Growth Hormone DeficiencyPhase 3foresiGHtNCT04615273
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
A Phase 3 study testing Lonapegsomatropin and Somatropin in people with Growth Hormone Deficiency and Endocrine System Diseases, run by Ascendis Pharma Endocrinology Division A/S at 113 sites in 24 countries.
Trial 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. A total of 264 adults (males and females) with growth hormone deficiency were included. Read more about this study
- Who is it for?
- Ages 23 to 80 years
- Conditions the study is for
- Growth Hormone Deficiency, Endocrine System Diseases, Hormone Deficiency
- What is being tested?
- Lonapegsomatropin and Somatropin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 264 participants
- Where
- 113 sitesin 24 countries
- Study dates
- 3 Dec 2020to 1 Dec 2023
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 23 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age between 23 and 80 years, inclusive, at screening.
- Adult Growth Hormone Deficiency (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).
- Participants with childhood-onset GHD must have had GH axis re-assessed at final height.
- In participants with TBI as a cause of GHD, GHD must be confirmed by GH -stimulation testing performed at least 12 months after the injury.
- For all countries except Japan: participants must have satisfied at least one of the following criteria:
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- Insulin tolerance test: peak growth hormone (GH) <=5 ng/mL
- Glucagon stimulation test according to body mass index (BMI)
- i. BMI <=30 kg/m^2: peak GH <=3 ng/mL
- ii. BMI >30 kg/m^2: peak GH <=1 ng/mL
- Three or four pituitary axis deficiencies (i.e., adrenal, thyroid, gonadal, and/or vasopressin; not including GH) with insulin-like growth factor-1 standard deviation score (IGF-1 SDS) <= -2.0 at screening
- Macimorelin test: peak GH <=2.8 ng/mL
- Growth hormone releasing hormone (GHRH) + arginine test according to BMI:
- i. BMI <25 kg/m^2, peak GH <11 ng/mL
- ii. BMI >=25-<=30 kg/m^2, peak GH <8 ng/mL
- iii. BMI >30 kg/m^2, peak GH <4 ng/mL
- For Japan only: Participants with AGHD and deficiency of at least one non-GH pituitary hormones need to satisfy one of the following GH stimulation tests. Participants with GHD without additional non-GH pituitary hormone deficiencies with or without and evidence of intracranial structure disorder need to satisfy at least 2 of the following stimulation tests:
- Insulin tolerance test: peak GH <=1.8 ng/mL
- Glucagon test: peak GH <=1.8 ng/mL
- Growth Hormone Releasing Peptide-2 (GHRP-2) tolerance test: peak GH <=9 ng/mL
- IGF-1 SDS <= -1.0 at screening as measured by central laboratory.
- hGH treatment naïve or no exposure to hGH therapy or GH secretagogue for at least 12 months prior to screening.
- For participants 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.
- For participants not on glucocorticoid replacement therapy, documentation of adequate adrenal function at screening defined as: morning (6:00-10:00 AM) serum cortisol >15.0 mcg/dL (measured at central laboratory) and/or adrenocorticotropic hormone (ACTH) stimulation test or insulin tolerance test with serum cortisol >18.0 mcg/dL at or within 90 days prior to screening.
- For males not on testosterone replacement therapy: morning (6:00 - 10:00AM) total testosterone within normal limits for age.
- 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.
- No plans to undergo bariatric surgery during the trial.
- 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 participants with a diagnosis of diabetes mellitus at screening, this must be documented with a fundus photograph.
- Able and willing to provide a written informed consent and authorization for protected health information (PHI) disclosure in accordance with Good Clinical Practice (GCP).
- Serum free thyroxine (fT4) in the normal range at screening as measured by central laboratory.
Who cannot join
- Known Prader-Willi Syndrome and/or other genetic diseases that may have an impact on an endpoint.
- Diabetes mellitus at screening if any of the following criteria are met:
- Poorly controlled diabetes, defined as HbA1c >7.5% at screening.
- 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
- Change in diabetes regimen (includes dose adjustment) within <90 days prior and throughout screening
- Use of any diabetes drugs other than metformin and/or dipeptidyl peptidase-4 (DPP-4) inhibitors for a cumulative duration of greater than 4 weeks within 12 months prior to screening
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- 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)
- Active malignant disease or history of malignancy. Exceptions to this exclusion criterion:
- Resection of in situ carcinoma of the cervix uteri
- Complete eradication of squamous cell or basal cell carcinoma of the skin
- Participants 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 participant's file (based on a Magnetic Resonance Imaging (MRI) result for intracranial malignant tumors)
- Evidence of growth of pituitary adenoma or other benign intracranial tumor within the last 12 months before screening.
- Participants with acromegaly without remission / with documented remission less than 24 months prior to screening.
- Participants with Cushing's disease without remission / with documented remission less than 24 months prior to screening.
- Participants with prior cranial irradiation or hypothalamic-pituitary surgery: the procedure was to take place less than 12 months prior to screening.
- Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m^2 determined based on Modification of Diet in Renal Disease (MDRD) equation.
- Hepatic transaminases (i.e., aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) >3 times the upper limit of normal.
- Heart failure New York Heart Association (NYHA) class 3 or greater (NYHA 1994).
- Q-T interval, corrected by Fridericia's method (QTcF) >= 451 milliseconds on 12-lead electrocardiogram (ECG) at screening.
- Poorly controlled hypertension, defined as supine systolic blood pressure >159 mmHg and/or supine diastolic blood pressure >95 mmHg at screening.
- Cerebrovascular accident within 5 years prior to screening.
- Anabolic steroids (other than gonadal steroid replacement therapy) or oral/intravenous/intramuscular corticosteroids within 90 days prior to or throughout screening.
- Currently using or have used within 26 weeks prior to screening any weight-loss or appetite-suppressive medications including orlistat, zonisamide, lorcaserin, bupropion, topiramate, sibutramine, stimulants, glucagon-like peptide 1 (GLP-1) receptor agonists, sodium-dependent glucose cotransporters (SGLT-2) inhibitors or medications that affects IGF-1 or GH measurements including cabergoline at doses above 0.5 mg weekly or bromocriptine at doses above 20 mg weekly.
- Known history of hypersensitivity and/or idiosyncrasy to any of the test compounds (somatropin) or excipients employed in this trial.
- Known history of neutralizing anti-hGH antibodies.
- Inability to undergo scanning by dual-energy x-ray absorptiometry (DXA) or a non-interpretable DXA scan at screening.
- 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.
- Male participants 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.
- 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).
- 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.
- Participation in another interventional clinical trial involving an investigational compound within 26 weeks prior to screening or in parallel to this trial.
- Currently using or have used within the last 3 days prior to screening: biotin >0.03 mg/day from supplements
- 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).
- 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.
Trial locations and contacts
113 sites in 24 countries.
113 sites in 24 countries
United States23 sites
Ascendis Pharma Investigational Site
Birmingham, Alabama, 35205
Ascendis Pharma Investigational Site
Boston, Massachusetts, 02114
Ascendis Pharma Investigational Site
Chicago, Illinois, 60611
Ascendis Pharma Investigational Site
Dallas, Texas, 75390
Ascendis Pharma Investigational Site
Dearborn, Michigan, 48126
Ascendis Pharma Investigational Site
Fresno, California, 93720
Ascendis Pharma Investigational Site
Indianapolis, Indiana, 46202
Ascendis Pharma Investigational Site
Las Vegas, Nevada, 89148
Ascendis Pharma Investigational Site
Los Angeles, California, 90048
Ascendis Pharma Investigational Site
Los Angeles, California, 90095
Ascendis Pharma Investigational Site
Morehead City, North Carolina, 28557
Ascendis Pharma Investigational Site
New York, New York, 10017
Ascendis Pharma Investigational Site
New York, New York, 10021
Ascendis Pharma Investigational Site
Palo Alto, California, 94304
Ascendis Pharma Investigational Site
Phoenix, Arizona, 85048
Ascendis Pharma Investigational Site
Pittsburgh, Pennsylvania, 15212
Ascendis Pharma Investigational Site
Portland, Oregon, 97239
Ascendis Pharma Investigational Site
Reno, Nevada, 89511
Ascendis Pharma Investigational Site
Rochester, Minnesota, 55905
Ascendis Pharma Investigational Site
San Antonio, Texas, 78232
Ascendis Pharma Investigational Site
Seattle, Washington, 98108
Ascendis Pharma Investigational Site
St Louis, Missouri, 63110
Ascendis Pharma Investigational Site
Torrance, California, 90509
Japan17 sites
Ascendis Pharma Investigational Site
Chiba, 260-8677
Ascendis Pharma Investigational Site
Fukuoka, 812-8582
Ascendis Pharma Investigational Site
Ishikawa, Okinawa, 920-0293
Ascendis Pharma Investigational Site
Kagoshima, 890-8520
Ascendis Pharma Investigational Site
Kashihara, Nara, 634-8522
Ascendis Pharma Investigational Site
Kawasaki, Kanagawa, 211-8533
Ascendis Pharma Investigational Site
Kawasaki, 216-8511
Ascendis Pharma Investigational Site
Kobe, Hyōgo, 650-0047
Ascendis Pharma Investigational Site
Matsumoto, Nagano, Japan
Ascendis Pharma Investigational Site
Nagakute, 480-1195
Ascendis Pharma Investigational Site
Okayama, 700-8558
Ascendis Pharma Investigational Site
Osaka, 550-0006
Ascendis Pharma Investigational Site
Suita, Osaka, 565-0871
Ascendis Pharma Investigational Site
Tokyo, 108-8329
Ascendis Pharma Investigational Site
Yamagata, 990-9585
Ascendis Pharma Investigational Site
Yokohama, Kanagawa, 222-0036
Ascendis Pharma Investigational Site
Yokohama, Kanagawa, 236-004
Australia6 sites
Ascendis Pharma Investigational Site
Box Hill, Victoria, 3128
Ascendis Pharma Investigational Site
Fitzroy, Victoria, 3065
Ascendis Pharma Investigational Site
Parkville, Victoria, 3050
Ascendis Pharma Investigational Site
Perth, Western Australia, 6009
Ascendis Pharma Investigational Site
Saint Leonards, New South Wales, 2065
Ascendis Pharma Investigational Site
Sydney, New South Wales, 2109
Spain6 sites
Ascendis Pharma Investigational Site
Alicante, 3010
Ascendis Pharma Investigational Site
Barcelona, 8035
Ascendis Pharma Investigational Site
Barcelona, 8041
Ascendis Pharma Investigational Site
Madrid, 28006
Ascendis Pharma Investigational Site
Santiago de Compostela, 15706
Ascendis Pharma Investigational Site
Seville, 41013
Turkey (Türkiye)6 sites
Ascendis Pharma Investigational Site
Ankara, 06560
Ascendis Pharma Investigational Site
Antalya, 07070
Ascendis Pharma Investigational Site
Aydin, 09010
Ascendis Pharma Investigational Site
Izmir, 35100
Ascendis Pharma Investigational Site
İzmit, 41001
Ascendis Pharma Investigational Site
Kayseri, 38039
Ukraine6 sites
Ascendis Pharma Investigational Site
Ivano-Frankivsk, 76008
Ascendis Pharma Investigational Site
Kharkiv, 61103
Ascendis Pharma Investigational Site
Kyiv, 03115
Ascendis Pharma Investigational Site
Kyiv, 04001
Ascendis Pharma Investigational Site
Kyiv, 04114
Ascendis Pharma Investigational Site
Vinnytsia, 21010
Poland5 sites
Ascendis Pharma Investigational Site
Krakow, 31-501
Ascendis Pharma Investigational Site
Lodz, 93-338
Ascendis Pharma Investigational Site
Poznan, 60-355
Ascendis Pharma Investigational Site
Warsaw, 03-242
Ascendis Pharma Investigational Site
Wroclaw, 50-367
France4 sites
Ascendis Pharma Investigational Site
Lyon, 69677
Ascendis Pharma Investigational Site
Marseille, 13385
Ascendis Pharma Investigational Site
Nantes, 44093
Ascendis Pharma Investigational Site
Paris, 75013
Greece4 sites
Ascendis Pharma Investigational Site
Athens, Attica, 10676
Ascendis Pharma Investigational Site
Athens, Attica, 11527
Ascendis Pharma Investigational Site
Thessaloniki, Central Macedonia, 54636
Ascendis Pharma Investigational Site
Thessaloniki, 546 42
Israel4 sites
Ascendis Pharma Investigational Site
Beersheba, 8410100
Ascendis Pharma Investigational Site
Haifa, 31048
Ascendis Pharma Investigational Site
Petah Tikva, 4941480
Ascendis Pharma Investigational Site
Tel Aviv, 6423906
Italy4 sites
Ascendis Pharma Investigational Site
Genova, 16132
Ascendis Pharma Investigational Site
Rome, 00161
Ascendis Pharma Investigational Site
Rome, 00168
Ascendis Pharma Investigational Site
Rozzano, 20089
Malaysia4 sites
Ascendis Pharma Investigational Site
George Town, 10450
Ascendis Pharma Investigational Site
Kota Bharu, 16150
Ascendis Pharma Investigational Site
Malacca, 75400
Ascendis Pharma Investigational Site
Putrajaya, 62250
South Korea4 sites
Ascendis Pharma Investigational Site
Seoul, 03722
Ascendis Pharma Investigational Site
Seoul, 05278
Ascendis Pharma Investigational Site
Seoul, 06591
Ascendis Pharma Investigational Site
Suwon, 443-721
Romania3 sites
Ascendis Pharma Investigational Site
Bucharest, 11868
Ascendis Pharma Investigational Site
Iași, 700106
Ascendis Pharma Investigational Site
Timișoara, 300723
United Kingdom3 sites
Ascendis Pharma Investigational Site
Cardiff, CF14 4XW
Ascendis Pharma Investigational Site
Coventry, CV2 2DX
Ascendis Pharma Investigational Site
Leeds, LS9 7TF
Canada2 sites
Ascendis Pharma Investigational Site
Halifax, Nova Scotia, B3H 1V7
Ascendis Pharma Investigational Site
Vancouver, British Columbia, V6Z 1Y6
Georgia2 sites
Ascendis Pharma Investigational Site
Tbilisi, 0144
Ascendis Pharma Investigational Site
Tbilisi, 0159
New Zealand2 sites
Ascendis Pharma Investigational Site
Palmerston North, Manawatu-Wanganui, 4440
Ascendis Pharma Investigational Site
Wellington, 6021
Serbia2 sites
Ascendis Pharma Investigational Site
Belgrade, 11000
Ascendis Pharma Investigational Site
Kragujevac, 34000
Slovakia2 sites
Ascendis Pharma Investigational Site
Bratislava, 82606
Ascendis Pharma Investigational Site
Ľubochňa, 3491
About this study
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
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. A total of 264 adults (males and females) with growth hormone deficiency were included. Randomization occurred in a 1:1:1 ratio (lonapegsomatropin: placebo: daily somatropin product). This is a global trial conducted in, but not limited to, the United States, Europe, and Asia.
- Being tested
- Lonapegsomatropin, Placebo, Somatropin
- Keywords
- 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
- Medical subject headings
- Dwarfism, Pituitary, Endocrine System Diseases, Failure to Thrive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LonapegsomatropinDrug
Due to the different human growth hormone (hGH) dose requirements, depending on participant'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.
PlaceboOther
The placebo for lonapegsomatropin drug product contained the same excipients as lonapegsomatropin drug product but does not contain lonapegsomatropin itself. The placebo solution was administered by subcutaneous (SC) injection via syringe and needle. Due to the different hGH dose requirements, depending on participant's age and concomitant use of oral estrogen, this trial has 3 dosing groups and the placebo received the same dose volume as if they were randomized to once-weekly lonapegsomatropin.
SomatropinDrug
Somatropin solution is provided in a pre-filled pen intended for daily subcutaneous injection. Due to the different hGH dose requirements, depending on participant'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.
| Study group | Role | What they receive |
|---|---|---|
| Lonapegsomatropin | Experimental | Lonapegsomatropin administered once-weekly by subcutaneous injection. Receives: Drug: Lonapegsomatropin |
| Placebo | Placebo comparator | Placebo for Lonapegsomatropin administered once-weekly by subcutaneous injection. Receives: Other: Placebo |
| Somatropin | Active comparator | Somatropin administered once-daily by subcutaneous injection. Receives: Drug: Somatropin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Trunk Percent Fat at Week 38
Trunk percent fat was assessed by dual-energy X-ray absorptiometry.
Measured: Baseline, Week 38
Secondary outcomes (3)
Change From Baseline in Total Body Lean Mass at Week 38
Total body lean mass was assessed by dual-energy X-ray absorptiometry.
Measured: Baseline, Week 38
Change From Baseline in Trunk Fat Mass at Week 38
Trunk fat mass was assessed by dual-energy X-ray absorptiometry.
Measured: Baseline, Week 38
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and TEAE Leading to Study Discontinuation
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with the treatment. An AE was considered a TEAE if it occurred on or after the first dose of investigational product and was not present prior to the first dose, or it was present at the first dose but increased in severity during the trial. A serious AE is any untoward medical occurrence at any dose: resulted in death; was life threatening; required prolong inpatient hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect or was considered a significant medical event by the investigator.
Measured: Up to 38 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2020
- Study start3 Dec 2020
- Primary completion2 Nov 2023
- Study completion1 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Growth Hormone DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Double-blind, placebo-controlled, parallel group with participants randomized into 3 treatment groups (1:1:1); lonapegsomatropin once-weekly, placebo for lonapegsomatropin once-weekly, somatropin daily.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 264 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ascendis Pharma Endocrinology Division A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, MD, Study director, Ascendis Pharma A/S
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04615273
- Sponsor's protocol ID
- TCH-306
- Other IDs
- 2020-000929-42
- Acronym
- foresiGHt
- Status last verified
- Jun 2026
- First submitted
- 29 Oct 2020
- Last updated
- 7 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No