Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04615273




Registration number
NCT04615273
Ethics application status
Date submitted
29/10/2020
Date registered
4/11/2020
Date last updated
21/12/2023

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
2020-000929-42
Secondary ID [2] 0 0
TCH-306
Universal Trial Number (UTN)
Trial acronym
foresiGHt
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Growth Hormone Deficiency 0 0
Endocrine System Diseases 0 0
Hormone Deficiency 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Other endocrine disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Lonapegsomatropin
Other interventions - Placebo
Treatment: Drugs - Somatropin

Experimental: Lonapegsomatropin - Lonapegsomatropin administered once-weekly by subcutaneous injection

Placebo comparator: Placebo - Placebo for Lonapegsomatropin administered once-weekly by subcutaneous injection

Active comparator: Somatropin - Somatropin administered once-daily by subcutaneous injection


Treatment: Drugs: 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.

Other interventions: 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.

Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from Baseline in Trunk Percent Fat
Timepoint [1] 0 0
38 weeks
Secondary outcome [1] 0 0
Incidence of Treatment-Emergent Adverse Events
Timepoint [1] 0 0
38 weeks
Secondary outcome [2] 0 0
Evaluate serum hGH, lonapegsomatropin, and mPEG levels
Timepoint [2] 0 0
38 weeks
Secondary outcome [3] 0 0
Evaluate serum IGF-1 and IGFBP-3 and IGF-1 SDS and IGFBP-3 SDS
Timepoint [3] 0 0
38 weeks
Secondary outcome [4] 0 0
Change from Baseline in Trunk Fat Mass
Timepoint [4] 0 0
38 weeks
Secondary outcome [5] 0 0
Change from Baseline in Total Body Lean Mass
Timepoint [5] 0 0
38 weeks

Eligibility
Key inclusion criteria
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).

A. 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)

* i. BMI =30 kg/m2: peak GH =3 ng/mL
* ii. BMI >30 kg/m2: peak GH =1 ng/mL
3. 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
4. Macimorelin test: peak GH =2.8 ng/mL
5. Growth hormone releasing hormone (GHRH) + arginine test according to BMI:

* i. BMI <25 kg/m2, peak GH <11 ng/mL
* ii. BMI =25-=30 kg/m2, peak GH <8 ng/mL
* iii. BMI >30 kg/m2, peak GH <4 ng/mL

B. 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
3. IGF-1 SDS = -1.0 at screening as measured by central laboratory.
4. hGH treatment naïve or no exposure to hGH therapy or GH secretagogue for at least 12 months prior to screening.
5. 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.
6. For subjects not on glucocorticoid replacement therapy, documentation of adequate adrenal function at screening defined.
7. For males not on testosterone replacement therapy: morning (6:00 - 10:00AM) total testosterone within normal limits for age.
8. 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.
9. No plans to undergo bariatric surgery during the trial.
10. 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.
11. Able and willing to provide a written informed consent and authorization for protected health information (PHI) disclosure in accordance with Good Clinical Practice (GCP).
12. Serum fT4 in the normal range at screening as measured by central laboratory.
Minimum age
23 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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:

1. Poorly controlled diabetes, defined as HbA1c >7.5% at screening.
2. 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
3. Change in diabetes regimen (includes dose adjustment) within <90 days prior and throughout screening
4. 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
5. 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)
3. Active malignant disease or history of malignancy. Exceptions to this exclusion criterion:

1. Resection of in situ carcinoma of the cervix uteri
2. Complete eradication of squamous cell or basal cell carcinoma of the skin
3. 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)
4. Evidence of growth of pituitary adenoma or other benign intracranial tumor within the last 12 months before screening.
5. Subjects with acromegaly without remission / with documented remission less than 24 months prior to screening.
6. Subjects with Cushing's disease without remission / with documented remission less than 24 months prior to screening.
7. Subjects with prior cranial irradiation or hypothalamic-pituitary surgery: the procedure took place less than 12 months prior to screening.
8. eGFR <60 mL/min/1.73m2 determined based on Modification of Diet in Renal Disease (MDRD) equation.
9. Hepatic transaminases (i.e., AST or ALT) >3 times the upper limit of normal.
10. Heart failure NYHA class 3 or greater (NYHA 1994).
11. QTcF = 451 milliseconds on 12-lead ECG at screening.
12. Poorly controlled hypertension, defined as supine systolic blood pressure >159 mmHg and/or supine diastolic blood pressure >95 mmHg at screening.
13. Cerebrovascular accident within 5 years prior to screening.
14. Anabolic steroids (other than gonadal steroid replacement therapy) or oral/intravenous/intramuscular corticosteroids within 90 days prior to or throughout screening.
15. 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, GLP-1 receptor agonists, 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.
16. Known history of hypersensitivity and/or idiosyncrasy to any of the test compounds (somatropin) or excipients employed in this trial.
17. Known history of neutralizing anti-hGH antibodies.
18. Inability to undergo scanning by DXA or a non-interpretable DXA scan at screening.
19. 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
20. 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.
21. 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).
22. 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.
23. Participation in another interventional clinical trial involving an investigational compound within 26 weeks prior to screening or in parallel to this trial.
24. Currently using or have used within the last 3 days prior to screening: biotin >0.03 mg/day from supplements
25. 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).
26. 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
3/12/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2023
Sample size
Target
Accrual to date
Final
264
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Ascendis Pharma Investigational Site - Saint Leonards
Recruitment hospital [2] 0 0
Ascendis Pharma Investigational Site - Sydney
Recruitment hospital [3] 0 0
Ascendis Pharma Investigational Site - Box Hill
Recruitment hospital [4] 0 0
Ascendis Pharma Investigational Site - Fitzroy
Recruitment hospital [5] 0 0
Ascendis Pharma Investigational Site - Parkville
Recruitment hospital [6] 0 0
Ascendis Pharma Investigational Site - Perth
Recruitment postcode(s) [1] 0 0
2065 - Saint Leonards
Recruitment postcode(s) [2] 0 0
2109 - Sydney
Recruitment postcode(s) [3] 0 0
3128 - Box Hill
Recruitment postcode(s) [4] 0 0
3065 - Fitzroy
Recruitment postcode(s) [5] 0 0
3050 - Parkville
Recruitment postcode(s) [6] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Indiana
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
Minnesota
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
Nevada
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United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
North Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Oregon
Country [14] 0 0
United States of America
State/province [14] 0 0
Pennsylvania
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
United States of America
State/province [16] 0 0
Washington
Country [17] 0 0
Armenia
State/province [17] 0 0
Yerevan
Country [18] 0 0
Canada
State/province [18] 0 0
British Columbia
Country [19] 0 0
Canada
State/province [19] 0 0
Nova Scotia
Country [20] 0 0
Denmark
State/province [20] 0 0
København
Country [21] 0 0
France
State/province [21] 0 0
Lyon
Country [22] 0 0
France
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Marseille
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France
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Nantes
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France
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Paris
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Georgia
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Tbilisi
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Germany
State/province [26] 0 0
Bayern
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Greece
State/province [27] 0 0
Attica
Country [28] 0 0
Greece
State/province [28] 0 0
Central Macedonia
Country [29] 0 0
Greece
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Thessaloníki
Country [30] 0 0
Israel
State/province [30] 0 0
Beer Sheva
Country [31] 0 0
Israel
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Haifa
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Israel
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Petah Tikva
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Israel
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Tel Aviv
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Italy
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Genova
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Italy
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Rome
Country [36] 0 0
Italy
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Rozzano
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Japan
State/province [37] 0 0
Hyogo
Country [38] 0 0
Japan
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Kanagawa
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Japan
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Nagano
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Japan
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Nara
Country [41] 0 0
Japan
State/province [41] 0 0
Okinawa
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Japan
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Osaka
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Japan
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Chiba
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Japan
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Fukuoka
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Japan
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Kagoshima
Country [46] 0 0
Japan
State/province [46] 0 0
Kawasaki
Country [47] 0 0
Japan
State/province [47] 0 0
Nagakute
Country [48] 0 0
Japan
State/province [48] 0 0
Okayama
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Japan
State/province [49] 0 0
Tokyo
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Japan
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Yamagata
Country [51] 0 0
Korea, Republic of
State/province [51] 0 0
Seoul
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Korea, Republic of
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Suwon
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Malaysia
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George Town
Country [54] 0 0
Malaysia
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Kota Bharu
Country [55] 0 0
Malaysia
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Melaka
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Malaysia
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Putrajaya
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Netherlands
State/province [57] 0 0
Leiden
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New Zealand
State/province [58] 0 0
Manawatu-Wanganui
Country [59] 0 0
New Zealand
State/province [59] 0 0
Wellington
Country [60] 0 0
Poland
State/province [60] 0 0
Kraków
Country [61] 0 0
Poland
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Poznan
Country [62] 0 0
Poland
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Warsaw
Country [63] 0 0
Poland
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Wroclaw
Country [64] 0 0
Poland
State/province [64] 0 0
Lódz
Country [65] 0 0
Romania
State/province [65] 0 0
Bucharest
Country [66] 0 0
Romania
State/province [66] 0 0
Iasi
Country [67] 0 0
Romania
State/province [67] 0 0
Timisoara
Country [68] 0 0
Serbia
State/province [68] 0 0
Belgrade
Country [69] 0 0
Serbia
State/province [69] 0 0
Kragujevac
Country [70] 0 0
Slovakia
State/province [70] 0 0
Bratislava
Country [71] 0 0
Slovakia
State/province [71] 0 0
Lubochna
Country [72] 0 0
Spain
State/province [72] 0 0
Alicante
Country [73] 0 0
Spain
State/province [73] 0 0
Barcelona
Country [74] 0 0
Spain
State/province [74] 0 0
Madrid
Country [75] 0 0
Spain
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Santiago De Compostela
Country [76] 0 0
Spain
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Sevilla
Country [77] 0 0
Turkey
State/province [77] 0 0
Ankara
Country [78] 0 0
Turkey
State/province [78] 0 0
Antalya
Country [79] 0 0
Turkey
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Aydin
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Turkey
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Izmir
Country [81] 0 0
Turkey
State/province [81] 0 0
Izmit
Country [82] 0 0
Turkey
State/province [82] 0 0
Kayseri
Country [83] 0 0
Ukraine
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Ivano-Frankivs'k
Country [84] 0 0
Ukraine
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Kharkiv
Country [85] 0 0
Ukraine
State/province [85] 0 0
Kyiv
Country [86] 0 0
Ukraine
State/province [86] 0 0
Vinnytsya
Country [87] 0 0
United Kingdom
State/province [87] 0 0
Cardiff
Country [88] 0 0
United Kingdom
State/province [88] 0 0
Coventry
Country [89] 0 0
United Kingdom
State/province [89] 0 0
Leeds

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Ascendis Pharma Endocrinology Division A/S
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT04615273