Conditions: Diamond Blackfan Anemia Pure Red Cell Aplasia
Keywords: Diamond Blackfan Anemia
Allocation: NON_RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 2
Healthy volunteers: no

Brief summary:
Diamond Blackfan anemia (DBA) is a rare inherited pure red cell aplasia. The two main non-stem cell transplant therapeutic options are corticosteroids and red blood cell (RBC) transfusions. About 80% of DBA patients initially respond to corticosteroids, however, half of the patients cannot continue due to side effects or loss of response. These patients are then typically dependent on RBC transfusions throughout life. Each of these treatments is fraught with many side effects and significant morbidity and mortality are potential consequences of hematopoietic stem cell transplantation (SCT). The majority of individuals with DBA have mutations in genes encoding structural proteins of the small or large ribosomal subunit leading to deficiency of the particular ribosomal protein (RP). Using the RP deficient zebrafish embryo model, high throughput drug screens have demonstrated a strong hematologic response to several calmodulin inhibitors. One of these chemicals is trifluoperazine (TFP). TFP treatment of a mouse model of DBA also increased the red blood cell count and the hemoglobin (Hb) levels in the mice. TFP is a FDA-approved typical antipsychotic agent that has been available since 1958 with a well-known safety profile. In the United States, TFP is approved for the short-term treatment of generalized non-psychotic anxiety; treatment or prevention of nausea and vomiting of various causes; and, management of psychotic disorders.

This study aims to determine the safety/tolerability of TFP in adult subjects with DBA. TFP's expected dose-limiting toxicity is primarily neurologic (extrapyramidal) when used long-term at typical anti-psychotic doses (range 10-50 mg daily). Non-neurologic adverse effects in subjects with DBA have not been investigated. We will perform a dose escalation study to define the safety and tolerability of lower doses of this agent in subjects with DBA. To mitigate the potential risks of administering TFP to this new population, we will (1) start dosing at dose levels well below those prescribed for psychosis, (2) dose escalate to a maximum of 10 mg daily (the lowest dose typically prescribed for psychosis), and (3) perform weekly safety monitoring. Given the positive signal in DBA animal models and the 60-year clinical experience with higher doses of TFP, this drug warrants a trial in humans to assess tolerability in DBA.

Detailed description:
This is a dose escalation safety/tolerability study to evaluate the presence of TFP-related adverse events in DBA subjects, and to determine the maximum tolerated dose (MTD) of TFP in DBA.

If tolerated, this trial will support either a proof of concept trial of low-dose TFP in DBA, or the advancement of a chemically modified TFP-like drug (to alleviate the neurologic toxicity) for the treatment of DBA.

Arms:
arm 1: Cohort A: Three subjects will receive Trifluoperazine (TFP) 1 mg PO daily.

* If there is no non-neurologic toxicity Grade 3 at the end of the 21 days, Cohort B will start.
* If 1/3 subjects in Cohort A demonstrates toxicity Grade 3, an additional 3 subjects will be enrolled in Cohort A.
* If 2 or more of the 6 subjects in Cohort A demonstrate toxicity Grade 3, the trial will be stopped; no MTD will be declared.
* If less than 2 of the 6 subjects in Cohort A demonstrate toxicity Grade 3 within 21 days of starting therapy, Cohort B will start. arm 2: Cohort B: Three subjects will receive TFP 2 mg PO daily.

* If there is no non-neurologic toxicity Grade 3 at the end of the 21 days, Cohort C will start.
* If 1/3 subjects in Cohort B demonstrates toxicity Grade 3, an additional 3 subjects will be enrolled in Cohort B:
* If 2 or more of the 6 subjects in Cohort B demonstrate toxicity Grade 3, the study will be stopped, and 1 mg/day will be declared the MTD.
* If \< 2 of the 6 subjects in Cohort B demonstrate toxicity Grade 3 within 21 days of starting therapy, Cohort C will start. arm 3: Cohort C: Three subjects will receive TFP 5 mg PO daily.

* If there is no non-neurologic toxicity ≥ Grade 3 at the end of the 21 days, Cohort D will start.
* If 1/3 subjects in Cohort C demonstrates toxicity Grade 3, an additional 3 subjects will be enrolled in Cohort C:
* If 2 or more of the 6 subjects in Cohort C demonstrate toxicity Grade 3, the study will be stopped, and 2 mg/day will be declared the MTD.
* If \< 2 of the 6 subjects in Cohort C demonstrate toxicity Grade 3 within 21 days of starting therapy, cohort D will start. arm 4: Cohort D: Three subjects will receive TFP 10 mg PO daily.

* If 0/3 subjects in Cohort D demonstrates toxicity Grade 3, the study will be stopped, and 10 mg/day will be declared the MTD.
* If 1/3 subjects in Cohort D demonstrates toxicity Grade 3, an additional 3 subjects will be enrolled in Cohort D.
* If 2 or more of the 6 subjects in Cohort D demonstrate toxicity Grade 3, the study will be stopped, and 5 mg/day will be declared the MTD.
* If \<2 of the 6 subjects in Cohort D demonstrate toxicity \> Grade 3 within 21 days of starting therapy, 10mg/day will be declared the MTD.

Interventions: intervention 1: Trifluoperazine
Intervention descriptions: intervention 1: Trifluoperazine (TFP)1mg, 2mg, 5mg, or 10mg will be given once daily by mouth for 21 days

Protocol document:
Prot_SAP_001.pdf: 
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Phase I/II, Open-Label Study to Determine Safety of Trifluoperazine (TFP) in 
Adults with Red Blood Cell Transfusion-Dependent Diamond Blackfan 
Anemia
Regulatory Sponsor:
Adrianna Vlachos, MD
Principal Coordinating Investigator
Division of Pediatric Hematology/Oncology and Stem Cell 
Transplantation  
Feinstein Institute for Medical Research of Northwell Health
Center for Autoimmune, Musculoskeletal and 
Hematopoietic Diseases 
350 Community Drive, Room 3146
Manhasset, NY 11030
Telephone: 516-562-1504
Fax: 516-562-1599
E-mail: avlachos@northwell.edu
Funding Sponsor:
CAMP4 Therapeutics 
One Kendall Square
Building 1400 West, 3rd Floor
Cambridge, MA 02139
617-766-3221
Study Product:
Trifluoperazine (TFP)
Protocol Number:
Pending
IND/IDE Number:
IND# 135289
Performance Site(s):
Feinstein Institutes for Medical Research, Manhasset, NY
Date:
10OCT2020
Amended:
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This document is confidential and the property of the Northwell Health.  No part of it may 
be transmitted, reproduced, published, or used by other persons without prior written 
authorization from the study sponsor.


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Table of Contents
STUDY SUMMARY ...................................................................................................................................................1
1
PREVIOUS STUDY HISTORY .......................................................................................................................2
2
BRIEF SUMMARY OF RESEARCH..............................................................................................................2
3
INTRODUCTION..............................................................................................................................................4
3.1
BACKGROUND..................................................................................................................................................5
DIAMOND BLACKFAN ANEMIA..................................................................................................................................6
3.2
INVESTIGATIONAL AGENT - TRIFLUOPERAZINE ...............................................................................................7
3.2.1 DESCRIPTION ....................................................................................................................................................8
3.2.2 PHARMACOKINETICS.........................................................................................................................................8
3.3
PRECLINICAL DATA .........................................................................................................................................9
3.3.1 In Vivo and In Vitro Activity in DBA Models............................................................................................10
3.4
CLINICAL DATA TO DATE ..............................................................................................................................11
3.5
DOSE RATIONALE AND RISK/BENEFITS..........................................................................................................12
3.5.1
Dose Escalation...................................................................................................................................12
3.5.2
Dose Modifications..............................................................................................................................13
4
STUDY OBJECTIVES....................................................................................................................................13
PRIMARY OBJECTIVE...............................................................................................................................................13
5
RESOURCES AVAILABLE TO CONDUCT THE HUMAN RESEARCH..............................................14
6
STUDY DESIGN..............................................................................................................................................14
6.1
GENERAL DESIGN ..........................................................................................................................................14
6.2
PRIMARY STUDY ENDPOINTS.........................................................................................................................17
6.3
SECONDARY STUDY ENDPOINTS....................................................................................................................17
6.4
PRIMARY SAFETY ENDPOINTS........................................................................................................................17
7
SUBJECT SELECTION AND WITHDRAWAL..........................................................................................18
7.1
INCLUSION CRITERIA .....................................................................................................................................18
7.2
EXCLUSION CRITERIA ....................................................................................................................................20
7.3
VULNERABLE POPULATIONS..........................................................................................................................20
7.4
SUBJECT RECRUITMENT AND SCREENING ......................................................................................................21
7.5
CONSENT PROCESS ........................................................................................................................................21
7.6
EARLY WITHDRAWAL OF SUBJECTS...............................................................................................................23
7.6.1
When and How to Withdraw Subjects..................................................................................................23
7.6.2
Data Collection and Follow-up for Withdrawn Subjects.....................................................................23
8
STUDY DRUG .................................................................................................................................................23
8.1
DESCRIPTION .................................................................................................................................................23
8.2
TREATMENT REGIMEN ...................................................................................................................................24
8.3
METHOD FOR ASSIGNING SUBJECTS TO TREATMENT GROUPS (RANDOMIZATION)..................................24
8.4
PREPARATION AND ADMINISTRATION OF STUDY DRUG.................................................................................24
8.5
SUBJECT COMPLIANCE MONITORING.............................................................................................................25
8.6
PRIOR AND CONCOMITANT THERAPY ............................................................................................................25
8.7
PACKAGING....................................................................................................................................................25
8.8
BLINDING OF STUDY DRUG/DEVICE ..............................................................................................................25
8.9
RECEIVING, STORAGE, DISPENSING AND RETURN..........................................................................................25
8.9.1
Receipt of Drug Supplies/Device .........................................................................................................25
8.9.2
Storage.................................................................................................................................................26
8.9.3
Dispensing of Study Drug....................................................................................................................26
8.9.4
Return or Destruction of Study Drug...................................................................................................26
9
STUDY PROCEDURES (SCREENING AND VISITS 1-4).........................................................................26


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9.1
SCREENING ....................................................................................................................................................26
9.2
VISIT 1 ...........................................................................................................................................................27
9.3
VISIT 2 ...........................................................................................................................................................27
9.4
VISIT 3 ...........................................................................................................................................................28
9.5
VISIT 4 ...........................................................................................................................................................28
10
RISKS TO SUBJECTS....................................................................................................................................29
11
POTENTIAL BENEFIT TO SUBJECTS......................................................................................................32
12
RESEARCH RELATED HARM/INJURY....................................................................................................33
13
PROVISIONS TO PROTECT PRIVACY INTERESTS OF SUBJECTS..................................................33
14
STATISTICAL PLAN.....................................................................................................................................33
14.1
SAMPLE SIZE DETERMINATION .................................................................................................................33
14.2
STATISTICAL METHODS.............................................................................................................................33
PRIMARY ENDPOINT(S)............................................................................................................................................34
SECONDARY ENDPOINT(S):......................................................................................................................................34
14.3
SUBJECT POPULATION FOR ANALYSIS.......................................................................................................34
15
SAFETY AND ADVERSE EVENTS (APPENDIX H) .................................................................................34
15.1
DEFINITIONS..............................................................................................................................................34
15.2
RECORDING OF ADVERSE EVENTS (APPENDIX H) .....................................................................................36
15.3
REPORTING OF SERIOUS ADVERSE EVENTS...............................................................................................37
15.3.1
Study Sponsor Notification by Investigator.....................................................................................37
15.3.2
IRB Notification by Investigator .....................................................................................................37
15.3.3
FDA Notification by Sponsor..........................................................................................................37
15.4
STOPPING RULES.......................................................................................................................................38
15.5
MEDICAL MONITORING.............................................................................................................................39
15.6
DATA AND SAFETY MONITORING..............................................................................................................39
16
DATA HANDLING AND RECORD KEEPING ..........................................................................................40
16.1
CONFIDENTIALITY.....................................................................................................................................40
16.2
SOURCE DOCUMENTS................................................................................................................................41
16.3
CASE REPORT FORMS................................................................................................................................41
16.4
RECORDS RETENTION................................................................................................................................41
17
STUDY MONITORING, AUDITING, AND INSPECTING .......................................................................41
17.1
STUDY MONITORING PLAN .......................................................................................................................41
17.2
AUDITING AND INSPECTING.......................................................................................................................42
18
ETHICAL CONSIDERATIONS....................................................................................................................42
19
STUDY FINANCES.........................................................................................................................................42
19.1
FUNDING SOURCE .....................................................................................................................................42
19.2
CONFLICT OF INTEREST.............................................................................................................................43
20
PUBLICATION PLAN....................................................................................................................................43
21
REFERENCES.................................................................................................................................................44
22
APPENDICES..................................................................................................................................................49
22.1
APPENDIX A - STUDY ASSESSMENT SCHEDULE.........................................................................................49
22.2
APPENDIX B - DIAMOND BLACKFAN ANEMIA DIAGNOSTIC CRITERIA ......................................................49
22.3
APPENDIX C - DEFINITIONS OF RBC-TRANSFUSION-DEPENDENCE AND              -INDEPENDENCE ..............49
22.4
APPENDIX D - COCKCROFT-GAULT ESTIMATION OF CREATININE CLEARANCE.........................................49
22.5
APPENDIX E - KARNOFSKY PERFORMANCE STATUS SCALE ......................................................................49
22.6
APPENDIX F - NEW YORK HEART ASSOCIATION – CLASSIFICATION OF HEART FAILURE..........................49
22.7
APPENDIX G - STUDY ANNOUNCEMENT....................................................................................................49


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22.8
APPENDIX H - SIDE EFFECTS GRADING AND REPORTING ..........................................................................49
22.9
APPENDIX I - STUDY MONITORING PLAN..................................................................................................49
22.10
APPENDIX J - BLOOD FOR PHARMACODYNAMIC DISEASE MARKER ANALYSIS.........................................49


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LIST OF ABBREVIATIONS
Abbreviation
Definition
AE
Adverse event
ALT
Alanine aminotransferase
ARC
Absolute reticulocyte count
AST
Aspartate aminotransferase
BFU-E
Burst-forming unit - erythroid
BL
Baseline
CFU-E
Colony-forming unit - erythroid
CNS
Central nervous system
CR
Complete response
CRF
Case report form
DBA
Diamond Blackfan anemia
DBAR
Diamond Blackfan Anemia Registry of North America
EoS
End of Study
EPO
Erythropoietin
FDA
Food and Drug Administration
FIH
First in human
GCP
Good Clinical Practice
Hb
Hemoglobin
HLA
Human leukocyte antigen
IA
Interim Analysis
IP
MTD
Intraperitoneal
Maximum tolerated dose
NCI-CTCAE
National Cancer Institute Common Terminology Criteria for Adverse Events
NMS
Neuroleptic malignant syndrome
NSUH
North Shore University Hospital
PHI
PK
Protected health information
Pharmacokinetic
PO
PoC
Orally
Proof of Concept
PR
Partial response
RBC
Red blood cell


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Abbreviation
Definition
SAE
Serious adverse event
SCT
Stem cell transplantation
shRNA
Small hairpin ribonucleic acid
S/T
Safety/Tolerability
TFP
Trifluoperazine
ULN
Upper limit of normal
UPIN
USP
Unique patient identification number
United States Pharmacopeia


Page 1 of 62
Study Summary
Title
Phase I/II, Open-Label Study to Determine Safety of Trifluoperazine 
(TFP) in Adults with Red Blood Cell Transfusion-Dependent Diamond 
Blackfan Anemia
Short Title
TFP in DBA
Protocol Number
17-0748
Phase
Phase I/II
Methodology
Open-Label, Non-Randomized
Study Duration
18-24 months
Study Center(s)
Single-center/Additional centers may be recruited if enrollment is slow
Objectives
To determine the safety and maximum tolerated dose (MTD) of TFP in 
red blood cell transfusion-dependent adults with Diamond Blackfan 
anemia
Number of Subjects
minimum 3, maximum 24
Diagnosis and Main 
Inclusion Criteria
Transfusion Dependent Adults Diagnosed with Diamond Blackfan 
Anemia
Study Product, Dose, 
Route, Regimen
Trifluoperazine (TFP)1mg, 2mg, 5mg, or 10mg once daily by mouth
Duration of 
administration
Maximum of 21 days
Reference therapy
Red Cell Transfusion
Statistical 
Methodology
N/A- dose escalation study for safety/tolerability


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1 Previous Study History
Has this study ever been reviewed and rejected/disapproved by another IRB prior to 
submission to this IRB?
No 
Yes   if yes, please explain: 
2 Brief Summary of Research
Diamond Blackfan anemia (DBA) is a rare inherited pure red cell aplasia. The two main non-
stem cell transplant therapeutic options are corticosteroids and red blood cell (RBC)
transfusions.  About 80% of DBA patients initially respond to corticosteroids, however, half of 
the patients cannot continue due to side effects or loss of response.  These patients are then
typically dependent on RBC transfusions throughout life. Each of these treatments is fraught 
with many side effects and significant morbidity and mortality are potential consequences of 
hematopoietic stem cell transplantation (SCT). The majority of individuals with DBA have 
mutations in genes encoding structural proteins of the small or large ribosomal subunit leading 
to deficiency of the particular ribosomal protein (RP). Studies in zebrafish with RP 
deficiencies confirmed the association between RP defects, p53 activation and the appearance 
of a DBA phenotype. Using the RP deficient zebrafish embryo model, high throughput drug 
screens have demonstrated a strong hematologic response to several calmodulin inhibitors. 
One of these chemicals is trifluoperazine (TFP). TFP treatment of a mouse model of DBA also 
increased the red blood cell count and the hemoglobin (Hb) levels in the mice. TFP is a FDA-
approved typical antipsychotic agent that has been available since 1958 with a well-known 
safety profile. In the United States, TFP is approved for the short-term treatment of 
generalized non-psychotic anxiety; treatment or prevention of nausea and vomiting of various 
causes; and, management of psychotic disorders.
In this study we aim to determine the safety and tolerability of TFP in adult subjects with 
DBA, as a prelude to a possible proof of concept (PoC) trial (as a separate study). TFP’s 
expected dose-limiting toxicity is primarily neurologic (extrapyramidal) when used long-term
at typical anti-psychotic doses (range 10-50 mg daily). Non-neurologic adverse effects in 


Page 3 of 62
subjects with DBA have not been investigated. We will perform a dose escalation study to 
define the safety and tolerability of lower doses of this agent in subjects with DBA.
This class of drugs has not been tested specifically in subjects with DBA prior to this study. To 
mitigate the potential risks of administering TFP to this new population, we will (1) start 
dosing at dose levels well below those prescribed for psychosis over the past several decades, 
(2) dose escalate to a maximum of 10 mg daily (the lowest dose typically prescribed for 
psychosis), and (3) perform weekly safety monitoring. Given the positive signal in DBA 
animal models and the 60-year clinical experience with higher doses of TFP, this drug 
warrants a trial in humans to assess tolerability in DBA. If tolerated, this trial will support 
either a PoC trial of low-dose TFP in DBA, or the advancement of a chemically modified 
TFP-like drug (to alleviate the neurologic toxicity) for the treatment of DBA. 
This is a dose escalation safety and tolerability study to evaluate the presence of TFP-related 
adverse events in DBA subjects, and to determine the maximum tolerated dose (MTD) of TFP 
in DBA. The dose escalation strategy is described in Section 3.5 Dose Rationale and 
Risk/Benefits. 
Some first-in-human (FIH) trials may implement an enrollment restriction rule such that two 
subjects are dosed in a given cohort, and a third subject is not dosed until both of the first two 
subjects have demonstrated tolerability. For this trial, we have elected not to use such an
enrollment restriction design for the following reasons:
a.
This is not a FIH trial: TFP has been in wide clinical use for 60 years.
b. Our dose levels (1 mg daily, up to max 10 mg daily) are all well within and 
below the safe range of clinical use. Doses in the 2-6 mg daily range have been 
shown to have a side effect profile similar to placebo in patients with anxiety 
(Mendels, 1986). A randomized clinical trial comparing TFP 15 mg/day vs. 
placebo in schizophrenic subjects revealed no difference in the rates of severe 
adverse effects, Parkinsonism or dystonia compared to placebo (Koch, 2014).  
Doses for psychosis range from 10 mg daily up to 40-50 mg daily, whereas we 
will dose at 1, 2, 5, and 10 mg daily only.


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c.
We will monitor for safety, specifically for any hematologic toxicity and for 
extrapyramidal/central nervous system (CNS) effects. Dose escalation criteria 
and actions, as well as subject and cohort stopping rules are detailed in Section 
6 Study Design.
3 Introduction
This document is a protocol for a human research study. This study is to be conducted 
according to US and international standards of Good Clinical Practice (FDA Title 21 part 312 
and International Conference on Harmonization guidelines), applicable government 
regulations, and Institutional research policies and procedures. 


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3.1
Background


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Diamond Blackfan Anemia
Diamond Blackfan anemia is a rare inherited pure red cell aplasia.  Over the past 20 years,
mutations have been described in genes encoding both the small and large ribosome associated 
proteins (Vlachos, 2014; Draptchinskaia, 1999; Gazda, 2006; Cmejla, 2007; Farrar, 2008; 
Gazda 2008; Doherty 2010). There is wide variability in clinical and biologic features, 
familial history, and therapeutic responses. Currently standard therapy includes 
corticosteroids, RBC transfusions or SCT (Vlachos, 2001a).  Approximately 80% of subjects 
have an initial response to corticosteroids.  Of these subjects, approximately half will fail to 
achieve a taper to a tolerable steroid dose or have intolerable side effects and will need to 
discontinue steroid therapy.  These subjects and the 20% who do not respond initially to such 
therapy must be maintained on a chronic RBC transfusion with iron chelation. Chronic 
transfusions have considerable treatment-related morbidity, most notably iron overload-related 
organ failure. 
SCT has proven to be effective therapy for a select group of subjects.  Allogeneic SCT with a 
histocompatible donor has been performed successfully in a number of subjects.  The 
Diamond Blackfan Anemia Registry of North America (DBAR) experience has been 
published (Vlachos, 2001b; Lipton 2006).  However, because of remissions (sustained 
physiologically acceptable erythropoiesis for ≥6 months without any medication or 
transfusion) in up to 20% of subjects with DBA, SCT, regardless of donor type, is not 
consistently offered to corticosteroid-dependent or transfusion-dependent subjects with DBA
and no other complications precluding corticosteroid or transfusion use. For many subjects, the 
lack of a suitable donor does not permit SCT as a therapeutic option, as human leukocyte 
antigen (HLA)-matched unrelated donor transplants have been associated with mortality and 
morbidity.  
Historically, the lack of truly effective and safe therapy has prompted the investigation of a 
number of other agents, including high-dose corticosteroids, immunosuppressive therapy 
(cyclosporine A and antithymocyte globulin), intravenous immunoglobulin, high-dose
erythropoietin, interleukin-3, metoclopramide and others; however, these modalities have 
achieved, at best, anecdotal success (Vlachos, 2008).


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3.2
Investigational Agent - Trifluoperazine


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3.2.1 Description
TFP is a piperazine phenothiazine antipsychotic with 5 mg orally equivalent to 100 mg of oral 
chlorpromazine, the prototype antipsychotic. TFP is a typical antipsychotic of the 
phenothiazine chemical class that has been used for the treatment of psychiatric subjects since 
1958 (Rudy, 1958). TFP acts as a dopamine antagonist with antipsychotic and antiemetic 
activities. TFP blocks CNS postsynaptic mesolimbic dopaminergic D1 and D2 receptors and 
depresses the release of hypothalamic and hypophyseal hormones and the reticular activating 
system, thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone, and 
emesis. In the United States, trifluoperazine hydrochloride tablets, USP, are approved for the 
short-term treatment of generalized non-psychotic anxiety; treatment or prevention of nausea 
and vomiting of various causes; and management of psychotic disorders. In part because of its 
side effect profile, TFP has been largely replaced by second and third generation anti-
psychotic medications.  It is associated with an increased risk of death in elderly subjects 
treated for dementia-related psychosis. Nevertheless, TFP remains commercially available 
worldwide and the risks attendant to its use are well understood and generally manageable.
3.2.2 Pharmacokinetics
Trifluoperazine may be administered orally or intramuscularly. This study will only use the 
oral route of administration. Following administration of the drug, antipsychotic effects are 
gradual, with considerable individual subject variation, and peak effects may not occur for 6 
weeks to 6 months. TFP is readily absorbed from the gastrointestinal tract and is subject to 
first-pass metabolism in the gut wall. It is metabolized in the liver and excreted in the urine 
and feces in the form of active and inactive metabolites. TFP is extensively bound to plasma 
proteins. The drug crosses the blood-brain barrier and its metabolites also cross the placental 
barrier and are excreted in milk (MHRA, PAR, 2006).
The single-dose pharmacokinetics (PK) of TFP were determined in 5 healthy adult male 
volunteers who received TFP 5 mg orally after an overnight fast (Midha, 1983). Peak TFP 
concentrations varied widely (range 0.53 to 3.09 ng/mL-1) and were reached at 2.8 ± 0.5 hours 
post-dose. The area under the plasma concentration-time curve also differed widely among 
subjects (range 5.9 to 17.6 ng/mL-1∙h; mean 11.7 ± 2.2 ng/mL-1∙h), suggesting large individual 


Page 9 of 62
differences in the extent of pre-systemic TFP elimination. The mean apparent terminal 
elimination half-life (t1/2) of TFP was 12.5 ± 1.4 hours. 
More relevant to its function as a potential medication in DBA, TFP also serves as an inhibitor 
of calmodulin, a multi-functional, intermediate calcium-binding messenger protein.
3.3
Preclinical Data


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3.3.1 In Vivo and In Vitro Activity in DBA Models
It has been demonstrated that zebrafish embryos with mutations in the rps29 gene have an 
erythroid defect, similar to that reported in subjects with DBA (Taylor, 2012).  Furthermore, 
zebrafish embryos also have endothelial defects as observed by decreased flk1 expression in 
the intersegmental vessels at 24 hours post-fertilization.  Consistent with other animal models 
of RP mutations, the p53 pathway is activated in the rps29-/- embryo, and p53 knockdown in 
the mutant zebrafish rescues the hematopoietic and endothelial defects (Taylor, 2012). 
In order to identify compounds with the ability to rescue DBA phenotypes in vivo, 
600 chemicals were screened for their ability to rescue flk intersegmental vessels and reverse 
the erythroid defect in rps29-/- zebrafish embryos. Findings revealed that several structurally 
diverse calmodulin inhibitors successfully rescued flk staining in the vasculature and Hb levels 
in the mutant embryo.
TFP was also tested in a murine model of DBA in which mice were transplanted with bone 
marrow from mice harboring a knock-in allele expressing a doxycycline-inducible rps19 
shRNA (Montague, 2014).  Following engraftment of the transplanted cells, recipient mice 
were administered doxycycline in drinking water to induce the rps19 deficiency, p53-induced 
p21 expression, and severe anemia.  Diseased mice then received an intraperitoneal (IP) 
injection of 5 mg/kg TFP every other day, and after two weeks, bone marrow was collected for 
quantitative polymerase change reaction (qPCR) analysis and blood was analyzed for RBC 
counts and Hb levels.  TFP treatment of rps19-deficient mice decreased p21 levels, indicating 
that TFP was hitting the expected target, and significantly increased both RBC counts and Hb 
levels compared to vehicle-treated controls (Macari, 2015).  Importantly, TFP reduced p53 
activity only in the presence of the stress-induced state of rps19 deficiency, while basal levels 
of p53 in wild-type mice actually increased modestly.  Furthermore, the levels of p53 activity 
in the rps19-deficient mice treated with TFP were not lower than those in wild type mice.  TFP 
was well tolerated in this model, indicating that the TFP dose resulting in improved anemia did 
not cause gross toxicity. 
3.3.2 In Vitro Activity of TFP in Human CD34+ Cells


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In vitro studies in normal human CD34+ cells transduced with small hairpin ribonucleic acid 
(shRNA) against RPS19 and in primary CD34+ bone marrow cells from subjects with DBA 
with RPS19 and RPS29 mutations confirmed the association of RP deficiency with 
upregulation of p53 and rescue of the ensuing DBA phenotype with TFP. (Macari, 2016)
The hypocellularity of bone marrow in subjects with DBA presents a challenge for obtaining 
adequate material for testing drugs, necessitating an alternative strategy.  Consequently, 
human CD34+ cells were transduced with shRNA against RPS19 and erythroid differentiation 
was evaluated in a two-stage process adapted from Zu et al. (Zu, 2013).  During the expansion 
phase, RPS19 knockdown increased p53 protein and p53 target gene, p21 and inhibited 
erythroid differentiation, demonstrated by a 30% reduction in CD71+ cells at Day 12.  
Treatment of these cells with TFP during the differentiation phase rescued CD71+ erythroid 
precursor cells to that of control and reduced expression of p21 (Macari, 2015). In addition, 
TFP treatment specifically decreased p53 in RPS19-deficient cells, but not in control cells.  
This demonstrates that the effect of TFP on p53 activity is specific to RP deficient cells and 
that TFP restores p53 to normal levels.
Primary CD34+ cells from bone marrow samples of two subjects with DBA (RPS19 R94X and 
RPS29 I31F) were treated in vitro with a single dose of TFP and improved erythroid 
differentiation was observed (Macari, unpublished data).
In summary, multiple lines of evidence demonstrate that TFP, the compound identified in a 
zebrafish chemical screen, restores erythropoiesis in models of DBA, providing a strong 
rationale for clinical studies in subjects with DBA.  Furthermore, TFP appears to lower 
elevated p53 activity levels in the diseased state with little effect on basal levels.  
3.4
Clinical Data to Date
There are no available clinical research data on TFP in subjects with DBA. 
A randomized, double-blind, placebo-controlled 4-week trial of low dose TFP (2–6 mg/day) in 
415 subjects with generalized anxiety disorder showed that the side effect profile of TFP and 


Page 12 of 62
placebo were similar. Anxiety was also significantly improved in the TFP treatment arm
(Mendels, 1986).
A randomized clinical trial comparing TFP 15 mg/day vs. placebo in schizophrenic subjects 
revealed no difference in the rates of severe adverse effects, Parkinsonism or dystonia 
compared to placebo. Subjects in the TFP group did experience higher rates of akathisia than 
did the placebo group. However, significantly more placebo arm subjects left the study early 
due to poor efficacy, in comparison to TFP-treated subjects (Koch, 2014).
3.5
Dose Rationale and Risk/Benefits
In an in vivo mouse model of DBA, TFP at a dose of 5 mg/kg intraperitoneally every other day 
reduced apparent p53 activity and raised the RBC count and Hb level after 2 weeks of 
treatment (Macari, 2016).  The murine dose scales allometrically to a daily dose of 12–15 mg 
of TFP in humans.  As the 5 mg/kg dose was the only dose tested in the mouse study, and 
daily administration of TFP may be more efficacious than every other day dosing, it is possible 
that a daily dose of 5 mg or less in humans may be efficacious.  Given the potential margin of 
error in the allometric calculation, a maximum dose of 10 mg daily may be tested in this trial.
The starting dose of TFP in subjects with DBA (1 mg) is lower than the starting dose in 
psychiatric indications, and the maximum TFP dose to be administered to subjects with DBA 
will not exceed 10 mg.  As side effects of TFP have been shown to be dose-/plasma level-
related, it is anticipated that the more severe side effects associated with TFP, including 
extrapyramidal symptoms, will be less likely to occur at doses ≤10 mg. The two trials cited in 
section 3.4 Clinical Data to Date also support the likely tolerability of the proposed dose range 
in this trial (Mendels, 1986; Koch, 2014).
3.5.1 Dose Escalation
Up to 4 cohort dose levels of TFP will be studied:  1, 2, 5, and 10 mg/day for up to 21 days 
each, as tolerated. Cohort A will start at 1 mg/day, and the dose will escalate to 2 mg/day in 
Cohort B, 5 mg/day in Cohort C, and 10 mg/day in Cohort D. At the start of each cohort, 3 
subjects will be enrolled, and an interim analysis (IA) for safety and tolerability will be 


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conducted after all 3 subjects have completed 21 days of treatment (See Section 6 Study 
Design for details). The 21-day time frame is based on the t1/2 from the healthy volunteer 5 
mg single dose TFP study (Midha, 1983), showing that TFP’s elimination t1/2 is 
approximately 12-14 hours. Therefore, steady state is reached approximately 3 days after 
initiating therapy, and 21 days of therapy provides at least 18 days of exposure at steady state 
(the 1 and 2 mg doses likely have shorter t1/2 and so steady state will be reached even sooner 
in the first 2 cohorts).
Whereas some FIH trials may use an enrollment restriction rule such that only two subjects are 
dosed at a time, this trial will not use such an enrollment restriction design. Please see Section 
2 Brief Summary of Research for the supporting rationale.
3.5.2 Dose Modifications
Dose of TFP will be discontinued in case of sustained increase of hemoglobin 2 gm/dL from 
the previous dose except those attributed to RBC transfusions.  Dose should be held in the 
event of an AE ≥ Grade 3 until resolution (to baseline) or < Grade 1. If AE is not resolved in 7 
days then TFP will be discontinued. The guidelines for dose modifications are listed below.
Dose Modification Guidelines
NCI Toxicity-
Grade
Event
Action
Hb 12 gm/dL (not associated with RBC 
transfusion)
Discontinue *
Grade 3
Any adverse event
Dose delay **
* Subject will discontinue the study drug.
** Delay dose of TFP for up to 7 days or until AE severity improves to Grade 1 or to Baseline status.
4 Study Objectives
Primary Objective

To evaluate the safety profile of a 21-day course of TFP at doses up to 10 mg/day in
RBC transfusion-dependent adults with DBA


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5 Resources Available to Conduct the Human Research
Adrianna Vlachos, MD is the PI and sponsor of this study and the Director of the Diamond 
Blackfan Anemia Registry (DBAR) of North America. The DBAR is housed at the Feinstein 
Institute for Medical Research. There are over 750 subjects with Diamond Blackfan anemia 
enrolled in the DBAR. Because of this, the investigator has access to the specific subject
population required for this study. Subjects/parents of subjects and their physicians contact the 
DBAR periodically to inquire about available studies. Also, the DBA Foundation (DBAF), the 
family support group, has access to most of the DBA families. The DBAF is highly supportive 
of the research and they also encourage the families to contact the DBAR for any available 
studies. We have prepared an announcement to inform the subjects of the study as we have for 
other studies in the past. This has worked well previously, and we do not expect having any 
issues in recruiting subjects.
With regards to the trial logistics, the protocol is reviewed at the site initiation visit with all 
study personnel, along with the trial-related duties and functions.
6 Study Design
6.1
General Design
This study is a multi-center, Phase I/II, dose escalation, open-label study to determine the 
safety of TFP in adult subjects with DBA and RBC-transfusion-dependence.  A 3+3 dose 
escalation regimen will be used. The maximum time on study drug will be 21 days with a 1
week post-treatment follow-up period. It is expected that up to 24 subjects can be recruited and 
complete the study within 12-18 months. The dose escalation study design is shown in Figure 
1:


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Figure 1. Dose escalation study design
1. Cohort A: Three subjects will receive TFP 1 mg PO daily. 
o
If there is no toxicity Grade 3 at the end of the 21 days, Cohort B will start.
o
If 1/3 subjects in Cohort A demonstrates toxicity Grade 3, an additional 3 
subjects will be enrolled in Cohort A:
o
If 2 or more of the 6 subjects in Cohort A demonstrate toxicity Grade 3, 
the trial will be stopped; no MTD will be declared.
o
If < 2 of the 6 subjects in Cohort A demonstrate toxicity Grade 3 within 
21 days of starting therapy, Cohort B will start.
2. Cohort B: Three subjects will receive TFP 2 mg PO daily.
o
If there is no toxicity Grade 3 at the end of the 21 days, Cohort C will start.
o
If 1/3 subjects in Cohort B demonstrates toxicity Grade 3, an additional 3 
subjects will be enrolled in Cohort B:


Page 16 of 62
o
If 2 or more of the 6 subjects in Cohort B demonstrate toxicity Grade 3,
the study will be stopped, and 1 mg/day will be declared the MTD.
o
If < 2 of the 6 subjects in Cohort B demonstrate toxicity Grade 3 within 
21 days of starting therapy, Cohort C will start.
3. Cohort C: Three subjects will receive TFP 5 mg PO daily.
o
If there is no toxicity ≥Grade 3 at the end of the 21 days, Cohort D will start.
o
If 1/3 subjects in Cohort C demonstrates toxicity Grade 3, an additional 3 
subjects will be enrolled in Cohort C:
o
If 2 or more of the 6 subjects in Cohort C demonstrate toxicity Grade 3, 
the study will be stopped, and 2 mg/day will be declared the MTD.
o
If < 2 of the 6 subjects in Cohort C demonstrate toxicity Grade 3 within 
21 days of starting therapy, cohort D will start.
4. Cohort D: Three subjects will receive TFP 10 mg PO daily.
o
If 0/3 subjects in Cohort D demonstrates toxicity Grade 3, the study will be 
stopped, and 10 mg/day will be declared the MTD.
o
If 1/3 subjects in Cohort D demonstrates toxicity Grade 3, an additional 3 
subjects will be enrolled in Cohort D.
o
If 2 or more of the 6 subjects in Cohort D demonstrate toxicity Grade 3, the 
study will be stopped, and 5 mg/day will be declared the MTD.
o
If <2 of the 6 subjects in Cohort D demonstrate toxicity > Grade 3 within 21 
days of starting therapy, 10mg/day will be declared the MTD.
Each subject will undergo safety assessments as per the required schedule while on the study 
drug. All dosed subjects will be followed for an additional 1 week after discontinuing study 
drug (post-study safety follow-up). There will be no more than 6 subjects enrolled at any 
particular time.


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Treatment will be discontinued for any subject if their Hb is > 12 gm/dL, not associated with 
RBC transfusions.
6.2
Primary Study Endpoints

Safety profile: No adverse events greater than Grade 3-4 

Safety:  Treatment-emergent adverse events (AEs)
6.3
Secondary Study Endpoints

Pharmacodynamic markers of TFP target engagement
6.4
Primary Safety Endpoints
The primary safety endpoint is to evaluate the safety profile of TFP for red blood cell 
transfusion-dependent adults with DBA.


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7 Subject Selection and Withdrawal
7.1
Inclusion Criteria


Page 19 of 62
In order to be eligible to participate subjects must meet all of the following criteria:
1. Men and women age: 18 years and <65 years of age.
2. Weight: ≥45 kilograms.
3. DBA diagnosed according to the DBA criteria (Vlachos, 2008) (Appendix B).
4. RBC transfusion-dependence (defined as 2 units packed RBCs per 28 days averaged 
over 84 days [12 weeks] prior to study entry) (Gale, 2011) (Appendix C).
5. Calculated creatinine clearance > 30 mL/min (Appendix D).
6. Karnofsky performance status scale score ≥ 70 (Appendix E).
7. Female subjects of childbearing potential participating in the study are to use highly 
effective methods of birth control (abstinence, oral contraceptives, barrier method with 
spermicide or surgical sterilization) during study participation and for 1 week 
following the last dose of TFP (a total of 4 weeks of the study). Female subjects of 
childbearing potential must have a negative serum β-human chorionic gonadotropin 
pregnancy test within 3 days prior to the start of TFP given on Day 1.  Subjects must 
be counseled concerning measures to be used to prevent pregnancy and potential 
toxicities prior to the first dose of TFP.  A female subject of childbearing potential is a 
sexually mature woman who has not undergone a hysterectomy or bilateral 
oophorectomy; or who has not been postmenopausal for at least 24 consecutive months 
(i.e., who has had menses at some time in the preceding 24 months).
8. Male subjects must agree to use a latex condom during any sexual contact with females 
of childbearing potential while participating in the study and for 1 week following the 
last dose of TFP, even if he has undergone a successful vasectomy (a total of 4 weeks 
of the study).  Male subjects must be counseled concerning measures to be used to 
prevent pregnancy and potential toxicities prior to the first dose of TFP.
9. Agreement to adhere to the study visit schedule, understand and comply with all 
protocol requirements.
10. The subjects are capable of giving informed consent.


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7.2
Exclusion Criteria
Subjects who meet any of the following criteria will not be eligible to participate in the study:
1. Liver: aspartate aminotransferase (AST) > 5 x the upper limit of normal (ULN), 
alanine aminotransferase (ALT) >5 x ULN, or bilirubin > 5 x ULN.
2. Heart disease (New York Heart Association classification of ≥ 3; Appendix F).
3. History of angina.
4. Uncontrolled hypertension.  If hypertension is considered clinically stable, systolic 
blood pressure must be <150 mmHg or diastolic blood pressure must be <100 mmHg.
5. Subjects currently responsive to corticosteroids for treatment of DBA.
6. Treatment with another investigational drug or device <56 days pre-study entry.
Subjects who participated in an earlier cohort of this trial may participate in a 
subsequent cohort if (a) they meet all eligibility criteria, (b) did not experience any 
adverse effects Grade 3 while on TFP, and (c) discontinued TFP 6 days (10 half-
lives) prior to day 1 of the subsequent cohort.
7. Pregnant or lactating females.
8. Any history of severe allergic reaction requiring the use of epinephrine.
9. Known hypersensitivity to the study drug or other phenothiazines.
10. History or presence of extrapyramidal signs.
11. History of cancer.
7.3
Vulnerable Populations
No vulnerable populations are specifically being targeted for this study. 
Children or viable neonate 
Cognitively impaired 
Pregnant Women, Fetuses or neonates of uncertain viability or nonviable 
Prisoners 
NSLIJ Employees, residents, fellows, etc
poor/uninsured
Students
Minorities
Elderly


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Healthy Controls
7.4
Subject Recruitment and Screening
Adrianna Vlachos, MD, is the PI and the Director and Jeffrey Lipton, MD, PhD is a Co-
Investigator and the Co-Director of the Diamond Blackfan Anemia Registry of North 
America, respectively. The DBAR is housed at the Feinstein Institute for Medical Research. 
There are over 750 subjects with Diamond Blackfan anemia enrolled in this Registry.  Because 
of this, the investigators have access to the specific subject population required for this study. 
Subjects contact the DBAR periodically to inquire about available studies. Also the DBA 
Foundation (DBAF) (the family group) has access to most of the DBA families.  The DBAF is 
highly supportive of the research and they also encourage the families to contact the DBAR
for any available studies. We have prepared a study announcement (Appendix G) to inform the 
subjects of the study as we have for other studies in the past. This will be posted on the DBAF 
website (mostly visited by subjects/families) and our DBAR website (often visited by 
physicians as well as subjects/families) and has worked well previously. 
Once informed consent is obtained from the subject, the following screening requirements will 
be performed:
1- Physical examination (including height at 1st visit only, weight, vital signs, blood 
pressure and neurological examination)
2- Hematology evaluation including RBC count, hemoglobin, hematocrit, absolute 
reticulocyte count, white blood cell count, absolute neutrophil count, and platelet count
3- Blood chemistry including blood urea nitrogen, creatinine, bilirubin [total and direct], 
aspartate aminotransferase [AST], and alanine aminotransferase [ALT]) 
4- If female, serum pregnancy test
5- Documentation of transfusion history for > 3 months before initiation of treatment
7.5
Consent Process
Informed consent will be obtained by the study PI or authorized co-investigators after they 
have fully explained the study. The study will be presented to all eligible subjects and 
explained in terms that are appropriate for each subject. After a full discussion and the 


Page 22 of 62
opportunity to ask questions, subjects will be consented. The subject may take as much time as 
needed to decide on his/her participation in the study, and may consent after the initial contact 
is made. The consent will be obtained either in the outpatient area at a regular office visit or 
via mail, after the study is discussed on a telephone call. 
The subjects with DBA who may be eligible for this study may live in any state in the United 
States. Since travel may be difficult, it is often necessary to screen the subject for eligibility 
before they travel for the study. Therefore the consent is mailed to the subject. Once the 
subject has the consent in hand, the consent will be reviewed with him/her over the phone in 
its entirety. Questions can be asked and answered and the subject can determine the 
appropriateness of the study for him/herself. Once consent is signed and received by the PI,
then the screening procedure can begin. Eligibility can therefore be determined prior to the 
subject’s travel and confirmed upon subject’s arrival to the office visit. A standard informed 
consent form will be utilized for this study. Subjects may have family members, their local 
physicians and any other chosen individuals review the consent with them prior to their 
signing. For subjects who sign consent remotely, the study PI or authorized co-investigator 
will review the study and the consent form again when the subject comes for the in-person 
physical examination and to begin the study. At that time an enrollment note will document 
the continued willingness of the subject to participate in the study.
The study is 4 weeks in duration and subjects may withdraw their consent at any time. 
Subjects will be seen weekly for the actual study drug timeframe of the study and will be 
given the opportunity to withdraw consent at any time. 
This study does not involve subjects less than 18 years of age.
This study does not involve cognitively impaired adults.
Non-English speaking subjects with DBA are eligible for this study. Our institution provides a 
translator service through Pacific Interpreters, Inc. Any language can be accommodated. The 
translator will be used to explain the consent and give the subject an opportunity to ask 
questions and have them answered. The subject will be given a short form of the consent to 
sign.


Page 23 of 62
7.6
Early Withdrawal of Subjects
7.6.1 When and How to Withdraw Subjects
The following reasons are considered sufficient for withdrawing a subject from the study drug 
and/or from the study:
•
Sustained hemoglobin > 12 mg/dL (not influenced by transfusions).
•
Any toxicity ≥ Grade 3 (Appendix H).
•
Adverse event that, in the judgment of the investigator, may cause severe or permanent 
harm or that rules out continuation of treatment.
•
Hypersensitivity reaction to TFP.
•
Withdrawal of consent.
•
Death.
•
Lost to follow-up.
•
Pattern of significant noncompliance.
The reason for subject withdrawal must be documented in the subject chart / source records.
7.6.2
Data Collection and Follow-up for Withdrawn Subjects
Subjects who discontinue from the Treatment Period early will still continue to the Follow-Up 
Period for 1 week from the last dose of TFP. For any subjects lost to follow-up, attempts will
be made by phone to obtain permission to record at least survival data up to the end of study
follow-up period.
8 Study Drug 
8.1
Description
TFP is a commercially-available phenothiazine tranquilizer with potent anti-psychotic, anti-
anxiolytic and antiemetic activity.  
TFP is commercially available in the United States in a variety of formulations, including the 
following:


Page 24 of 62
1 mg tablets are lavender, film-coated, round, unscored tablets debossed with 1 on one 
side of the tablet and GG51 on the other side.  They are available as follows: NDC 
0781-8028-01, in bottles of 100 tablets.
5 mg tablets are lavender, film-coated, round, unscored tablets debossed with 5
on one side of the tablet and GG55 on the other side.  They are available as follows:
NDC 0781-8034-01, in bottles of 100 tablets.
8.2
Treatment Regimen
Trifluoperazine will be given orally once daily as 1 mg, 2 mg (two 1mg tablets), 5 mg, or 10
mg (two 5mg tablets). The treatment duration will be up to 21 days (3 weeks).
8.3
Method for Assigning Subjects to Treatment Groups
(RANDOMIZATION)
There is no randomization in this study. All subjects who qualify for the study will be enrolled 
into the study and receive up to 3 weeks of TFP.  A unique multi-digit subject identification 
number will be manually assigned by the site staff to each subject who signs consent.
8.4
Preparation and Administration of Study Drug
The staff in the pharmacy will fill out the following information on the Trifluoperazine Drug 
Accountability Log upon distribution to the subject:
•
Date
•
Visit
•
Subject Number
•
Subject Initials
•
Dose
•
Number of pills dispensed
•
Lot Number


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The site personnel will confirm the lot number for TFP and the number of pills dispensed and 
record this information on the Trifluoperazine Drug Accountability Log and in the pharmacy 
records.
8.5
Subject Compliance Monitoring
The study team will assess compliance with the study treatment by report at each study visit. 
The subject may be discontinued by the study PI at any time for non-compliance with the 
study treatment regimen.
8.6
Prior and Concomitant Therapy
All concomitant medications will be collected. Prior corticosteroid therapy will be collected as 
well. All concomitant medications except for steroids are permitted during the study.  
8.7
Packaging
TFP is to be dispensed in a tight, light-resistant container, as defined in the USP, using a 
child-resistant closure. The subject will receive a 21 day supply of 1 mg or 5 mg tablets. The 
label for TFP will include the institution name, address and telephone number, the protocol 
number, drug name, dosage form and strength, amount of drug per container, lot number, 
expiration date, medication identification, dosing instructions, storage conditions, and 
required caution statements and/or regulatory statements as applicable.  Additional 
information may be included on the label as applicable per local regulations.
8.8
Blinding of Study Drug/Device
There is no blinding of the study drug in this study.
8.9
Receiving, Storage, Dispensing and Return
8.9.1 Receipt of Drug Supplies/Device
Upon receipt of the study drug, an inventory must be performed and a Drug Receipt Log filled 
out and signed by the person accepting the shipment.  It is important that the designated study 
staff counts and verifies that the shipment contains all the items noted in the shipment 
inventory.  Any damaged or unusable study drug in a given shipment will be documented in 


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the study files.  The investigator must notify study sponsor of any damaged or unusable study 
drug that were supplied to the investigator’s site.
8.9.2 Storage
TFP tablets are to be stored at 20° to 25°C (68° to 77°F) in the study pharmacy.  
8.9.3 Dispensing of Study Drug
The subject will be dispensed a 21 day supply of 1 mg or 5 mg tablets based on Dose Level 1, 
2, or 3 and 4, respectively. The subject will receive study drug once during this study.
8.9.4 Return or Destruction of Study Drug
At the completion of the study, there will be a final reconciliation of drug shipped, drug 
consumed and drug remaining. This reconciliation will be logged on the drug reconciliation 
form, signed and dated.  Any discrepancies noted will be investigated, resolved, and 
documented prior to return or destruction of unused study drug.  Drug destroyed on site will be 
documented in the study files.
9 Study Procedures (Screening and Visits 1-4)
Please see Appendix A for a Schedule of Study Assessments.
9.1
Screening
The Screening Period is from Day -28 to Day -1 prior to the subject starting the study drug on 
Day 1 of the study. If consent was not previously obtained by mail then the PI will obtain 
informed consent at a Screening visit. If the consent was obtained by mail then the consent 
will be reviewed again with the subject at the initial visit. The subject will be then be assessed 
for inclusion and exclusion criteria with a review of his/her medical record, including prior 
treatments, procedures, and transfusion history (for the previous 12 weeks at least). A physical 
examination including height at 1st visit, weight, vital signs, blood pressure and neurological 
exam will be performed on the subject. Karnofsky performance status will be assessed. Blood 
work will be performed for a complete blood count (CBC; RBC count, hemoglobin, 
hematocrit, absolute reticulocyte count, white blood cell count, absolute neutrophil count, and 


Page 27 of 62
platelet count), serum chemistry panel for hepatic and renal function (blood urea nitrogen, 
creatinine, bilirubin [total and direct], aspartate aminotransferase [AST], and alanine 
aminotransferase [ALT]). If the subject is a female, then menstrual status will be assessed and 
a serum pregnancy test will also be performed. If all the criteria are evaluated and subject is 
confirmed to start the study, Screening and Visit 1 may be combined into one visit and the 
Screening blood work can be used as the Visit 1 blood work if within + 1 day.
9.2
Visit 1
Visit 1 will be Day 1 of the study and will be the day that the subject starts the study drug. If 
Screening assessments were completed the day before then the subject’s physical examination 
and blood work results can be used for Visit 1 as well. A physical examination including 
height at 1st visit, weight, vital signs, blood pressure and neurological exam will be performed 
on the subject. Karnofsky performance status will be assessed. Blood work will be performed 
for a complete blood count (CBC; RBC count, hemoglobin, hematocrit, absolute reticulocyte 
count, white blood cell count, absolute neutrophil count, and platelet count), serum chemistry 
panel for hepatic and renal function (blood urea nitrogen, creatinine, bilirubin [total and 
direct], aspartate aminotransferase [AST], and alanine aminotransferase [ALT]). If the subject 
is a female, then menstrual status will be assessed and a serum pregnancy test will also be 
performed. Blood for pharmacodynamic marker analysis will be collected, if applicable
(Appendix J). All concomitant therapies will be documented. The subject will be dispensed a 
21-day supply of the study drug once all evaluable criteria are met and will start the study drug 
on Day 1. Visit 1 should occur within 7 days following a blood transfusion.
9.3
Visit 2
Visit 2 will be Day 11 (± 1 day) of the study. The subject will undergo full safety analysis, 
including a physical examination (including weight, vital signs, blood pressure and 
neurological exam). Karnofsky performance status will be assessed. Blood work will be 
performed for a complete blood count (CBC; RBC count, hemoglobin, hematocrit, absolute 
reticulocyte count, white blood cell count, absolute neutrophil count, and platelet count), 
serum chemistry panel for hepatic and renal function (blood urea nitrogen, creatinine, bilirubin 
[total and direct], aspartate aminotransferase [AST], and alanine aminotransferase [ALT]), and 


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pharmacodynamic marker analysis, if applicable (Appendix J). If the subject is a female, 
menstrual status will be assessed and a serum pregnancy test will also be performed. 
Transfusion history will be documented.  The subject will be questioned and evaluated for any 
adverse events. All concomitant therapies will be documented.
9.4
Visit 3
Visit 3 will be Day 22 (± 2 days) of the study. The subject will undergo full safety analysis, 
including a physical examination (including weight, vital signs, blood pressure and 
neurological exam). Karnofsky performance status will be assessed. Blood work will be 
performed for a complete blood count (CBC; RBC count, hemoglobin, hematocrit, absolute 
reticulocyte count, white blood cell count, absolute neutrophil count, and platelet count), 
serum chemistry panel for hepatic and renal function (blood urea nitrogen, creatinine, bilirubin 
[total and direct], aspartate aminotransferase [AST], and alanine aminotransferase [ALT]), and 
pharmacodynamic marker analysis, if applicable (Appendix J). If the subject is a female, 
menstrual status will be assessed. Transfusion history will be documented.  The subject will be 
questioned and evaluated for any adverse events.  All concomitant therapies will be 
documented.
9.5
Visit 4
Visit 4 will be Day 29 (± 2 days) of the study (Follow-up Period). The subject will undergo 
post-treatment safety assessment including a physical examination and blood work (CBC and 
chemistry panel). Transfusion history will be documented. The subject will be questioned and 
evaluated for any adverse events. This visit may be done virtually through a system that can 
visually assess the subject for neurologic issues. Blood work may be done at a local 
laboratory.


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10 Risks to Subjects
Adverse reactions with TFP include drowsiness, dizziness, skin reactions, rash, dry mouth, 
insomnia, amenorrhea, fatigue, muscular weakness, anorexia, lactation, blurred vision, and 
neuromuscular (extrapyramidal) reactions.  Details regarding extrapyramidal and other adverse 
reactions with TFP follow:
• Neuromuscular (Extrapyramidal) Reactions:  These symptoms are characterized by 
motor restlessness.  They may be of the dystonic type, or they may resemble Parkinsonism 
(described below).
• Motor Restlessness:  Symptoms may include agitation or jitteriness and sometimes 
insomnia.  These symptoms often disappear spontaneously. 
• Dystonia (Class Effect):  Symptoms of dystonia, prolonged abnormal contractions of 
muscle groups, may occur in susceptible individuals during the first few days of treatment.  
Dystonic symptoms include spasm of the neck muscles, sometimes progressing to 
tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the 
tongue.  While these symptoms can occur at low doses, they occur more frequently at 
higher doses of first generation antipsychotic drugs. 
• Pseudoparkinsonism:  Symptoms may include mask-like facies, drooling, tremors, pill-
rolling motion, cogwheel rigidity, and shuffling gait. 
• Tardive Dyskinesia:  Tardive dyskinesia is a rare syndrome characterized by rhythmical 
involuntary movements of the tongue, face, mouth, or jaw (e.g., protrusion of tongue, 
puffing of cheeks, puckering of mouth, chewing movements).  These symptoms may be 
accompanied by involuntary movements of extremities.  In rare instances, these 
involuntary movements of the extremities are the only manifestations of tardive 
dyskinesia.  Symptoms may persist for months or years and, while they gradually 
disappear in some subjects, they may be irreversible in others.  The risk appears to be 
greatest in elderly subjects (especially women) on prolonged, high-dose therapy.  There is 
no known effective treatment for tardive dyskinesia.  It has been reported that fine 
vermicular movements of the tongue may be an early sign of the syndrome and if the 
medication is stopped at that time the syndrome may not develop.
• Adverse Reactions Reported with TFP or Other Phenothiazine Derivatives:  Adverse 
effects with different phenothiazines vary in type, frequency, and mechanism of 


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occurrence, i.e. some are dose-related, while others involve individual subject sensitivity.  
Some adverse effects may be more likely to occur, or occur with greater intensity, in 
subjects with special medical problems, e.g., subjects with mitral insufficiency or 
pheochromocytoma have experienced hypotension following recommended doses of 
certain phenothiazines. 
- Neuroleptic malignant syndrome (NMS) has been reported in association with 
antipsychotic drugs.  Cardinal features of NMS are hyperpyrexia, muscle rigidity, 
altered mental status (including catatonic signs), and evidence of autonomic instability 
(irregular pulse or blood pressure).  Additional signs may include elevated creatine 
phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.  NMS is 
potentially fatal and requires symptomatic treatment and immediate discontinuation of 
neuroleptic treatment.
- Not all of the following adverse reactions have been observed with every 
phenothiazine derivative, but they have been reported with one or more and should be 
borne in mind when drugs of this class are administered: extrapyramidal symptoms 
(opisthotonos, oculogyric crisis, hyperreflexia, dystonia, akathisia, dyskinesia, 
parkinsonism) some of which have lasted months and even years–particularly in 
elderly subjects with previous brain damage; grand mal and petit mal convulsions, 
particularly in subjects with electroencephalogram abnormalities or history of such 
disorders; altered cerebrospinal fluid proteins; cerebral edema; intensification and 
prolongation of the action of central nervous system depressants (opiates, analgesics, 
antihistamines, barbiturates, alcohol), atropine, heat, organophosphorus insecticides; 
autonomic reactions (dryness of mouth, nasal congestion, headache, nausea, 
constipation, obstipation, adynamic ileus, ejaculatory disorders/impotence, priapism, 
atonic colon, urinary retention, miosis and mydriasis); reactivation of psychotic 
processes, catatonic-like states; hypotension (sometimes fatal); cardiac arrest; blood 
dyscrasias (pancytopenia, thrombocytopenic purpura, leukopenia, agranulocytosis, 
eosinophilia, hemolytic anemia, aplastic anemia); liver damage (jaundice, biliary 
stasis); endocrine disturbances (hyperglycemia, hypoglycemia, glycosuria, lactation, 
galactorrhea, gynecomastia, menstrual irregularities, false-positive pregnancy tests); 
skin disorders (photosensitivity, itching, erythema, urticaria, eczema up to exfoliative 


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dermatitis); other allergic reactions (asthma, laryngeal edema, angioneurotic edema, 
anaphylactoid reactions); peripheral edema; reversed epinephrine effect; hyperpyrexia; 
increased appetite; increased weight; a systemic lupus erythematosus-like syndrome; 
pigmentary retinopathy; with prolonged administration of substantial doses, skin 
pigmentation, epithelial keratopathy, and lenticular and corneal deposits.
- Electrocardiogram changes, particularly nonspecific, usually reversible Q and T wave 
distortions, have been observed in some subjects receiving phenothiazine 
antipsychotics. 
There have been occasional reports of sudden death in subjects receiving phenothiazines.  In 
some cases, the cause appeared to be cardiac arrest or asphyxia due to failure of the cough 
reflex.
The effects of TFP on fertility or a fetus are not known. The side effects of TFP on newborns 
are also not known, therefore breastfeeding will not be allowed on the study. The subject will 
be removed from the study if she becomes pregnant during the study.
Adult subjects with DBA who are on chronic transfusion therapy may have iron overload 
despite iron chelation or due to non-compliance.  Iron overload can lead to liver dysfunction 
(liver function test elevations initially and eventual fibrosis and cirrhosis), cardiac dysfunction 
(arrhythmias and eventual heart failure), and endocrine dysfunction (hypothyroidism, diabetes 
mellitus, growth hormone deficiency, hypogonadism, premature ovarian failure, etc.).  If such 
dysfunction is documented but is adequately addressed, then these subjects will be eligible for 
this study.  If any of these potential side effects occur for the first time while on the subject is 
on the study drug, the event will be treated as an adverse event (AE).
Subjects with DBA have RBC aplasia, thus necessitating transfusion therapy.  As this is a 
bone marrow failure syndrome these subjects also can have other cytopenias including 
neutropenia and thrombocytopenia, and often pancytopenia (not necessarily consistent with 
aplastic anemia).  The eligibility criteria for entry into the study allow mild abnormalities in all 
the cell lines, but subjects with severe cytopenia are ineligible. 


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In the present study, TFP will be investigated in subjects with DBA over a lower dose range 
than is generally employed in subjects with schizophrenia.  The maximum anticipated daily 
dose will be 10 mg.  In contrast, the usual initial adult dose of TFP for schizophrenia is 2 to 5 
mg orally 2 times a day with a maintenance dose of 15 to 20 mg/day and a maximum dose of 
40 mg/day.  Therefore, more severe adverse reactions with TFP may be less likely to occur in 
the current study.
The only alternative to this treatment is not to participate in this trial. The subject will continue 
on transfusion therapy during this trial and be transfused every 3-4 weeks when the 
hemoglobin is less than 8 gm/dL as prior.
Given the serious potential side effects of chronic, often life-long transfusion therapy and the 
continuous need for chelation therapy, the risks of this short, 3-week study (plus 1 week 
follow-up) are reasonable for this subject population. The preliminary data from the zebrafish 
and mice models and information gained from this study will be proof-of-principle of the use 
of this drug in the treatment of DBA. If no significant toxicity to this drug is noted, the drug 
will be chemically altered as to not cross the blood-brain barrier and potentially be a viable 
treatment for DBA, without the untoward neurological side effects.    
11 Potential Benefit to Subjects
This is a safety study but the possible benefits from participation in this study include an 
improvement in the anemia of DBA and a decrease in the amount of transfusions needed by 
the subject. Since the study drug will be used for only 21 days, the risks to subjects are 
reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the 
knowledge that may reasonably be expected to result. If the study drug is safe then it would 
introduce a new class of therapeutic agents to this rare population.


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12 Research Related Harm/Injury
You will receive medical care and treatment as needed from Northwell Health. However, you 
will be responsible for the costs of such medical treatment, directly or through your medical 
insurance or other forms of medical coverage. No money will be given to you for participation 
in the study.
13 Provisions to Protect Privacy Interests of Subjects
There are over 750 subjects with Diamond Blackfan anemia enrolled in this Registry.  Because 
of this, the investigators have access to the specific subject population required for this study. 
Subjects contact the DBAR periodically to inquire about available studies. Also the 
announcement (Appendix G) informs potential subjects of the study and we anticipate the 
subjects calling us if they are interested in the study. The consent will be mailed to the subject 
or handed to the subject at an office visit. 
Once consented, subjects will be assigned a unique patient identification number (UPIN) that 
is used for entering data into the database. Protected health information (PHI) collected 
includes: name, address, contact numbers, email, and date of birth. Hard copies of study 
documents will be stored in a locked fireproof cabinet. Any research data that will be emailed 
will be encrypted. 
14 Statistical Plan
14.1
Sample Size Determination
This is a 4-Cohort, 3+3 study, and will therefore enroll a minimum of 3 patients and a 
maximum of 24 patients. Sample size power to detect a given effect does not apply.
14.2
Statistical Methods
All subjects who received at least one dose of study drug will be included for safety analysis. 
Demographics and baseline characteristics will be summarized by dose levels. 


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Primary Endpoint(s)

All AEs (including non-serious and serious) will be summarized.  Key laboratory 
results will be summarized using CTCAE grade.
Secondary Endpoint(s):

Not applicable.
14.3 Subject Population for Analysis
There is no randomization for this study. All enrolled subjects will be included in the study 
analysis for the primary endpoint.
15 Safety and Adverse Events (Appendix H)
15.1
Definitions
Adverse Event
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that 
may appear or worsen in a subject during the course of a study.  It may be a new 
intercurrent illness, a worsening concomitant illness, an injury, or any concomitant 
impairment of the subject’s health, including laboratory test values (as specified by the 
criteria below), regardless of etiology.  Any worsening (i.e., any clinically significant 
adverse change in the frequency or intensity) of a pre-existing condition should be 
considered an AE.  A diagnosis or syndrome should be recorded on the AE page of the case 
report forms (CRF) rather than the individual signs or symptoms of the diagnosis or 
syndrome. 
Abnormal results of diagnostic procedures are considered to be adverse events if the 
abnormality:

results in study withdrawal

is associated with a serious adverse event

is associated with clinical signs or symptoms

leads to additional treatment or to further diagnostic tests

is considered by the investigator to be of clinical significance
Serious Adverse Event


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A serious adverse event (SAE) is one that at any dose (including overdose):

Results in death

Is life-threatening1

Requires inpatient hospitalization or prolongation of existing hospitalization

Results in persistent or significant disability or incapacity2

Results in a congenital anomaly or birth defect

Is an important medical event3
Important medical events are those that may not be immediately life threatening, but are 
clearly of major clinical significance. They may jeopardize the subject, and may require 
intervention to prevent one of the other serious outcomes noted above.  
An overdose, accidental or intentional, whether or not it is associated with an AE, or abuse, 
withdrawal, sensitivity or toxicity to an investigational product should be reported as an 
AE.  If an overdose is associated with an AE, the overdose and adverse event should be 
reported as separate terms.
All subjects will be monitored for AEs during the study.  Assessments may include 
monitoring of any or all of the following parameters:  the subject’s clinical symptoms, 
laboratory, pathological, radiological or surgical findings, physical examination findings, or 
other appropriate tests and procedures.
Adverse Event Reporting Period
All AEs will be recorded by the Investigator from the time the subject signs informed 
consent to 7 days after the last dose (completion of the 4th week).  AEs and SAEs will be 
recorded on the AE page of the CRF and in the subject’s source documents.  All SAEs must 
be reported within 24 hours of the Investigator’s knowledge of the event by facsimile, or 
other appropriate method, using the SAE Report Form, or approved equivalent form.
Preexisting Condition
Any worsening (i.e., any clinically significant adverse change in the frequency or intensity) 
of a pre-existing condition should be considered an AE. 
General Physical Examination Findings
At screening, any clinically significant abnormality should be recorded as a preexisting 
condition.  At the end of the study, any new clinically significant findings/abnormalities 
that meet the definition of an adverse event must also be recorded and documented as an 
AE.
Post-study Adverse Event
                                                
1
“Life-threatening” means that the subject was at immediate risk of death at the time of the serious adverse event; it does not 
refer to a serious adverse event that hypothetically might have caused death if it were more severe.
2
“Persistent or significant disability or incapacity” means that there is a substantial disruption of a person’s ability to carry 
out normal life functions.
3
Medical and scientific judgment should be exercised in deciding whether expedited reporting is appropriate in situations 
where none of the outcomes listed above occurred.  Important medical events that may not be immediately life-threatening 
or result in death or hospitalization but may jeopardize the subject or may require intervention to prevent one of the other 
outcomes listed in the definition above should also usually be considered serious.  Examples of such events include allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions that do not 
result in patient hospitalization, or the development of drug dependency or drug abuse.  A new diagnosis of cancer during 
the course of a treatment should be considered as medically important.


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All unresolved AEs should be followed by the investigator until the events are resolved, the 
subject is lost to follow-up, or the AE is otherwise explained.  At the last scheduled visit, 
the investigator should instruct each subject to report any subsequent event(s) that the 
subject, or the subject’s personal physician, believes might reasonably be related to 
participation in this study.  The investigator should notify the study sponsor of any death or 
AE occurring at any time after a subject has discontinued or terminated study participation 
that may reasonably be related to this study.  
Abnormal Laboratory Values
A clinical laboratory abnormality should be documented as an AE if any one of the 
following conditions is met:

The laboratory abnormality is not otherwise refuted by a repeat test to confirm the 
abnormality

The abnormality suggests a disease and/or organ toxicity

The abnormality is of a degree that requires active management; e.g. change of 
dose, discontinuation of the drug, more frequent follow-up assessments, further 
diagnostic investigation, etc.
Hospitalization, Prolonged Hospitalization or Surgery
Any AE that results in hospitalization or prolonged hospitalization should be documented 
and reported as a SAE unless specifically instructed otherwise in this protocol.  Any 
condition responsible for surgery should be documented as an AE if the condition meets 
the criteria for an AE.
Neither the condition, hospitalization, prolonged hospitalization, nor surgery are reported 
as an AE in the following circumstances:

Hospitalization or prolonged hospitalization for diagnostic or elective surgical 
procedures for a preexisting condition.  Surgery should not be reported as an 
outcome of an AE if the purpose of the surgery was elective or diagnostic and the 
outcome was uneventful.

Hospitalization or prolonged hospitalization required to allow efficacy 
measurement for the study.

Hospitalization or prolonged hospitalization for therapy of the target disease of the 
study, unless it is a worsening or increase in frequency of hospital admissions as 
judged by the clinical investigator.
15.2
Recording of Adverse Events (Appendix H)
At each contact with the subject, the investigator must seek information on adverse events by 
specific questioning and, as appropriate, by examination.  Toxicity will be scored using the NCI 
CTCAE, Version 5.0.  A copy of the CTCAE, Version 5.0, can be downloaded from 
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_50. All 
appropriate treatment areas should have access to a copy of the CTCAE, Version 5.0. All adverse 
clinical experiences, whether observed by the investigator or reported by the subject, must be 
recorded, with details about the duration and intensity of each episode, the action taken with 
respect to the test drug, and the subject’s outcome.  The investigator must evaluate each adverse 
experience for its relationship to the test drug and for its seriousness.


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All AEs occurring during the study period must be recorded.  The clinical course of each event 
should be followed until resolution, stabilization, or until it has been determined that the study 
treatment or participation is not the cause.  Serious adverse events that are still ongoing at the 
end of the study period must be followed up to determine the final outcome.  Any SAE that 
occurs after the study period and is considered to be possibly related to the study treatment or 
study participation should be recorded and reported immediately.
The investigator must appraise all abnormal laboratory results for their clinical significance.  If 
any abnormal laboratory result is considered clinically significant, the investigator must provide 
details about the action taken with respect to the test drug and about the subject’s outcome.
15.3
Reporting of Serious Adverse Events
15.3.1
Study Sponsor Notification by Investigator
All SAEs must be reported within 24 hours of the Investigator’s knowledge of the event by 
facsimile, or other appropriate method, using the SAE Report Form, or approved equivalent 
form. The investigator will keep a copy of this SAE form on file at the study site.  Report 
SAEs by phone and facsimile to:
[Adrianna Vlachos, MD
516-562-1504
516-562-1599
At the time of the initial report, the following information should be provided:

Study identifier

Study center

Subject number

A description of the event

Date of onset

Current status

Whether study treatment was 
discontinued

The reason why the event is classified 
as serious

Investigator assessment of the 
association between the event and 
study treatment
Within the following 48 hours, the investigator must provide further information on the 
SAE in the form of a written narrative.  This should include a copy of the completed SAE
form, and any other diagnostic information that will assist the understanding of the event.  
Significant new information on ongoing SAEs should be provided promptly to the study 
sponsor.
15.3.2
IRB Notification by Investigator
The Principal Investigator is required to notify his/her Institutional Review Board (IRB) of 
a SAE according to institutional policy.  Copies of each report and documentation of IRB 
notification and receipt will be kept in the Clinical Investigator’s binder.
15.3.3
FDA Notification by Sponsor
SAEs that are unlisted/unexpected, and at least possibly associated to the drug, and that 
have not previously been reported in the Investigators’ brochure, or reference safety
information document should be reported promptly to the FDA by telephone or by fax.  


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The study sponsor shall notify the FDA by telephone or by facsimile transmission of any 
unexpected fatal or life-threatening experience associated with the use of the drug as soon 
as possible but no later than 7 calendar days from the sponsor’s original receipt of the 
information.
All other SAEs that meet the criteria for reporting to the FDA must be reported to the FDA 
within 15 calendar days after awareness of the event.  A clear description of the suspected 
reaction should be provided along with an assessment as to whether the event is drug or 
disease related. 
15.4 Stopping Rules 
The stopping rules are as follows:
Scenario 1:  The occurrence of extrapyramidal symptoms, symptoms suggestive of 
tardive dyskinesia (including vermicular movements of the tongue), neuroleptic 
malignant syndrome or any SAE or treatment-emergent AE Grade 3 felt to be 
causally related to TFP in a single subject:

Rule:  Treatment will be immediately stopped in that subject and the subject
will be discontinued from the study.
Scenario 2:  The occurrence of the extrapyramidal symptoms, symptoms suggestive of 
tardive dyskinesia (including vermicular movements of the tongue), neuroleptic 
malignant syndrome or the same SAE or treatment-emergent AE Grade 3 felt to be 
causally related to TFP in more than 1 subject:

Rules:
a.
Treatment will be immediately stopped in those subjects and those subjects 
will be discontinued from the study.
b. If the 2 or more subjects are in Cohort A, the trial will be stopped; no MTD 
will be declared.
c.
If the 2 or more subjects are in Cohort B, the study will be stopped, and 1 
mg/day will be declared the MTD. 


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15.5
Medical Monitoring
It is the responsibility of the Principal Investigator to oversee the safety of the study at his/her 
site. This safety monitoring will include careful assessment and appropriate reporting of adverse 
events as noted above, as well as the construction and implementation of a site data and safety
monitoring plan (see Section 17 Auditing, Monitoring and Inspecting).  Medical monitoring will 
include a regular assessment of the number and type of SAEs.
15.6
Data and Safety Monitoring 
The medical monitor will serve as the monitoring entity for this study.  The monitor will be a 
qualified physician, other than the Principal Investigator, who is not associated with the 
protocol, and will monitor the study to protect the safety and well-being of the subjects.  The 
medical monitor plays a role in reviewing serious adverse events and unanticipated problems.
d. If the 2 or more subjects are in Cohort C, the study will be stopped, and 2 
mg/day will be declared the MTD. 
e.
If the 2 or more subjects are in Cohort D, the study will be stopped, and 5 
mg/day will be declared the MTD. 
Scenario 3:  Hemoglobin > 12 mg/dL in a subject sustained for more than 7 days (not 
associated with RBC transfusion)

Rule:  The subject will be considered a complete responder, treatment will be 
discontinued, and the duration of the effect will be monitored until day 29 after 
start of treatment.
In addition to the stopping rules, a subject may be discontinued by the investigator at any time 
for failure to comply with protocol requirements, in the event that the investigator feels that 
continuation in the study poses a risk to the health of the subject, or if the subject withdraws 
consent.
The reason for treatment discontinuation must be documented in the subject chart / source 
records.
The trial will be stopped, as noted above, if more than one subject experiences the occurrence 
of the extrapyramidal symptoms, symptoms suggestive of tardive dyskinesia, neuroleptic 
malignant syndrome, the same SAE or treatment-emergent AE Grade 3 felt to be causally 
related to TFP at the lowest dose level.


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The physician will not be involved with the conduct of the study, but will serve as a 
hematology consultant.  
For this study Dr. Lawrence Wolfe has been selected as the Medical Monitor. He has served in 
this role in a prior DBA clinical study. He is the Deputy Chief, Operations and Safety, in the 
Division of Hematology/Oncology and Stem Cell Transplantation at Cohen Children’s 
Medical Center and as such meets the criteria stated above.
Summary data related to the study will be provided to the medical monitor in written form.  
The following materials will be provided:  a report of all deaths, a summary of cumulative 
adverse event data with intervention causality, a summary of assessment of conduct of the 
study (e.g. site enrollment, subject enrollment (target vs. actual), protocol compliance per site, 
informed consent records, treatment received), and a summary of assessment to evaluate 
factors that may impact on the safety of study subjects.
Adverse Event (AE) Data:  The frequencies of each type of AE will be tabulated and the 
incidence rate will computed as the percentage of subjects experiencing that AE at some time 
during the course of the trial. These intervals will be used by the medical monitor for 
determining whether a particular AE or class of AEs should be “flagged” for safety concerns.
Severe AE/Major Protocol Deviation: Should any major or serious adverse event or protocol 
deviation occur that requires rapid action, the Sponsor-Investigator will notify the IRB, and 
FDA by telephone, and in writing within 24 hours.
Meeting Schedule: The medical monitor will review the data quarterly, or as necessary for 
major infractions of protocol or SAEs.  Meetings may be by telephone.
Reports from the Medical Monitor:  After the Medical Monitor meets, a written summary of 
the meeting will be provided to the Sponsor-Investigator.  The summary will include: 
•
Date that the meeting took place 
•
Summary of cumulative adverse event data
•
Recommendations 
Distribution of Report:  The Sponsor-Investigator will distribute the report to the Northwell 
IRB and all co-investigators, and the FDA.
16 Data Handling and Record Keeping
16.1 Confidentiality
Information about study subjects will be kept confidential and managed according to the 
requirements of the Health Insurance Portability and Accountability Act of 1996 (HIPAA).  
Those regulations require a signed subject authorization informing the subject of the following: 

What protected health information (PHI) will be collected from subjects in this study

Who will have access to that information and why


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
Who will use or disclose that information

The rights of a research subject to revoke their authorization for use of their PHI. 
In the event that a subject revokes authorization to collect or use PHI, the investigator, by 
regulation, retains the ability to use all information collected prior to the revocation of subject 
authorization.  For subjects that have revoked authorization to collect or use PHI, attempts 
should be made to obtain permission to collect at least vital status (i.e. that the subject is alive) at 
the end of their scheduled study period.
16.2 Source Documents
Source data is all information, original records of clinical findings, observations, or other 
activities in a clinical trial necessary for the reconstruction and evaluation of the trial.  Source 
data are contained in source documents.   Examples of these original documents, and data 
records include: hospital records, clinical and office charts, laboratory notes, memoranda, 
subjects’ diaries or evaluation checklists, pharmacy dispensing records, recorded data from 
automated instruments, copies or transcriptions certified after verification as being accurate and 
complete, microfiches, photographic negatives, microfilm or magnetic media, x-rays, subject 
files, and records kept at the pharmacy, at the laboratories, and at medico-technical departments 
involved in the clinical trial.
16.3 Case Report Forms
The study case report form (CRF) is the primary data collection instrument for the study.  All 
data requested on the CRF must be recorded.  All missing data must be explained.  If a space on 
the CRF is left blank because the procedure was not done or the question was not asked, write 
“N/D”.  If the item is not applicable to the individual case, write “N/A”.  All entries should be 
printed legibly in black ink.  If any entry error has been made, to correct such an error, draw a 
single straight line through the incorrect entry and enter the correct data above it.  All such 
changes must be initialed and dated.  DO NOT ERASE OR WHITE OUT ERRORS.  For 
clarification of illegible or uncertain entries, print the clarification above the item, then initial and 
date it.
16.4 Records Retention
It is the Investigator’s responsibility to retain study essential documents for at least 2 years after 
the last approval of a marketing application in their country and until there are no pending or 
contemplated marketing applications in their country or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the investigational product.  These documents 
should be retained for a longer period if required by an agreement with the sponsor.  In such an 
instance, it is the responsibility of the sponsor to inform the investigator/institution as to when 
these documents no longer need to be retained. 
17 Study Monitoring, Auditing, and Inspecting
17.1 Study Monitoring Plan
This study will be monitored according to the study monitoring plan in Appendix I.  The
Investigator will allocate adequate time for such monitoring activities.  The Investigator will also 


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ensure that the monitor or other compliance or quality assurance reviewer is given access to all 
the above noted study-related documents and study related facilities (e.g. pharmacy, diagnostic 
laboratory, etc.), and has adequate space to conduct the monitoring visit.
17.2 Auditing and Inspecting
The Investigator will permit study-related monitoring, audits, and inspections by the IRB, the 
sponsor, government regulatory bodies, and University compliance and quality assurance groups 
of all study related documents (e.g. source documents, regulatory documents, data collection 
instruments, study data etc.).  The Investigator will ensure the capability for inspections of 
applicable study-related facilities (e.g. pharmacy, diagnostic laboratory, etc.).
Participation as an Investigator in this study implies acceptance of potential inspection by 
government regulatory authorities and applicable University compliance and quality assurance 
offices.
18 Ethical Considerations
This study is to be conducted according to US and international standards of Good Clinical 
Practice (FDA Title 21 part 312 and International Conference on Harmonization guidelines), 
applicable government regulations and Institutional research policies and procedures.
This protocol and any amendments will be submitted to a properly constituted independent 
Ethics Committee (EC) or Institutional Review Board (IRB), in agreement with local legal 
prescriptions, for formal approval of the study conduct.  The decision of the EC/IRB concerning 
the conduct of the study will be made in writing to the Investigator and a copy of this decision 
will be provided to the sponsor before commencement of this study.  The Investigator should 
provide a list of EC/IRB members and their affiliate to the sponsor.
All subjects for this study will be provided a consent form describing this study and providing 
sufficient information for subjects to make an informed decision about their participation in this 
study. This consent form will be submitted with the protocol for review and approval by the IRB 
for the study.  The formal consent of a subject, using the IRB-approved consent form, must be 
obtained before that subject is submitted to any study procedure. This consent form must be 
signed by the subject or legally acceptable surrogate, and the investigator-designated research 
professional obtaining the consent. 
19 Study Finances
19.1 Funding Source
Funding for this research study is provided by CAMP4 Therapeutics and the National 
Institutes of Health National Heart, Lung, and Blood Institute. Study related travel costs will 
be offset by the National Organization of Rare Diseases (NORD) so that subjects will not 
incur any additional costs as a result of participating in this trial.   


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19.2 Conflict of Interest
Any investigator who has a conflict of interest with this study (patent ownership, royalties, or 
financial gain greater than the minimum allowable by their institution, etc.) must have the 
conflict reviewed by a properly constituted Conflict of Interest Committee with a Committee-
sanctioned conflict management plan that has been reviewed and approved by the study sponsor 
prior to participation in this study.  All Northwell Health investigators will follow the University 
conflict of interest policy.
20 Publication Plan
Neither the complete nor any part of the results of the study carried out under this protocol, nor 
any of the information provided by the sponsor for the purposes of performing the study, will be 
published or passed on to any third party without the consent of the study sponsor.  Any 
investigator involved with this study is obligated to provide the sponsor with complete test 
results and all data derived from the study.


Version 5
CONFIDENTIAL
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14OCT2020
21 References
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Response of Diamond-Blackfan anemia to metoclopramide: evidence for a role for 
prolactin in erythropoiesis. Blood. 2002;100:2687-2691.
3. Alter BP, Modell CB, Fairweather D, Hobbins JC, Mahoney MJ, Frigoletto FD, 3et al. 
Prenatal diagnosis of hemoglobinopathies. A review of 15 cases. N Engl J Med. 
1976;295(26):1437-43.
4. Bastion Y, Bordigoni P, Debré M, Girault D, Leblanc T, Tchernia G, et al. Sustained 
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5. Chakraborty A, Uechi T, Higa S, Torihara H, Kenmochi N. Loss of ribosomal protein 
L11 affects zebrafish embryonic development through a p53-dependent apoptotic 
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6. Cmejla R, Cmejlova J, Handrkova H, Petrak J, Pospisilova D. Ribosomal protein S17 
gene (RPS17) is mutated in Diamond-Blackfan anemia. Hum Mutat. 2007;28(12):1178-
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7. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. 
Nephron. 1976;16(1):31-41.
8. Da Costa L, Moniz H, Simansour M, Tchernia G, Mohandas N, Leblanc T. Diamond-
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9. Danilova A, Torihara H, Kenmochi N. Loss of ribosomal protein L11 affects zebrafish 
embryonic development through a p53-dependent apoptotic response. PLoS One. 
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10. Danilova N, Sakamoto KM, Lin S. Ribosomal protein L11 mutation in zebrafish leads to 
haematopoietic and metabolic defects. Br J Haematol. 2011;152:217–228.


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11. Doherty L, Sheen MR, Vlachos A, Choesmel V, O'Donohue MF, Clinton C, et al. 
Ribosomal protein genes RPS10 and RPS26 are commonly mutated in Diamond-
Blackfan anemia. Am J Hum Genet. 2010;86(2):222-8.
12. Draptchinskaia N, Gustavsson P, Andersson B, Pettersson M, Willig TN, Dianzani I, et 
al. The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia. 
Nat Genet. 1999;21(2):169-75.
13. Drugs.com. Product monograph for trifluoperazine. Available at:  
https://www.drugs.com/monograph/trifluoperazine-hydrochloride.html. Accessed 
28 September, 2016.
14. Farrar JE, Nater M, Caywood E, McDevitt MA, Kowalski J, Takemoto CM, et al. 
Abnormalities of the large ribosomal subunit protein, Rpl35a, in Diamond-Blackfan 
anemia. Blood. 2008;112(5):1582-92.
15. Fumagalli S, Di Cara A, Neb-Gulati A, Natt F, Schwemberger S, Hall J, et al. Absence of 
nucleolar disruption after impairment of 40S ribosome biogenesis reveals an rpL11-
translation-dependent mechanism of p53 induction. Nat Cell Biol. 2009;11:501–508.
16. Gale RP, Barosi G, Barbui T, Cervantes F, Dohner K, Dupriez B, et. al. What are RBC-
transfusion-dependence and –independence. Leuk Res. 2011;35(1):8-11. 
17. Gazda HT, Grabowska A, Merida-Long LB, Latawiec E, Schneider HE, Lipton JM, et al. 
Ribosomal protein S24 gene is mutated in Diamond-Blackfan anemia. Am J Hum Genet.
2006;79(6):1110-8.
18. Gazda HT, Sheen MR, Vlachos A, Choesmel V, O'Donohue MF, Schneider H, et al. 
Ribosomal protein L5 and L11 mutations are associated with cleft palate and abnormal 
thumbs in Diamond-Blackfan anemia subjects. Am J Hum Genet. 2008;83(6):769-80.
19. Glader BE, Backer K, Diamond LK. Elevated erythrocyte adenosine deaminase activity 
in congenital hypoplastic anemia. N Engl J Med. 1983; 309(24):1486-90.
20. Gustavsson P, Skeppner G, Johansson B, Berg T, Gordon L, Kreuger A, Dahl N. 
Diamond-Blackfan anaemia in a girl with a de novo balanced reciprocal X;19 
translocation. J Med Genet. 1997;34:779-782.


Page 46 of 62
21. Jones NC, Lynn ML, Gaudenz K, Sakai D, Aoto K, Rey JP, et al. Prevention of the 
neurocristopathy Treacher Collins syndrome through inhibition of p53 function. Nat 
Med. 2008;14:125–133.
22. Koch K, Mansi K, Haynes E, Adams CE, Sampson S, Furtado VA. Trifluoperazine
versus placebo for schizophrenia. Cochrane Database Syst Rev. 2014;(1) Art. No.: 
CD010226.
23. Leblanc TM, Da Costa L, Marie I, Demolis P, Tchernia G. Metoclopramide treatment in 
DBA subjects: no complete response in a French prospective study. Blood. 
2007;109:2266-2267.
24. Lipton JM, Atsidaftos E, Zyskind I, Vlachos A.  Improving clinical care and elucidating 
the pathophysiology of Diamond Blackfan anemia: an update from the Diamond 
Blackfan Anemia Registry. Pediatr Blood Cancer. 2006;46(5):558-64.
25. Lipton JM, Kudisch M, Gross R, Nathan DG. Defective erythroid progenitor 
differentiation system in congenital hypoplastic (Diamond-Blackfan) anemia. Blood. 
1986;67(4):962-8.
26. Luke DR, Halstenson CE, Opsahl JA, Matzke GR. Validity of creatinine clearance 
estimates in the assessment of renal function. Clin Pharmacol Ther. 1990 Nov;48(5):503-
8.
27. Macari ER, Taylor AM, Raiser DM, Siva K, McGrath K, Humphries JM, et al. 
Calmodulin inhibition rescues the effects of ribosomal protein deficiency in in vitro and 
in vivo Diamond Blackfan anemia models. Blood. 2015;126:672.
28. Macari ER, Taylor AM, Raiser D, Siva K, McGrath K, Humphries JM, et al. Calmodulin 
inhibition rescues DBA models with ribosomal protein deficiency through reduction of 
RSK signaling. Blood. 2016;128(22):332. 
29. McGowan KA, Li JZ, Park CY, Beaudry V, Tabor HK, Sabnis AJ, et al. Ribosomal 
mutations cause p53-mediated dark skin and pleiotropic effects. Nat Genet. 2008;40:963–
70.


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30. Medicines and Healthcare Products Regulatory Agency (MHRA) Public Assessment 
Report (PAR). Trifluoperazine 1mg and 5 mg Tablets (Trifluoperazine Hydrochloride) 
PL 08553/0097-8, 2006.
31. Mendels J, Krajewski TF, Huffer V, Taylor RJ, Secunda S, Schless A, Sebastian JA, 
Semchyshyn G, Durr MJ, Melmed AS, et al. Effective short-term treatment of
generalized anxiety disorder with trifluoperazine. J Clin Psychiatry. 1986 Apr;47(4):170-
4.
32. Midha KK, Korchinski ED, Verbeeck RK, Roscoe RM, Hawes EM, Cooper JK, McKay 
G. Kinetics of oral trifluoperazine disposition in man. Br J Clin Pharmacol. 
1983;15(3):380-2.
33. Montague TG, Cruz JM, Gagnon JA, Church GM, Valen E. CHOPCHOP: a 
CRISPR/Cas9 and TALEN web tool for genome editing. Nucleic Acids Res. 
2014;42(Web Server issue):W401-7.
34. Rudy LH, Rinaldi F, Costa E, Himwich HE, Tuteur W, GLotzer J. Trifluoperazine in the 
treatment of psychotic patients. Am J Psychiatry. 1958;115(4):364-5.
35. Taylor AM, Humphries JM, White RM, Murphey RD, Burns CE, Zon LI. Hematopoietic
defects in rps29 mutant zebrafish depend upon p53 activation. Exp Hematol. 
2012;40(3):228-237.e5.
36. Vlachos A, Federman N, Reyes-Haley C, Abramson J, Lipton JM. Hematopoietic stem 
cell transplantation for Diamond Blackfan anemia: a report from the Diamond Blackfan 
Anemia Registry. Bone Marrow Transplant. 2001 Feb;27(4):381-6.
37. Vlachos A, Klein GW, Lipton JM. The Diamond Blackfan Anemia Registry: tool for 
investigating the epidemiology and biology of Diamond-Blackfan anemia. J Pediatr 
Hematol Oncol. 2001 Aug-Sep;23(6):377-82.
38. Vlachos A, Ball S, Dahl N, Alter BP, Sheth S, Ramenghi U, et al., Diagnosing and 
treating Diamond Blackfan anaemia: results of an international clinical consensus 
conference. Br J Haematol 2008;142(6):859-76.


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39. Vlachos A, Blanc L, Lipton JM. Diamond Blackfan anemia: a model for the translational 
approach to understanding human disease. Expert Rev Hematol. 2014 Jun;7(3):359-72.
40. Zu Y, Tong X, Wang Z, Liu D, Pan R, Li Z, et al. TALEN-mediated precise genome 
modification by homologous recombination in zebrafish. Nat Methods 2013;10(4):329-
31.


Version 5
CONFIDENTIAL
Page 49 of 62
14OCT2020
22 Appendices
22.1
Appendix A - Study Assessment Schedule
22.2
Appendix B - Diamond Blackfan Anemia Diagnostic Criteria
22.3
Appendix C - Definitions of RBC-Transfusion-Dependence and              
-Independence
22.4
Appendix D - Cockcroft-Gault Estimation of Creatinine Clearance
22.5
Appendix E - Karnofsky Performance Status Scale
22.6
Appendix F - New York Heart Association – Classification of Heart 
Failure
22.7
Appendix G - Study Announcement
22.8
Appendix H - Side Effects Grading and Reporting
22.9
Appendix I - Study Monitoring Plan
22.10 Appendix J - Blood for Pharmacodynamic Disease Marker Analysis


Version 5
CONFIDENTIAL
Page 50 of 62
14OCT2020
22.1 Appendix A: Study Assessment Schedule
Screening
Period
Treatment Period
Follow-Up
Screening
Visit 1
Visit 2
Visit 3
Visit 4
Day -28 to 
Day -1
Day 1a
(±1d)
Day 11
(±1d)
Day 22
(±2d)
Day 29
(±2d)
Obtain subject informed 
consent form

-
-
-
-
Assess inclusion/
exclusion criteria

-
-
-
-
Obtain medical subject
history

-
-
-
-
Record prior treatments 
and procedures 
(including transfusion 
history)

-
-
-
-
Physical examination 
(including height at 1st
visit only, weight, vital 
signs, blood pressure and 
neurological 
examination)





Karnofsky performance 
status (Appendix E)




-
Hematology b,*





Blood chemistry, hepatic 
function, kidney function
c,*





Blood for 
pharmacodynamic  
disease marker analysis 
(Appendix J)d
-



-
Menstrual status




-
Pregnancy test e,*



-
-
Transfusion assessment f





Adverse events
-




Concomitant therapies 
/procedures 
-



-
Provide study drug (21-
day supply)
-

-
-
-


Page 51 of 62
22.1 Appendix A continued
*Historical clinical laboratory evaluations performed for medical evaluation within 28 days are acceptable for study entry.
a:
All Day 1 assessments are to be done prior to TFP administration. TFP should be initiated within 7 days following a blood 
transfusion.
b:
Hematology laboratory evaluations (RBC count, hemoglobin, hematocrit, absolute reticulocyte count, white blood cell 
count, absolute neutrophil count, and platelet count) will be collected at Screening and at subsequent visits during the 
Treatment and Follow-Up Periods, as referenced in the schedule above.  Any laboratory evaluations may be repeated more 
frequently if clinically indicated.
c:
Serum chemistry laboratory evaluations (blood urea nitrogen, creatinine, bilirubin [total and direct], aspartate 
aminotransferase [AST], alanine aminotransferase [ALT]) will be collected at Screening and at subsequent visits during the 
Treatment and Follow-Up Periods, as referenced in the schedule above.  Any laboratory evaluations may be repeated more 
frequently if clinically indicated.
d:
Blood for pharmacodynamic disease marker analysis will be shipped to supporting company (see Appendix F).
e:
Females of childbearing potential:  A female of childbearing potential is a sexually mature woman who has not undergone a 
hysterectomy or who has not been postmenopausal for at least 24 consecutive months (i.e., who has had menses at some 
time in the preceding 24 months).  A serum pregnancy test (which must be negative) must be performed not more than 3 
days from the start of TFP administration (Study Day 1).  Subjects must agree to use highly effective methods of birth 
control during study participation and for at least 1 week following the last dose of TFP.  Subjects must be counseled 
concerning measures to be used to prevent pregnancy and potential toxicities prior to the first dose of TFP.  Serum 
pregnancy tests will be performed according to the above schedule during study participation.  
f:
Subjects must have documented transfusion history for > 12 weeks before inclusion/initiation of treatment.


Version 5
CONFIDENTIAL
Page 52 of 62
14OCT2020
22.2 Appendix B: Diamond Blackfan Anemia Diagnostic Criteria
Diagnostic Criteria

Age less than 1 year

Macrocytic anemia with no other significant cytopenias

Reticulocytopenia

Normal marrow cellularity with a paucity of erythroid precursors
Supporting Criteria
Major

Ribosomal protein gene mutation described in “classical” DBA

Positive family history
Minor

Elevated erythrocyte adenosine deaminase activity

Congenital anomalies described in “classical” DBA

Elevated fetal hemoglobin

No evidence of another inherited bone marrow failure syndrome
A diagnosis of “classical” DBA is made if all the diagnostic criteria are met.  When there is a 
positive family history, an otherwise normal individual should be considered as having “non-
classical” DBA if a mutation shared by affected family members is present.  Anyone suspected 
of having DBA, but with insufficient diagnostic criteria, should be considered as having non-
classical DBA if a reported mutation is present.  A subject can be assigned as having a 
“probable” diagnosis, with a decreasing degree of certitude if: 

3 diagnostic criteria are present along with a positive family history; 

2 diagnostic criteria and 3 minor supporting criteria are present; or, 

positive family history and 3 minor supporting criteria are evident, even in the absence of 
diagnostic criteria.    


Page 53 of 62
22.3 Appendix C: Definitions of RBC-Transfusion-Dependence and              
-Independence
RBC transfusions
Hb 
(gm/dL)
Surveillance 
Interval
RBC transfusion dependence
10 cc/kg/month
Or 2 units/month for 
subjects >50 kg
< 8
6 months
RBC transfusion independence
None
> 9
6 months


Page 54 of 62
22.4 Appendix D: Cockcroft-Gault Estimation of Creatinine Clearance
Cockcroft-Gault estimation of creatinine clearance (CrCl) (Cockcroft, 1976; Luke 1990): 
CrCl (mL/min) = 
    (140 –age) x (weight, kg)__
(Males)
72 x (serum creatinine, mg/dL)
CrCl (mL/min) = 
    (140 –age) x (weight, kg)_   x 0.85
(Females)
72 x (serum creatinine, mg/dL)


Page 55 of 62
22.5 Appendix E: Karnofsky Performance Status Scale
The Karnofsky Performance Scale Index allows subjects to be classified as to their functional 
impairment. This can be used to compare effectiveness of different therapies and to assess the 
prognosis in individual subjects. 
%
Criterion
100
Normal; no complaints; no evidence of disease
90
Able to carry on normal activity; minor signs or symptoms of disease
80
Normal activity with effort; some signs or symptoms of disease
70
Cares for self; unable to carry on normal activity or do active work
60
Requires occasional assistance but is able to care for most of his/her needs
50
Requires considerable assistance and frequent medical care
40
Disabled, requires special care and assistance
30
Severely disabled; hospitalization is indicated though death is not imminent
20
Very sick; hospitalization is necessary
10
Moribund; fatal processes progressing rapidly
0
Dead
References:
Crooks, V, Waller S, et al. The use of the Karnofsky Performance Scale in determining outcomes 
and risk in geriatric outsubjects. J Gerontol. 1991; 46: M139-M144.
de Haan R, Aaronson A, et al. Measuring quality of life in stroke. Stroke. 1993; 24:320- 327.
Hollen PJ, Gralla RJ, et al. Measurement of quality of life in subjects with lung cancer in 
multicenter trials of new therapies. Cancer. 1994; 73: 2087-2098.
O'Toole DM, Golden AM. Evaluating cancer subjects for rehabilitation potential. West J Med. 
1991; 155:384-387.
Oxford Textbook of Palliative Medicine, Oxford University Press. 1993;109.
Schag CC, Heinrich RL, Ganz PA. Karnofsky performance status revisited: Reliability, validity, 
and guidelines. J Clin Oncology. 1984; 2:187-193.


Page 56 of 62
22.6 Appendix F: New York Heart Association – Classification of 
Heart Failure
Class
Symptoms
Class 1
No limitation of activities.  No symptoms from ordinary activities
Class 2
Mild limitation of activity.  Comfortable with rest or mild exertion
Class 3
Marked limitation of activity and be comfortable only at rest
Class 4
Complete rest, confined to bed or chair; any physical activity brings on 
discomfort and symptoms occur at rest


Page 57 of 62
22.7 Appendix G: Study Announcement
The Feinstein Institute for Medical Research and Cohen Children’s Medical Center Announce a 
Clinical Trial of Trifluoperazine for Transfusion-Dependent Adult Patients with Diamond 
Blackfan Anemia
Dear DBA Patients and Families: 
We are pleased to announce the opening of:
“Phase I/II, Open-Label Study to Determine Safety of Trifluoperazine (TFP) in Adults with 
Red Blood Cell Transfusion-Dependent Diamond Blackfan Anemia”
    
Diamond Blackfan Anemia (DBA) is a rare pure red cell anemia resulting from a failure of the 
bone marrow to make red blood cells. The anemia may present in infancy, in childhood, or 
occasionally in adulthood.  For some patients a genetic cause for DBA can be found but for 
others no known genetic mutation is known at this time. Some patients have little or no anemia 
after treatment with steroids, whereas others may need continuous red blood cell transfusions or 
steroid therapy for a long time, sometimes for life. Steroids may control DBA in many patients at 
first, but after some time, the steroids may not work as well anymore. Unfortunately red cell 
transfusions have many possible negative side effects, such as iron overload. Iron overload can 
occur in the liver, heart, and endocrine organs which can cause more complicated health 
problems such as liver or heart failure, diabetes, thyroid issues, gonadal dysfunction, etc. 
Purpose of this study
The purpose of this study is to find an alternative treatment for patients with DBA who are 
dependent upon transfusions. This study will use a medication called trifluoperazine (TFP) and 
determine if it is safe for the treatment of DBA in adult patients who require chronic blood 
transfusions. This is a research study because TFP has never been tested in patients with DBA. 
TFP is a drug that has been approved by the Food and Drug Administration (FDA) for the 
treatment of psychiatric disorders. TFP has not been previously approved by the FDA for 
treatment of DBA. In this research study the safety of TFP is being tested at different dose levels 
in patients with DBA.  A total of 24 patients with DBA may be enrolled on this study. 
About the study drug, Trifluoperazine or TFP 
TFP is a typical oral antipsychotic medication that has been used for the treatment of psychiatric 
patients since 1958.  In the United States, TFP is approved for the short-term treatment of 
anxiety; treatment or prevention of nausea and vomiting of various causes; and management of 
psychotic disorders.  In part because of its side effect profile, TFP has been largely replaced by 
second and third generation anti-psychotic medications.  Nevertheless, TFP remains 
commercially available worldwide and the risks associated with its use are well understood and 
generally manageable.
Description of procedure
The study is 29 days long and consists of taking the study drug TFP for 21 days and being 
monitored for an additional 8 days. The patient will have a total of 4 visits over the period of 29 
days. A review of the patient’s history, physical examination, and laboratory blood work will be 


Page 58 of 62
done in order to determine if the patient is eligible to participate. While the patient is taking the 
TFP, he or she will need to be seen at The Feinstein Institutes for Medical Research or the 
participating institution 3 times over the first 21 days and virtually for the last visit. During the
first 21 days the patient will be taking TFP once a day, orally as a tablet, and will continue the 
red blood cell transfusions as routinely scheduled, every 3-4 weeks.  
The following are some of the basic inclusion and exclusion criteria for this pilot trial.
Inclusion Criteria
- Diagnostic and supporting criteria for the diagnosis of DBA
- Transfusion dependence every 3-4 weeks
- Age greater than or equal to 18 years and less than 65 years
- Weight greater than or equal to 45 kilograms or 99 lbs                                                                    
- Negative pregnancy test  
- Signed informed consent 
Exclusion Criteria
- Have a known allergy to TFP or other phenothiazines (class of drugs including TFP)
- Evidence of kidney or liver dysfunction
- Evidence of heart disease or history of angina
- Uncontrolled high blood pressure
- Pregnancy, or plans to become pregnant during duration of trial  
- History of cancer
Please refer to the website link: http://www.clinicaltrials.gov and enter the search term 
“Diamond-Blackfan Anemia and trifluoperazine” for full eligibility criteria and additional trial 
information.
CONTACT INFORMATION
Principal Investigator:
Adrianna Vlachos, MD
Feinstein Institutes for Medical Research/Cohen Children’s Medical Center of NY
Scientific Co-Investigators:
Jeffrey M. Lipton, MD, PhD
Feinstein Institutes for Medical Research/Cohen Children’s Medical Center of NY 
Please contact Eva Atsidaftos:
TEL: 877-322-6877 or 516-562-1505
FAX: 516-562-1599
Email: eatsidaf@northwell.edu
Also, feel free to contact Dr. Vlachos by email: avlachos@northwell.edu.


Page 59 of 62
22.8 Appendix H: Side Effects Grading and Reporting
Side effects will be graded according to the NCI-CTCAE (version 5).
Link for NCI-CTCAE version 5:  
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_50


Page 60 of 62
22.9 Appendix I: Clinical Trial Services Study Monitoring Plan
Services Provided to:
Adrianna Vlachos, MD 
Regulatory Sponsor (IND#TBD)
Feinstein Institutes for Medical Research
Pediatric Hematology/Oncology
350 Community Drive
Manhasset, NY  11030
Services Provided for:
Phase I/II, Open-Label Study to Determine Safety of 
Trifluoperazine (TFP) in Adults with Red Blood Cell Transfusion-
Dependent Diamond Blackfan Anemia
Performance Sites:
Feinstein Institutes for Medical Research/Cohen Children’s 
Medical Center 
Services Provided by:
The Office of Research Compliance
Regulatory Affairs Division
Northwell Health
3333 New Hyde Park Rd., Suite 317
New Hyde Park, NY 11042
Scope of Services
The Office of Research Compliance (ORC) will provide clinical research monitoring services as 
outlined in the Risk Based Monitoring Plan for all subjects to be enrolled in this protocol at the 
above referenced performance site to include the general areas:

Good Clinical Practice Regulatory Review

Subject Case Review of Critical Study Data and Processes Including:
o
Case Report Form Completion and Source Document Verification
o
Protocol and Informed Consent Compliance

Protocol Drug Accountability
In addition the ORC will provide regulatory consultative services to the research team in addition 
to training in Good Clinical Practice (GCP) requirements for all participating site personnel.   
Review Schedule
The ORC agrees to provide primarily remote monitoring services for all performance sites 
including the following:

Site Initiation: Prior to study start-up for GCP and protocol overview

Routine monitoring: Occurs annually with the frequency outlined in the monitoring plan 
as long as the site continues to enroll subjects. However, additional visits may be 
performed for targeted reviews as required. 

Final monitoring: Study close out 


Page 61 of 62
Post-monitoring activities include follow-up with site for additional information required to 
complete monitoring, resolution of issues and report writing.
Reporting
Regular monitoring reports will be generated by the ORC after each review and will be provided 
to the respective performance site and Sponsor-Investigator and Data Coordinator.  Resolution of 
queries and outstanding issues or concerns will be the responsibility of the individual 
performance site, Sponsor-Investigator, and Data Coordinator.
The Northwell Sponsor-Investigator will be responsible for reporting incidents of IRB non-
compliance to the Northwell Human Research Protection Program (HRPP) (in compliance with 
regulations on the protection of human subjects and institutional policy and procedures) and 
responsible for securing compliance at all trials sites.


Page 62 of 62
22.10 Appendix J: Blood for Pharmacodynamic Disease 
MarkerAnalysis
Descriptive pilot laboratory investigations will be performed to explore assay feasibility for 
TFP target engagement. Samples from each subject will be collected to study the 
pharmacodynamic effect of the drug TFP. Ten mL whole blood will be collected in EDTA 
(lavender) tubes prior to start of drug administration and at each visit of treatment for a total 
of 3 samples per subject. The sample will be used to isolate CD34+ cells (precursors for 
erythrocytes). Total protein and mRNA will be isolated and used to analyze disease markers.
In addition whole blood will be collected in a 3ml EDTA (lavender top) tube to measure the 
drug amount in serum, to understand the relationship between drug amount and the 
exploratory physiological impact being monitored. This sample will need to undergo 
centrifugation prior to shipment of the plasma as per the laboratory manual..
These samples should be shipped right after collection by FedEx First Overnight Delivery to:
Attn: Gavin Whissell
CAMP4 Therapeutics
One Kendall Square
Suite B14301
Cambridge, MA 02139
Tel:  (617)766-3221
The specimens must be labelled with the subject’s study ID and study week, as well as date 
collected.

ICF_000.pdf: 
9/18/18
IRB# 17-0748
Version 5
Page 1 of 11
Northwell Health
Feinstein Institute for Medical Research
Cohen Children’s Medical Center of New York
Consent for Participation in a Research Study
Title: Phase I/II, Open-Label Study to Determine Safety of Trifluoperazine (TFP) in Adults with 
Red Blood Cell Transfusion-Dependent Diamond Blackfan Anemia
Principal Investigator: Adrianna Vlachos, MD
Supporter: CAMP4 (previously Marauder Therapeutics), National Institutes of Health National 
Heart, Lung, and Blood Institute
Introduction
You are being asked to join a research study. The purpose of a research study is to answer 
specific questions, sometimes about the safety of a drug or device and how well it works. Being 
in a research study is different from being a patient. When you are a patient, you and your doctor 
have freedom in making decisions about your healthcare. When you are in a research study, the 
researcher will follow the rules of the research study as closely as possible, while monitoring 
your health.
This consent form will explain:

the purpose of the study

what you will be asked to do 

the potential risks and benefits
It will also explain that you do not have to be in this study to receive medical care. You should 
ask questions before you decide if you want to participate. You can also ask questions at any 
time during the study. 
Why is this research study being done?
The purpose of this research study is to determine if the medication trifluoperazine (TFP) is safe 
in patients with Diamond Blackfan anemia (DBA) who require chronic red blood cell 
transfusions. You are being asked to participate in this study because you have been diagnosed 
with Diamond Blackfan anemia and require chronic red blood cell transfusions. 
Research has demonstrated that zebrafish with mutations (defects) in the one of the genes known 
to cause DBA were able to make red blood cells and increase their hemoglobin (Hb) levels when 
treated with TFP. TFP was also tested in a mouse model of DBA and showed significant increase 
in both red blood cell counts and Hb levels. TFP was well tolerated and resulted in improved 
anemia without any gross side effects in the mice. 
 
 IRB APPROVED
 
September 18, 2018


9/18/18
IRB# 17-0748
Version 5
Page 2 of 11
TFP was also tried in cells from DBA patients and the red blood cell production was increased 
with improvement of the anemia. 
Why is this research?
This is a research study because TFP has never been tested in patients with DBA. TFP is a drug 
that has been approved by the Food and Drug Administration (FDA) for the treatment of 
psychiatric disorders. TFP has not been approved by the FDA to be used in patients with DBA. 
In this research study the safety of TFP is being tested at different dose levels in patients with 
DBA.
How many people will take part in this study?
This research study may enroll up to 24 participants.
How long will you be in this study?
If you choose to take part in this study, you will take the study drug TFP for 21 days, and you 
will be monitored for an additional 7 days. If you stop taking TFP before the 21 days are 
completed, you will still be followed for a total of 29 days from the first day you took TFP. You 
will be asked to attend 4-5 visits over the period of 4 weeks. The initial screening visit will last 
approximately 2-3 hours; the other 4 visits will last about 1 hour each. The screening visit may 
also be considered as the first visit if the patient has previously signed this consent form and the 
screening has been completed at the time of the visit.
What will happen in this research study?
This is a dose escalation, open-label study testing the safety of TFP in patients with DBA who 
require chronic red blood cell transfusions.
TFP is a tablet that is taken orally and has been approved by the FDA since 1958 for the 
short-term treatment of psychotic disorders, anxiety, and nausea. 
An Open-Label Study is a study in which all parties (the patient taking part in the study, 
the doctor and the study coordinator) know the drug and dose being given. In an open-
label study, none of the participants are given placebo tablets (a tablet which looks like 
the study drug but has no real medicine in it).
A Dose Escalation Study is as a study in which the amount of the investigational drug is 
increased during the study.
If you decide to participate in this study and you sign this informed consent form, a review of 
your medical records which includes your diagnostic work up, transfusion history, physical 
examination, and laboratory blood work results, will be performed in order to determine if you 
are able to participate. A list of all of the procedures that will be performed at the visits during 
this study follows. 
The initial Screening visit is the visit at which the doctor conducting the study will decide if you 
are able to participate in this study based on the answers to multiple questions, the results of a 
physical examination, and the results of blood tests. 
 
 IRB APPROVED
 
September 18, 2018


9/18/18
IRB# 17-0748
Version 5
Page 3 of 11
At the first Treatment study visit you will undergo a history, physical examination and blood 
tests. You will be asked to take one TFP tablet orally for 21 days. There will be 4 dose levels of 
TFP (1 mg, 2 mg, 5 mg and 10 mg [taking two 5mg tablets]). You will be assigned to a dose 
level based on how many patients are on the study before you. You will be asked to take the 
same dose of TFP for up to 21 days. During these 21 days you will return to the study center 
once every 7 days (3 times) to complete a study visit, including history, physical examination, 
and bloodwork. Any and all adverse events will be assessed at each visit. At the end of the 21 
days you will discontinue TFP.
Once you have completed the 21 days of TFP, you will return to the study center for one Follow-
Up visit 8 days later.   
A summary of the plan for your visits follows:
Visits
What Happens
Treatment Plan
Screening
(Day -28 to Day -1)
Sign consent; get all prior records for 
review; physical exam; bloodwork; 
pregnancy test (if female)
None
Visit 1
Day 1
Physical exam; bloodwork; pregnancy test 
(if female); assess any adverse events
Receive 21 day supply of study drug; 
start designated dose on Day 1 then 
daily
Visit 2
Day 8
Physical exam; bloodwork; assess any 
adverse events
Continue daily dose of study drug
Visit 3
Day 15
Physical exam; bloodwork; pregnancy test 
(if female) ; assess any adverse events
Continue daily dose of study drug; will 
discontinue on day 21
Visit 4
Day 22
Physical exam; bloodwork; assess any 
adverse events
Return the day after stopping study 
drug 
Visit 5
Day 29
Physical exam; bloodwork; assess any 
adverse events
Return for one follow-up visit 8 days 
after stopping study drug
You will be given the 21-day supply of TFP tablets at one time. TFP can be taken in the morning 
or the evening but should be taken at the same time every day. It can be taken before or after 
meals. 
During the course of this study the following procedures will be performed:
Informed consent: If you choose to participate in the study you will be asked to sign this 
form before any study procedures are performed.
Medical History: The study doctor will ask you a series of questions about your health 
in order to determine your medical condition. This may include questions about family 
members, use of medications, and any surgeries or procedures that you have had. At each 
study visit, you will also be asked about your transfusion history and any changes in your 
health or medications while taking the study drug.
Physical examination: This will include height at first visit only, weight, vital signs, 
blood pressure, and neurological exam.
 
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Bloodwork: You will have blood taken at every visit. Depending on the study visit you 
will have between 15 to 20 ml of blood drawn (3 to 4 teaspoons).
Pregnancy test (females only): You will have a blood pregnancy test at the screening 
visit (before any study drug is given) and at visits 1 and 3. You will be withdrawn from 
the study if it is found that you are pregnant. You must notify the study doctor 
immediately if you think you may be pregnant.
Drug Dispensation:  You will be given the 21-day supply of TFP tablets at one time. 
TFP can be taken in the morning or the evening, but should be taken at the same time 
every day. It can be taken before or after meals. 
Birth Control:  The study drug may affect a baby, before or after the baby is born. As a 
result, women should not be in this study if they are:

pregnant, 

breast-feeding, or

trying to become pregnant.
If you are a female who is able to become pregnant while participating in the study, you 
are to use highly effective methods of birth control for the entire time you are on the 
study drug and for 1 week after the last dose of TFP, i.e. for a total of 29 days. Hormonal 
methods (oral birth control pills, etc.), double-barrier methods (condom with spermicidal, 
sponge with spermicidal or diaphragm with spermicidal), or not having sex may be used. 
Your doctor will discuss these with you. 
If you are a man, you should not have unprotected sex with your partner while on this 
study. You and your partner should use birth control for the entire time you are on the 
study drug and for 1 week after the last dose of TFP, i.e. for a total of 29 days. Hormonal 
methods (oral birth control pills, etc.), double-barrier methods (condom with spermicidal, 
sponge with spermicidal or diaphragm with spermicidal), or not having sex may be used. 
Your doctor will discuss these with you. 
As noted before, females of child-bearing potential will have a blood pregnancy test at 
the screening visit (before any study drug is given) and at visits 1 and 3. You will be 
withdrawn from the study if it is found that you are pregnant. You should notify the 
study doctor immediately if you think you may be pregnant. 
What are the risks of the research study? What could go wrong?
Blood Draws:  There are no major risks of having blood drawn. It can be uncomfortable 
and can sometimes cause a bruise. In rare cases, it can cause fainting. Only trained staff 
will draw your blood.
Trifluoperazine:  Common possible side effects of TFP may include: 

agitation

constipation

drowsiness
 
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
dizziness 

dry mouth

jitteriness

loss of appetite

nausea

tiredness

increased sensitivity to the sun
To reduce the risk of dizziness you should get up slowly when rising from a sitting or 
lying position. You should not drink alcohol while taking TFP. You should also check 
with your doctor about taking other medicines that may cause drowsiness while taking 
TFP. TFP may cause you to become sunburned more easily so you should use sunscreen 
or wear protective clothing if outside for more than a short period of time.
Unlikely but severe side effects of TFP may include:

severe allergic reactions (skin reactions, rash, hives, itching, difficulty breathing, 
swelling of mouth, lips or tongue, wheezing)

confusion

decreased coordination

sleeplessness

muscular weakness

muscle spasms of the face, neck or back

uncontrolled twisting or twitching movements (twitching of face or tongue, loss 
of balance, uncontrolled movements of arms or legs; trouble speaking or 
swallowing)

restlessness

shuffling walk

lactation and/or loss of your menstrual cycle

blurred vision

difficulty urinating
The muscle/nervous system problems possibly caused by this class of drugs including 
TFP are also called extrapyramidal symptoms or EPS. Your doctor may prescribe another 
medication to decrease these side effects. Stop taking the TFP and tell your doctor 
right away if you notice any of the following side effects: 

feelings of anxiety or agitation or jitteriness

drooling or trouble swallowing
 
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
restlessness or constant need to move

shaking (tremor)

shuffling walk

stiff muscles

severe muscle spasms or cramping (such as twisting neck, arching back, abnormal 
eye movements, eyes rolling up, tongue sticking out, lip smacking)

mask-like expression of the face
Symptoms of motor restlessness and agitation often disappear spontaneously. Symptoms 
of prolonged abnormal contractions of muscle groups may occur in susceptible 
individuals during the first few days of treatment. While these symptoms can occur at 
low doses, they occur more frequently at higher doses. In very rare cases, involuntary 
(non-purposeful), stiff or jerky movements of the arms or legs can occur. This is called 
tardive dyskinesia. Sometimes symptoms may persist for months or years and, while they 
gradually disappear in some patients, they may never go away (be irreversible) in rare 
patients.  The risk appears to be greatest in elderly patients (which are not included in this 
study) on prolonged, high-dose therapy.  There is no known effective treatment for 
tardive dyskinesia. This is why it is important to call your doctor immediately if you 
experience any of these rare symptoms. 
Rarely, Neuroleptic Malignant Syndrome (NMS) has been reported in association with 
antipsychotic drugs, of which TFP is one. Cardinal features of NMS are high fever, stiff 
muscles, confusion, abnormal thinking, fast or irregular heartbeat and sweating. NMS is 
potentially fatal and requires symptomatic treatment so you should contact your doctor 
immediately if you have any of these symptoms.
Collection of Sensitive Information
Some of the questions we will ask you are personal. You may feel embarrassed or stressed. You 
may ask to see the questions before deciding whether or not to take part in this study.
Unknown Side Effects
As with any drug, there might be side effects that are unknown at this time. You will be closely 
watched for side effects. You should report any unusual events to the study staff.
Risks to Women of Childbearing Potential and Pregnant Women 
We do not know the effects of TFP on fertility or a fetus. For this reason, if you believe you are 
pregnant or have a chance of becoming pregnant, you should not take part in this study. A blood 
pregnancy test will be performed prior to the start of study procedures and during the study. If 
you are pregnant, you will not be allowed to be in the study. 
If you become pregnant during the study, you will be immediately withdrawn from the study and 
closely monitored through your entire pregnancy.
The side effects of TFP on newborns are also not known; therefore, if you are currently 
breastfeeding you cannot be in this study.
 
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You will be closely watched for side effects. You should report any unusual events to the study 
staff or Dr. Adrianna Vlachos at (718) 470-3460 or (516) 562-1504 immediately.
What are the benefits of this research study?
The possible benefits you may experience from the drug described in this study include an 
improvement in the anemia of DBA and a decrease in the amount of transfusions that you may 
need. 
This research may not benefit you directly. However, information we learn about this disease 
may help patients in the future.
Drug Availability after Completion of Study 
There is no plan to continue study drug after the study is complete because of the possible side 
effects that become more prevalent the longer a patient is on TFP.
If you do not want to take part in this research study, what are your other choices?
If you do not join this study, you will continue to receive red cell transfusions as per your usual 
schedule. 
Are there any costs for being in this research study? 
You will not have any added costs from being in this study. All study related visits, procedures 
and study drug will be given to you at no cost. Neither you nor your insurance company will be 
billed for your participation in this research. All other routine costs such as transfusions will be 
billed to you and your insurance company in the usual way, as part of your standard care.
Will you receive any payments for participating in this research study?
You will not receive any payment for participating in this research study.
If the research produces marketable products, will you receive any payment?
If this research produces a marketable product, there are no plans for you to receive any money.
What happens if you are injured while participating in this study?
If you are sick or hurt from being in the study as a direct result of a properly performed study 
procedure or because you are taking the Study Drug as directed, you will receive medical care 
and treatment as needed from Northwell Health. The Sponsor will pay for the reasonable and 
necessary costs associated with this care. No other compensation or payment will be provided to 
you, including lost wages. 
What are your rights as a research participant?
Your participation in this study is voluntary. The quality of your medical care will be the same, 
whether you join, refuse to join, or decide to leave the study.
If you do not join the study you will not be penalized or lose benefits to which you are entitled. If 
you join the study you may withdraw at any time without prejudice to your future care at 
Northwell Health. Follow-up examinations may be needed to assure your well-being. 
 
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Could you be taken off the study before it is over?
It is possible that your participation in this study may end without your consent. This decision 
may be made by a researcher, study sponsor or the Institutional Review Board (IRB; the 
committee that oversees research at this institution).
Reasons for withdrawal may include:

failure to follow instructions, 

failure to show up for study visits, 

it is not in your best interest to continue on this study, or 

the study is stopped. 
If you withdraw from this study or if you are withdrawn from the study, any data (or samples) 
already collected will continue to be used. However, no new tests will be performed or data will 
be collected. 
For safety reasons, if you withdraw from the study, you will be urged to return for final safety 
testing.
What happens if new information is learned?
You will be told of any new findings that may change your decision to continue to participate. 
Your consent to continue to take part in this study may be obtained again. 
What information will be collected and used for this study?
If you agree to be in this study, we will collect health information that identifies you. We will 
collect the results of your tests. We may also collect information from your medical record. We 
will only collect information that is needed for the research study. This information has been 
described in this consent form. If you sign this consent form, you are giving us permission to 
collect, use and share your health information. This permission is called authorization. If you do 
not want to provide authorization, then you cannot participate in this research study.
Who else will see your information? 
Study records that identify you will be kept private. You will not be identified in study records or 
publications disclosed outside Northwell Health.
The following reviewers may access your study and medical records to make sure that this study 
is being done properly: 

Representatives from federal funding agencies such as the National Institutes of Health 
National Heart, Lung, and Blood Institute,

Representatives from federal and state government oversight agencies such as the U.S. 
FDA, 

Representatives from Northwell Health’s Human Research Protection Program (the 
group of people that oversee research at this institution),

The medical monitor of the study, and 
 
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
CAMP4 (the supporter of the study).
We will do our best to protect the privacy of your records but it is possible that once information 
is shared with people listed on this form, it may be released to others. If this happens, your 
information may no longer be protected by the federal law.
In the future, we may publish results of this study in scientific journals and may present it at 
scientific meetings. If we do we will not identify you. 
If the researchers learn about potential serious harm to you or someone else or other public 
health concerns, it will be shared with the appropriate authorities.
Will you be able to access your records?
If your research records are used for decisions related to your clinical care, then you have the 
right to review this information and request changes. This is limited to information about your 
treatment, and does not include information related to procedures or tests that are for research 
purposes only. You may access this information only after the study analysis is complete. You 
have the right to know who has and who will see your records. To request this information, 
please call the Institutional Review Board/Human Research Protection Program at 516-465-
1910.
How long will your health information be kept? 
There is no limit on the length of time we will keep your information for this research study 
because it may be analyzed for many years. We will keep it as long as it is useful, unless you 
decide you no longer want to take part or we close the study. You are allowing access to this 
information indefinitely. 
Can you change your mind?
If you change your mind about being in the study, you may withdraw at any time. If you want us 
to stop collecting your health information, you need to send a letter to the researcher at the 
following address:
Adrianna Vlachos, MD
The Feinstein Institute for Medical Research
350 Community Drive
Manhasset, NY 11030
Your letter needs to say that you have changed your mind and do not want the researcher to 
collect and share your health information. You may also need to leave the research study if we 
cannot collect any more health information. We may still use the information we have already 
collected. We need to know what happens to everyone who starts a research study, not just those 
people who stay in it.
Will information about this study be available to the public?
A description of this clinical trial will be available on http://www.Clinical Trials.gov, as required 
by U.S. Law. This Web site will not include information that can identify you. At most, the 
website will include a summary of the results. You can search this website at any time.
 
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Does the investigator of this study receive money if you take part?
There is funding provided to conduct the study and supply the medication. The investigators do 
not financially benefit from your participation.  Funding for this research study is provided by 
CAMP4 and the National Institutes of Health National Heart, Lung, and Blood Institute. If your 
doctor is an investigator for this study s/he is interested in both your healthcare and the conduct 
of this research. You do not have to take part in a research study conducted by your doctor.
Who can answer your questions about this study?
If you have any questions about the study, you may call Dr. Adrianna Vlachos, MD, at (516) 
562-1504. If you have questions about side effects or injury caused by research you should call 
Dr. Adrianna Vlachos, MD, at (516) 562-1504. If you need emergency care, dial 911 or go to the 
nearest Emergency Room. If you have questions about your rights as a research participant, or 
concerns about being in the study, or would like to offer input, you may contact the Office of the 
Institutional Review Board (the committee that oversees research at this institution) at 516-465-
1910. A signed copy of this consent form will be given to you.
[Signature Page Follows]
 
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Summation/Signature
You have read the above description of the research study. You have been told of the risks and 
benefits involved and all your questions have been answered to your satisfaction. A member of 
the research team will answer any future questions you may have. You voluntarily agree to join 
this study and know that you can withdraw from the study at any time without penalty. By 
signing this form, you have not given up any of your legal rights.
___________________________________________________
______________
Signature of Participant
Date
___________________________________________________
Printed Name of Participant
___________________________________________________
______________
Signature of Witness
Date
(Note: A witness can be a member of the research team, but cannot be the same person signing 
consent as the investigator)
___________________________________________________
Witness’s Printed Name
Investigator’s Statement 
In addition to advising the above participant of other forms of treatment and therapy which are 
appropriate, I have offered an opportunity for further explanation of the risks and discomforts 
which are, or may be associated with this study and to answer any further questions relating to it.
___________________________________________________
________________
Investigator’s Signature
Date
___________________________________________________
Investigator’s Printed Name
 
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