Impact of Vitamin D Therapy on Thyroid Function and Antibody Levels in Pediatric Graves' Disease: A Pilot Feasibility Trial
Phase: PHASE2
Conditions: Graves Disease, Graves' Disease, Hyperthyroidism
Sponsor: Northwell Health

 
 
 
PROTOCOL: INTERVENTION STUDY (CLINICAL TRIALS)  
Title: Impact of Vitamin D Therapy on Thyroid Function and Antibody Levels in Pediatric  
 
Graves’ Disease: A Pilot Feasibility Trial  
  
Protocol Number: 25-0285  
  
  
Principal Investigator:   
Name Sharon Hyman, MD  
Title Pediatric Endocrinologist  
Address 1991 Marcus Ave, Suite M100, New Hyde Park NY 11042  
Phone number 516 472 3750  
Email address  
  
Investigational Product Name(s): ergocalciferol  
  
  
PIND 176865 
  
  
Regulatory Sponsor (Sponsor-Investigator or IND/IDE holder, if applicable): NA  
 Name  
Address  
Phone number  
Email address  
  
Date of FDA IND Exemption: 4/30/2025 
  
  
  
  
  
  
  
  
  
 

 
Reference ID: 5581964 
  
  
  
Template version: xx,xx, 202  
 
PIND 176865 
EXEMPT 
Sharon Hyman, MD 
Cohen Childrens Medical Center 
1991 Marcus Ave 
Suite M100 
New Hyde Park, NY 11042 
Dear Dr. Hyman: 
We have received your submission dated April 10, 2025, for vitamin D2 (ergocalciferol). 
This submission contains an investigational new drug (IND) exemption request for the 
use of vitamin D2 (ergocalciferol) in a proposed clinical study. 
After reviewing the information contained in your submission, we have concluded that 
your study entitled, “Impact of Vitamin D Therapy on Thyroid Function and Antibody 
Levels in Pediatric Graves’ Disease: A Pilot Feasibility Trial”, meets all of the 
requirements for exemption from the investigational new drug (IND) regulations and, 
therefore, an IND is not required to conduct your investigation.  
The IND regulations [21 CFR 312.2(b)] state that the clinical investigation of a drug 
product, including a biological product, that is lawfully marketed in the United States, is 
exempt from the requirements for an IND if all of the following apply: 
(1) The investigation is not intended to be reported to FDA as a well-controlled study 
in support of a new indication for use, nor intended to be used to support any 
other significant change in the labeling for the drug. 
(2) The investigation is not intended to support a significant change in the 
advertising for a prescription drug product. 
(3) The investigation does not involve a change in route of administration, dosage 
level, or patient population, or other factor that significantly increases the risks (or 
decreases the acceptability of risks) associated with use of the drug product. 

PIND 176865 
Page 2 
U.S. Food and Drug Administration 
Silver 
Spring, 
MD 
20993 
www.fda.gov 
Reference ID: 5581964 
(4) The investigation is conducted in compliance with the requirements for 
institutional review (21 CFR 56) and informed consent (21 CFR 50). 
(5) The investigation is conducted in compliance with the requirements of 21 CFR 
312.7, i.e., the drug may not be represented as safe or effective, nor may it be 
commercially distributed, for the purposes for which it is under investigation. 
In addition, 21 CFR 312.2(b)(5) exempts from the IND requirements a clinical 
investigation that involves use of a placebo if the investigation does not otherwise 
require submission of an IND. 
We remind you that exemption from the requirements for an IND does not in any way 
exempt you from complying with the requirements for informed consent under 21 CFR 
50.20 or from initial and continuing Institutional Review Board review under 21 CFR 56. 
You are also responsible for complying with the applicable provisions of sections 402(i) 
and 402(j) of the Public Health Service Act (PHS Act) [42 U.S.C. §§ 282(i) and (j)], which 
was amended by Title VIII of the Food and Drug Administration Amendments Act of 
2007 (FDAAA) (Public Law No. 110-85, 121 Stat. 904). 
Title VIII of FDAAA amended the PHS Act by adding new section 402(j) [42 USC § 
282(j)], which expanded the current database known as ClinicalTrials.gov to include 
mandatory registration and reporting of results for applicable clinical trials of human 
drugs (including biological products) and devices. Please note that, if in the future you 
submit an application under sections 505, 515, or 520(m) of the FDCA [21 USC §§ 355, 
360(e), or 360(j)(m)], or under section 351 of the PHS Act (21 U.S.C. § 262), or you 
submit a report under section 510(k) of the FDCA [21 USC § 360(k)], the application or 
submission must be accompanied by a certification that all applicable requirements of 
section 402(j) of the PHS Act [42 USC § 282(j)] have been met. Where available, such 
certification must include the appropriate National Clinical Trial (NCT) control numbers 
[42 USC § 282(j)(5)(B)]. Additional information regarding the certification is available at  
FDA.gov.1 Additional information regarding Title VIII of FDAAA is available at NIH.gov.2  
Additional information on registering your clinical trial(s) is available at the Protocol 
Registration System website.3  
For additional information about IND regulations, you can check our web site.4 
 
1 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/form-fda-3674-
certificationsaccompany-drug-biological-product-and-device-applicationssubmissions 
2 http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-014.html 
3 http://prsinfo.clinicaltrials.gov/ 
4 http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm 

 
Reference ID: 5581964 
SUBMISSION REQUIREMENTS 
For archival and documentation purposes only, we have assigned a Pre-Investigational 
New Drug Application (PIND) number for this drug product. Cite the PIND number listed 
above at the top of the first page of any communications concerning this application.  
Electronic submissions: 
You may choose to submit future amendments, that are not in eCTD format, to your 
PIND electronically via the FDA CDER NextGen Portal. You will need to request an  

PIND 176865 
Page 4 
U.S. Food and Drug Administration 
Silver 
Spring, 
MD 
20993 
www.fda.gov 
Reference ID: 5581964 
account in order to log in and utilize the portal. For additional information, see  
FDA.gov.5,6 
If you choose to submit future amendments to your PIND electronically in eCTD format, 
the FDA Electronic Submissions Gateway (ESG) is the central transmission point, and you 
should obtain an ESG account. For additional information, see FDA.gov.7 
Paper submissions: 
FDA will also accept submissions in paper and on certain physical media (e.g. CDs, 
DVDs (up to 6 pieces), external hard drives); a printed copy of the cover letter should be 
included with submissions on electronic media. Send all submissions, electronic or paper, 
including those sent by overnight mail or courier, to the following address: 
Food and Drug Administration 
Center for Drug Evaluation and Research 
Central Document Room 
5901-B Ammendale Road 
Beltsville, MD 20705-1266 
All regulatory documents submitted in paper should be three-hole punched on the left 
side of the page and bound. The left margin should be at least three-fourths of an inch 
to assure text is not obscured in the fastened area. Standard paper size (8-1/2 by 11 
inches) should be used; however, it may occasionally be necessary to use individual 
pages larger than standard paper size. Non-standard, large pages should be folded and 
mounted to allow the page to be opened for review without disassembling the jacket 
and refolded without damage when the volume is shelved. Shipping unbound 
documents may result in the loss of portions of the submission or an unnecessary delay 
in processing which could have an adverse impact on the review of the submission. For 
additional information, see FDA.gov.8 
If you have any questions, contact Elisabeth Hanan, Chief, Project Management Staff, 
at 240-402-0350 or Elisabeth.Hanan@fda.hhs.gov. 
Sincerely, 
{See appended electronic signature page} 
Theresa E. Kehoe, MD 
 
5 https://edm.fda.gov/ 
6 https://www.fda.gov/media/128774/download 
7 http://www.fda.gov/ForIndustry/ElectronicSubmissionsGateway  
8 https://www.fda.gov/drugs/investigational-new-drug-ind-application/information-sponsor-investigatorssubmitting-
investigational-new-drug-applications-inds 

 
Reference ID: 5581964 
Director 
Division of General Endocrinology 
Office of Cardiology, Hematology, Endocrinology, 
and Nephrology Office of New Drugs 
Center for Drug Evaluation and Research

PIND 176865 
Page 6 
U.S. Food and Drug Administration 
Silver 
Spring, 
MD 
20993 
www.fda.gov 
Reference ID: 5581964 
Signature Page 1 of 1 
-------------------------------------------------------------------------------------------- 
This is a representation of an electronic record that was signed 
electronically. Following this are manifestations of any and all 
electronic signatures for this electronic record. 
-------------------------------------------------------------------------------------------- 
/s/ 
------------------------------------------------------------ 
THERESA E KEHOE 
04/30/2025 12:13:05 PM 

PIND 176865
EXEMPT
Sharon Hyman, MD
Cohen Childrens Medical Center
1991 Marcus Ave
Suite M100
New Hyde Park, NY 11042
Dear Dr. Hyman:
We have received your submission dated April 10, 2025, for vitamin D2 (ergocalciferol). 
This submission contains an investigational new drug (IND) exemption request for the 
use of vitamin D2 (ergocalciferol) in a proposed clinical study.
After reviewing the information contained in your submission, we have concluded that 
your study entitled, “Impact of Vitamin D Therapy on Thyroid Function and Antibody 
Levels in Pediatric Graves’ Disease: A Pilot Feasibility Trial”, meets all of the 
requirements for exemption from the investigational new drug (IND) regulations and, 
therefore, an IND is not required to conduct your investigation. 
The IND regulations [21 CFR 312.2(b)] state that the clinical investigation of a drug 
product, including a biological product, that is lawfully marketed in the United States, is 
exempt from the requirements for an IND if all of the following apply:
(1) The investigation is not intended to be reported to FDA as a well-controlled study 
in support of a new indication for use, nor intended to be used to support any 
other significant change in the labeling for the drug.
(2) The investigation is not intended to support a significant change in the 
advertising for a prescription drug product.
(3) The investigation does not involve a change in route of administration, dosage 
level, or patient population, or other factor that significantly increases the risks (or 
decreases the acceptability of risks) associated with use of the drug product.
(4) The investigation is conducted in compliance with the requirements for 
institutional review (21 CFR 56) and informed consent (21 CFR 50).
(5) The investigation is conducted in compliance with the requirements of 
21 CFR 312.7, i.e., the drug may not be represented as safe or effective, nor 
may it be commercially distributed, for the purposes for which it is under 
investigation.
Reference ID: 5581964

PIND 176865
Page 2
U.S. Food and Drug Administration
Silver Spring, MD 20993
www.fda.gov
In addition, 21 CFR 312.2(b)(5) exempts from the IND requirements a clinical 
investigation that involves use of a placebo if the investigation does not otherwise 
require submission of an IND.
We remind you that exemption from the requirements for an IND does not in any way 
exempt you from complying with the requirements for informed consent under 21 CFR 
50.20 or from initial and continuing Institutional Review Board review under 21 CFR 56. 
You are also responsible for complying with the applicable provisions of sections 402(i) 
and 402(j) of the Public Health Service Act (PHS Act) [42 U.S.C. §§ 282(i) and (j)], 
which was amended by Title VIII of the Food and Drug Administration Amendments Act 
of 2007 (FDAAA) (Public Law No. 110-85, 121 Stat. 904).
Title VIII of FDAAA amended the PHS Act by adding new section 402(j) [42 USC 
§ 282(j)], which expanded the current database known as ClinicalTrials.gov to include 
mandatory registration and reporting of results for applicable clinical trials of human 
drugs (including biological products) and devices. Please note that, if in the future you 
submit an application under sections 505, 515, or 520(m) of the FDCA [21 USC §§ 355, 
360(e), or 360(j)(m)], or under section 351 of the PHS Act (21 U.S.C. § 262), or you 
submit a report under section 510(k) of the FDCA [21 USC § 360(k)], the application or 
submission must be accompanied by a certification that all applicable requirements of 
section 402(j) of the PHS Act [42 USC § 282(j)] have been met. Where available, such 
certification must include the appropriate National Clinical Trial (NCT) control numbers 
[42 USC § 282(j)(5)(B)]. Additional information regarding the certification is available at 
FDA.gov.1 Additional information regarding Title VIII of FDAAA is available at NIH.gov.2 
Additional information on registering your clinical trial(s) is available at the Protocol 
Registration System website.3 
For additional information about IND regulations, you can check our web site.4
SUBMISSION REQUIREMENTS
For archival and documentation purposes only, we have assigned a Pre-Investigational 
New Drug Application (PIND) number for this drug product. Cite the PIND number listed 
above at the top of the first page of any communications concerning this application. 
Electronic submissions:
You may choose to submit future amendments, that are not in eCTD format, to your 
PIND electronically via the FDA CDER NextGen Portal. You will need to request an 
1 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/form-fda-3674-certifications-
accompany-drug-biological-product-and-device-applicationssubmissions
2 http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-014.html
3 http://prsinfo.clinicaltrials.gov/
4 http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm
Reference ID: 5581964

PIND 176865
Page 3
U.S. Food and Drug Administration
Silver Spring, MD 20993
www.fda.gov
account in order to log in and utilize the portal. For additional information, see 
FDA.gov.5,6
If you choose to submit future amendments to your PIND electronically in eCTD format, 
the FDA Electronic Submissions Gateway (ESG) is the central transmission point, and 
you should obtain an ESG account. For additional information, see FDA.gov.7
Paper submissions:
FDA will also accept submissions in paper and on certain physical media (e.g. CDs, 
DVDs (up to 6 pieces), external hard drives); a printed copy of the cover letter should be 
included with submissions on electronic media. Send all submissions, electronic or 
paper, including those sent by overnight mail or courier, to the following address:
Food and Drug Administration
Center for Drug Evaluation and Research
Central Document Room
5901-B Ammendale Road
Beltsville, MD 20705-1266
All regulatory documents submitted in paper should be three-hole punched on the left 
side of the page and bound. The left margin should be at least three-fourths of an inch 
to assure text is not obscured in the fastened area. Standard paper size (8-1/2 by 11 
inches) should be used; however, it may occasionally be necessary to use individual 
pages larger than standard paper size. Non-standard, large pages should be folded and 
mounted to allow the page to be opened for review without disassembling the jacket 
and refolded without damage when the volume is shelved. Shipping unbound 
documents may result in the loss of portions of the submission or an unnecessary delay 
in processing which could have an adverse impact on the review of the submission. For 
additional information, see FDA.gov.8
5 https://edm.fda.gov/
6 https://www.fda.gov/media/128774/download
7 http://www.fda.gov/ForIndustry/ElectronicSubmissionsGateway 
8 https://www.fda.gov/drugs/investigational-new-drug-ind-application/information-sponsor-investigators-
submitting-investigational-new-drug-applications-inds
Reference ID: 5581964

PIND 176865
Page 4
U.S. Food and Drug Administration
Silver Spring, MD 20993
www.fda.gov
If you have any questions, contact Elisabeth Hanan, Chief, Project Management Staff,
at 240-402-0350 or Elisabeth.Hanan@fda.hhs.gov.
Sincerely,
{See appended electronic signature page}
Theresa E. Kehoe, MD
Director
Division of General Endocrinology
Office of Cardiology, Hematology, Endocrinology, 
and Nephrology
Office of New Drugs
Center for Drug Evaluation and Research
Reference ID: 5581964

--------------------------------------------------------------------------------------------
This is a representation of an electronic record that was signed
electronically. Following this are manifestations of any and all
electronic signatures for this electronic record.
--------------------------------------------------------------------------------------------
/s/
------------------------------------------------------------
THERESA E KEHOE
04/30/2025 12:13:05 PM
Signature Page 1 of 1
Reference ID: 5581964