The Pediatric Artificial Pancreas (PEDAP) Trial: A Randomized Controlled Comparison of the Control-IQ Technology Versus Standard of Care in Young Children in Type 1 Diabetes
Phase: NA
Conditions: Type 1 Diabetes
Sponsor: Marc Breton

The Pediatric Artificial Pancreas (PEDAP) trial: A 
1 
Randomized Controlled Comparison of the Control-
2 
IQ technology Versus Standard of Care in Young 
3 
Children in Type 1 Diabetes 
4 
Study Sponsor 
5 
Marc D. Breton, Ph.D. 
6 
University of Virginia 
7 
Center for Diabetes Technology 
8 
 Protocol Chair 
9 
R. Paul Wadwa, MD 
10 
Barbara Davis Center 
11 
University of Colorado 
12 
Participating Institutions 
13 
University of Virginia, Charlottesville, Virginia 
14 
Barbara Davis Center, University of Colorado, Colorado 
15 
Stanford University, California 
16 
 
17 
Coordinating Center 
18 
Jaeb Center for Health Research 
19 
 
20 
 
21 
 
22 
 
 
Version Number: v11.0  / NCT#04796779 
23 
DECEMBER 3, 2021 
24 

 
 
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KEY ROLES 
25 
 
Sponsor Chair / IDE Chair 
 
Name, degree 
Marc D. Breton, Ph.D. 
Institution Name 
University of Virginia, Center for Diabetes Technology 
 
 
Protocol Chair/Director 
 
Name, degree 
R. Paul Wadwa, MD 
Institution Name 
Barbara Davis Center, University of Colorado  
 
JCHR Coordinating Center Director 
 
Name, degree 
John Lum, MS 
Institution Name 
Jaeb Center for Health Research 
 
Medical Monitor 
 
Name, degree 
Roy Beck, M.D., Ph.D. 
Institution Name 
Jaeb Center for Health Research 
 
26 
 
 
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PROTOCOL VERSION HISTORY 
28 
Version 
Number 
Author(s) 
Approver 
Effective 
Date 
Revision Description 
1.0 
R. Paul Wadwa 
John Lum 
Roy Beck 
R. Paul Wadwa 
23 Nov 2020 
Original protocol   
2.0 
John Lum 
R. Paul Wadwa 
21 Dec 2020 
Pre-clinical revisions to accommodate requests 
for changes by IRB and FDA reviewers 
3.0 
John Lum 
R. Paul Wadwa 
13 Jan 2021 
Pre-clinical revisions to accommodate request by 
IRB reviewers for changes to framing of 
extension phase participation 
4.0 
John Lum 
R. Paul Wadwa 
29 Jan 2021 
Pre-clinical revisions to visit window details in 
Chapters 5 and 6 to ensure that window 
definitions are consistent between RCT and 
Extension period and that associated body text 
agrees with visit window table text. Initial 
version used for study. 
5.0 
Shannon Hiser, John 
Lum 
R. Paul Wadwa 
7 May 2021 
Addition of inclusion criterion requiring U.S. 
residency; typo correction in 9.2.4 
6.0 
John Lum 
R. Paul Wadwa 
16 Jun 2021 
Addition of SUS Questionnaire, addition of the 
use of the new version of Control-IQ for the 
extension phase of the study, updated statistical 
analyses for the extension phase of the study. 
7.0 
John Lum 
R. Paul Wadwa 
15 Jul 2021 
Per FDA request, inclusion of all study 
participants in the 13 week + 3 day call, 14-week 
call, and 15-week visit 
8.0 
John Lum 
R. Paul Wadwa 
10 Sep 2021 
Addition of ancillary study during Extension 
Phase to obtain system performance data during 
meal/exercise challenges; associated revisions to 
Stats chapter, plus minor unrelated Stats edits. 
9.0 
John Lum 
R. Paul Wadwa 
04 Oct 2021 
Revisions to exercise and meal bolus challenges 
to address FDA requests during IDE review 
10.0 
John Lum 
R. Paul Wadwa 
26 Oct 2021 
Revisions to exercise and meal bolus challenges 
to address IRB requests during IRB review 
11.0 
John Lum 
R. Paul Wadwa 
03 Dec 2021 
Introduction of Extended Use period 
 
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TABLE OF CONTENTS 
30 
CHAPTER 1: BACKGROUND INFORMATION ............................................................................................. 22 
31 
 Introduction .......................................................................................................................... 22 
32 
 Rationale .............................................................................................................................. 22 
33 
 Potential Risks and Benefits of the Investigational Device ................................................. 23 
34 
1.3.1 Known Potential Risks ................................................................................................... 23 
35 
1.3.1.1 Potential Risks and Benefits of the CLC System .................................................. 23 
36 
1.3.1.2 Risk of Hypoglycemia ........................................................................................... 23 
37 
1.3.1.3 Risk of Hyperglycemia .......................................................................................... 23 
38 
1.3.1.4 Fingerstick Risks .................................................................................................... 23 
39 
1.3.1.5 Subcutaneous Catheter Risks (CGM) .................................................................... 23 
40 
1.3.1.6 Risk of Device Reuse ............................................................................................. 24 
41 
1.3.1.7 Questionnaires and Focus Groups ......................................................................... 24 
42 
1.3.1.8 Other Risks ............................................................................................................ 24 
43 
1.3.2 Known Potential Benefits .............................................................................................. 25 
44 
1.3.3 Risk Assessment ............................................................................................................ 25 
45 
 General Considerations ........................................................................................................ 25 
46 
CHAPTER 2: STUDY ENROLLMENT AND SCREENING .............................................................................. 27 
47 
 Participant Recruitment and Enrollment.............................................................................. 27 
48 
2.1.1 Informed Consent and Authorization Procedures .......................................................... 27 
49 
 Participant Inclusion Criteria ............................................................................................... 27 
50 
 Participant Exclusion Criteria .............................................................................................. 28 
51 
 Eligibility Assessment and Baseline Data Collection.......................................................... 29 
52 
 Historical Information.......................................................................................................... 29 
53 
 Screening Testing and Procedures ....................................................................................... 29 
54 
 Screen Failures ..................................................................................................................... 30 
55 
CHAPTER 3: CGM RUN-IN PHASE............................................................................................................ 31 
56 
 CGM Run-in Phase Overview ............................................................................................. 31 
57 
 Initiation of CGM ................................................................................................................ 31 
58 
3.2.1 CGM Training ................................................................................................................ 31 
59 
 Blood Glucose and Ketone Testing ..................................................................................... 32 
60 
 Assessment of Successful Completion of the Run-in Phase................................................ 32 
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 Optimization of Insulin Therapy.......................................................................................... 33 
62 
CHAPTER 4: RANDOMIZATION VISIT ....................................................................................................... 34 
63 
 Visit Timing ......................................................................................................................... 34 
64 
4.1.1 Randomization ............................................................................................................... 34 
65 
4.1.2 Baseline HbA1c Determination ..................................................................................... 34 
66 
CHAPTER 5: MAIN STUDY PROCEDURES ................................................................................................. 35 
67 
 Visit and Contact Schedule .................................................................................................. 35 
68 
 CGM Initiation and Training ............................................................................................... 35 
69 
 Procedures for the CLC Group ............................................................................................ 35 
70 
5.3.1 Study Pump Training ..................................................................................................... 35 
71 
5.3.2 Initiation of Pump by MDI Participants......................................................................... 36 
72 
5.3.3 System Use Guidelines .................................................................................................. 37 
73 
5.3.4 Home Use of the Study System ..................................................................................... 37 
74 
5.3.5 Study Device Download ................................................................................................ 38 
75 
5.3.6 3-Day Phone Contact ..................................................................................................... 38 
76 
5.3.7 1-Week Phone Contact .................................................................................................. 38 
77 
5.3.8 2-Week Visit .................................................................................................................. 38 
78 
 Procedures for the SC Group ............................................................................................... 39 
79 
5.4.1 Study Device Data Download ........................................................................................ 39 
80 
5.4.2 1-Week Phone Contact .................................................................................................. 39 
81 
5.4.3 2-Week Visit .................................................................................................................. 39 
82 
 Follow-up Visits and Phone Contacts for Both Groups ...................................................... 40 
83 
5.5.1 Visits .............................................................................................................................. 40 
84 
5.5.2 Phone Contacts............................................................................................................... 40 
85 
5.5.3 Optimization of Insulin Therapy .................................................................................... 40 
86 
5.5.4 13-Week Visit ................................................................................................................ 41 
87 
 Early Termination Visit (If Applicable) .............................................................................. 41 
88 
 Unscheduled Visits .............................................................................................................. 41 
89 
CHAPTER 6: EXTENSION PHASE PROCEDURES ....................................................................................... 42 
90 
 Visit and Contact Schedule .................................................................................................. 42 
91 
 Study Pump Initiation .......................................................................................................... 42 
92 
 Visits, Videoconferences, and Phone Calls for All Participants.......................................... 43 
93 
6.3.1 13-Week + 3-Day Phone Contact .................................................................................. 43 
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6.3.2 14-Week Phone Contact ................................................................................................ 43 
95 
6.3.3 15-Week Visit ................................................................................................................ 43 
96 
6.3.4 19-Week Visit ................................................................................................................ 43 
97 
6.3.5 23-Week Phone Call ...................................................................................................... 43 
98 
6.3.6 26-Week Visit ................................................................................................................ 43 
99 
6.3.7 Optimization of Insulin Therapy .................................................................................... 43 
100 
 Unscheduled Visits .............................................................................................................. 43 
101 
 Participant Access to Study Device at Study Closure ......................................................... 44 
102 
CHAPTER 7: EXTENDED USE PERIOD PROCEDURES ............................................................................... 45 
103 
 Visit and Contact Schedule .................................................................................................. 45 
104 
 Visits, Videoconferences, and Phone Calls for Participants Re-Initiating Study Pump Use 
105 
After a Gap in Use ..................................................................................................................... 45 
106 
7.2.1 Study Pump Retraining Visit ......................................................................................... 45 
107 
7.2.2 3-Day Phone Contact ..................................................................................................... 46 
108 
7.2.3 1-Week Phone Contact .................................................................................................. 46 
109 
 Visits, Videoconferences, and Phone Calls for All Participants.......................................... 46 
110 
7.3.1 13-Week Visit and Subsequent Visits Every 13 Weeks ................................................ 46 
111 
7.3.2 Final Visit....................................................................................................................... 46 
112 
7.3.3 Optimization of Insulin Therapy .................................................................................... 46 
113 
 Unscheduled Visits .............................................................................................................. 47 
114 
 Participant Access to Study Device at Study Closure ......................................................... 47 
115 
CHAPTER 8: STUDY DEVICES .................................................................................................................... 48 
116 
 Description of the Investigational Device ........................................................................... 48 
117 
8.1.1 Insulin Pump .................................................................................................................. 48 
118 
8.1.2 Continuous Glucose Monitoring .................................................................................... 48 
119 
8.1.3 Blood Glucose Meter and Strips .................................................................................... 48 
120 
8.1.4 Ketone Meter and Strips ................................................................................................ 48 
121 
8.1.5 Study Device Accountability Procedures ...................................................................... 48 
122 
8.1.6 Blood Ketone Testing .................................................................................................... 48 
123 
 Safety Measures ................................................................................................................... 48 
124 
8.2.1 CGM Calibration ........................................................................................................... 48 
125 
8.2.2 System Failure ............................................................................................................... 49 
126 
8.2.3 Hypoglycemia Threshold Alert and Safety Protocol ..................................................... 49 
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8.2.4 Hyperglycemia Threshold Alert and Safety Protocol .................................................... 49 
128 
CHAPTER 9: TESTING PROCEDURES, QUESTIONNAIRES, AND FOCUS GROUPS .................................... 51 
129 
 Laboratory Testing ............................................................................................................... 51 
130 
9.1.1 HbA1c: ........................................................................................................................... 51 
131 
 Questionnaires ..................................................................................................................... 51 
132 
9.2.1 PedsQL Diabetes Module – Parent ................................................................................ 51 
133 
9.2.2 Pediatric Inventory for Parents ...................................................................................... 51 
134 
9.2.3 INSPIRE Survey – Parent .............................................................................................. 51 
135 
9.2.4 Pittsburgh Sleep Quality Index (PSQI) – Parent............................................................ 52 
136 
9.2.5 Hypoglycemia Fear Survey-Parent (HFS-P) ................................................................. 52 
137 
9.2.6 Hypoglycemia Confidence Scale ................................................................................... 52 
138 
9.2.7 System Usability Scale (SUS) ....................................................................................... 52 
139 
 Focus Groups ....................................................................................................................... 53 
140 
CHAPTER 10: UNANTICIPATED PROBLEM, ADVERSE EVENT, AND DEVICE ISSUES REPORTING ........ 54 
141 
 Unanticipated Problems ..................................................................................................... 54 
142 
 Adverse Events .................................................................................................................. 54 
143 
10.2.1 Definitions.................................................................................................................... 54 
144 
10.2.2 Reportable Adverse Events .......................................................................................... 55 
145 
10.2.3 Hypoglycemic Events .................................................................................................. 56 
146 
10.2.4 Hyperglycemic/Ketotic Events .................................................................................... 56 
147 
10.2.5 Relationship of Adverse Event to Study Device.......................................................... 57 
148 
10.2.6 Severity (Intensity) of Adverse Events ........................................................................ 57 
149 
10.2.7 Expectedness ................................................................................................................ 58 
150 
10.2.8 Coding of Adverse Events ........................................................................................... 58 
151 
10.2.9 Outcome of Adverse Events ........................................................................................ 58 
152 
 Reportable Device Issues ................................................................................................... 59 
153 
 Timing of Event Reporting ................................................................................................ 59 
154 
 Safety Oversight ................................................................................................................ 60 
155 
 Stopping Criteria ................................................................................................................ 60 
156 
10.6.1 Participant Discontinuation of Study Device ............................................................... 60 
157 
10.6.2 Criteria for Suspending or Stopping Overall Study ..................................................... 61 
158 
CHAPTER 11: MISCELLANEOUS CONSIDERATIONS ................................................................................. 62 
159 
 Drugs Used as Part of the Protocol .................................................................................... 62 
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 Collection of Medical Conditions and Medications .......................................................... 62 
161 
 Prohibited Medications, Devices, Treatments, and Procedures......................................... 62 
162 
 Precautionary Medications, Treatments, and Procedures .................................................. 62 
163 
 Prophylactic Medications, Treatments, and Procedures .................................................... 62 
164 
 Rescue Medications, Treatments, and Procedures............................................................. 63 
165 
 Participant Compensation .................................................................................................. 63 
166 
 Participant Withdrawal ...................................................................................................... 63 
167 
 Confidentiality ................................................................................................................... 63 
168 
CHAPTER 12: STATISTICAL CONSIDERATION ......................................................................................... 64 
169 
 Statistical and Analytical Plans.......................................................................................... 64 
170 
 Statistical Hypotheses ........................................................................................................ 64 
171 
 Sample Size........................................................................................................................ 64 
172 
 Efficacy Outcome Measures .............................................................................................. 65 
173 
12.4.1 Primary Efficacy Endpoint .......................................................................................... 65 
174 
12.4.2 Secondary Efficacy Endpoints ..................................................................................... 65 
175 
12.4.2.1 Secondary Efficacy Endpoints Included in Hierarchical Analysis ...................... 65 
176 
12.4.2.2 Other Secondary Efficacy Endpoints ................................................................... 65 
177 
12.4.3 CGM Metrics Calculations .......................................................................................... 66 
178 
 Analysis Datasets and Sensitivity Analyses ...................................................................... 67 
179 
12.5.1 Per Protocol Analyses .................................................................................................. 67 
180 
12.5.2 Other Sensitivity Analyses ........................................................................................... 67 
181 
 Analysis of the Primary Efficacy Endpoint ....................................................................... 68 
182 
 Analysis of the Secondary Endpoints ................................................................................ 68 
183 
12.7.1 Hierarchical Analyses .................................................................................................. 68 
184 
12.7.2 Other Endpoint Analyses ............................................................................................. 69 
185 
 Safety Analyses.................................................................................................................. 70 
186 
 Intervention Adherence...................................................................................................... 71 
187 
 Protocol Adherence and Retention .................................................................................. 71 
188 
 Baseline Descriptive Statistics ......................................................................................... 71 
189 
 Device Issues ................................................................................................................... 72 
190 
 Planned Interim Analyses ................................................................................................ 72 
191 
 Subgroup Analyses .......................................................................................................... 72 
192 
 Multiple Comparison/Multiplicity ................................................................................... 73 
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 Exploratory Analyses ....................................................................................................... 73 
194 
 Extension Phase ............................................................................................................... 74 
195 
12.17.1 Exclusion of Ancillary Study Data ............................................................................ 75 
196 
 Extended Use Period ........................................................................................................ 75 
197 
CHAPTER 13: DATA COLLECTION AND MONITORING ............................................................................ 76 
198 
 Case Report Forms and Device Data ................................................................................. 76 
199 
 Study Records Retention ................................................................................................... 76 
200 
 Quality Assurance and Monitoring .................................................................................... 76 
201 
 Protocol Deviations............................................................................................................ 77 
202 
CHAPTER 14: ETHICS/PROTECTION OF HUMAN PARTICIPANTS ............................................................ 78 
203 
 Ethical Standard ................................................................................................................. 78 
204 
 Institutional Review Boards............................................................................................... 78 
205 
 Informed Consent Process ................................................................................................. 78 
206 
14.3.1 Consent Procedures and Documentation ..................................................................... 78 
207 
14.3.2 Participant and Data Confidentiality ............................................................................ 78 
208 
CHAPTER 15: ANCILLARY STUDY TO TEST CONTROL-IQ SYSTEM WITH MEAL BOLUS AND EXERCISE 
209 
CHALLENGES ............................................................................................................................................. 80 
210 
 Objective ............................................................................................................................ 80 
211 
 Sample Size........................................................................................................................ 80 
212 
 Eligibility Criteria .............................................................................................................. 80 
213 
 Study Procedures ............................................................................................................... 80 
214 
 Outcomes and Analysis Plan ............................................................................................. 82 
215 
Safety Monitoring ...................................................................................................................... 83 
216 
CHAPTER 16: REFERENCES ....................................................................................................................... 84 
217 
218 

 
 
 
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LIST OF ABBREVIATIONS 
219 
ABBREVIATION 
DEFINITION 
AP 
Artificial Pancreas 
BG 
Blood Glucose 
BT/BTLE 
Bluetooth, Bluetooth low energy 
CRF 
Case Report Form 
CGM 
Continuous Glucose Monitoring System  
CLC 
Closed-Loop Control 
CSII 
Continuous Subcutaneous Insulin Injection 
CTR 
Control-to-Range 
DiAs 
Diabetes Assistant 
DKA 
Diabetic Ketoacidosis 
EC 
European Commission 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HbA1c 
Hemoglobin A1c 
ID 
Identification 
iDCL 
International Diabetes Closed Loop 
IDE 
Investigational Device Exemption 
IOB 
Insulin-on-Board 
IQR 
Interquartile Range 
JDRF 
Juvenile Diabetes Research Foundation 
LGS 
Low Glucose Suspend 
PLGS 
Predictive Low Glucose Suspend 
POC 
Point-of-Care 
QA 
Quality Assurance 
QC 
Quality Control 
RBM 
Risk-Based Monitoring 
RCT 
Randomized Control Trial 
SC 
Standard of Care group 
SD 
Standard Deviation 
TDD 
Total Daily Dose 
UI 
User Interface 
 
220 
221 

 
 
 
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Signature Page 
222 
Translation of the UVA Advanced Automated Insulin Delivery 
223 
Systems to Clinical Care in Young Children: Glycemic Control, 
224 
Regulatory Acceptance, and Optimization of Day to Day Use 
225 
Protocol Identifying Number: PEDAP 
226 
IND/IDE Sponsor: University of Virginia 
227 
Version Number: 11.0 
228 
03 DEC 2021 
229 
 
Protocol Chair 
 
Name, Institution 
R. Paul Wadwa, M.D. / University of Colorado – Barbara Davis Center 
Signature/Date 
 
 
Sponsor (IDE Holder) 
 
Name/Institution 
Marc D. Breton, Ph.D. / University of Virginia 
Signature/Date 
 
 
Coordinating Center Director 
 
Name, Institution 
John Lum, MS / Jaeb Center for Health Research 
Signature/Date 
 
 
Medical Monitor 
 
Name, Institution 
Roy Beck, MD, Ph.D. / Jaeb Center for Health Research 
Signature/Date 
 

 
 
 
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CLINICAL CENTER PRINCIPAL INVESTIGATOR STATEMENT OF 
230 
COMPLIANCE 
231 
Protocol Title: The Pediatric Artificial Pancreas (PEDAP) trial: A Randomized Controlled 
232 
Comparison of the Control-IQ technology Versus Standard of Care in Young Children in 
233 
Type 1 Diabetes 
234 
Protocol Version/Date: 11.0 / 03 DEC 2021 
235 
I have read the protocol specified above.  In my formal capacity as a Clinical Center Principal 
236 
Investigator, my duties include ensuring the safety of the study participants enrolled under my 
237 
supervision and providing the Jaeb Center for Health Research, with complete and timely 
238 
information, as outlined in the protocol.  It is understood that all information pertaining to the 
239 
study will be held strictly confidential and that this confidentiality requirement applies to all 
240 
study staff at this clinical center. 
241 
This trial will be carried out in accordance with ICH E6 Good Clinical Practice (GCP) and as 
242 
required by the following: United States (US) Code of Federal Regulations (CFR) applicable to 
243 
clinical studies (45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 
244 
CFR Part 812). 
245 
As the Principal Investigator, I will assure that no deviation from, or changes to the protocol 
246 
will take place without prior agreement from the sponsor and documented approval from the 
247 
Institutional Review Board (IRB), or other approved Ethics Committee, except where necessary 
248 
to eliminate an immediate hazard(s) to the trial participants. 
249 
All key personnel (all individuals responsible for the design and conduct of this trial) have 
250 
completed Human Participants Protection Training and Good Clinical Practice Training.  
251 
Further, I agree to ensure that all staff members involved in the conduct of this study are 
252 
informed about their obligations in meeting the above commitments. 
253 
Investigator’s Signature __________________________________ Date: _____ / _____ / _____ 
254 
 
dd 
mmm 
yyyy 
255 
Investigator’s Name: ____________________________________ 
256 
Clinical Center Name/Number: _____________________________________ 
257 

 
 
 
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PROTOCOL SUMMARY 
258 
PARTICIPANT AREA 
DESCRIPTION 
Title 
The Pediatric Artificial Pancreas (PEDAP) trial: A Randomized 
Controlled Comparison of the Control-IQ technology Versus Standard 
Care in Young Children in Type 1 Diabetes 
Précis 
A randomized controlled trial of at-home closed loop system vs. standard 
care (defined as either multiple daily injections of insulin [MDI] or use of 
an insulin pump without hybrid closed-loop control capabilities [low-
glucose suspend or predictive low-glucose suspend functionality is 
permitted]) in youth age 2 to <6 years old. 
Investigational Device 
t:slim X2 with Control-IQ and Dexcom G6 system 
Objectives 
The objective of the study is to assess efficacy, quality of life, and safety 
of a closed loop control (CLC) system (t:slim X2 with Control-IQ 
Technology) in a randomized controlled trial with partial crossover. 
Study Design 
First phase: a 13-week parallel group randomized clinical trial with 2:1 
randomization to intervention with the closed loop system vs. standard 
care (SC); Second Phase: following the RCT, a 13-week period where the 
Standard Care (SC) group will transition to use CLC and the experimental 
arm will extend the use of CLC for the same period. After 26 weeks, 
participants may continue using CLC for an additional Extended Use 
period. A subset of participants will be invited to join an optional 
exercise/meal challenge ancillary study. 
Number of Clinical Centers 
~3 US clinical centers 
Endpoints 
Efficacy 
The primary outcome for the RCT is time in target range 70-180 mg/dL 
(TIR) measured by CGM in CLC group vs. SC group over 13 weeks 
The primary outcome for the extension phase assessed separately for each 
treatment group is change in TIR comparing extension phase with RCT 
phase.  
 
Quality of Life 
Patient-reported outcome questionnaires will be completed. 
 
Safety 
The key safety outcomes are severe hypoglycemia and ketoacidosis. 
Population 
Inclusion Criteria 
1. 
Clinical diagnosis, based on investigator assessment, of type 1 
diabetes for at least 6 months and using insulin for at least 6 months  
2. 
Familiarity and use of a carbohydrate ratio for meal boluses. 
3. 
Age ≥2 and <6 years old 
4. 
Living with one or more parent/legal guardian knowledgeable about 
emergency procedures for severe hypoglycemia and able to contact 
emergency services and study staff. 
5. 
Investigator has confidence that the parent can successfully operate 
all study devices and is capable of adhering to the protocol 
6. 
Willingness to switch to lispro (Humalog) or aspart (Novolog) if not 
using already, and to use no other insulin besides lispro (Humalog) 
or aspart (Novolog) during the study for participants using a study-
provided Tandem pump during the study. 
7. 
Total daily insulin dose (TDD) at least 5 U/day 
8. 
Body weight at least 20 lbs 

 
 
 
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PARTICIPANT AREA 
DESCRIPTION 
9. 
Willingness not to start any new non-insulin glucose-lowering agent 
during the course of the trial 
10. Participant and parent(s)/guardian(s) willingness to participate in all 
training sessions as directed by study staff.  
11. Parent/guardian proficient in reading and writing English 
12. Live in the United States, with no plans to move outside the United 
States during the study period 
 
Exclusion Criteria  
1. 
Concurrent use of any non-insulin glucose-lowering agent (including 
GLP-1 agonists, Symlin, DPP-4 inhibitors, SGLT-2 inhibitors, 
sulfonylureas). 
2. 
Hemophilia or any other bleeding disorder 
3. 
History of >1 severe hypoglycemic event with seizure or loss of 
consciousness in the last 3 months 
4. 
History of >1 DKA event in the last 6 months not related to illness, 
infusion set failure, or initial diagnosis 
5. 
History of chronic renal disease or currently on hemodialysis 
6. 
History of adrenal insufficiency 
7. 
Hypothyroidism that is not adequately treated 
8. 
Use of oral or injectable steroids within the last 8 weeks  
9. 
Known, ongoing  adhesive intolerance 
10. Plans to receive blood transfusions or erythropoietin injections 
during the course of the study 
11. A condition, which in the opinion of the investigator or designee, 
would put the participant or study at risk 
12. Currently using any closed-loop system, or using an insulin pump 
that is incompatible with use of the study CGM 
13. Participation in another pharmaceutical or device trial at the time of 
enrollment or during the study 
14. Employed by, or having immediate family members employed by 
Tandem Diabetes Care, Inc., or having a direct supervisor at place of 
employment who is also directly involved in conducting the clinical 
trial (as a study investigator, coordinator, etc.); or having a first-
degree relative who is directly involved in conducting the clinical 
trial 
Sample Size 
Up to 150 screened participants with the goal of randomizing 102 
participants. 
Treatment Groups 
• Intervention Group: t:slim X2 with Control-IQ Technology and 
Study CGM. 
• Control Group: Standard care (SC) - defined as either multiple daily 
injections of insulin (MDI) or use of an insulin pump without hybrid 
closed-loop control capabilities (low-glucose suspend or predictive 
low-glucose suspend functionality is permitted) in conjunction with 
study CGM 
All participants will be offered to extend the study for an additional 13 
weeks, with the SC group switching to the t:slim X2 with Control-IQ 
System after the 13-week RCT period. After 26 weeks, participants may 
continue using CLC for an additional Extended Use period.  
Participant Duration 
~26-32 weeks for RCT and Extension Phase, depending on duration of 
run-in phase; up to an additional ~7 months in Extended Use period 
Protocol Overview/Synopsis 
After consent is signed, eligibility will be assessed.  Eligible participants 
not currently using an insulin pump and Dexcom G5 or Dexcom G6 CGM 
with minimum data requirements will initiate a run-in phase of 2 to 6 
weeks that will be customized based on whether the participant is already 

 
 
 
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PARTICIPANT AREA 
DESCRIPTION 
a CGM user.  Participants who skip or successfully complete the run-in 
will be randomly assigned 2:1 to an intervention using Tandem t:slim X2 
with Control-IQ Technology  or the standard care control group using 
existing insulin therapy in conjunction with study CGM. All participants 
will  continue their participation by using the t:slim X2 with Control-IQ 
system in an Extension Phase. [Figure 1] After 26 weeks, participants 
may continue using CLC for an additional Extended Use period through 
no later than July 31, 2022. A subset of participants will complete an 
optional exercise/meal challenge ancillary study. 
 
259 
 
 
260 

 
 
 
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261 
Figure 1: Study Design: Participants Randomized 2:1 Control-IQ Control (CLC) vs. 
262 
Standard Care (SC) Groups. Extension phase with partial crossover of SC Group 
263 
switching to use Control-IQ. Subsequent Extended Use period through no later than July 
264 
31, 2022. 
265 

 
 
 
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SCHEMATIC OF STUDY DESIGN 
266 
 
267 
Figure 2: Overview of Study Design 
 
268 
Screening/Enrollment 
•
Eligibility assessment and informed consent 
•
Device download and adherence assessment for current CGM user 
CGM Placement/Training 
2-6 Week Run-In with home use of study CGM  
Run-in Review  
Reassess Eligibility 
Randomization 
 
Eligible 
To Skip 
Run-In*? 
No 
Yes 
*Current use of Dexcom G5 or G6 CGM with readings captured on at least 
11 out of the previous 14 days 
13 Weeks - End of RCT; start of Extension Phase - 
all participants use Control-IQ 
26 Weeks - End of Extension Phase 
13-Week RCT  
13-Week Extension Phase  
End of Study 
Extended Use Period through July 31, 2022 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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269 
Figure 3:  Schematic of Study Design (Post-Randomization through 26 Weeks) 
270 
Randomization 
Week 2 Videoconference or Visit 
Refresher training on devices 
Phone Contact: Week 10 
Videoconference or Clinic Visit: Weeks 6, 13 
 
Study pump 
training and 
transition to 
study pump 
Primary Outcome 
 (13 weeks)  
CLC Group 
SC Group 
Continued use of study 
closed-loop system 
Continued use of study 
CGM along with current 
insulin delivery (MDI or 
personal pump) 
Continued use of study CGM along with 
current insulin delivery 
Week 1 Phone Contact 
System data assessment 
Study pump training and transitions as shown 
above for CLC Group, then use of updated 
Control-IQ system for 13 weeks 
Videonconference/Phone Contact: Day 3; 
Phone Contact: Weeks 14, 23; 
Videoconference or Clinic Visit: Weeks 15, 19 
End of Extension Phase (26 weeks) 
Transition to updated Control-IQ closed-
loop system for 13 additional weeks. 
Training will be provided on new features. 
Videonconference/Phone Contact: Day 3; 
Phone Contact: Weeks 14, 23; 
Videoconference or Clinic Visit: Weeks 15, 19 
MDI User? 
Study pump training and 
transition from MDI to pump 
Yes 
No 
3-Day Videoconference or Call 
Pump settings adjustment 
Week 1 Phone Contact 
CGM data assessment 
CLC Group 
SC Group 

 
 
 
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271 
Figure 4:  Schematic of Study Design (Extended Use Period)
272 
Study pump retraining visit and 
transition back to study pump 
 
No 
Yes 
Gap between 26-Week visit and 
start of Extended Use phase? 
Continued use of study 
closed-loop system 
Continued use of study 
closed-loop system 
Videoconference/Phone Contact 
Day 3; Week 1 
Every 13 Weeks 
Videoconference/Clinic Visit 
Final Visit; End of Study* 
* Final Visit to occur no later than July 31, 2022 

 
 
 
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273 
1 Only for participants on MDI at enrollment assigned to the CLC group  
274 
 
275 
Table 1. Schedule of Study Visits and Procedures (through 26-Week Visit) 
276 
 
 
277 
 
Pre 
Pre 
0 
3d1 
1w 
2w 
6w 
10w 
13w 
13w + 
3d 
14w 
15w 
19w 
23w 
26w 
Visit (V), 
Videoconference (VC), 
or Phone (P) 
VC/V 
VC/V 
VC/V 
VC/ 
P 
P 
VC/V 
VC/
V 
P 
VC/
V 
VC/ 
P 
P 
VC/
V 
VC/
V 
P 
VC/
V 
Comment 
Screen/
Enroll 
Run-in 
Rand 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility Assessment 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
HbA1c (Central lab) 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
Device Data 
download(s) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Review diabetes 
management and AEs 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Questionnaires as 
defined in section 9.2 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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278 
 
279 
 
280 
 
281 
 
282 
 
283 
 
284 
 
285 
 
286 
1 Participants are eligible to initiate Extended Use period if they completed the 26-Week Visit within the prior 4 months 
287 
2 Only for participants who had a gap between the 26-Week Visit and the initiation of the Extended Use period during  
288 
which they stopped use of the study pump and reverted to MDI or personal pump insulin therapy 
289 
 
290 
Table 2. Schedule of Study Visits and Procedures (Extended Use Period) 
291 
 
292 
 
293 
Days/Weeks after 
26-Week Visit => 
02 
3d2 
1w2 
13w 
26w, 39w, 
etc. 
Final 
Visit 
Visit (V), 
Videoconference (VC), 
or Phone (P) 
VC/V 
VC/ 
P 
VC/ 
P 
VC/V 
VC/V 
VC/V 
Eligibility Assessment1,2 
X 
 
 
 
 
 
Study Pump Retraining2 
X 
 
 
 
 
 
HbA1c (Central lab) 
 
 
 
X 
X 
 
Device Data download(s) 
 
X 
X 
X 
X 
X 
Review diabetes 
management and AEs 
 
X 
X 
X 
X 
X 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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Chapter 1: Background Information 
294 
 Introduction 
295 
The Tandem X2 insulin pump with Control-IQ Technology is a third-generation closed-loop 
296 
control (CLC) system retaining the same control algorithm that was initially tested by UVA’s DiAs 
297 
system and then implemented in the inControl system (TypeZero Technologies, Inc.). 
298 
The system has received FDA approval for use in individuals ≥6 years old following a pair of 
299 
pivotal trials that demonstrated the system’s safety and efficacy, first in participants ≥14 years old 
300 
(1) and then subsequently in participants ≥6 years old (2).  
301 
Closed-Loop Control System 
302 
The Closed-Loop Control System contained in t-slim X2 with Control-IQ Technology is described 
303 
in Master File MAF-2032/A008. Control-IQ Technology is derived from inControl previously 
304 
described in IDE# G160097, G160181, G150240 and G140169/S010. The CLC is an “artificial 
305 
pancreas” (AP) application that uses advanced closed loop control algorithms to automatically 
306 
manage blood glucose levels for people with Type 1 Diabetes. The system modulates insulin to 
307 
keep blood glucose in a targeted range. The system components include the t:slim X2 with 
308 
Control-IQ Technology and the Dexcom CGM G6. 
309 
 
310 
Figure 5. t:slim X2 with Control-IQ and Dexcom G6 system 
311 
 Rationale 
312 
The objective of this randomized clinical trial is to assess the efficacy and safety of the Control-
313 
IQ closed loop system over a 13-week period compared with standard care. In addition, the data 
314 
from this trial may be used for subsequent regulatory submissions for this system in the age group 
315 
studied. 
316 
The extension phase will allow for additional exposure time to the Tandem t:slim X2 with Control-
317 
IQ Technology and evaluation of the SC arm after crossing over to use Control-IQ for a 13-week 
318 
period.  
319 

 
 
 
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 Potential Risks and Benefits of the Investigational Device 
320 
Risks and Benefits are detailed below. Loss of confidentiality is a potential risk; however, data are 
321 
handled to minimize this risk.  Hypoglycemia, hyperglycemia and ketone formation are always a 
322 
risk in participants with type 1 diabetes and participants will be monitored for these events. 
323 
 
324 
1.3.1.1 Potential Risks and Benefits of the CLC System 
325 
Even though the study system has been tested prior to this study, there is still a risk that parts of 
326 
the system may not function properly. The following are possible reasons the system may deliver 
327 
too much insulin or incorrectly stop insulin delivery: 
328 
• CGM sensor reads higher or lower than the actual glucose level which increases risk for 
329 
hypoglycemia and hyperglycemia with automated insulin delivery system; 
330 
• Device malfunctions that could produce a suspension of insulin delivery or over delivery 
331 
of insulin. 
332 
1.3.1.2 Risk of Hypoglycemia 
333 
As with any person having type 1 diabetes and using insulin, there is always a risk of having a low 
334 
blood sugar (hypoglycemia).  The frequency of hypoglycemia should be no more and possibly less 
335 
than it would be as part of daily living.  Symptoms of hypoglycemia can include sweating, 
336 
jitteriness, and not feeling well.  Just as at home, there is the possibility of fainting or seizures 
337 
(convulsions) and that for a few days the participant may not be as aware of symptoms of 
338 
hypoglycemia.  A CGM functioning poorly and significantly over-reading glucose values could 
339 
lead to inappropriate insulin delivery. 
340 
1.3.1.3 Risk of Hyperglycemia 
341 
Hyperglycemia and ketonemia could occur if insulin delivery is attenuated or suspended for an 
342 
extended period or if the pump or infusion set is not working properly.  A CGM functioning poorly 
343 
and significantly under-reading glucose values could lead to inappropriate suspension of insulin 
344 
delivery. 
345 
1.3.1.4 Fingerstick Risks 
346 
At various times several drops of blood will be removed by fingerstick. This is a standard method 
347 
used to obtain blood for routine hospital laboratory tests.  Pain is common at the time of lancing.  
348 
In about 1 in 10 cases, a small amount of bleeding under the skin will produce a bruise.  A small 
349 
scar may persist for several weeks.  The risk of local infection is less than 1 in 1000.  This should 
350 
not be a significant contributor to risks in this study as fingersticks are part of the usual care for 
351 
people with diabetes. 
352 
1.3.1.5 Subcutaneous Catheter Risks (CGM) 
353 
Participants using the CGM will be at low risk for developing a local skin infection at the site of 
354 
the sensor needle placement.  If a catheter is left under the skin for more than 24 hours, it is possible 
355 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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to get an infection where it goes into the skin, with swelling, redness and pain.  There may be 
356 
bleeding where the catheter is put in and bleeding under the skin causes a bruise (1 in 10 risk). 
357 
Study staff should verbally alert the participant that on rare occasions, the CGM may break and 
358 
leave a small portion of the sensor under the skin that may cause redness, swelling or pain at the 
359 
insertion site.  The participant should be further instructed to notify the study coordinator 
360 
immediately if this occurs. 
361 
1.3.1.6 Risk of Device Reuse 
362 
The study CGM system is labeled for single use only. The sensor (the component of the system 
363 
that enters the skin) will be single use only. The receiver, if used, is a hand-held device. The 
364 
transmitter and receiver may be reused during the study after cleaning the device using a hospital-
365 
approved cleaning procedure. The transmitter is attached to the sensor but does not enter the skin. 
366 
Participants will be informed that FDA or relevant national authorities have approved these devices 
367 
for single use and that by using them among multiple patients, bloodborne pathogens (i.e. Hepatitis 
368 
B) may be spread through the use of multiple users. 
369 
The study insulin pump is labeled for single-patient use. During the study, this device may be 
370 
reused after cleaning adhering to a hospital-approved cleaning procedure. All infusion set 
371 
equipment will be single patient use only (infusion set insertion kits, tubing, cartridges etc.)  
372 
Participants will be informed that FDA or relevant national authorities typically approve the insulin 
373 
pump device for single use and that by using them among multiple patients, bloodborne pathogens 
374 
(i.e. Hepatitis B) may be spread through the use of multiple users. 
375 
The study blood glucose meter and blood ketone meter are labeled for single-patient use. 
376 
During the study, only one person can use each device as there are rare risks that bloodborne 
377 
pathogens (i.e. Hepatitis B) may be spread through the use of multiple users. 
378 
1.3.1.7 Questionnaires and Focus Groups 
379 
As part of the study, parents of participants will complete questionnaires which include questions 
380 
about their private attitudes, feelings and behavior related to the investigational equipment as well 
381 
as managing diabetes.  Parents may also participate in a focus group session to explore their 
382 
feelings about using the closed-loop system. It is possible that some people may find these 
383 
questionnaires or focus groups to be mildly upsetting. Similar questionnaires and focus groups 
384 
have been used in previous research and these types of reactions have been uncommon. 
385 
1.3.1.8 Other Risks 
386 
Some participants may develop skin irritation or allergic reactions to the adhesives used to secure 
387 
the CGM, or to secure the insulin infusion sets for the continuous subcutaneous insulin infusion.  
388 
If these reactions occur, different adhesives or “under-taping” (such as with IV 3000, Tegaderm, 
389 
etc.) will be tried, sites will be rotated frequently, and a mild topical steroid cream or other 
390 
medication may be required. 
391 
Whenever the skin is broken there is the possibility of an infection.  The CGM and pump infusion 
392 
sites are inserted under the skin.  It is possible that any part that is inserted under the skin may 
393 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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cause an infection.  These occur very infrequently, but, if an infection was to occur, oral and/or 
394 
topical antibiotics can be used.  The risk of skin problems could be greater if you use a sensor for 
395 
longer than it is supposed to be used.  Therefore, participants (and parents) will be carefully 
396 
instructed about proper use of the sensor. 
397 
Data downloaded from the CGM, pump, and the home glucose and ketone meter will be collected 
398 
for the study as measures of diabetes self-management behaviors.  Some people 
399 
may be uncomfortable with the researchers' having such detailed information about their daily 
400 
diabetes habits. 
401 
 
402 
One purpose of this research is to reduce the frequency of hypoglycemia and severe hypoglycemic 
403 
events. Hypoglycemia is the number one fear of many individuals and families with someone who 
404 
has type 1 diabetes and this fear often prevents optimal glycemic control. 
405 
It is expected that this protocol will yield increased knowledge about using an automated 
406 
closed-loop system to control the glucose level and is intended to develop data to support future 
407 
device approval in the age group studied. The individual participant may not benefit from study 
408 
participation. 
409 
 
410 
Based on the facts that (1) children with diabetes experience mild hypoglycemia and 
411 
hyperglycemia frequently as a consequence of the disease and its management, (2) the study 
412 
intervention involves periodic automated insulin dosing that may reduce the likelihood of 
413 
hypoglycemia, and periodic automated attenuation of insulin delivery that may reduce the 
414 
likelihood of hyperglycemia, (3) if any, hypo and/or hyperglycemia occur, mitigations are in place, 
415 
and have been tested in prior studies using the investigational device system in the home setting, 
416 
that limit the likelihood of excessive insulin dosing or prolonged withdrawal of insulin, and (4) 
417 
rapid reversal of hypoglycemia and hyperglycemia can be achieved, it is the assessment of the 
418 
investigators that this protocol falls under DHHS 45 CFR 46.405 and 21 CFR 50.52 as a clinical 
419 
investigation involving greater than minimal risk but presenting the prospect of direct benefit to 
420 
individual subjects. In addition, it is the belief of the investigators that this study also presents 
421 
prospect of general benefit to others with diabetes. 
422 
 General Considerations 
423 
The study is being conducted in compliance with the policies described in the study policies 
424 
document, with the ethical principles that have their origin in the Declaration of Helsinki, with the 
425 
protocol described herein, and with the standards of Good Clinical Practice (GCP). 
426 
There is no restriction on the number of participants to be enrolled by each clinical center toward 
427 
the overall recruitment goal. 
428 
The protocol is considered a significant risk device study, due to the fact that the closed loop 
429 
system is experimental in the population under study.  Therefore, an investigational device 
430 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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exemption (IDE) from the U.S. Food and Drug Administration (FDA) is required to conduct the 
431 
study. 
432 

 
 
 
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Chapter 2: Study Enrollment and Screening 
433 
 Participant Recruitment and Enrollment 
434 
Enrollment will proceed with the goal of having 102 participants randomized.  A maximum of 150 
435 
individuals may be enrolled into screening for the study in order to achieve this goal. 
436 
Study participants will be recruited at ~3 clinical centers in the United States without regard to 
437 
gender, race, or ethnicity.  There is no restriction on the number of participants to be enrolled by 
438 
each clinical center toward the overall recruitment goal. 
439 
The study team will make every effort to have the following minimum numbers of participants 
440 
complete the trial in the specified subgroups at the time of enrollment: 
441 
• Approximately two-thirds of the participants with most recent available HbA1c ≥ 7.5% 
442 
• Approximately 30 participants in the age range ≥24 months to <48 months 
443 
• At least 20% of participants who are on multiple daily injections (MDI) rather than pump 
444 
 
445 
Potential eligibility may be assessed as part of a routine-care examination.  Before completing any 
446 
procedures or collecting any data that are not part of usual care, electronic informed consent will 
447 
be obtained. 
448 
A parent/legal guardian (referred to subsequently as “parent”) will be provided with the Informed 
449 
Consent Form to read and will be given the opportunity to ask questions either via 
450 
phone/videoconference or by mail or email. If the parent and child are interested in the study, the 
451 
investigator will schedule a virtual or in-person visit to discuss study, and if the parent and child 
452 
agree to participate, the Informed Consent Form will be electronically signed through the JCHR 
453 
website.  A copy of the electronically signed consent form can be printed by the parent and another 
454 
copy will be printed by the site to add to the participant’s study record. 
455 
As part of the informed consent process, the parent will be asked to sign an authorization for release 
456 
of personal information. This may be done electronically with the consent, or on paper if the site 
457 
requires their own process. The investigator, or his or her designee, will review the study-specific 
458 
information that will be collected and to whom that information will be disclosed.  After speaking 
459 
with the parent, questions will be answered about the details regarding authorization. 
460 
A participant is considered enrolled when the informed consent form has been electronically 
461 
signed and HIPAA authorization has been provided. 
462 
 Participant Inclusion Criteria 
463 
Individuals must meet all of the following inclusion criteria in order to be eligible to participate in 
464 
the study. 
465 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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1. Clinical diagnosis, based on investigator assessment, of type 1 diabetes for at least 6 months 
466 
and using insulin for at least 6 months  
467 
2. Familiarity and use of a carbohydrate ratio for meal boluses. 
468 
3. Age ≥2 and <6 years old 
469 
4. Living with one or more parent/legal guardian knowledgeable about emergency procedures for 
470 
severe hypoglycemia and able to contact emergency services and study staff. 
471 
5. Investigator has confidence that the parent can successfully operate all study devices and is 
472 
capable of adhering to the protocol 
473 
6. Willingness to switch to lispro (Humalog) or aspart (Novolog) if not using already, and to use 
474 
no other insulin besides lispro (Humalog) or aspart (Novolog) during the study for participants 
475 
using a study-provided Tandem pump during the study. 
476 
• Study will not be providing insulin; therefore, participants will need to have access to 
477 
either lispro or aspart 
478 
7. Total daily insulin dose (TDD) at least 5 U/day 
479 
8. Body weight at least 20 lbs 
480 
9. Willingness not to start any new non-insulin glucose-lowering agent during the course of the 
481 
trial (see section 2.3) 
482 
10. Participant and parent(s)/guardian(s) willingness to participate in all training sessions as 
483 
directed by study staff.  
484 
11. Parent/guardian proficient in reading and writing English 
485 
12. Live in the United States, with no plans to move outside the United States during the study 
486 
period 
487 
 Participant Exclusion Criteria 
488 
Individuals meeting any of the following exclusion criteria at baseline will be excluded from study 
489 
participation. 
490 
1. Concurrent use of any non-insulin glucose-lowering agent (including GLP-1 agonists, Symlin, 
491 
DPP-4 inhibitors, SGLT-2 inhibitors, sulfonylureas). 
492 
2. Hemophilia or any other bleeding disorder 
493 
3. History of >1 severe hypoglycemic event with seizure or loss of consciousness in the last 3 
494 
months 
495 
4. History of >1 DKA event in the last 6 months not related to illness, infusion set failure, or 
496 
initial diagnosis 
497 
5. History of chronic renal disease or currently on hemodialysis 
498 
6. History of adrenal insufficiency 
499 
7. Hypothyroidism that is not adequately treated 
500 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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8. Use of oral or injectable steroids within the last 8 weeks  
501 
9. Known, ongoing  adhesive intolerance 
502 
10. Plans to receive blood transfusions or erythropoietin injections during the course of the study 
503 
11. A condition, which in the opinion of the investigator or designee, would put the participant or 
504 
study at risk (specified in the study procedure manual); the investigator will take into account 
505 
the participant’s HbA1c level, compliance with current diabetes management, and prior acute 
506 
diabetic complications 
507 
12. Currently using any closed-loop system, or using an insulin pump that is incompatible with 
508 
use of the study CGM 
509 
13. Participation in another pharmaceutical or device trial at the time of enrollment or during the 
510 
study 
511 
14. Employed by, or having immediate family members employed by Tandem Diabetes Care, Inc., 
512 
or having a direct supervisor at place of employment who is also directly involved in 
513 
conducting the clinical trial (as a study investigator, coordinator, etc.); or having a first-degree 
514 
relative who is directly involved in conducting the clinical trial 
515 
 Eligibility Assessment and Baseline Data Collection 
516 
Potential participants will be evaluated for study eligibility through the elicitation of a medical 
517 
history and local laboratory testing as needed in the judgment of the investigator (as part of usual 
518 
care). 
519 
The screening visit and subsequent scheduled study visits may be conducted virtually via 
520 
videoconference at the discretion of the study investigator, for example due to institutional 
521 
restrictions or the participant or investigator’s preference for a remote visit. Study staff will 
522 
discuss the feasibility of conducting virtual visits with each participant and provide support as 
523 
needed to ensure adequate access. The screening visit must be completed within 28 days of 
524 
participant enrollment. 
525 
 Historical Information  
526 
A history will be elicited from the parent and extracted from available medical records with 
527 
respect to the participant’s diabetes history, current diabetes management, other past and current 
528 
medical problems, past and current medications, and drug allergies.   
529 
 Screening Testing and Procedures 
530 
At the Screening Visit the following procedures will be performed: 
531 
• Informed consent process 
532 
• Assessment of eligibility 
533 
• Contact information (retained at the clinical center and not entered into study database) 
534 
• Demographics (date of birth, sex, race and ethnicity) 
535 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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• Measurement of height/weight 
536 
o If the visit is conducted virtually, a verbal report of the participant’s weight and 
537 
verbal report of height will be acceptable. A scale will be provided for 
538 
participants who do not already have a scale at home. 
539 
• Determination of most recent HbA1c level from medical records or verbal report 
540 
• Participants’ parents will complete a set of baseline questionnaires, described in 
541 
section 9.2. 
542 
 Screen Failures 
543 
Individuals who do not initially meet study eligibility requirements may be rescreened at a later 
544 
date per investigator discretion. 
545 

 
 
 
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Chapter 3: CGM Run-In Phase 
546 
 CGM Run-in Phase Overview 
547 
This phase must begin (supplies shipped) within 3 days of completion of the Screening visit. The 
548 
purpose of this CGM run-in phase is to 1) assess compliance with study procedures and 2) to 
549 
introduce the study CGM to study participants without current use of a Dexcom CGM. 
550 
Participants who currently use a Dexcom G5 or G6 with CGM data captured on at least 11 out of 
551 
the previous 14 days prior to the time of enrollment can skip the run-in phase. Participants who do 
552 
not currently use a Dexcom G5 or G6 CGM, or who do use that CGM but have readings captured 
553 
on fewer than 11 out of the previous 14 days prior to time of enrollment, will be required to 
554 
participate in the CGM run-in phase. 
555 
Participants and their parent(s) will receive training on the study CGM as detailed below. This will 
556 
be an unblinded use of the study CGM.  
557 
 Initiation of CGM 
558 
Study CGM supplies will be provided to the participant either in-person at the clinic, or via 
559 
delivery by other means (personal delivery, overnight shipment, etc.).   
560 
Once the supplies have been received, the participant and parent will be instructed to use the study 
561 
CGM on a daily basis. Participants using a personal CGM prior to the study will discontinue the 
562 
personal CGM beginning in this period. 
563 
 
564 
CGM training (in-person or via videoconference) will be provided by a qualified trainer to 
565 
participants not currently using a personal CGM identical to the study CGM as to how to use it in 
566 
real-time to make management decisions and how to review the data after an upload for 
567 
retrospective review. The participating child will participate in training sessions to the degree 
568 
judged appropriate by the parent and trainer. CGM training will include: 
569 
• Instruction on how to insert the sensor and transmitter, including observation/supervision 
570 
of placement of a sensor 
571 
• Instruction on how to calibrate the CGM unit, if needed 
572 
• Guidance on accessing the CGM trace, either through a manufacturer-provided software 
573 
app or via a study-provided CGM receiver unit, or via a personal insulin pump if 
574 
participants use a pump that integrates with the study CGM  
575 
• Parents will be asked to perform fingerstick blood glucose measurements in accordance 
576 
with the labeling of the study CGM device 
577 
A copy of the study CGM user’s guide will be provided to the participant’s parents. 
578 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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 Blood Glucose and Ketone Testing 
579 
Participants will receive supplies for blood glucose and ketone testing. 
580 
• Blood glucose testing 
581 
o Participants will be provided with a study blood glucose meter, test strips, and standard 
582 
control solution to perform quality control (QC) testing at home per manufacturer 
583 
guidelines. 
584 
o All study blood glucose meters will be QC tested with control solution if available prior to 
585 
dispensation and during all office visits.  A tested meter will not be used in a study if it 
586 
does not read within the target range at each concentration per manufacturer labeling.   
587 
o Participants will be reminded to use the study blood glucose meter for all fingerstick BGs 
588 
during the study. 
589 
o Participants will be given guidelines for treatment of low or high blood glucose. 
590 
• Blood ketone testing 
591 
o Participants will be provided with a study blood ketone meter, test strips, standard control 
592 
solution to perform QC testing at home per manufacturer guidelines, and 
593 
software/hardware needed to download meter datafiles. 
594 
o All study blood ketone meters will be QC tested with control solution if available prior to 
595 
dispensation and during all office visits.  A tested meter will not be used in a study if it 
596 
does not read within the target range at each concentration per manufacturer labeling.  
597 
o Participants will be instructed to perform blood ketone testing as described in section 7.1.6. 
598 
o Participants will be given guidelines for treatment of elevated blood ketones 
599 
• Participants will be required to have glucagon at home. Participants who currently do not have 
600 
one will be given a prescription for glucagon (either emergency kit or nasal glucagon per 
601 
investigator discretion for participants over 4 years of age). 
602 
 Assessment of Successful Completion of the Run-in Phase 
603 
Enrolled participants will have a follow-up visit or videoconference approximately 14 days after 
604 
initiation of the run-in phase to assess progress or successful completion of the phase.  If needed, 
605 
one or more interim visits or videoconference/phone contacts may occur to assist the participant 
606 
with any CGM use issues. Procedures will include downloading of the study CGM data and the 
607 
following: 
608 
Assessment of compliance with the use of CGM for at least 11 out of the prior 14 days 
609 
Assessment of skin reaction in areas where a CGM sensor was worn or other safety issues 
610 
associated with CGM use 
611 
Assessment of eligibility to continue to the randomized control trial (RCT) phase of the study 
612 
 
613 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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Participants Using a Personal CGM at Enrollment 
614 
Participants who had currently been using a personal CGM at the time of enrollment (but did not 
615 
meet requirements to skip run-in) and satisfy the CGM use criteria above without any major safety 
616 
issues and otherwise meet study eligibility requirements can be randomized.  
617 
Participants who fail to meet the minimum CGM use requirement, or who the investigator believes 
618 
may benefit from an extension of the CGM run-in period, may at the investigator’s discretion be 
619 
allowed to continue CGM run-in for a maximum of two additional 2-week periods. These 
620 
participants will have a follow-up visit or videoconference approximately 14 days after each prior 
621 
assessment for a reassessment using the same procedures as described above. 
622 
Participants who do not meet CGM use requirements after three 2-week periods of CGM run-in or 
623 
otherwise fail to meet study eligibility requirements will be withdrawn from the study. 
624 
Participants Not Using a Personal CGM at Enrollment 
625 
Participants who had not currently been using a personal CGM at the time of enrollment will be 
626 
assessed as described above. If there are no major safety issues and the investigator believes that 
627 
the participant will remain adherent to use of the study CGM, the participant will be asked to 
628 
continue the run-in phase for an additional 2-week period to establish baseline glycemic control 
629 
while using the study CGM. These participants will have a follow-up visit or videoconference 
630 
approximately 14 days for a second follow-up visit with the same visit procedures as described 
631 
above. 
632 
Participants who fail to meet the minimum CGM use requirement at the second follow-up, or who 
633 
the investigator believes may benefit from a further extension of the CGM run-in period, may at 
634 
the investigator’s discretion be allowed to continue CGM run-in for one additional 2-week period. 
635 
These participants will have a follow-up visit or videoconference approximately 14 days after the 
636 
second follow-up visit for a reassessment using the same procedures as described above. 
637 
Participants who do not meet CGM use requirements after three 2-week periods of CGM run-in or 
638 
otherwise fail to meet study eligibility requirements will be withdrawn from the study. 
639 
 Optimization of Insulin Therapy 
640 
Data will be obtained from CGM and/or pump downloads prior to CGM run-in review contacts. 
641 
Adjustments to pump settings (basal rates, correction factor, insulin-to-carbohydrate ratio, etc.) or 
642 
injection strategies will be made in response to major trends observed in the CGM data, with 
643 
flexibility for clinicians to adhere to guidelines and practices established at each individual practice 
644 
rather than a fixed set of heuristics for all clinical centers. 
645 

 
 
 
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Chapter 4: Randomization Visit 
646 
 Visit Timing 
647 
The visit, which may be in-clinic or virtual, may occur on the same day as the Screening or Run-
648 
in Review Visit, or on a subsequent day. If deferred, the randomization visit should occur no more 
649 
than 14 days after successful completion of the run-in phase or within 14 days of screening if run-
650 
in is skipped. 
651 
 
652 
Eligible participants will be randomly assigned to one of two treatment groups in a 2:1 ratio: 
653 
1. Control-IQ Closed-Loop Control (CLC) Group 
654 
2. Standard Care (SC) Group 
655 
The participant’s randomization group assignment is determined by completing a Randomization 
656 
Visit case report form on the study website. The randomization list will use a permuted block 
657 
design, stratified by clinical center. 
658 
The participant will be included in the data analysis regardless of whether or not the protocol for 
659 
the assigned randomization group is followed.  Thus, the investigator must not randomize a 
660 
participant until he/she is convinced that the participant/parent will accept assignment to either 
661 
of the two groups. 
662 
It was decided that it was more important to stratify randomization by clinical center than by 
663 
factors such as baseline time in range, HbA1c, or device use since these factors will be easier to 
664 
adjust for in analysis than will clinical center. 
665 
 
666 
A capillary blood sample will be obtained for baseline HbA1c determination. Capillary collection 
667 
supplies will be provided to the participant within 3 days of randomization. This may occur either 
668 
in-person at the clinic, or via delivery by other means (personal delivery, overnight shipment, etc.).   
669 

 
 
 
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Chapter 5: Main Study Procedures  
670 
 Visit and Contact Schedule 
671 
During the RCT period, visits and contacts will be scheduled as outlined in Table 3 below: 
672 
Table 3: RCT Visit and Phone Contact Schedule 
673 
Target Day/Week 
Contact Type1 
Target/Allowable Window 
(around Target Day/Week) 
3 days2 
VC/P 
± 2 days 
1 week 
P 
± 2 days 
2 weeks 
VC/V 
± 4 days 
6 weeks 
VC/V 
± 7 days 
10 weeks 
P 
± 7 days 
13 weeks 
VC/V 
± 7 days 
1 Contact Types are defined as Clinic Visit (V), Videoconference (VC), or Phone call (P); Phone calls may be replaced by 
674 
Videoconferences or Clinic Visits and Videoconferences may be replaced by Clinic Visits at investigator discretion 
675 
2 Only for participants on MDI at enrollment assigned to the CLC group; timing will be with respect to the start of home use of 
676 
the study system, rather than with respect to the start of the RCT 
677 
Additional contacts or visits may occur as needed. 
678 
 CGM Initiation and Training 
679 
Participants who skipped CGM run-in will be provided with study CGM supplies and training as 
680 
described in section 3.2 and instructed to use the study CGM on a daily basis. Participants 
681 
currently using a personal CGM identical to the study CGM may skip the training. 
682 
Provision of CGM supplies and training should be completed within 3 days of randomization. 
683 
 Procedures for the CLC Group 
684 
The study pump, associated supplies, and training will be provided to participants assigned to the 
685 
CLC group within 3 days of randomization. Dispensation of supplies may occur either in-person 
686 
at the clinic, or via delivery by other means (personal delivery, overnight shipment, etc.). 
687 
 
688 
Parents of participants will receive study pump training by a qualified trainer. The participating 
689 
child will participate in training sessions to the degree judged appropriate by the parent and 
690 
trainer. Pump training (in-person or via videoconference) will be provided by a qualified trainer 
691 
to all CLC Group participants. 
692 
Parents will be fully instructed on the study insulin pump. The trainer will discuss differences from 
693 
the participant’s personal pump, if applicable, in important aspects such as calculation of insulin 
694 
on board and correction boluses and optional additional topics such as: infusion site initiation, 
695 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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cartridge/priming procedures, setting up the pump, charging the pump, navigation through menus, 
696 
bolus procedures including stopping a bolus, etc. 
697 
Parents will be instructed to change the study insulin pump infusion set at least once every 3 days 
698 
or per manufacturer guidelines, whichever is shorter. 
699 
Parents will be trained to use the bolus calculator following the standard t:slim X2 training if they 
700 
are not already using the t:slim X2 bolus calculator. Parent/guardians with prior 
701 
education/experience with using this bolus calculator will be offered refresher training. 
702 
• The study team will assist the parent in study pump infusion site initiation and will start 
703 
the participant on the study pump. The study pump will be programmed with the 
704 
participant’s usual basal rates and pump parameters, if applicable. The participant’s 
705 
personal pump, if any, will be removed. 
706 
• The parent will be supervised with the study pump during at least one meal or snack bolus 
707 
to ensure participant understanding of the pump features. 
708 
• The parent will be encouraged to review the literature provided with the pump and infusion 
709 
sets after the training is completed. 
710 
• The parent will be trained on severe hypoglycemia emergency procedures including 
711 
removal of the study pump and administration of glucagon. 
712 
Pump training specific to the Control-IQ Technology functions will include: 
713 
• How to turn on and off Control-IQ technology. 
714 
• How to understand when Control-IQ is increasing or decreasing basal rates. 
715 
• How to administer a meal or correction boluses 
716 
• What to do when exercising while using the system 
717 
• How to enable the sleep function and set the sleep schedule 
718 
• The parent will be assessed for understanding of the system interface and how to react to 
719 
safety/alert messages. 
720 
The parent will be given a User Guide as a reference. 
721 
 
722 
For MDI participants being started on the study pump, an initial basal insulin profile will be 
723 
customized on a per-participant basis. Total daily insulin dose will be reduced by approximately 
724 
20% as a general rule, with a recommended method outlined in a separate procedures’ manual. 
725 
Further adjustments to total daily dose (TDD) and intraday basal rate profile may be made during 
726 
the initial 2-week use period. 
727 
Participants and parent(s) will complete training on the study pump as described above, with  
728 
additional emphasis on topics relevant to new pump users, such as infusion site initiation, 
729 
cartridge/priming procedures, setting up the pump, charging the pump, navigation 
730 
through menus, bolus procedures including stopping a bolus, etc. 
731 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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The study team will assist the participant/parent in study pump infusion site initiation and will start 
732 
the participant on the study pump. The study pump will be programmed with the participant’s 
733 
insulin requirements. 
734 
 
735 
The participant/parent will be instructed to use the system in closed-loop mode except if insulin is 
736 
delivered by any means other than the study pump (e.g. injection of subcutaneous insulin via 
737 
syringe in the event of infusion site failure). If insulin is delivered by any means other than the 
738 
study pump, the parent will be instructed to turn off Control-IQ for approximately four hours. 
739 
The parent will also be instructed to contact study staff if the participating child has illness with 
740 
an elevated temperature >101.5 degrees Fahrenheit (38.6 degrees Celsius), other periods of 
741 
significant illness, or during periods of use of medications such as epinephrine for the emergency 
742 
treatment of a severe allergic reaction or asthma attack in addition to use of oral or injectable 
743 
glucocorticoids to determine if closed-loop use should be temporarily discontinued. 
744 
Parents will be provided with sufficient supplies to last until the subsequent visit. 
745 
Parents will be provided with contact information and will be asked to call the study clinical staff 
746 
for any health-related issues and for technical issues with the system. Participants may use the 
747 
study pump without Control-IQ activated and study CGM during periods of component 
748 
disconnections or technical difficulties.  Parents will also receive study staff contact information 
749 
to ask any questions they may have during the study. 
750 
Study staff will discuss with the parent that routine contact is required and will make arrangements 
751 
with the parent for the contacts.  If the parent cannot be reached, the participant’s other contact 
752 
methods will be utilized, including the emergency contact.  Parents who are not compliant with 
753 
the arranged contacts on two separate occasions may be discontinued at the discretion of the 
754 
investigator.  
755 
Upon completion of the CGM or study pump training components, as applicable, study staff will 
756 
document, using a checklist, that the parent is familiar with the functions/features/tasks addressed 
757 
during the training. 
758 
Parents will be provided Hypoglycemia, Hyperglycemia and Ketone Guidelines (section 8.2) for 
759 
when their glucose levels are >300 mg/dL for more than 90 minutes or >400 mg/dL at any time or 
760 
<70 mg/dL or ketones ≥1.0 mmol/L. 
761 
 
762 
After training on the study system has been completed, participants will proceed with home use 
763 
(meaning free-living use at school, home, etc.) of the study pump. 
764 
Parents may use available manufacturer-provided software and features of the study CGM related 
765 
to mobile data access or remote monitoring, but will be instructed not to use any third-party 
766 
components for this purpose. 
767 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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768 
Parents will be instructed to download the study CGM and pump and ketone meter prior to each 
769 
phone or videoconference contact or on at least an every 4-week basis throughout the remainder 
770 
of the study. 
771 
 
772 
For participants who were on MDI at the time of enrollment, study staff will perform a phone call 
773 
or videoconference with the parent within 3 (±2) days following initiation of study pump use. 
774 
The following will occur: 
775 
• Assessment of compliance with study device use by review of any available device data 
776 
• Assessment of adverse events, adverse device effects, and device issues 
777 
• Study staff will answer any questions related to device use and follow the procedure for 
778 
insulin pump optimization described above using the study CGM available data from the 
779 
previous two weeks. 
780 
 
781 
Study staff will perform a phone call/videoconference with the parent within 7 (±2) days following 
782 
randomization. 
783 
The following will occur: 
784 
• Assessment of compliance with study device use by review of any available device data 
785 
• Assessment of adverse events, adverse device effects, and device issues 
786 
• Study staff will answer any questions related to device use and follow the procedure for 
787 
insulin pump optimization described above using the study CGM available data from the 
788 
previous two weeks. 
789 
 
790 
Participants will have a follow-up visit 14 (±4) days from the date of randomization. 
791 
The parent will be offered review training to address any questions on the use of the study device 
792 
including meal bolus strategies and strategies related to pump use and exercise. 
793 
The following will occur: 
794 
• Assessment of compliance with study device use by review of any available device data 
795 
• Assessment of adverse events, adverse device effects, and device issues 
796 
• Study staff will answer any questions related to device use and follow the procedure for 
797 
insulin pump optimization described above using the study CGM available data from the 
798 
previous two weeks. 
799 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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• At in-clinic visits, the blood glucose meter and study ketone meter will be downloaded and 
800 
QC tested with control solution. 
801 
 Procedures for the SC Group 
802 
Participants in the SC group will continue to use their existing insulin therapy (personal pump or 
803 
MDI) for the treatment of their diabetes, in conjunction with use of the study CGM, study blood 
804 
glucose meter, and study ketone meter. 
805 
If a participant is using a pump with an LGS/PLGS feature, he/she will be allowed to continue 
806 
using this feature during the trial. 
807 
Parents may use available manufacturer-provided software and features of the study CGM related 
808 
to mobile data access or remote monitoring, but will be instructed not to use any third-party 
809 
components for this purpose. 
810 
 
811 
Parents will be instructed to upload/email data from the study CGM and study ketone meter using 
812 
commercially available software prior to each phone or videoconference contact below for 
813 
clinician review.  Parents will be provided with any software and hardware needed to perform 
814 
these data uploads. 
815 
 
816 
Study staff will perform a phone call/videoconference with the participant 7(+2) days following 
817 
randomization. 
818 
The following will occur: 
819 
• Assessment of compliance with study device use by review of any available device data 
820 
• Assessment of adverse events, adverse device effects, and device issues 
821 
• Study staff will answer any questions related to device use 
822 
 
823 
Participants will have a follow-up visit 14 (±4) days from the date of randomization. 
824 
The parent will be offered review training on the use of SC during the remainder of the study, 
825 
including meal bolus strategies and strategies related to exercise. 
826 
The following will occur: 
827 
• Assessment of compliance with study device use by review of any available device data 
828 
• Assessment of adverse events, adverse device effects, and device issues 
829 
• Study staff will review uploaded CGM data, answer any questions related to device use, 
830 
and provide any recommendations for insulin therapy adjustment. 
831 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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• If visit is in-clinic, the study blood glucose meter and study ketone meter will be 
832 
downloaded and QC tested. 
833 
The parent will be instructed to upload data from the study CGM and ketone meter at least once 
834 
every 4 weeks for the remainder of the study. 
835 
 Follow-up Visits and Phone Contacts for Both Groups 
836 
After the first 2 weeks, the schedule for remaining follow-up contacts is the same for both 
837 
treatment groups. Study staff will discuss with the parent that periodic contact is required and will 
838 
make arrangements with the parent for the contacts.  If the parent cannot be reached, the 
839 
participant’s other contact methods will be utilized, including the emergency contact. 
840 
 
841 
A follow-up in-clinic visit will occur at 6 weeks (±7 days). The following procedures are 
842 
performed in both groups, unless otherwise specified below: 
843 
Assessment of compliance with study device use by review of any available device data 
844 
Assessment of adverse events, adverse device effects, and device issues 
845 
Download of device data (study system or personal pump and study CGM, study BG meter, study 
846 
ketone meter); in the case of videoconferences, participants will upload or email available data 
847 
prior to the visit, including CGM, pump, and ketone meter, so that clinic staff can review and 
848 
download the data 
849 
 
850 
A follow-up phone call or videoconference will occur at 10 weeks (±7 days). At the discretion of 
851 
the investigator, this scheduled phone contact may be replaced by an in-clinic visit. 
852 
The following procedures are performed in both treatment groups: 
853 
• Review of available CGM, ketone meter, and/or system data to identify any safety issues 
854 
associated with current insulin therapy and diabetes management approach 
855 
• Assessment of adverse events, adverse device effects, and device issues 
856 
Additional phone contacts may be performed as needed. 
857 
 
858 
If needed for safety reasons at the criteria of the physician at each clinical center, optimization may 
859 
be done via phone contacts, videoconferences, or in-clinic visits. 
860 
Data will be obtained from CGM and/or pump downloads during the contact. Adjustments to pump 
861 
settings (basal rates, correction factor, insulin-to-carbohydrate ratio, etc.) or injection strategies 
862 
will be made in response to major trends observed in the CGM data, with flexibility for clinicians 
863 
to adhere to guidelines and practices established at each individual practice rather than a fixed set 
864 
of heuristics for all clinical centers. 
865 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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866 
All participants will have a 13-Week (±7 days) visit during which the following will occur: 
867 
• Collection of a blood sample to send to the central laboratory for HbA1c determination. 
868 
• Completion of questionnaires  
869 
• Weight and height measurements will be repeated 
870 
• Assessment of adverse events, adverse device effects, and device issues 
871 
• Download of device data (study system or personal pump and study CGM, study BG meter, 
872 
study ketone meter) as available 
873 
 Early Termination Visit (If Applicable) 
874 
Participants will be asked to come for an end of study visit in the event of withdrawal or early 
875 
termination. 
876 
 Unscheduled Visits 
877 
Participants may have unscheduled visits during the study period if required for additional device 
878 
training or other unanticipated needs per the study investigator discretion. 
879 
 
 
880 

 
 
 
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Chapter 6: Extension Phase Procedures   
881 
At the conclusion of the 13-week RCT, all participants will use the Control-IQ closed-loop 
882 
system during a 13-week Extension Phase.  
883 
An updated version of the Control-IQ system with enhanced usability will be used during the 
884 
Extension Phase. Participants assigned to the SC group during the RCT period will receive 
885 
training based on the updated pump as described below. Participants assigned to the CLC group 
886 
will receive a brief training session to review any new or changed features of the pump.  
887 
Initiation of the updated Control-IQ pump may be deferred by up to 2 weeks if needed, with the 
888 
participant continuing on the treatment used during the RCT period during this time and the 
889 
overall duration of the Extension Phase increasing by up to 2 weeks.  
890 
 Visit and Contact Schedule 
891 
During the Extension period, visits and contacts will be scheduled as outlined in Table 4 below: 
892 
Table 4: Extension Phase Visit and Phone Contact Schedule 
893 
Target Day/Week1 
Contact Type2 
Target/Allowable Window 
(around Target Day/Week) 
13 weeks + 3 days 
VC/P 
± 2 days 
14 weeks 
P 
± 2 days 
15 weeks 
VC/V 
± 4 days 
19 weeks 
VC/V 
± 7 days 
23 weeks 
P 
± 7 days 
26 weeks 
VC/V 
± 7 days 
1 The “13 weeks” and subsequent visit targets reflect a participant who had no delay between the 13-week visit of the RCT and 
894 
initiation of use of the updated Control-IQ pump. Targets and associated windows may be shifted by up to 2 weeks for 
895 
participants whose initiation is delayed.  
896 
2 Contact Types are defined as Clinic Visit (V), Videoconference (VC), or Phone call (P); Phone calls may be replaced by 
897 
Videoconferences or Clinic Visits and Videoconferences may be replaced by Clinic Visits at investigator discretion 
898 
 
899 
 Study Pump Initiation  
900 
Participants assigned to the SC group during the initial 13-Week RCT period will initiate use of 
901 
the updated study pump either the same day as the 13-Week visit or within 2 weeks of this visit. 
902 
The procedures described in section 5.3 above will be followed to initiate these participants on 
903 
the study pump.   
904 
Participants assigned to the CLC group during the RCT period will switch to the updated version 
905 
of the Control-IQ system and will receive training on its new features. This will occur either the 
906 
same day as the 13-Week visit or within 2 weeks of this visit. 
907 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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 Visits, Videoconferences, and Phone Calls for All Participants 
908 
 
909 
Study staff will perform a phone call or videoconference with the parent within 3 (±2) days 
910 
following initiation of Extension Phase study pump use. Procedures will mirror those described in 
911 
section 5.3.6 above. 
912 
 
913 
Participants will have a phone call or videoconference at 14 Weeks (±2 days). Procedures will 
914 
mirror those described in section 5.3.7 above. 
915 
 
916 
Participants will have a follow-up visit at 15 Weeks (±4 days). Procedures will mirror those 
917 
described in section 5.3.8 above. 
918 
 
919 
A follow-up in-clinic visit will occur at 19 weeks (±7 days). Procedures will mirror those 
920 
described in section 5.5.1 above. 
921 
 
922 
A follow-up phone call will occur at 23 weeks (±7 days). Procedures will mirror those described 
923 
in section 5.5.2 above. 
924 
 
925 
A follow-up in-clinic visit will occur at 26 weeks (±7 days). Procedures will mirror those 
926 
described in section 5.5.4 above. 
927 
Participants will have the opportunity to participate in Focus Group sessions as described in 
928 
section 9.3 below. 
929 
Participants will be given the option to continue use of the Control-IQ closed-loop system during 
930 
an additional Extended Use period as described in the next chapter. Participants who do not wish 
931 
to continue to the Extended Use period will be switched back to the insulin pump or MDI 
932 
therapy that was in use prior to the study. 
933 
 
934 
If needed for safety reasons at the criteria of the physician at each clinical center, optimization 
935 
may be done via phone contacts, videoconferences, or in-clinic visits as described in section 
936 
5.5.3 above. 
937 
 Unscheduled Visits 
938 
Participants may have unscheduled visits during the study period if required for additional device 
939 
training or other unanticipated needs per the study investigator discretion. 
940 

 
 
 
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 Participant Access to Study Device at Study Closure 
941 
Participants not continuing to the Extended Use period will return all investigational study devices 
942 
and supplies (insulin pump, CGM and related supplies).  Participants may keep the study ketone 
943 
meter and study glucometer if these devices are not marked for investigational use only. 
944 
 
 
945 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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Chapter 7: Extended Use Period Procedures   
946 
At the 26-Week Visit of the Extension Phase, participants will be given the option to continue 
947 
use of the Control-IQ closed-loop system during an additional Extended Use period. Participants 
948 
who completed the 26-Week Visit before the addition of this Extended Use period to the study 
949 
protocol will be eligible to rejoin the study and participate as long as they completed their 26-
950 
Week Visit within the prior 4 months. 
951 
The same version of the Control-IQ system in use during the 13-Week Extension Phase will be 
952 
used during the Extended Use period. 
953 
Informed Consent will be obtained from eligible participants who are interested in participating 
954 
in the Extended Use period. The informed consent process will mirror the process described 
955 
above in section 2.1.1. 
956 
 Visit and Contact Schedule 
957 
During the Extended Use period, visits and contacts will be scheduled as outlined in Table 5 
958 
below: 
959 
Table 5: Extended Use Period Visit and Phone Contact Schedule 
960 
Target Day/Week with 
respect to initiation of 
Extended Use period 
Contact Type1 
Target/Allowable Window 
(around Target Day/Week) 
0 days (Retraining) 2 
VC/V 
N/A 
3 days2 
VC/P 
± 2 days 
1 week2 
VC/P 
± 2 days 
13 weeks 
VC/V 
± 7 days 
26 weeks 
VC/V 
± 7 days 
Final Visit 
VC/V 
N/A 
1 Contact Types are defined as Clinic Visit (V), Videoconference (VC), or Phone call (P); Phone calls may be replaced by 
961 
Videoconferences or Clinic Visits and Videoconferences may be replaced by Clinic Visits at investigator discretion 
962 
2 Only for participants who had a gap between the 26-Week Visit and the initiation of the Extended Use period during which they 
963 
stopped use of the study pump and reverted to MDI or personal pump insulin therapy 
964 
 Visits, Videoconferences, and Phone Calls for Participants Re-Initiating Study Pump 
965 
Use After a Gap in Use 
966 
 
967 
Participants who had a gap between the 26-Week Visit and the initiation of the Extended Use 
968 
period during which they reverted to MDI or personal pump insulin therapy will have a visit to 
969 
receive retraining on the study pump prior to re-initiation of study pump use. 
970 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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The procedures described in section 5.3 above will be followed to re-initiate these participants on 
971 
the study pump.   
972 
 
973 
Study staff will perform a phone call or videoconference with the parent within 3 (±2) days 
974 
following re-initiation of study pump use. Procedures will mirror those described in section 5.3.6 
975 
above. 
976 
 
977 
Participants will have a phone call or videoconference within 7 days (±2 days) following re-
978 
initiation of study pump use. Procedures will mirror those described in section 5.3.7 above. 
979 
 Visits, Videoconferences, and Phone Calls for All Participants 
980 
 
981 
A follow-up in-clinic visit will occur 13 weeks (±7 days) after the start of the Extended Use period. 
982 
The following procedures will be performed in both groups: 
983 
• Collection of a blood sample to send to the central laboratory for HbA1c determination  
984 
• Assessment of compliance with study device use by review of any available device data 
985 
• Assessment of adverse events, adverse device effects, and device issues 
986 
• Download of device data (study system or personal pump and study CGM, study BG meter, 
987 
study ketone meter); in the case of videoconferences, participants will upload or email 
988 
available data prior to the visit, including CGM, pump, and ketone meter, so that clinic 
989 
staff can review and download the data 
990 
Every 13 weeks (±7 days) thereafter, another follow-up clinic visit will occur involving the same 
991 
procedures described above. 
992 
 
993 
A final follow-up in-clinic or videoconference visit will occur no later than July 31, 2022. 
994 
Procedures will mirror those described in section 7.3.1 above, except that no blood sample will 
995 
be collected. 
996 
Participants will be switched back to the insulin pump or MDI therapy that was in use prior to 
997 
the study. 
998 
 
999 
If needed for safety reasons at the criteria of the physician at each clinical center, optimization 
1000 
may be done via phone contacts, videoconferences, or in-clinic visits as described in section 
1001 
5.5.3 above. 
1002 

 
 
 
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 Unscheduled Visits 
1003 
Participants may have unscheduled visits during the study period if required for additional device 
1004 
training or other unanticipated needs per the study investigator discretion. 
1005 
 Participant Access to Study Device at Study Closure 
1006 
Participant will return all investigational study devices and supplies (insulin pump, CGM and 
1007 
related supplies) at study closure.  Participant may keep the study ketone meter and study 
1008 
glucometer if these devices are not marked for investigational use only. 
1009 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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Chapter 8: Study Devices 
1010 
 Description of the Investigational Device 
1011 
 
1012 
The study system will include the Tandem t:slim X2 with Control-IQ technology. 
1013 
 
1014 
The study CGM will include Dexcom G6 transmitter and sensors.  The CGM sensor will be 
1015 
replaced at least once every 10 days. 
1016 
 
1017 
Blood glucose levels will be measured using the study’s blood glucose meter (glucometer) and the 
1018 
CGM device will be calibrated if needed using the study glucometer and strips in accordance with 
1019 
the manufacturer’s labeling. 
1020 
 
1021 
Blood ketone levels will be measured using the Abbott Precision Xtra meter and strips in 
1022 
accordance with the manufacturer’s labeling.  The blood glucose meter component of the Precision 
1023 
Xtra device will not be used. 
1024 
 
1025 
Device accountability procedures will be detailed in the clinical center procedures manual. 
1026 
 
1027 
Participants to perform QC testing at home per manufacturer guidelines. 
1028 
All study blood ketone meters will be QC tested with control solution if available during all office 
1029 
visits.  A tested meter will not be used in a study if it does not read within the target range at each 
1030 
concentration per manufacturer labeling.  The participant will be instructed to contact study staff 
1031 
for a replacement of the meter, test strips, and control solution if a meter fails QC testing at home. 
1032 
Participants will be instructed on how to perform blood ketone testing. 
1033 
Participants will be given guidelines for treatment of elevated blood ketones. 
1034 
 Safety Measures 
1035 
 
1036 
Throughout the study, participants will be instructed to calibrate the study CGM in accordance 
1037 
with manufacturer labelling. 
1038 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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1039 
If the CGM signal becomes unavailable for more than 20 minutes consecutively, Control-IQ or 
1040 
closed loop will not operate to automatically adjust insulin. If the CGM is not connected, the 
1041 
system will revert to usual function of the pump and deliver insulin with the insulin dosing 
1042 
parameters programmed in the system for that individual. Resumption of Closed-Loop will 
1043 
occur automatically once CGM signal is available again. 
1044 
If the study system is unable to activate Control-IQ for any reason, the pump will automatically 
1045 
revert to preprogrammed basal insulin delivery without any need for instruction from the user. 
1046 
If the pump detects a system error that does not allow it to operate, the Malfunction Alarm will 
1047 
display and the participant will be instructed to contact Tandem Technical Support via the study 
1048 
team. 
1049 
 
1050 
During the course of the study, participants will be permitted to change the CGM low glucose 
1051 
threshold alert setting on their device or mobile app, but will be instructed to choose a value no 
1052 
less than 70 mg/dL. 
1053 
The t:slim X2 with Control-IQ system will issue a predictive hypoglycemia alert (Control-IQ Low 
1054 
Alert) when the system predicts BG <70 mg/dL within the next 15 minutes (<80 mg/dL when 
1055 
exercise mode is activated). 
1056 
If the participant receives a Control-IQ Low Alert, a message appears on the user interface (UI) 
1057 
that is accompanied by vibration followed by vibrations and/or sound if not acknowledged by the 
1058 
user in 5 minutes.  This alert remains on the screen until acknowledged by the user. The user is 
1059 
prompted to test blood sugar and treat with carbs. 
1060 
 
1061 
During the course of the study, participants will be permitted to change the CGM high glucose 
1062 
threshold alert setting on their device or mobile app, but will be instructed to choose a value no 
1063 
greater than 300 mg/dL. 
1064 
The t:slim X2 with Control-IQ system will issue a predictive hyperglycemia alert (Control-IQ 
1065 
High Alert) when the system has increased insulin delivery, but detects a CGM value above 200 
1066 
mg/dL and does not predict the value will decrease in the next 30 minutes. 
1067 
If the participant receives a Control-IQ High Alert, a message appears on the UI that is 
1068 
accompanied by vibration followed by vibrations and/or sound if not acknowledged by the user in 
1069 
5 minutes. This alert remains on the screen until acknowledged by the user. The user is prompted 
1070 
to check the site for occlusion and test blood glucose. 
1071 
If a participant’s CGM reading is >300 mg/dL for over 90 minutes or ≥400 mg/dL at any point, or 
1072 
if CGM reading is >250 mg/dL more than 3 hours after a meal, the participant took correction 
1073 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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insulin, and CGM didn’t decrease by at least 50 mg/dL, the participant will be instructed to take 
1074 
the following steps: 
1075 
Inspect infusion site for problems 
1076 
Perform a blood glucose meter check. 
1077 
If the blood glucose is >300 mg/dL, check for blood ketones with the study ketone meter. 
1078 
If the ketone level is ≥1.0 mmol/L, take correction insulin, change insulin (pump) infusion site and 
1079 
contact study staff. 
1080 
If a participant administers correction insulin via insulin syringe, participants will be instructed to 
1081 
turn Control-IQ off for approximately four hours. 
1082 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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Chapter 9: Testing Procedures, Questionnaires, and Focus Groups 
1083 
 Laboratory Testing 
1084 
 
1085 
Performed at the Randomization visit, 13-Week visit, and 26-Week visit 
1086 
Blood samples will be sent to the central laboratory for sample analysis using an NGSP approved 
1087 
method. 
1088 
 Questionnaires 
1089 
The questionnaires listed below are completed by participants’ parents at Screening, 13 weeks, 
1090 
and 26 weeks for all participants except as noted.  The questionnaires will be family and age 
1091 
appropriate and are described briefly below.  The procedures for administration are described in 
1092 
the clinical center procedures manual. 
1093 
Pediatric Quality of Life – Parent  
1094 
Pediatric Inventory for Parents 
1095 
INSPIRE Survey – Parent 
1096 
Pittsburgh Sleep Quality Index (PSQI) – Parent 
1097 
Fear of Hypoglycemia Survey-Parents (HFS-P) 
1098 
Hypoglycemia Confidence Scale (HCS) 
1099 
System Usability Scale (SUS) (Closed-Loop participants only at 13 and 26 weeks) 
1100 
Administration time is approximately 35 minutes. 
1101 
 
1102 
This is a 32-item scale developed and validated for the measurement of diabetes-specific quality 
1103 
of life. Participants record the extent to which their child experienced each of 32 problems 
1104 
related to diabetes in the prior month.  
1105 
Administration time is approximately 5 minutes. 
1106 
 
1107 
This is a widely-used, 42-item measure of parenting stress designed for parents of youth with 
1108 
type 1 diabetes.  
1109 
Administration time is approximately 6 minutes. 
1110 
 
1111 
The INSPIRE (Insulin Delivery Systems: Perceptions, Ideas, Reflections and Expectations) survey 
1112 
was developed to assess various aspects of a user’s experience regarding automated insulin 
1113 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
PAGE 52 OF 84 
 
delivery for both patients and family members. The surveys include various topics important to 
1114 
patients with type 1 diabetes and their family members based upon >200 hours of qualitative 
1115 
interviews and focus groups. The parent pre-assessment survey and parent post-assessment survey 
1116 
both contain 19 items. Response options for all surveys include a 5-point Likert scale from strongly 
1117 
agree to strongly disagree, along with an N/A option. 
1118 
Administration time is approximately 5 minutes. 
1119 
 
1120 
An abbreviated 9-question version of the Pittsburgh Sleep Quality Index (PSQI), a validated tool 
1121 
for assessing self-reported sleep quantity and quality, will be completed by parents. Seven 
1122 
component scores are derived, each scored 0 (no difficulty) to 3 (severe difficulty). The 
1123 
component scores are summed to produce a global score (range 0 to 21). Higher scores indicate 
1124 
worse sleep quality. 
1125 
Administration time is approximately 3 minutes. 
1126 
 
1127 
The Hypoglycemia Fear Survey-Parent is a validated tool of 25 items to assess parents’ anxiety 
1128 
and behavior concerning possible hypoglycemia. Items are rated on a 5-point Likert scale 
1129 
(0=never, 4=always), with higher scores indicating higher fear of hypoglycemia.  
1130 
Administration time is approximately 4 minutes. 
1131 
 
1132 
The scale comprises 8 items and measures confidence hypoglycemia can be treated or prevented 
1133 
in various situations.  
1134 
Administration time is approximately 3 minutes. 
1135 
 
1136 
The System Usability Scale (SUS) is a 10-item questionnaire that measures the overall usability 
1137 
of a system. It is a valid and reliable measure of the perceived usability of a system and is 
1138 
technology-agnostic. The questionnaire presents statements with five response options (anchoring 
1139 
the options from strongly disagree to strongly agree) and asks users to rate their agreement to the 
1140 
statements.  User scores are transformed into a composite score, from 0 to 100, and this score is 
1141 
taken as an overall measure of the system’s usability; higher scores indicate better perceived 
1142 
usability. 
1143 
Administration time is approximately 5 minutes. 
1144 
 
1145 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
PAGE 53 OF 84 
 
 Focus Groups 
1146 
Focus groups will be completed following the 26-Week Visit. The focus groups will be conducted 
1147 
virtually using HIPAA-approved software. 
1148 
Focus groups will include 3-5 individuals and a script of open-ended questions to gather feedback 
1149 
and reactions to the closed loop system, the clinical trial, and QoL changes. There will also be time 
1150 
for discussion of content raised by parents. If parents are able to have the child participant attend 
1151 
briefly to answer a few questions, this will be attempted.  
1152 
Sessions will be audio- and video-taped and transcribed by a professional transcription service. 
1153 
Otherwise, these recordings will not be shared for any non-study purposes. Transcriptions will use 
1154 
a code for participants, such as “Participant 1”, and will not contain names or other identifiers of 
1155 
participants.  
 
1156 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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Chapter 10: Unanticipated Problem, Adverse Event, and Device Issues 
1157 
Reporting 
1158 
 Unanticipated Problems 
1159 
Site investigators will promptly report to the Coordinating Center on an eCRF all unanticipated 
1160 
problems meeting the criteria below. Problems meeting IRB reporting requirements will be 
1161 
reported to the IRB within 7 calendar days of the site becoming aware of the problem. For this 
1162 
protocol, an unanticipated problem is an incident, experience, or outcome that meets all of the 
1163 
following criteria: 
1164 
• Unexpected (in terms of nature, severity, or frequency) given (a) the research procedures 
1165 
that are described in the protocol related documents, such as the IRB-approved research 
1166 
protocol and informed consent document; and (b) the characteristics of the subject 
1167 
population being studied 
1168 
• Related or possibly related to participation in the research (possibly related means there is 
1169 
a reasonable possibility that the incident, experience, or outcome may have been caused 
1170 
by the procedures involved in the research) 
1171 
• Suggests that the research places participants or others at a greater risk of harm than was 
1172 
previously known or recognized (including physical, psychological, economic, or social 
1173 
harm) 
1174 
The Coordinating Center also will report to the IRB all unanticipated problems not directly 
1175 
involving a specific site such as unanticipated problems that occur at the Coordinating Center or 
1176 
at another participating entity such as a pharmacy or laboratory. These instances must be 
1177 
reported to the JCHR IRB within seven calendar days of recognition. The Director of the Human 
1178 
Research Protection Program will report to the appropriate regulatory authorities if the IRB 
1179 
determines that the event indeed meets the criteria of an Unanticipated Problem requiring 
1180 
additional reporting. 
1181 
 Adverse Events 
1182 
 
1183 
Adverse Event (AE): Any untoward medical occurrence in a study participant, irrespective of the 
1184 
relationship between the adverse event and the device(s) under investigation. 
1185 
Serious Adverse Event (SAE): Any untoward medical occurrence that: 
1186 
Results in death. 
1187 
Is life-threatening; (a non-life-threatening event which, had it been more severe, might have 
1188 
become life-threatening, is not necessarily considered a serious adverse event). 
1189 
Requires inpatient hospitalization or prolongation of existing hospitalization. 
1190 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
PAGE 55 OF 84 
 
Results in persistent or significant disability/incapacity or substantial disruption of the ability to 
1191 
conduct normal life functions (sight threatening). 
1192 
Is a congenital anomaly or birth defect. 
1193 
Is considered a significant medical event by the investigator based on medical judgment (e.g., may 
1194 
jeopardize the participant or may require medical/surgical intervention to prevent one of the 
1195 
outcomes listed above). 
1196 
Unanticipated Adverse Device Effect (UADE): Any serious adverse effect on health or safety or 
1197 
any life-threatening problem or death caused by, or associated with, a device, if that effect, 
1198 
problem, or death was not previously identified in nature, severity, or degree of incidence in the 
1199 
investigational plan or application (including a supplementary plan or application), or any other 
1200 
unanticipated serious problem associated with a device that relates to the rights, safety, or welfare 
1201 
of participants (21 CFR 812.3(s)). 
1202 
Adverse Device Effect (ADE): Any untoward medical occurrence in a study participant which the 
1203 
device may have caused or to which the device may have contributed (Note that an Adverse Event 
1204 
Form is to be completed in addition to a Device Deficiency or Issue Form, unless excluded from 
1205 
reporting as defined in section 10.3). An event that occurs solely due to participant (i.e., user) 
1206 
error in which the device functions properly generally will not be considered an ADE unless it is 
1207 
determined that the instructions on the screen of the device or user manual (or similar training 
1208 
materials) may have contributed to the event (note: the event may still meet criteria for reporting 
1209 
as an adverse event). 
1210 
Device Complaints and Malfunctions: A device complication or complaint is something that 
1211 
happens to a device or related to device performance, whereas an adverse event happens to a 
1212 
participant.  A device complaint may occur independently from an AE, or along with an AE.  
1213 
An AE may occur without a device complaint or there may be an AE related to a device complaint.  
1214 
A device malfunction is any failure of a device to meet its performance specifications or otherwise 
1215 
perform as intended.  Performance specifications include all claims made in the labeling for the 
1216 
device.  The intended performance of a device refers to the intended use for which the device is 
1217 
labeled or marketed. (21 CFR 803.3).  Note: for reporting purposes, sites will not be asked to 
1218 
distinguish between device complaints and malfunctions. 
1219 
 
1220 
For this protocol, a reportable adverse event includes any untoward medical occurrence that meets 
1221 
one of the following criteria: 
1222 
1. An SAE or an AE associated with a visit to a hospital emergency department 
1223 
2. An ADE as defined in section 10.2.1, unless excluded from reporting in section 10.3 
1224 
3. An AE as defined in section 10.2.1 occurring in association with a study procedure 
1225 
4. An AE as defined in section 10.2.1 not related to a device issue which leads to temporary or 
1226 
permanent discontinuation of a study device 
1227 
5. An AE as defined in section 10.2.1 that affects the participant’s ability to complete any study 
1228 
procedures 
1229 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
PAGE 56 OF 84 
 
6. Hypoglycemia meeting the definition of severe hypoglycemia as defined below  
1230 
7. Diabetic ketoacidosis (DKA) as defined below or in the absence of DKA, a hyperglycemic or 
1231 
ketosis event meeting the criteria defined below 
1232 
Hypoglycemia and hyperglycemia not meeting the criteria below will not be recorded as adverse 
1233 
events unless associated with an Adverse Device Effect.  Skin reactions from sensor placement are 
1234 
only reportable if severe and/or required treatment. 
1235 
All reportable AEs—whether volunteered by the participant, discovered by study personnel during 
1236 
questioning, or detected through physical examination, laboratory test, or other means—will be 
1237 
reported on an AE form online.  Each AE form is reviewed by the Medical Monitor to assess safety 
1238 
and to verify the coding and the reporting that is required. 
1239 
 
1240 
Hypoglycemia not associated with an Adverse Device Effect is only reportable as an adverse event 
1241 
when the following definition for severe hypoglycemia is met:  the event required assistance of 
1242 
another person due to altered consciousness, and required another person to actively administer 
1243 
carbohydrate, glucagon, or other resuscitative actions.  This means that the participant was 
1244 
impaired cognitively to the point that he/she was unable to treat himself/herself, was unable to 
1245 
verbalize his/ her needs, was incoherent, disoriented, and/or combative, or experienced seizure or 
1246 
loss of consciousness.  These episodes may be associated with sufficient neuroglycopenia to 
1247 
induce seizure or loss of consciousness.  If plasma glucose measurements are not available during 
1248 
such an event, neurological recovery attributable to the restoration of plasma glucose to normal is 
1249 
considered sufficient evidence that the event was induced by a low plasma glucose concentration. 
1250 
When a hypoglycemic event meets the above reporting requirements, a Hypoglycemia Form 
1251 
should be completed in addition to the Adverse Event Form. Severe hypoglycemia events should 
1252 
be considered to be serious adverse events with respect to reporting requirements. 
1253 
 
1254 
Hyperglycemia not associated with an Adverse Device Effect is only reportable as an adverse 
1255 
event when one of the following criteria is met:  
1256 
the event involved DKA, as defined by the Diabetes Control and Complications Trial (DCCT) and 
1257 
described below 
1258 
evaluation or treatment was obtained at a health care provider facility for an acute event involving 
1259 
hyperglycemia or ketosis, or the participant contacted the site and received guidance on how to 
1260 
manage the hyperglycemia/ketosis 
1261 
blood ketone level ≥1.0 mmol/L, even if there was no communication with a health care provider 
1262 
at the time of the event 
1263 
Hyperglycemic events are classified as DKA if the following are present: 
1264 
Symptoms such as polyuria, polydipsia, nausea, or vomiting; 
1265 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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Serum ketones ≥1.5 mmol/L or large/moderate urine ketones; 
1266 
Either arterial blood pH <7.30 or venous pH <7.24 or serum bicarbonate (or CO2) <15; and 
1267 
Treatment provided in a health care facility 
1268 
When a hyperglycemia/ketotic qualifies as an SAE as defined in section 10.2.1, a 
1269 
Hyperglycemia/DKA Form should be completed in addition to the Adverse Event Form. Events 
1270 
meeting DKA criteria should be considered to be serious adverse events with respect to reporting 
1271 
requirements. Hyperglycemia events not meeting criteria for DKA generally will not be considered 
1272 
as serious adverse events unless one of the SAE criteria in section 10.2.1 is met. 
1273 
 
1274 
The study investigator will assess the relationship of any adverse event to be related or unrelated 
1275 
by determining if there is a reasonable possibility that the adverse event may have been caused by 
1276 
the study device. 
1277 
To ensure consistency of adverse event causality assessments, investigators should apply the 
1278 
following general guideline when determining whether an adverse event is related: 
1279 
Yes 
1280 
There is a plausible temporal relationship between the onset of the adverse event and the study 
1281 
intervention, and the adverse event cannot be readily explained by the participant’s clinical state, 
1282 
intercurrent illness, or concomitant therapies; and/or the adverse event follows a known pattern of 
1283 
response to the study intervention; and/or the adverse event abates or resolves upon discontinuation 
1284 
of the study intervention or dose reduction and, if applicable, reappears upon re-challenge. 
1285 
No 
1286 
Evidence exists that the adverse event has an etiology other than the study intervention (e.g., 
1287 
preexisting medical condition, underlying disease, intercurrent illness, or concomitant 
1288 
medication); and/or the adverse event has no plausible temporal relationship to study intervention. 
1289 
 
1290 
The severity (intensity) of an adverse event will be rated on a three point scale: (1) mild, (2) 
1291 
moderate, or (3) severe.  A severity assessment is a clinical determination of the intensity of an 
1292 
event. Thus, a severe adverse event is not necessarily serious.  For example, itching for several 
1293 
days may be rated as severe, but may not be clinically serious. 
1294 
• MILD: Usually transient, requires no special treatment, and does not interfere with the 
1295 
participant’s daily activities. 
1296 
• MODERATE: Usually causes a low level of inconvenience, discomfort or concern to the 
1297 
participant and may interfere with daily activities, but is usually ameliorated by simple 
1298 
therapeutic measures and participant is able to continue in study. 
1299 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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• SEVERE: Interrupts a participant’s usual daily activities, causes severe discomfort, may 
1300 
cause discontinuation of study device, and generally requires systemic drug therapy or 
1301 
other treatment. 
1302 
 
1303 
For a serious adverse event that is considered possibly related to study device, the Medical 
1304 
Monitor will classify the event as unexpected if the nature, severity, or frequency of the event is 
1305 
not consistent with known risk information. 
1306 
 
1307 
Adverse events will be coded using the MedDRA dictionary. To facilitate coding, the site will 
1308 
enter a preliminary MedDRA code which the Medical Monitor may accept or change (the Medical 
1309 
Monitor’s MedDRA coding will be used for all reporting). The Medical Monitor will review the 
1310 
investigator’s assessment of causality and may agree or disagree.  Both the investigator’s and 
1311 
Medical Monitor’s assessments will be recorded.  The Medical Monitor will have the final say in 
1312 
determining the causality as well as whether an event is classified as a serious adverse event and/or 
1313 
an unanticipated adverse device effect. 
1314 
 
1315 
The outcome of each reportable adverse event will be classified by the investigator as follows: 
1316 
RECOVERED/RESOLVED – The participant recovered from the AE/SAE without sequelae.  
1317 
Record the AE/SAE stop date. 
1318 
RECOVERED/RESOLVED WITH SEQUELAE – The event persisted and had stabilized without 
1319 
change in the event anticipated.  Record the AE/SAE stop date. 
1320 
FATAL – A fatal outcome is defined as the SAE that resulted in death.  Only the event that was 
1321 
the cause of death should be reported as fatal.  AEs/SAEs that were ongoing at the time of death; 
1322 
however, were not the cause of death, will be recorded as “resolved” at the time of death. 
1323 
NOT RECOVERED/NOT RESOLVED (ONGOING) – An ongoing AE/SAE is defined as the 
1324 
event was ongoing with an undetermined outcome. 
1325 
o An ongoing outcome will require follow-up by the site in order to determine the final 
1326 
outcome of the AE/SAE. 
1327 
o The outcome of an ongoing event at the time of death that was not the cause of death, 
1328 
will be updated and recorded as “resolved” with the date of death recorded as the stop 
1329 
date. 
1330 
UNKNOWN – An unknown outcome is defined as an inability to access the participant or the 
1331 
participant’s records to determine the outcome (for example, a participant that was lost to follow-
1332 
up). 
1333 
If any reported adverse events are ongoing when a participant completes the study (or withdraws), 
1334 
adverse events classified as UADEs will be followed until they are either resolved, or have no 
1335 
prospect of improvement or change, even after the participant has completed all applicable study 
1336 
visits/contacts. For all other adverse events, data collection will end at the time the participant 
1337 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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completes the study. Note: participants should continue to receive appropriate medical care for an 
1338 
adverse event after their participation in the study ends. 
1339 
 Reportable Device Issues 
1340 
All UADEs and ADEs as defined in section 10.2.1 will be reported on both a device issue form 
1341 
and AE form, except for skin reactions from CGM sensor placement or pump infusion set 
1342 
placement that do not require pharmacologic treatment.  As noted in section 10.2.1, events that 
1343 
occur due to participant (user) error generally will not require completion of a device issue form. 
1344 
Such ‘errors’ could include improper use of an insulin pump or using a pump infusion set or 
1345 
CGM sensor for a period of time longer than its labeling. 
1346 
Device complaints and device malfunctions will be reported except in the following 
1347 
circumstances. These occurrences are expected and will not be reported on a Device Issue Form 
1348 
assuming criteria for a UADE or ADE have not been met: 
1349 
CGM sensor lasting fewer days than expected per manufacturer 
1350 
CGM tape adherence issues 
1351 
Battery lifespan deficiency due to inadequate charging or extensive wireless communication 
1352 
Intermittent device component disconnections/communication failures not requiring system 
1353 
replacement or workaround/resolution not specified in user guide/manual. 
1354 
Device issues clearly addressed in the user guide manual that do not require additional 
1355 
troubleshooting 
1356 
 Timing of Event Reporting 
1357 
SAEs possibly related to a study device or study participation and UADEs must be reported to 
1358 
the Coordinating Center within 24 hours of the site becoming aware of the event.  This can occur 
1359 
via phone or email, or by completion of the online serious adverse event form and device issue 
1360 
form if applicable. If the form is not initially completed, it should be competed as soon as 
1361 
possible after there is sufficient information to evaluate the event. All other reportable ADEs and 
1362 
other reportable AEs should be submitted by completion on the online form within 7 days of the 
1363 
site becoming aware of the event. 
1364 
The Coordinating Center will notify all participating investigators of any adverse event that is 
1365 
serious, related, and unexpected. Notification will be made within 10 working days after the 
1366 
Coordinating Center becomes aware of the event. 
1367 
Each principal investigator is responsible for reporting serious study-related adverse events and 
1368 
abiding by any other reporting requirements specific to his/her Institutional Review Board or 
1369 
Ethics Committee. Sites must report all serious, related adverse events within seven calendar 
1370 
days. 
1371 
Upon receipt of a qualifying event, the Sponsor will investigate the event to determine if a 
1372 
UADE is confirmed, and if indicated, report the results of the investigation to all overseeing 
1373 
IRBs, and the FDA within 10 working days of the Sponsor becoming aware of the UADE per 
1374 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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21CFR 812.46(b) (2).  The Medical Monitor must determine if the UADE presents an 
1375 
unreasonable risk to participants.  If so, the Medical Monitor must ensure that all investigations, 
1376 
or parts of investigations presenting that risk, are terminated as soon as possible but no later than 
1377 
5 working days after the Medical Monitor makes this determination and no later than 15 working 
1378 
days after first receipt notice of the UADE. 
1379 
Device malfunctions will be handled by the Sponsor or designee as described below.  In the case 
1380 
of a CGM transmitter or sensor device malfunction, information will be forwarded to Dexcom by 
1381 
the site personnel, to be handled by their complaint management system. 
1382 
 Safety Oversight 
1383 
The study Medical Monitor will review all adverse events and adverse device events that are 
1384 
reported during the study.  SAEs typically will be reviewed within 24 hours of reporting.  Other 
1385 
AEs typically will be reviewed on a weekly basis. Additionally, the Medical Monitor will review 
1386 
compiled safety data at periodic intervals (generally timed to the review of compiled safety data 
1387 
by the DSMB). 
1388 
The Protocol Chair will be informed of all cases of severe hypoglycemia and DKA and the 
1389 
Medical Monitor’s assessment of relationship to the study device; and informed of all reported 
1390 
device issues. 
1391 
A Data and Safety Monitoring Board (DSMB) will be informed of all cases of severe 
1392 
hypoglycemia and diabetic ketoacidosis irrespective of device relationship, all device-related 
1393 
SAEs, and all UADEs at the time that they occur during the study and will review compiled 
1394 
safety data at periodic intervals. The DSMB also will be informed of any ADEs not meeting 
1395 
criteria for a UADE if the Medical Monitor requests the DSMB review. The DSMB can request 
1396 
modifications to the study protocol or suspension or outright stoppage of the study if deemed 
1397 
necessary based on the totality of safety data available. Details regarding DSMB review will be 
1398 
documented in a separate DSMB document. 
1399 
 Stopping Criteria 
1400 
 
1401 
In the case of an unanticipated system malfunction resulting in a severe hypoglycemia or DKA 
1402 
event (or a malfunction that could have led to severe hypoglycemia or DKA), use of the study 
1403 
pump will be suspended while the problem is diagnosed. The UADE will be reported to the IRB, 
1404 
DSMB, and FDA. After assessment of the problem and any correction, use of the closed-loop 
1405 
functionality will not be restarted until approval is received from the IRB, DSMB, and FDA. 
1406 
In the absence of a device malfunction, use of the study pump by a participant will be 
1407 
discontinued if any of the following occur:  
1408 
The investigator believes it is unsafe for the participant to continue on the intervention.  This could 
1409 
be due to the development of a new medical condition or worsening of an existing condition; or 
1410 
participant behavior contrary to the indications for use of the device that imposes on the 
1411 
participant’s safety 
1412 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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The participant’s parent requests that the treatment be stopped 
1413 
Two distinct episodes of DKA as defined in section 10.2.4 
1414 
Two distinct severe hypoglycemia events as defined in section 10.2.3 
1415 
One episode of DKA as defined in section 10.2.4 and one severe hypoglycemia event as defined 
1416 
in section 10.2.3 
1417 
Each DKA or severe hypoglycemia event will be reviewed by the Medical Monitor and by the 
1418 
DSMB with respect to determination of cause and whether the occurrence of the event can be 
1419 
attributed to use of the Control-IQ closed-loop feature.  
1420 
An additional requirement for continued study pump use following a single DKA or severe 
1421 
hypoglycemia event will be that (1) the site investigator believes that the event is explainable, 
1422 
unlikely to recur, and that it is safe for the participant to continue to use the system and (2) the 
1423 
Medical Monitor and DSMB concur. If either the Medical Monitor or DSMB determines that the 
1424 
occurrence of the event indicates that it is not safe for the participant to continue to use the study 
1425 
pump, use will be discontinued. 
1426 
Even if the study device system is discontinued, the participant will be encouraged to remain in 
1427 
the study through the final study visit 
1428 
 
1429 
In the case of an unanticipated system malfunction resulting in a severe hypoglycemia or severe 
1430 
hyperglycemia event (as defined in section 10.2.4), use of the study pump will be suspended while 
1431 
the problem is diagnosed. 
1432 
In addition, study activities could be similarly suspended if the manufacturer of any constituent 
1433 
study device requires stoppage of device use for safety reasons (e.g. product recall).  The affected 
1434 
study activities may resume if the underlying problem can be corrected by a protocol or system 
1435 
modification that will not invalidate the results obtained prior to suspension.  
1436 
The study Medical Monitor and DSMB will review all adverse events and adverse device events 
1437 
that are reported during the study. SH and DKA event review will occur for each such event on an 
1438 
expedited basis, and compiled safety data, including SH and DKA event rates, will be reviewed at 
1439 
approximately 6-month intervals. The DSMB will be provided with age-specific DKA and SH 
1440 
rates from the T1D Exchange registry for means of comparison. The Medical Monitor or DSMB 
1441 
may request suspension of study activities or stoppage of the study if deemed necessary based on 
1442 
the totality of safety data available.
1443 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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Chapter 11: Miscellaneous Considerations 
1444 
 Drugs Used as Part of the Protocol 
1445 
Participants will use lispro, aspart, or glusiline rapid-acting insulin prescribed by their personal 
1446 
physician. 
1447 
 Collection of Medical Conditions and Medications 
1448 
Pre-Existing Condition: Any medical condition that is either present at screening, a chronic 
1449 
disease, or a prior condition that could impact the participant’s health during the course of the 
1450 
study (e.g., prior myocardial infarction or stroke). 
1451 
Medical Conditions during the study: In addition to conditions meeting the reporting 
1452 
requirements for an adverse event or device issue as described above, the following medical 
1453 
conditions should also be reported: (1) new diagnosis of a chronic disease (i.e., not present at the 
1454 
time of enrollment), and (2) any medical condition that could affect the participant’s ability to 
1455 
carry out any aspect of the protocol or could affect an outcome assessment. 
1456 
Medications: All medication for the treatment of chronic pre-existing conditions, medical 
1457 
conditions (including medical conditions that do not require recording), and/or adverse events 
1458 
that the participant is currently taking at screening and during the course of the study should be 
1459 
recorded.  Nutraceuticals and preventative treatment also should be recorded.  Medications only 
1460 
taken as needed either can be recorded when prescribed or only recorded if used during the 
1461 
study.  Glucagon for treatment of severe hypoglycemia will only be recorded if used during the 
1462 
study. 
1463 
 Prohibited Medications, Devices, Treatments, and Procedures 
1464 
Participants using glulisine at the time of enrollment will be asked to contact their personal 
1465 
physician to change their prescribed personal insulin to lispro or aspart for the duration of the trial 
1466 
in the case they are randomized to experimental arm. 
1467 
Treatment with any non-insulin glucose-lowering agent (including GLP-1 agonists, Symlin, DPP-
1468 
4 inhibitors, SGLT-2 inhibitors, biguanides, sulfonylureas and naturaceuticals) will not be 
1469 
permitted. 
1470 
The investigational study devices (t:slim X2 insulin pump, study CGM systems) must be removed 
1471 
before Magnetic Resonance Imaging (MRI), Computed Tomography (CT) or diathermy treatment. 
1472 
Participants may continue in the trial after temporarily discontinuing use if requiring one of the 
1473 
treatments above.  
1474 
 Precautionary Medications, Treatments, and Procedures 
1475 
Not applicable. 
1476 
 Prophylactic Medications, Treatments, and Procedures 
1477 
Not applicable. 
1478 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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 Rescue Medications, Treatments, and Procedures 
1479 
All participants will be required to have a commercially available glucagon (or glucagon analog) 
1480 
preparation for treatment as needed of severe hypoglycemia. 
1481 
 Participant Compensation 
1482 
Participant compensation will be specified in the informed consent form. 
1483 
 Participant Withdrawal 
1484 
Participation in the study is voluntary, and a participant may withdraw at any time.  For participants 
1485 
who withdraw, their data will be used up until the time of withdrawal. 
1486 
 Confidentiality 
1487 
For security and confidentiality purposes, participants will be assigned an identifier that will be 
1488 
used instead of their name.  Protected health information gathered for this study will be shared 
1489 
with the coordinating center, the Jaeb Center for Health Research in Tampa, FL.  De-identified 
1490 
participant information may also be provided to research sites involved in the study. 
1491 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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Chapter 12: Statistical Consideration 
1492 
 Statistical and Analytical Plans 
1493 
The approach to sample size and statistical analyses are summarized below. A detailed statistical 
1494 
analysis plan will be written and finalized prior to the completion of the study. 
1495 
 Statistical Hypotheses 
1496 
The primary outcome for this study is CGM-measured % in range 70-180 mg/dL over a 13-week 
1497 
period. The intervention will be considered effective if the Closed-Loop Control [CLC] is 
1498 
superior to Standard Care [SC] using a statistical significance of α=0.05 and the model specified 
1499 
below in Section 6 (i.e., p < 0.05). 
1500 
The null/alternative hypotheses are: 
1501 
a. Null Hypothesis: There is no difference in mean CGM-measured % in range 70-180 
1502 
mg/dL over 13 weeks between SC and CLC  
1503 
b. Alternative Hypothesis: The mean CGM-measured % in range 70-180 mg/dL over 13 
1504 
weeks is different for SC and CLC. 
1505 
 Sample Size 
1506 
Based on data from the DCLP5 study mentioned above, we conservatively estimate the standard 
1507 
deviation (SD) for the primary outcome, time in range (TIR), to be 10%. A sample size of N=90 
1508 
subjects (60 in the CLC arm and 30 in the SC arm) therefore will give 90% power to detect a 7.5% 
1509 
improvement in TIR with a two-sided test and type 1 error of 5%. Accounting for potential attrition 
1510 
rate of up to 10%, the total sample size for the PEDAP Study is estimated at N=102. 
1511 
 
1512 
The following table shows the minimum detectable difference with a total sample size N=90 for 
1513 
key secondary outcomes. The observed standard deviations are taken from the DCLP5 study. 
1514 
 
Standard Deviation 
Correlation 
with 
Baseline 
Effective 
SD a 
Detectable 
Difference 
with N=90 b 
Outcome 
CLC 
(n=78) 
SC 
(N=22) 
Pooled 
(N=100) 
% >250 mg/dL c 
5.5% 
9.9% 
6.5% 
0.69 
4.7% 
3.4% 
Mean Glucose d 
18 
26 
20 
0.68 
14 
10 
HbA1c 
0.8% 
0.9% 
0.8% 
0.70 
0.6% 
0.4% 
% <70 mg/dL c 
1.07% 
1.13% 
1.08% 
0.61 
0.86% 
0.63% 
% <54 mg/dL c 
0.23% 
0.23% 
0.23% 
0.54 
0.19% 
0.14% 
a – After accounting for the baseline value as a covariate in the regression model. 
1515 
b – With 90% power and two-sided type 1 error rate = 5%. 
1516 
c – Outcomes with a skewed distribution winsorized at the 10th and 90th percentiles. 
1517 
d – Units for mean glucose are mg/dL. 
1518 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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 Efficacy Outcome Measures 
1519 
 
1520 
• CGM-measured % in range 70-180 mg/dL 
1521 
 
1522 
12.4.2.1 Secondary Efficacy Endpoints Included in Hierarchical Analysis 
1523 
The following secondary endpoints will be tested in a hierarchical fashion as described in 
1524 
section 12.7.1. 
1525 
• CGM-measured % above 250 mg/dL 
1526 
• CGM-measured mean glucose 
1527 
• HbA1c at 13 weeks 
1528 
• CGM-measured % below 70 mg/dL  
1529 
• CGM-measured % below 54 mg/dL 
1530 
12.4.2.2 Other Secondary Efficacy Endpoints 
1531 
The following endpoints are considered exploratory. Type 1 error for these endpoints will be 
1532 
controlled using the false discovery rate (FDR) instead of the familywise error rate (FWER).   
1533 
CGM-Measured: 
1534 
• % above 180 mg/dL 
1535 
• % in range 70-140 mg/dL  
1536 
• glucose variability measured with the coefficient of variation (CV) 
1537 
• glucose variability measured with the standard deviation (SD) 
1538 
• % <60 mg/dL 
1539 
• low blood glucose index (LBGI)* 
1540 
• hypoglycemic events (defined as at least 15 consecutive minutes <54 mg/dL) 
1541 
• hyperglycemic events (defined as at least 90 consecutive minutes >300 mg/dL) 
1542 
• % >300 mg/dL  
1543 
• high blood glucose index (HBGI)* 
1544 
• % in range 70-180 mg/dL improvement from baseline to 13 weeks ≥5% 
1545 
• % in range 70-180 mg/dL improvement from baseline to 13 weeks ≥10% 
1546 
• % time in range 70-180 mg/dL >70% and % time <70 mg/dL <4% 
1547 
HbA1c: 
1548 
• HbA1c <7.0% at 13 weeks 
1549 
• HbA1c <7.5% at 13 weeks 
1550 
• HbA1c improvement from baseline to 13 weeks >0.5% 
1551 
• HbA1c improvement from baseline to 13 weeks >1.0% 
1552 
• HbA1c relative improvement from baseline to 13 weeks >10% 
1553 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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• HbA1c absolute improvement from baseline to 13 weeks >1.0% or HbA1c <7.0% at 13 
1554 
weeks 
1555 
Questionnaires 
1556 
• PedsQL Diabetes Module – total score and 5 subscales: 
1557 
o Diabetes 
1558 
o Treatment I 
1559 
o Treatment II 
1560 
o Worry 
1561 
o Communication 
1562 
• Pediatric Inventory for Parents (PIP) 2 domains each with a total score and 4 subscales for 
1563 
(5x2=10 difference scores) 
1564 
o Frequency 
1565 
 Total Score 
1566 
 Communication 
1567 
 Medical Care 
1568 
 Role Function 
1569 
 Emotional Functioning 
1570 
o Difficulty 
1571 
 Same total + 4 subscales as above for Frequency 
1572 
• INSPIRE (CLC arm only) 
1573 
• Pittsburgh Sleep Quality Index (PSQI) global score 
1574 
• Fear of Hypoglycemia Survey for Parents (HFS-P) – total score, 2 subscales and 4 factor 
1575 
scores: 
1576 
o Behavior  
1577 
 Avoidance 
1578 
 Maintain high BG 
1579 
o Worry  
1580 
 Helplessness  
1581 
 Social consequences 
1582 
 
1583 
*Note that LBGI and HBGI will be calculated using all available CGM readings as described 
1584 
below. Therefore, they may not be comparable to the same metrics calculated with SMBG data. 
1585 
Other: 
1586 
• Insulin 
1587 
♦ Total daily insulin (units/kg) 
1588 
♦ Percentage of total insulin delivered via basal 
1589 
•  Weight and Body Mass Index (BMI) 
1590 
 
1591 
Randomization is preceded by 2-6 weeks of CGM run-in, which will be used in the calculation 
1592 
of baseline CGM metrics. For participants who are eligible to skip the run-in, comparable 
1593 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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amount of CGM data from their own sensors will be taken before randomization visit to 
1594 
calculate baseline CGM metrics. 
1595 
CGM data starting from randomization visit through the 13-week visit will be included in the 
1596 
calculation of each CGM metric. Percentages in range 70-180 mg/dL (and all other CGM-based 
1597 
metrics) will be calculated giving equal weight to each CGM point for each participant. 
1598 
 Analysis Datasets and Sensitivity Analyses 
1599 
All analyses comparing the CLC arm with SC arm will follow intention-to-treatment approach, 
1600 
which means participants will be analyzed in the treatment arm assigned by randomization 
1601 
regardless of actual system use. All randomized participants will be included in the primary 
1602 
analysis and secondary hierarchical analyses of CGM metrics. For other secondary outcomes, 
1603 
only participants with non-missing outcome data will be included. 
1604 
Safety outcomes will be reported for all enrolled participants, irrespective of whether the 
1605 
participant was randomized or the study was completed. 
1606 
 
1607 
Per-protocol analyses will be performed for primary outcome and secondary hierarchical 
1608 
outcomes only if >5% of participants will be excluded: 
1609 
• CLC arm: Closed loop mode active for at least 80% of the time 
1610 
• SC arm: CGM use for at least 80% of the time 
1611 
 
1612 
Confounding 
1613 
A sensitivity analysis will also be conducted if potential confounding factors collected at 
1614 
baseline are detected.  
1615 
The imbalance will be assessed based on clinical judgement reviewing the distributions in the 
1616 
two treatment arms, not on a p-value. The person making this judgement will be unaware of 
1617 
whether there is an association between baseline variables and study outcome. All variables 
1618 
obtained on a continuous scale will be entered into the models as continuous variables, unless it 
1619 
is determined that a variable does not have a linear relationship with the outcome. In such a case, 
1620 
categorization and/or transformation will be explored. 
1621 
Exclude First 2 Weeks of CGM Data 
1622 
The primary analysis will be repeated by excluding the first 2 weeks of post-randomization CGM 
1623 
data. 
1624 
Missing Data 
1625 
Missing data will be handled using direct likelihood method for the primary analysis. It is worth 
1626 
noting that all statistical methods for handling missing data rely on untestable assumptions and 
1627 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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there is no one correct way to handle missing data. Our goal is to minimize the amount of 
1628 
missing data so that the results will not be sensitive to which statistical method is used.  
1629 
To that end, sensitivity analyses will be performed to explore whether results are similar for 
1630 
primary analysis when using different methods. The following methods will be applied: 
1631 
• Rubin’s multiple imputation with treatment group in the imputation model 
1632 
• Available cases only  
1633 
• Multiple imputation with pattern mixture model assuming the dropout trajectory of the 
1634 
CLC group was that of the SC group (Mallinckrodt and Clark, 2003) (3) 
1635 
 Analysis of the Primary Efficacy Endpoint 
1636 
Summary statistics (mean ± SD or median (quartiles)) will be reported by treatment group for the 
1637 
CGM-measured % in range 70-180 mg/dL at baseline, 13 weeks intervention and change from 
1638 
baseline to 13 weeks. 
1639 
CGM-measured % in range 70-180 mg/dL between two treatment arms will be compared using a 
1640 
linear mixed effects regression model while adjusting for baseline CGM-measured % in range 
1641 
70-180 mg/dL, age, prior CGM and pump use, and clinical center (random effect). A point 
1642 
estimate, 95% confidence interval and two-sided p-value will be reported for the treatment effect 
1643 
based on the linear regression model and a 5% level will be used to declare statistical 
1644 
significance. Residual values will be examined for an approximate normal distribution. If values 
1645 
are highly skewed then robust regression using M-estimation will be used instead. However, 
1646 
previous experience suggests that the residual values for % time glucose in target range will 
1647 
follow an approximately normal distribution. Imbalances between groups in important covariates 
1648 
are not expected to be of sufficient magnitude to produce confounding. However, the presence of 
1649 
confounding will be evaluated in the sensitivity analyses by including factors potentially 
1650 
associated with the outcome for which there is an imbalance between groups (12.5.2). 
1651 
In the primary analysis, any missing data at baseline or follow-up will be handled using direct 
1652 
likelihood. A longitudinal linear regression model will be fit with the percent of time in range at 
1653 
baseline and follow-up as the dependent variable. This model will adjust for age, prior CGM use 
1654 
and pump use as fixed effects and clinical center as a random effect. This model adjusts for 
1655 
baseline time in range by forcing the treatment groups to have the same mean value at baseline. 
1656 
 Analysis of the Secondary Endpoints 
1657 
Point estimates and confidence intervals for the treatment arm differences will be presented for 
1658 
all secondary metrics. The models will adjust for the corresponding baseline metric, age, prior 
1659 
CGM and pump use, and clinical center (random effect). 
1660 
 
1661 
To preserve the overall type 1 error for selected key secondary endpoints, a hierarchical testing 
1662 
procedure will be used. If the primary analysis for time in range described above results in a 
1663 
statistically significant result (p < 0.05), then testing (similar to the model described above 
1664 
for the primary outcome) will proceed to the next outcome metric in the following order: 
1665 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
PAGE 69 OF 84 
 
• CGM-measured % in range 70-180 mg/dL (primary outcome) 
1666 
• CGM-measured % above 250 mg/dL 
1667 
• CGM-measured mean glucose 
1668 
• HbA1c at 13 weeks 
1669 
• CGM-measured % below 70 mg/dL 
1670 
• CGM-measured % below 54 mg/dL 
1671 
 
1672 
This process continues iteratively moving to the next variable down on the list until a non-
1673 
significant result (p ≥ 0.05) is observed, or all six variables have been tested. If a non-significant 
1674 
result is encountered, then formal statistical hypothesis testing is terminated and any variables 
1675 
below on the list are not formally tested. 
1676 
Regardless of the results of the hierarchical testing, summary statistics appropriate to the 
1677 
distribution will be tabulated by treatment arm for each hierarchical outcome.  A 95% confidence 
1678 
interval for the treatment arm difference will also be calculated for all five secondary hierarchical 
1679 
outcomes listed above.  However, a confidence interval that excludes zero will not be considered 
1680 
a statistically significant result if an outcome variable higher on the hierarchical list failed to 
1681 
reach statistical significance. 
1682 
Analysis for each of the CGM metrics listed above for the hierarchical analysis will parallel the 
1683 
analysis described for the primary outcome in Section 12.6. 
1684 
HbA1c at 13 weeks will be compared between the two treatment arms using a linear model while 
1685 
adjusting for baseline HbA1c, age, prior CGM and pump use, and clinical center (random 
1686 
factor). Missing data will be handled using direct likelihood in a regression model including all 
1687 
available central laboratory HbA1c measurements at baseline and 13-week visits. 
1688 
For all above analyses, regression diagnostics will be employed analogous to as described in 
1689 
Section 12.6 for the primary outcome. 
1690 
 
1691 
For all other secondary endpoints, only participants with non-missing data will be included in 
1692 
analyses (available cases method). Summary statistics (mean ± SD, median (IQR) or n (%)) 
1693 
appropriate to the distribution will be tabulated for them at baseline, 13 weeks and for the 
1694 
changes from baseline to 13 weeks. For continuous outcomes, linear regression models will be 
1695 
used to compare the treatment effects while adjusting for corresponding baseline values (e.g., 
1696 
baseline % in range 70-140 mg/dL for comparing change in % in range 70-140 mg/dL from pre-
1697 
randomization CGM wear to 13 weeks post-randomization period), age, prior CGM and pump 
1698 
use, and clinical center as a random effect. Comparisons of body weight and BMI will also be 
1699 
adjusted for gender. 
1700 
For CGM-measured hypoglycemia/hyperglycemia events, event rates per week will be compared 
1701 
using similar linear mixed effects regression models as described above for the primary outcome. 
1702 
 
1703 
Binary HbA1c and CGM Outcomes 
1704 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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For the binary HbA1c outcomes, risk-adjusted percentages by treatment group will be computed 
1705 
at 13 weeks from a logistic regression model. The logistic regression will adjust for baseline 
1706 
HbA1c (as a continuous factor), age, prior CGM and pump use as fixed effects, and clinical site 
1707 
as a random effect. Similar analyses will be done for the binary CGM outcomes. 
1708 
Questionnaires  
1709 
For each questionnaire, mean ± SD or percentiles appropriate to the distribution will be given by 
1710 
treatment group at baseline and 13 weeks. Group comparisons will be conducted for the total 
1711 
score (mean score) and subscales from participant version and parent version separately using 
1712 
similar linear models as described above. The INSPIRE and SUS post-treatment surveys will 
1713 
only be administered to the CLC group at the 13-week visit, and thus the scores will only be 
1714 
tabulated. 
1715 
Focus Groups 
1716 
Qualitative data from focus groups will be analyzed using NVIVO (release 11.2; QSR 
1717 
International) to organize and manage the entire corpus of focus group data. Analysis begins 
1718 
with an initial coding procedure to capture and describe the range of responses to the 
1719 
intervention. A second, more focused and detailed level of coding will be applied to major 
1720 
categories of findings in the initial review to determine themes in response to the clinical trial, 
1721 
use of the closed loop system, and quality of life changes. The video data from the co-regulation 
1722 
interaction will be submitted to the validated coding system and frequencies of positive and 
1723 
negative interactions, treatment discussions, and CLC comments will be calculated with simple 
1724 
descriptive statistics. Change from pre to post treatment will be analyzed in the similar GLM 
1725 
framework to evaluate whether there is improvement in co-regulation across the study. 
1726 
Boxplots 
1727 
Boxplots stratified by treatment group will be given for the primary outcome and each of the key 
1728 
secondary endpoints in specified time periods over the 13-week course of follow-up. 
1729 
 Safety Analyses 
1730 
All randomized participants will be included in these analyses and all their post-randomization 
1731 
safety events will be reported. Any pre-randomization adverse events will be tabulated separately 
1732 
and will include any participants who were never randomized. 
1733 
Safety analyses of the main study (randomized trial phase) will include events occurring on or 
1734 
after randomization until and including the 13-week visit or Day 105 from randomization, 
1735 
whichever occurs first. Safety analyses of the extension phase will include subsequent events 
1736 
until the last visit date or the last event date (whichever is later). 
1737 
For the following outcomes, the number of events will be tabulated by treatment group. Formal 
1738 
statistical comparisons (main study phase only) will be performed if there are enough events (at 
1739 
least 5 events combined between the two treatment groups): 
1740 
• Number of SH events and SH event rate per 100 person-years 
1741 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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• Number of DKA events and DKA event rate per 100 person-years 
1742 
• Other serious adverse events 
1743 
• Any adverse event rate 
1744 
• Number of calendar days with any ketone level ≥1.0 mmol/L (if ≥5 total calendar days 
1745 
combined) 
1746 
• Worsening of HbA1c from baseline to 13 weeks by >0.5% 
1747 
• Investigational device related (intervention group only): 
1748 
o Adverse device effects (ADE) 
1749 
o Serious adverse device events (SADE) 
1750 
o Unanticipated adverse device effects (UADE) 
1751 
 
1752 
For DKA and SH events, if enough events, the rates will be compared between the two treatment 
1753 
arms during the main study phase using a robust Poisson regression. The regression will adjust 
1754 
for the participant-reported number of SH events 12 months prior to the start of the study and 
1755 
clinical center as random effect. The amount of follow up will be included as an offset covariate 
1756 
to compare the rates. A similar analysis will be done for DKA, if at least 5 total DKA events 
1757 
among both treatment groups.  
1758 
 
1759 
 Intervention Adherence 
1760 
The following tabulations and analyses will be performed by treatment group to assess 
1761 
intervention adherence for the study: 
1762 
• Sensor use –percent time of use, overall for 13-week visit 
1763 
For CLC arm only, the following will be tabulated to assess adherence: 
1764 
• Closed loop system use–percent time of use, overall for 13-week visit 
1765 
• % time in different operational modes - overall and by specified time periods 
1766 
 Protocol Adherence and Retention 
1767 
The following tabulations and analyses will be performed by treatment group to assess protocol 
1768 
adherence for the study: 
1769 
• Number of protocol and procedural deviations  
1770 
• Flow chart accounting for all enrolled participants up to randomization 
1771 
• Flow chart of all randomized participants at all scheduled visits and phone contacts post 
1772 
treatment initiation 
1773 
• Number of and reasons for unscheduled visits and phone calls 
1774 
• Number of participants who stopped treatment and reasons 
1775 
 Baseline Descriptive Statistics 
1776 
Baseline demographic and clinical characteristics of the cohort of all randomized participants 
1777 
will be summarized in a table using summary statistics appropriate to the distribution of each 
1778 
variable. Descriptive statistics will be displayed by treatment group for the following: 
1779 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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• Age 
1780 
• Sex 
1781 
• Race/Ethnicity 
1782 
• Parent’s income, education, and/or insurance status 
1783 
• Diabetes duration 
1784 
• Insulin method before enrollment (pump vs. MDI) 
1785 
• CGM use before enrollment 
1786 
• HbA1c 
1787 
• BMI % 
1788 
• Participant-reported number of SH and DKA 12 months prior to the start of the study 
1789 
• Baseline CGM metrics including: 
1790 
• % in range 70-180 mg/dL 
1791 
• % time > 180 mg/dL 
1792 
• Mean glucose 
1793 
• % time < 70 mg/dL 
1794 
• % time < 54 mg/dL 
1795 
 Device Issues 
1796 
The following tabulations and analyses will be performed by treatment group to assess device 
1797 
issues: 
1798 
• Device malfunctions requiring study team contact and other reported device issues 
1799 
• Rate of different failure events and alarms per 24 hours recorded by the Control-IQ system – 
1800 
overall and by month 
1801 
 Planned Interim Analyses 
1802 
No formal interim efficacy analyses are planned. The analysis of the RCT will be performed on 
1803 
completion of the RCT prior to the completion of the extension phase. 
1804 
In addition, the DSMB will review safety data at intervals, with no formal stopping rules.  
1805 
 Subgroup Analyses 
1806 
In exploratory analyses, the primary outcome (time 70-180 mg/dL), % time <70 mg/dL and HbA1c 
1807 
at 13 weeks will be assessed separately in various subgroups. Subgroups will be defined according 
1808 
to the baseline value of the factors, which will be noted in the SAP. Tests for interaction 
1809 
with treatment group will be performed. 
1810 
Interpretation of subgroup analyses will be viewed with caution, particularly in the absence of an 
1811 
overall significant difference. For continuous variables, results will be displayed in subgroups 
1812 
based on cutpoints although the analysis will utilize the variable as continuous. If there is 
1813 
insufficient sample size in a given subgroup, the cutpoints for continuous measures may be 
1814 
adjusted per the observed distribution of values. Cutpoint selection for display purposes will be 
1815 
made masked to the outcome data. 
1816 

 
 
 
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 Multiple Comparison/Multiplicity 
1817 
Primary Analysis 
1818 
Since there will be a single comparison for the primary outcome (CGM-measured % 70-180 
1819 
mg/dL), no adjustment is needed. 
1820 
Secondary Hierarchical Analyses 
1821 
The hierarchical testing procedure described above in section 12.7.1 will be used to control the 
1822 
overall type 1 error for the primary outcome plus five key secondary outcomes identified above. 
1823 
All Other Secondary Analyses 
1824 
For comparison of all other efficacy endpoints, the false discovery rate will be controlled using the 
1825 
adaptive Benjamini-Hochberg procedure (4). 
1826 
P-values from safety analyses, sensitivity analyses, and per-protocol analyses will not be adjusted 
1827 
for multiple comparisons. 
1828 
 Exploratory Analyses 
1829 
CGM Metrics 
1830 
In addition to the analysis for the CGM-measured endpoints described earlier, separate analyses 
1831 
will be conducted for daytime and nighttime of the following metrics: 
1832 
• % time in range 70-180 mg/dL 
1833 
• Mean glucose 
1834 
• % above 180 mg/dL 
1835 
• % below 70 mg/dL 
1836 
• coefficient of variation 
1837 
 
1838 
Above selected CGM metrics also will be reported by restricting the CGM data in the CLC arm 
1839 
based on following criteria. No p-values will be calculated for following analyses.  
1840 
• using only the CGM data when the closed-loop is active 
1841 
 
1842 
Additional Insulin Metrics 
1843 
The following insulin metrics will be tabulated by treatment groups at baseline, 13 weeks and for 
1844 
the changes from baseline to 13 weeks. No p-values will be calculated for these metrics. 
1845 
• Total daily basal insulin (units/kg) 
1846 
• Total daily bolus insulin (units/kg) 
1847 
• Total daily manual bolus (units/kg) 
1848 
• Total daily automated bolus (units/kg) 
1849 
• Total daily short-acting injections for injection users 
1850 
 
1851 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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The following will be calculated for the CLC group in the 1-week prior to randomization and by 
1852 
1-week follow-up periods from pump data only: 
1853 
• Total daily insulin (units/kg) 
1854 
• Total daily basal insulin (units/kg) 
1855 
• Total daily bolus insulin (units/kg) 
1856 
o Total daily manual bolus (units/kg) 
1857 
o Total daily automated bolus (units/kg) 
1858 
• Number of manual insulin doses per day 
1859 
• Number of manual insulin doses with carb announcement per day 
1860 
 
1861 
 Extension Phase 
1862 
Analyses for the extension phase will be primarily exploratory.  
1863 
 
1864 
For both treatment arms, summary statistics will be given for all outcomes listed above in 
1865 
Section 12.4 at RCT baseline (pre-randomization), 13 weeks, and 26 weeks. In addition, boxplots 
1866 
will be constructed for each of the outcome metrics listed above showing both treatment arms 
1867 
over the course of the combined RCT and extension (where both arms using CLC) phases. 
1868 
Formal statistical comparisons between the two study phases (i.e., primary RCT and extension 
1869 
phases) will be performed for key outcome measures including: 
1870 
• CGM-measured % in range 70-180 mg/dL 
1871 
• CGM-measured % above 250 mg/dL 
1872 
• CGM-measured mean glucose 
1873 
• HbA1c at 13 weeks 
1874 
• CGM-measured % below 70 mg/dL 
1875 
• CGM-measured % below 54 mg/dL 
1876 
• PedsQL Diabetes Module – total score 
1877 
• Pediatric Inventory for Parents (PIP) 
1878 
 Frequency domain total score 
1879 
 Difficulty domain total score 
1880 
• INSPIRE Survey 
1881 
• Pittsburgh Sleep Quality Index (PSQI) global score 
1882 
• Fear of Hypoglycemia Survey for Parents (HFS-P) – total score 
1883 
• Hypoglycemia Confidence Scale (HCS) 
1884 
• System Usability Scale (SUS) 
1885 
For each of these outcomes a longitudinal regression model will be fit combining data from the 
1886 
RCT and extension phases accounting for the correlated data from repeated measures. Treatment 
1887 
group will be a time dependent factor in this model. A point estimate and 95% confidence 
1888 
interval will be given for the estimated effects of each CLC version used during the study, both 
1889 
with respect to SC and with respect to one another. Safety analyses of the Extension Phase will 
1890 
include events occurring on or after the Extension training visit until the end of the 26-Week visit 
1891 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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or the end of Day 105 from the Extension training visit — whichever occurs first. Safety 
1892 
outcomes will include those specified in section 12.8 with the exception of worsening of HbA1c. 
1893 
Summary statistics appropriate to the distribution will be tabulated without any formal 
1894 
comparisons by treatment group for the safety outcomes noted in section 12.8. 
1895 
 
1896 
According to Chapter 14, during the extension phase, 30 – 40 participants will be sought to 
1897 
enroll in an ancillary study to test the Control-IQ system with meal bolus and exercise 
1898 
challenges. The analyses for this ancillary study are specified in Section 14.5. Data collected 
1899 
from the start of each of these challenges until 5:59 AM the following morning will be excluded 
1900 
from the analysis of the extension phase. 
1901 
 
1902 
 Extended Use Period 
1903 
Analyses for the extended use phase will be exploratory.  
1904 
 
1905 
Summary statistics will be given for all outcomes listed above in Section 12.4 for each of the 13-
1906 
week periods following initiation of the Extended Use period. In addition, boxplots will be 
1907 
constructed for each of the outcome metrics listed above for these periods. 
1908 
 
1909 
Safety analyses of the Extended Use period will include events until the last visit date or the last 
1910 
event date (whichever is later). Safety outcomes will include those specified in section 12.8 with 
1911 
the exception of worsening of HbA1c. 
1912 
 
 
1913 

 
 
 
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Chapter 13: Data Collection and Monitoring 
1914 
 Case Report Forms and Device Data 
1915 
The main study data are collected on electronic case report forms (CRFs). When data are directly 
1916 
collected in electronic case report forms, this will be considered the source data. For any data 
1917 
points for which the eCRF is not considered source (e.g. lab results that are transcribed from a 
1918 
printed report into the eCRF), the original source documentation must be maintained in the 
1919 
participant’s study chart or medical record. This source must be readily verifiable against the 
1920 
values entered into eCRF. Even where all study data are directly entered into the eCRFs at office 
1921 
visits, evidence of interaction with a live subject must be recorded (e.g., office note, visit record, 
1922 
etc.).    
1923 
Electronic device data files are obtained from the study software and individual hardware 
1924 
components.  These electronic device files are considered the primary source documentation. 
1925 
 Study Records Retention 
1926 
Each participating site will maintain appropriate medical and research records for this trial, in 
1927 
compliance with ICH E6 and regulatory and institutional requirements for the protection of 
1928 
confidentiality of participants. 
1929 
Study documents should be retained for a minimum of 2 years after the last approval of a marketing 
1930 
application in an ICH region and until there are no pending or contemplated marketing applications 
1931 
in an ICH region or until at least 2 years have elapsed since the formal discontinuation of clinical 
1932 
development of the investigational product.  These documents should be retained for a longer 
1933 
period, however, if required by local regulations.  No records will be destroyed without the written 
1934 
consent of the sponsor, if applicable.  It is the responsibility of the sponsor to inform the 
1935 
investigator when these documents no longer need to be retained. 
1936 
 Quality Assurance and Monitoring 
1937 
Designated personnel from the Coordinating Center will be responsible for maintaining quality 
1938 
assurance (QA) and quality control (QC) systems to ensure that the clinical portion of the trial is 
1939 
conducted and data are generated, documented and reported in compliance with the protocol, 
1940 
Good Clinical Practice (GCP) and the applicable regulatory requirements, as well as to ensure 
1941 
that the rights and wellbeing of trial participants are protected and that the reported trial data are 
1942 
accurate, complete, and verifiable.  Adverse events will be prioritized for monitoring. 
1943 
A risk-based monitoring (RBM) plan will be developed and revised as needed during the course 
1944 
of the study, consistent with the FDA “Guidance for Industry Oversight of Clinical 
1945 
Investigations — A Risk-Based Approach to Monitoring” (August 2013).  Study conduct and 
1946 
monitoring will conform with 21 Code of Federal Regulations (CFR) 812. This plan describes in 
1947 
detail who will conduct the monitoring, at what frequency monitoring will be done, at what level 
1948 
of detail monitoring will be performed, and the distribution of monitoring reports. 
1949 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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The data of most importance for monitoring at the site are participant eligibility and adverse 
1950 
events.  Therefore, the RBM plan will focus on these areas.  As much as possible, remote 
1951 
monitoring will be performed in real-time with on-site monitoring performed to evaluate the 
1952 
verity and completeness of the key site data.  Elements of the RBM may include: 
1953 
• Qualification assessment, training, and certification for sites and site personnel 
1954 
• Oversight of Institutional Review Board (IRB) coverage and informed consent procedures 
1955 
• Central (remote) data monitoring: validation of data entry, data edits/audit trail, protocol 
1956 
review of entered data and edits, statistical monitoring, study closeout 
1957 
• On-site monitoring (site visits): source data verification, site visit report 
1958 
• Agent/Device accountability 
1959 
• Communications with site staff 
1960 
• Patient retention and visit completion 
1961 
• Quality control reports 
1962 
• Management of noncompliance 
1963 
• Documenting monitoring activities 
1964 
• Adverse event reporting and monitoring 
1965 
Coordinating Center representatives or their designees may visit the study facilities at any time in 
1966 
order to maintain current and personal knowledge of the study through review of the records, 
1967 
comparison with source documents, observation and discussion of the conduct and progress of the 
1968 
study. The investigational site will provide direct access to all trial related sites, source 
1969 
data/documents, and reports for the purpose of monitoring and auditing by the sponsor, and 
1970 
inspection by local and regulatory authorities. 
1971 
 Protocol Deviations 
1972 
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or procedure 
1973 
requirements.  The noncompliance may be either on the part of the participant, the investigator, 
1974 
or the study site staff.  As a result of deviations, corrective actions are to be developed by the site 
1975 
and implemented promptly. 
1976 
The site PI/study staff is responsible for knowing and adhering to their IRB requirements.  Further 
1977 
details about the handling of protocol deviations will be included in the monitoring plan. 
1978 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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Chapter 14: Ethics/Protection of Human Participants 
1979 
 Ethical Standard 
1980 
The investigator will ensure that this study is conducted in full conformity with Regulations for 
1981 
the Protection of Human Participants of Research codified in 45 CFR Part 46, 21 CFR Part 50, 21 
1982 
CFR Part 56, and/or the ICH E6. 
1983 
 Institutional Review Boards 
1984 
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
1985 
be submitted to the IRB for review and approval.  Approval of both the protocol and the consent 
1986 
form must be obtained before any participant is enrolled.  Any amendment to the protocol will 
1987 
require review and approval by the IRB before the changes are implemented to the study.  All 
1988 
changes to the consent form will be IRB approved; a determination will be made regarding whether 
1989 
previously consented participants need to be re-consented. 
1990 
 Informed Consent Process 
1991 
 
1992 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in 
1993 
the study and continues throughout the individual’s study participation.  Extensive discussion of 
1994 
risks and possible benefits of participation will be provided to the participants and their families.  
1995 
Consent forms will be IRB-approved and the participant will be asked to read and review the 
1996 
document.  The investigator will explain the research study to the participant and answer any 
1997 
questions that may arise.  All participants will receive a verbal explanation in terms suited to 
1998 
their comprehension of the purposes, procedures, and potential risks of the study and of their 
1999 
rights as research participants.  Participants will have the opportunity to carefully review the 
2000 
written consent form and ask questions prior to signing. 
2001 
The participants should have the opportunity to discuss the study with their surrogates or think 
2002 
about it prior to agreeing to participate.  The participant will sign the informed consent document 
2003 
prior to any procedures being done specifically for the study. The participants may withdraw 
2004 
consent at any time throughout the course of the trial.  A copy of the informed consent document 
2005 
will be given to the participants for their records.  The rights and welfare of the participants will 
2006 
be protected by emphasizing to them that the quality of their medical care will not be adversely 
2007 
affected if they decline to participate in this study. 
2008 
 
2009 
Participant confidentiality is strictly held in trust by the participating investigators, their staff, 
2010 
and the sponsor(s) and their agents.  This confidentiality is extended to cover testing of 
2011 
biological samples and genetic tests in addition to the clinical information relating to 
2012 
participants.  Therefore, the study protocol, documentation, data, and all other information 
2013 
generated will be held in strict confidence.  No information concerning the study or the data will 
2014 
be released to any unauthorized third party without prior written approval of the sponsor. 
2015 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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The study monitor, other authorized representatives of the sponsor, representatives of the IRB, 
2016 
regulatory agencies or  company supplying study product may inspect all documents and records 
2017 
required to be maintained by the investigator, including but not limited to, medical records 
2018 
(office, clinic, or hospital) and pharmacy records for the participants in this study.  The clinical 
2019 
study site will permit access to such records. 
2020 
The study participant’s contact information will be securely stored at each clinical site for 
2021 
internal use during the study.  At the end of the study, all records will continue to be kept in a 
2022 
secure location for as long a period as dictated by the reviewing IRB, institutional policies, or 
2023 
sponsor requirements. 
2024 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, 
2025 
will be transmitted to and stored at the Jaeb Center for Health Research (JCHR).  This will not 
2026 
include the participant’s contact or identifying information, unless otherwise specified in the 
2027 
informed consent form.  Rather, individual participants and their research data will be identified 
2028 
by a unique study identification number.  The study data entry and study management systems 
2029 
used by clinical sites and by JCHR research staff will be secured and password protected.  At the 
2030 
end of the study, all study databases will be de-identified and archived at the JCHR and the 
2031 
University of Virginia Center for Diabetes Technology. 
2032 
 
 
2033 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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Chapter 15: Ancillary Study to Test Control-IQ System with Meal 
2034 
Bolus and Exercise Challenges 
2035 
 Objective 
2036 
This Ancillary Study will assess the safety of using the study system during exercise and meal 
2037 
bolus-related challenges. Outcome data are expected to be used to support regulatory filings for 
2038 
the device system.  
2039 
 Sample Size 
2040 
Participation in the Ancillary Study will be offered to participants who are currently in the 
2041 
Extension Phase of the main study. The goal for sample size is to have 30-40 individuals 
2042 
participate in the Ancillary Study. 
2043 
 Eligibility Criteria 
2044 
Participants must be currently in the Extension Phase of the main study, with at least 2 weeks 
2045 
and no more than 11 weeks completed to ensure sufficient comfort with the study pump and 
2046 
sufficient time to complete the protocol below.  
2047 
Inclusion in the Ancillary Study requires investigator judgment that it is safe for the individual to 
2048 
participate.  
2049 
 Study Procedures 
2050 
On the day of enrollment into the Ancillary Study, informed consent will be obtained from 
2051 
interested participants, and eligibility will be verified. 
2052 
A paper logbook will be provided to participants that includes a page to record details about each 
2053 
challenge and procedural instructions about how participants will conduct these challenges. This 
2054 
material will be reviewed with each participant. 
2055 
During home use, each participant will perform 3 exercise and meal bolus-related challenges 
2056 
(details below) appropriate for the age of the participant. Each challenge will be separated from 
2057 
the other challenges by at least 48 hours. Before starting each challenge, caregivers of the child 
2058 
must assure the child has a working CGM and Control-IQ is active. If activity is paused during 
2059 
an exercise-related challenge, the challenge may be continued to allow for continuation of the 
2060 
activity if the participant is able and willing to continue. 
2061 
Participants will receive a guidance document for performing the challenges that includes the 
2062 
following safety mitigations: 
2063 
• The participant’s parent or guardian must remain with the child at all times and 
2064 
monitor CGM readings frequently during and for at least two hours after completion 
2065 
of each challenge. 
2066 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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• The hyperglycemia safety protocol described in section 8.2.4 will be followed during 
2067 
each challenge. 
2068 
• The parent/guardian must have an on-call phone number for the study team prior to 
2069 
initiation of each challenge. 
2070 
• CGM glucose must be ≥120 mg/dL prior to initiation of each exercise-related 
2071 
challenge. 
2072 
• Exercise may not be initiated during an exercise-related challenge if the CGM trend 
2073 
arrows on the study insulin pump indicate Falling glucose (down arrow) or Rapidly 
2074 
Falling glucose (double down arrow). 
2075 
• Snacks and glucagon must be available for use during and after each exercise-related 
2076 
challenge. 
2077 
• Control-IQ exercise activity mode must be activated at least 30 minutes prior to the 
2078 
start of exercise during each exercise-related challenge and kept active for at least 30 
2079 
minutes after completion of the exercise period. 
2080 
• Additional carbohydrate may be given as needed at the start of, during, or after each 
2081 
exercise-related challenge. 
2082 
• The temporary basal rate feature of the study pump may be used if desired to reduce 
2083 
insulin delivery during the exercise period of each exercise-related challenge.  
2084 
• Fingersticks will be performed for any low CGM value <70 mg/dL, and any exercise 
2085 
should be stopped if BG is confirmed <70 mg/dL. Exercise may be stopped for 
2086 
concerns for CGM decreasing at any time, even if CGM is >70 mg/dL. 
2087 
• A parent/guardian will sleep in the same home as the child overnight and closely 
2088 
monitor CGM readings following days when one of the challenges was performed. 
2089 
Contact with the study investigator may be initiated at any time. 
2090 
Challenge Details: 
2091 
Missed Meal Bolus Challenge: Participants will skip their meal bolus for an afternoon meal of 
2092 
at least 20 grams carbohydrate. The meal timing and carb amount and any additional snacks 
2093 
given will be recorded on a study exercise log. Additional insulin boluses may be given for 
2094 
hyperglycemia as needed. The hyperglycemia safety protocol described in section 8.2.4 will be 
2095 
followed. 
2096 
Full Meal Bolus Plus Exercise Challenge: Participants will receive a full meal bolus for an 
2097 
afternoon meal of at least 20 grams carbohydrate. The pump’s Exercise Activity setting will be 
2098 
turned on upon completion of the meal. Beginning 30 minutes after completion of the meal, a 
2099 
parent/guardian will try to keep the child physically active (walking, running, playing) for at 
2100 
least 30 minutes if possible, or longer if desired. This can be mixed with mild activity. The meal 
2101 
timing and carb amount, the actual stop and start time of exercise, any associated hypoglycemia 
2102 
treatments, and any additional snacks given will be recorded on a study exercise log. 
2103 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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Exercise Challenge: At least 2 hours after the child finishes an afternoon meal, a 
2104 
parent/guardian will try to keep the child physically active (walking, running, playing) for at 
2105 
least 30 minutes if possible, or longer if desired. This can be mixed with mild activity. The 
2106 
pump’s Exercise Activity setting will be turned on 90 minutes after completion of the meal. The 
2107 
meal timing and carb amount of the last meal prior to exercise, the actual start and stop time of 
2108 
exercise, any associated hypoglycemia treatments, and any additional snacks given will be 
2109 
recorded on a study exercise log. 
2110 
A challenge may be stopped for any reason, including participant non-cooperation, or concern 
2111 
for hypoglycemia, or repeated hypoglycemia. 
2112 
 Outcomes and Analysis Plan 
2113 
A separate statistical analysis plan will be written for the Ancillary Study. 
2114 
Outcomes will include the following: 
2115 
Key Safety Outcomes: 
2116 
• Severe hypoglycemia 
2117 
• Other adverse events 
2118 
All adverse events will be listed. Listings will include Participant ID, the event, whether the 
2119 
event was serious, whether the event was related to the study device, the event outcome, and a 
2120 
description of the event. 
2121 
 
2122 
Other Outcomes 
2123 
• CGM-measured % <54 mg/dL overnight (all challenge types) 
2124 
• CGM-measured % <70 mg/dL overnight (all challenge types) 
2125 
• CGM-measured % >180 mg/dL overnight (all challenge types) 
2126 
• CGM-measured % <54 mg/dL during the two hours immediately following the start of 
2127 
exercise for each exercise-related challenge 
2128 
• CGM-measured % <70 mg/dL during the two hours immediately following the start of 
2129 
exercise for each exercise-related challenge 
2130 
• CGM-measured % >180 mg/dL during the four hours following the announced meal, or 
2131 
until the next meal bolus is given, for the missed meal bolus challenge 
2132 
• CGM-measured % >300 mg/dL during the four hours following the announced meal, or 
2133 
until the next meal bolus is given, for the missed meal bolus challenge 
2134 
The percentage of time spent below 54 mg/dL from 10 PM – 5:59 AM the night of an exercise 
2135 
challenge will be compared with percentage of time spent below 54 mg/dL the previous night 
2136 
using a linear mixed effects regression model. A point estimate, 95% confidence interval and 
2137 
two-sided p-value will be reported for the challenge effect based on the linear regression model 
2138 
and a 5% level will be used to declare statistical significance. Residual values will be examined 
2139 
for an approximate normal distribution. If values are highly skewed, then robust regression using 
2140 
M-estimation will be used instead. Analysis of the percentage of time spent below 70 mg/dL 10 
2141 

 
 
 
PEDAP PROTOCOL V11.0 CLEAN 
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PM – 5:59 AM the night of an exercise challenge will be performed in the same manner. 
2142 
 
2143 
The percentage of time spent above 180 mg/dL from 10 PM – 5:59 AM the night of a missed 
2144 
meal bolus challenge will be compared with percentage of time spent above 180 mg/dL the 
2145 
previous night using a linear mixed effects regression model. A point estimate, 95% confidence 
2146 
interval and two-sided p-value will be reported for the challenge effect based on the linear 
2147 
regression model and a 5% level will be used to declare statistical significance. Residual values 
2148 
will be examined for an approximate normal distribution. If values are highly skewed, then 
2149 
robust regression using M-estimation will be used instead. Analysis of the percentage of time 
2150 
spent above 300 mg/dL 10 PM – 5:59 AM the night of a missed meal bolus challenge will be 
2151 
performed in the same manner. 
2152 
 
2153 
CGM-measured % <54 mg/dL during the two hours immediately following the start of exercise 
2154 
for each exercise challenge will be compared between the two exercise challenge groups using a 
2155 
paired t-test. CGM-measured % <70 mg/dL during this same period will be analyzed in the same 
2156 
manner. 
2157 
 
2158 
For each challenge type, the mean, standard deviation, and range will be given for the outcomes 
2159 
listed above relevant to the challenge type. Summary statistics for the overnight periods 
2160 
preceding the challenges will be presented with summary statistics for each challenge type. 
2161 
Safety Monitoring 
2162 
Safety oversight will be the same as for the main study, as described in Chapter 10:.    
2163 

 
 
 
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Chapter 16: References 
2164 
1. Brown S, Kovatchev B, Raghinaru D, Lum JW, Buckingham BA, Kudva YC, Laffel LM, 
2165 
Levy CJ, Pinsker JE, Wadwa RP, Dassau E, Doyle FJ, Anderson SM, Church MM, Dadlani 
2166 
V, Ekhlaspour L, Forlenza GP, Isganaitis E, Lam DW, Kollman C, and Beck RW, for the 
2167 
iDCL Trial Research Group: Six-Month Randomized, Multicenter Trial of Closed-Loop 
2168 
Control in Type 1 Diabetes. N Engl J Med. 2019 Oct 31;381(18):1707-1717. doi: 
2169 
10.1056/NEJMoa1907863. 
2170 
2. Breton MD, Kanapka LG, Beck RW, Ekhlaspour L, Forlenza GP, Cengiz E, Schoelwer M, 
2171 
Ruedy KJ, Jost E, Carria L, Emory E, Hsu LJ, Oliveri M, Kollman CK, Dokken BB, Weinzimer 
2172 
SA, DeBoer MD, Buckingham BA, Cherñavvsky D, and Wadwa RP, for the iDCL Trial 
2173 
Research Group: A Randomized Trial of Closed-Loop Control in Children with Type 1 
2174 
Diabetes. N Engl J Med. 2020 Aug 27;383(9):836-845. doi: 10.1056/NEJMoa2004736. 
2175 
3. Mallinckrodt CH, Clark WS, et al: Assessing responses profiles from incomplete longitudinal 
2176 
clinical trial data under regulatory considerations, J. Biopharm. Stat., 2003; 13(2): 179-190. 
2177 
4. Benjamini, Y. and Hochberg, Y. (1995) Controlling the false discovery rate: a practical and 
2178 
powerful approach to multiple testing. J. R. Statist. Soc. B, 57, 289–300. 
2179