United States	63110
9	Ascendis Pharma Investigational Site	Las Vegas	Nevada	United States	89148
10	Ascendis Pharma Investigational Site	Reno	Nevada	United States	89511
11	Ascendis Pharma Investigational Site	New York	New York	United States	10016
12	Ascendis Pharma Investigational Site	Morehead City	North Carolina	United States	28557
13	Ascendis Pharma Investigational Site	Portland	Oregon	United States	97239
14	Ascendis Pharma Investigational Site	Pittsburgh	Pennsylvania	United States	15212
15	Ascendis Pharma Investigational Site	Dallas	Texas	United States	75390
16	Ascendis Pharma Investigational Site	Houston	Texas	United States	77074
17	Ascendis Pharma Investigational Site	San Antonio	Texas	United States	78229
18	Ascendis Pharma Investigational Site	Seattle	Washington	United States	98108
19	Ascendis Pharma Investigational Site	Yerevan		Armenia	0075
20	Ascendis Pharma Investigational Site	Saint Leonards	New South Wales	Australia	2065
21	Ascendis Pharma Investigational Site	Sydney	New South Wales	Australia	2109
22	Ascendis Pharma Investigational Site	Box Hill	Victoria	Australia	3128
23	Ascendis Pharma Investigational Site	Fitzroy	Victoria	Australia	3065
24	Ascendis Pharma Investigational Site	Parkville	Victoria	Australia	3050
25	Ascendis Pharma Investigational Site	Perth	Western Australia	Australia	6009
26	Ascendis Pharma Investigational Site	Vancouver	British Columbia	Canada	V6Z 1Y6
27	Ascendis Pharma Investigational Site	Halifax	Nova Scotia	Canada	B3H 1V7
28	Ascendis Pharma Investigational Site	Tbilisi		Georgia	0144
29	Ascendis Pharma Investigational Site	Tbilisi		Georgia	0144
30	Ascendis Pharma Investigational Site	Tbilisi		Georgia	0144
31	Ascendis Pharma Investigational Site	Tbilisi		Georgia	0159
32	Ascendis Pharma Investigational Site	Athens	Attica	Greece	10676
33	Ascendis Pharma Investigational Site	Athens	Attica	Greece	11527
34	Ascendis Pharma Investigational Site	Athens	Attica	Greece	11527
35	Ascendis Pharma Investigational Site	Thessaloníki	Central Macedonia	Greece	54636
36	Ascendis Pharma Investigational Site	Kobe	Hyogo	Japan	650-0047
37	Ascendis Pharma Investigational Site	Kawasaki	Kanagawa	Japan	211-8533
38	Ascendis Pharma Investigational Site	Yokohama	Kanagawa	Japan	222-0036
39	Ascendis Pharma Investigational Site	Yokohama	Kanagawa	Japan	236-004
40	Ascendis Pharma Investigational Site	Matsumoto	Nagano	Japan	Japan
41	Ascendis Pharma Investigational Site	Ishikawa	Okinawa	Japan	920-0293
42	Ascendis Pharma Investigational Site	Suita	Osaka	Japan	565-0871
43	Ascendis Pharma Investigational Site	Chiba		Japan	260-8677
44	Ascendis Pharma Investigational Site	Fukuoka		Japan	812-8582
45	Ascendis Pharma Investigational Site	Kagoshima		Japan	890-8520
46	Ascendis Pharma Investigational Site	Okayama		Japan	700-8558
47	Ascendis Pharma Investigational Site	Tokyo		Japan	108-8329
48	Ascendis Pharma Investigational Site	Yamagata		Japan	990-9585
49	Ascendis Pharma Investigational Site	Palmerston North	Manawatu-Wanganui	New Zealand	4440
50	Ascendis Pharma Investigational Site	Wellington		New Zealand	6021
51	Ascendis Pharma Investigational Site	Kraków		Poland	31-501
52	Ascendis Pharma Investigational Site	Warsaw		Poland	03-242
53	Ascendis Pharma Investigational Site	Wrocław		Poland	50-367
54	Ascendis Pharma Investigational Site	Łódź		Poland	93-338
55	Ascendis Pharma Investigational Site	Bratislava		Slovakia	82606
56	Ascendis Pharma Investigational Site	Lubochna		Slovakia	3491
57	Ascendis Pharma Investigational Site	Aydın		Turkey	09010
58	Ascendis Pharma Investigational Site	Kayseri		Turkey	38039
59	Ascendis Pharma Investigational Site	Ivano-Frankivs'k		Ukraine	76008
60	Ascendis Pharma Investigational Site	Kharkiv		Ukraine	61103
61	Ascendis Pharma Investigational Site	Kyiv		Ukraine	03115
62	Ascendis Pharma Investigational Site	Kyiv		Ukraine	04001
63	Ascendis Pharma Investigational Site	Kyiv		Ukraine	04114
64	Ascendis Pharma Investigational Site	Vinnytsya		Ukraine	21010

Sponsors and Collaborators

• Ascendis Pharma Endocrinology Division A/S

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ascendis Pharma Endocrinology Division A/S
• ClinicalTrials.gov Identifier: NCT04615273
• Other Study ID Numbers: TCH-306; 2020-000929-42
• First Posted: Nov 4, 2020
• Last Update Posted: Apr 13, 2022
• Last Verified: Apr 1, 2022

• 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; rhGH; GHD; Adult Growth Hormone Deficiency; Long Acting Growth Hormone; Lonapegsomatropin; Prodrug; Growth Failure; Growth Hormone Replacement Therapy; Sustained Release Growth Hormone; Growth Hormone Deficiency; TransCon hGH
• Additional relevant MeSH terms: Dwarfism, Pituitary; Endocrine System Diseases

Study Results

No Results Posted as of Apr 13, 2022