A Multicenter, Comparative Safety and Efficacy Study of ACTHar Gel Alone or in Combination With Oral Tacrolimus to Reduce Urinary Proteinuria in Patients With Idiopathic DNAJB9 Positive Fibrillary Glomerulopathy
Phase: PHASE4
Conditions: Fibrillary Glomerulonephritis
Sponsor: NephroNet, Inc.

NephroNet, Inc.       
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CLINICAL STUDY PROTOCOL
Protocol Title: 
Generic Title:
Protocol Number: 
Phase:
Indication:
Sponsor: 
Sponsor Medical
Director/Lead PI:
Funding Source: 
IND Number: 
IND Holder: 
Protocol Version:
A Multicenter, Comparative Safety and Efficacy Study of 
ACTHar gel alone or in combination with oral Tacrolimus to 
reduce urinary proteinuria in patients with idiopathic DNA-
JB9 Positive Fibrillary glomerulopathy
Fibrillary ACTH Tacrolimus Trial (FACT-Trial)
NN-002
4
Reduction of urinary protein excretion & slowing of GFR 
progression
NephroNet, Inc.
923 Preserve Bluff Drive
Atlanta GA, 30518
Telephone: 770-490-9203
James A. Tumlin, MD
Mallinckrodt Pharmaceuticals
TBA
NephroNet Inc
3.0, Dated 14March2019
CONFIDENTIALITY STATEMENT 
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suspected breach of this obligation, NephroNet must be promptly notified. 

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FINAL PROTOCOL APPROVAL SHEET 
CONFIDENTIAL 
14March2019
A Multicenter, Comparative Safety and Efficacy Study of ACTHar gel alone 
or in combination with oral Tacrolimus to reduce urinary proteinuria in 
patients with idiopathic DNA-JB9 Positive Fibrillary glomerulopathy 
NephroNet, Inc. Approval: 
James A. Tumlin, MD 
President/CEO 
923 Preserve Bluff Drive 
Atlanta GA, 30518 
Telephone: + 1. 770-490-9203 
Email: jamestumlinmdnephronet@gmail.com 
Date 
- 2 -

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SIGNATURE OF INVESTIGATOR
PROTOCOL TITILE:
A Multicenter, Comparative Safety and Efficacy Study of 
ACTHar gel alone or in combination with oral Tacrolimus to reduce urinary proteinuria in 
patients with idiopathic DNA-JB9 Positive Fibrillary glomerulopathy
PROTOCOL NUMBER:
NN-002
VERSION NUMBER:
VERSION DATE:
2.0
14March2019
I agree to conduct this clinical trial according to the protocol described herein, and to comply 
with its requirements, subject to ethical and safety considerations and guidelines. I also agree to 
conduct this study in compliance with Good Clinical Practice (GCP) standards as defined by the 
International Conference on Harmonisation (ICH) Guideline for Good Clinical Practice, all 
applicable national, state, and local regulations, as well as the requirements of the appropriate 
Institutional Review Board/Independent Ethics Committee (IRB/IEC) and any other institutional 
requirements.
I understand that the information in this protocol is confidential and should not be disclosed to 
others without written authorization from Epizon Pharma, Inc., except to the extent necessary to: 
(1) obtain informed consent from persons to whom the drug may be administered; and (2)
inform those directly involved in the execution or the scientific/ethical review of the study.
I understand that failure to comply with the requirements of the protocol may lead to my 
participation as an Investigator for this study to be terminated. 
Principal Investigator’s Name (print) 
Principal Investigator’s Signature 
Date 
Please retain the signed original of this form for your study files. Please return a copy of the 
signed form as instructed by your local clinical research associate (CRA).

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TABLE OF CONTENTS 
FINAL PROTOCOL APPROVAL SHEET ......................................................................... - 2 - 
SIGNATURE OF INVESTIGATOR ................................................................................... - 3 - 
TABLE OF CONTENTS ................................................................................................... - 4 - 
LIST OF ABBREVIATIONS .............................................................................................. - 5 - 
PROTOCOL ..................................................................................................................... - 8 - 
SCHEDULE OF EVENTS 
- 2 4 -

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3. LIST OF ABBREVIATIONS
AE 
adverse event 
AESI 
adverse event of special interest 
ALT 
alanine transaminase 
AST 
aspartate transaminase 
AUC 
area under the concentration-time curve 
BUN 
blood urea nitrogen 
β-hCG 
beta-human chorionic gonadotropin  
CBC 
complete blood count  
CFR 
Code of Federal Regulations  
CHD 
coronary heart disease  
CKD 
chronic kidney disease 
CMP 
comprehensive metabolic panel 
CRA 
clinical research associate  
CRO 
contract research organization 
CVA 
cerebrovascular accident  
DNA 
deoxyribonucleic acid 
eCRF 
electronic Case Report Form 
ECG 
Electrocardiogram 
EDC 
electronic data capture 
EOS 
End-of-Study (visit) 
EOT 
End-of-Treatment (visit) 
ESRD 
end-stage renal disease 

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FDA 
Food and Drug Administration 
FSI 
first subject in 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
human immunodeficiency virus 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 
ID 
Identification 
IEC 
Independent Ethics Committee 
IND 
Investigational New Drug application 
INR 
International Normalized Ratio 
IOM 
Institute of Medicine  
LSLV 
last subject last visit  
MedDRA 
Medical Dictionary for Regulatory Activities 
mRNA 
messenger ribonucleic acid  
NADP 
nicotinamide adenine dinucleotide phosphate 
NOAEL 
no-observed-adverse-effect-level  
PCR 
polymerase chain reaction 
PT 
Pro thrombin Time  
PTT 
partial thromboplastin time 
RBC 
red blood cell 
RNA 
ribonucleic acid 
SAE 
serious adverse event 
SD 
standard deviation 

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SMF 
Site Master File 
SOC 
System Organ Class  
SRC 
Safety Review Committee 
TIA 
transient ischemic attack 
U-VEGF121 
 
Urinary Vascular Endothelial Growth Factors Isoform 121 
Urinary VEGF-165 
Urinary Vascular Endothelial Growth Factors Isoform 165 
Urinary VEGF-189 
Urinary Vascular Endothelial Growth Factors Isoform 189 
Urinary VEGF-206 
Urinary Vascular Endothelial Growth Factors Isoform 189 
Urinary MCP-1 Monocyte chemoattractant protein 1, 
Urinary Synaptopodin Urinary Synaptopodin 
Urinary TGF-beta 
Urinary Transforming Growth Factor Beta 
Urinary Podocalyxin 
Urinary Podocalyxin 
Urinary Nephrin 
Urinary Nephrin 
WBC 
white blood cell  
WHO 
 
World Health Organization 

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Study Title 
A Multicenter, Comparative Safety and Efficacy Study of 
ACTHar gel alone or in combination with oral Tacrolimus to 
reduce urinary proteinuria in patients with idiopathic DNA-
JB9 Positive Fibrillary Glomerulopathy 
Study Number 
NN-002 
Clinical Phase 
Phase 4 
Indication 
Reduction of urinary protein excretion & slowing of GFR 
progression 
Projected Number 
Enrolled Patients: 
34 
Projected Number 
NephroNet Sites: 
7-10
Background 
Fibrillary glomerulonephritis (FGN) is a rare primary 
glomerular disease that is characterized by glomerular 
accumulations of nonbranching, randomly arranged fibrils. 
The most common histologic presentation is mesangial 
proliferative with areas of sclerosis. It is unknown whether 
specific histologic patterns have a better or worse prognosis. 
The deposition of fibrils can be found in the mesangium, 
basement membranes of glomerular endothelial cells and 
within the sub-epithelial space. Fibrillary proteins differ from 
amyloid both in diameter, arrangement the and lack of 
Congo red staining. A recent review of all renal biopsies 
Arkana Laboratories between 2014-2015 demonstrated that 
105 patients were diagnosed with Fibrillary GN (unpublished 
data). The mean age of these patients was 60 years old with 
a mean eGFR of 45 mls/min and UP/Cr ratio of 5.380 grams. 
The majority of these patients had been previously treated 
with 2 or more different immunosuppressive agents with little 
to no success.  
      There are currently no approved or generally accepted 
therapies for Fibrillary GN. Previous studies have shown that 
up to 70% of patients progress to ESRD within 4years9. 
Rituximab has been studied in two previous trials with an 
approximate response rate of 20%. A recent study treated 
15 patients with refractory Fibrillary GN for an average of 6 
months with ACTHar gel and achieved a complete or partial 
remission 59% of patients. Among the 7 ACTHar responsive 
patients, the UP/Cr ratio dropped by 75% from a mean of 

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Background 
5435 to 1335 mg/gm. The efficacy of combination therapy 
with ACTHar and Tacrolimus was recently shown in a study 
of 22 patients with idiopathic Membranous GN (9) or FSGS 
(13). After 6 months of ACTHar gel therapy alone, 59% of 
patients achieved a complete or partial remission. When oral 
Tacrolimus was added to existing ACTHar gel, complete and 
partial response rates increased significantly to over 90%. 
  As shown in figure-1, the addition of tacrolimus to patients 
exhibiting a partial response to ACTH resulted in a further 
reduction in UP/Cr.  While the number of patients in these 
trials are quite small, they suggest that combining a 
calcineurin inhibitor with a melanocortin receptor agonists 
could reduce proteinuria and stabilize renal function. The 
NephroNet clinical trial consortium is proposing a multicenter 
study investigating the safety and efficacy of ACTHar gel 
alone or combination with oral Tacrolimus in patients with 
Fibrillary glomerulopathy.  
Study Design 
This is a multicenter, Phase 4, prospective, open labeled 
study to compare the safety, tolerability, and efficacy of a 12-
month course of ACTHar Gel alone or in combination with 
oral Tacrolimus to reduce UP/Cr ratio in patients with DNA-
JB9 positive Fibrillary Glomerulopathy.   

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Hypothesis and  
Specific Aims 
Hypothesis#1: A 12-month treatment with combination 
ACTHar gel and Tacrolimus therapy will be superior to 
ACTHar gel therapy alone in lowering urinary protein to 
creatinine (UP/Cr) ratios in patients with idiopathic DNA-JB9 
positive Fibrillary GN 
Specific Aim #1-will randomize 35 patients with biopsy 
proven DNA-JB9 positive Fibrillary glomerulopathy to receive 
a 12-month course of ACTHar gel at 80 units SQ  2X/week 
alone or in combination with oral Tacrolimus at 1.0 mg BID 
(targeting for trough Tacrolimus dose of 4-6 ng/ml).   
Hypothesis#2: Treatment with combination ACTHar gel and 
Tacrolimus therapy will result in a higher eGFR after 24 
months of follow up than patients randomized to  ACTHar gel 
therapy alone  
Specific Aim #2-will determine the change in eGFR from 
baseline to 24 months of follow for patients with biopsy 
proven DNA-JB9 positive Fibrillary glomerulopathy. It is 
anticipated that at 24 months (12 months after completing 
therapy)  patients randomized to ACTHar gel plus 
Tacrolimus will have higher eGFR compared to patients 
receiving ACTHar gel alone. 
Hypothesis #3:  Combination therapy of ACTHar Gel and 
Tacrolimus in patients with DNA-JB9 positive Fibrillary 
Glomerulopathy will lead to significantly lower urinary markers of 
podocyte injury compared to patients receiving ACTHar gel 
therapy alone. 
Specific Aim #3-will compare the relative changes in the 
following urinary biomarkers will be performed: 
1. Urinary VEGF 121, VEGF-165
2. Urinary VEGF-189, VEGF-206
3. Urinary MCP-1
4. Urinary Synaptopodin
5. Urinary TGF-beta
6. Urinary Podocalyxin
7. Urinary Nephrin
Levels will be measured at baseline prior to treatment and 
after 12 months of ACTHar ge therapyl alone or in 
combination with oral Tacrolimus. The relative reduction 
urinary biomarkers will also be compared between the two 
treatment groups. 

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Study Population
A total of 34 patients will be enrolled.
Group 1 (17 patients) ACTHar gel 80 units 2X/week alone 
for 12 months of therapy. 
Group 2 (17 patients) ACTHar get 80 units 2X/week plus oral 
Tacrolimus 1.0 mg BID titrated to trough Tacrolimus levels 
between 4-6 ng/ml
Anticipated drop out rate 10%. 
Inclusion Criteria
Histologic Inclusion Criteria
Histologic Criteria: All patients with a diagnosis of The
Fibrillary GN will be classified according to the Nasr 
nomenclature:
1) Renal 
biopsy 
demonstrating 
DNA-JB9 
Positive 
staining within 3 years of study randomization
2) Mesangial 
expansion 
with/without 
glomerular 
sclerosis
3) Membranous changes with or without diffuse sclerosis
4) Crescents or endocapillary proliferation
5) Level of interstitial fibrosis
Note: Patients with > 50% interstitial fibrosis will not be 
eligible for study participation
Note: Patients with monoclonal staining of fibrillary fibers will 
not be eligible for study participation
Inclusion Criteria: 
1) Male/Female age > 18
2) Biopsy proven Fibrillary GN within 3 years of study 
randomization
3) Stable Maximum RAAS inhibition X 4 weeks prior to 
randomization
Note: Maximum RAAS inhibition will be left to the 
discretion of the site PI
4) eGFR > 25 mls/min calculate by the CKD-EPI formula
5) UP/Cr ratio > 2000 mg/gm

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Exclusion Criteria 
5) Note: IF UP/Cr less than 2000 mg/gm, a formal 24-
hour urine collection for total protein can be 
performed.  The total 24-hour protein will need to >/= 
2000mg.
6) Blood pressure targeted to < 140/90 at the time of 
randomization
7) Patients with MGUS without history of myeloma WILL 
be eligible.
8) Patients with monoclonal staining for fibrillary fibers 
will be excluded
9) Patients with Type II non-insulin dependent diabetes 
WILL be eligible provided the renal biopsy does not 
show nodular Kimmelstiel Wilson lesions
Exclusion Criteria; 
1) Patients with MGUS and history of myeloma WILL
NOT be eligible
2) Patients with active viral production of either hepatitis
B or C as evidence by historical PCR test positive for
active viral shedding
3) HIV seropositivity
4) Renal biopsy data with > 50% Interstitial Fibrosis
5) Patient with active or a known history lymphoma
6) Patients with insulin Dependent diabetes mellitus will
be excluded
Note: patients with Type II diabetes mellitus that are 
well controlled WITHOUT the need for insulin WILL 
be eligible for the study. 
7) Patients with Type II non-insulin dependent diabetes
WILL be eligible provided the renal biopsy does not
show nodular Kimmelstiel Wilson lesions.
8) Patients receiving steroids, MMF, cyclophosphamide,
Azathioprine or other immunosuppressive agent with
4 weeks of study randomization
Note: Washout of these medications will be allowed at
the screening visit
9) Patients having received Rituximab or B cell
modifying biologic therapy within 6 months of
randomization

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Primary Endpoint: 
Secondary Endpoint 
Primary Endpoint: 
The change in UP/Cr ratio in patients with biopsy proven 
Fibrillary GN after 12 months of treatment with  treated with 
ACTHar gel (80 units SQ 2X/week) alone OR in combination 
with oral Tacrolimus (1.0 mg PO BID). The change in UP/Cr 
for each group will also be compared to baseline UP/Cr 
ratios prior to randomization  
Secondary Endpoints: 
1) The relative change in UP/Cr at 24 months (12
months after stopping both ACTH and Tacrolimus) in
the ACTHar gel group and the ACTHar gel +
Tacrolimus group.
2) The percentage of patients in the ACTHar gel alone
versus ACTHar gel + Tacrolimus group that achieves
complete, partial or clinical responses after 12 months
of  therapy
3) The change in eGFR (measured by CKD-EPI formula)
between the ACTHar gel and ACTHar Gel +
Tacrolimus groups after 24 months of treatment with
ACTHar gel alone or in combination with oral
Tacrolimus. In addition, we will also compare the
relative change in eGFR between those patients
receiving ACTHar gel alone with those randomized to
combination therapy.
4) To compare the change in urinary biomarkers (see
below) at baseline and after 12 months of treatment
with ACTHar gel alone or in combination with
Tacrolimus. The patients urinary biomarker levels
after 12 months of therapy will be compared between
the ACTHar gel alone group  and ACTHar gel +
Tacrolimus group.
a) Urinary VEGF 121, 165 189, and206
b) Urinary MCP-1
c) Urinary Synaptopodin
d) Urinary TGF-beta
e) Urinary Podocalyxin
f)
Urinary Nephrin
Fibrillary GN patients with concurrent Type II diabetes 
mellitus:  
To determine whether ACTHar gel therapy resulted in 

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Pre-Defined Sub-
Groups for Post-Hoc 
Analysis: 
hyperglycemia in patients with concurrent Diabetes and 
whether that led to early termination from the study. We will 
also determine whether the presence of diabetes led to 
increased proteinuria over time, led to more rapid decline in 
renal 
function 
and 
altered 
the 
response 
to 
immunosuppressive therapy.  
Fibrillary Patients with Low Urinary Levels of VEGF 121, 
165, 189, 206 
To determine whether ACTH alone or in combination with 
Tacrolimus can restore production of urinary VEGF. The 
level of urinary VEGF will also be corrected with the level of 
GFR and the number of senescent glomeruli and degree of 
interstitial fibrosis on the primary biopsy.   
Fibrillary GN Patients with the presence of Cellular 
Crescents 
To determine whether this specific histologic finding 
correlated with increased or reduced responsiveness to 
ACTHar gel alone or in combination with Tacrolimus  
Study Schedule 
Duration of Study 
Trial Endpoint 
Definitions: 
Year 1: Study recruitment of 34 patients with biopsy proven 
DNA-JB9 positive Fibrillary Glomerulopathy 
Each patient will undergo 12 months of treatment with 17 
patients randomized to ACTHar gel alone (17 patients) or to 
ACTHar gel plus oral Tacrolimus (17 patients) 
Year 2: Follow up and observation for 12 months OFF 
ACTHar gel or ACTHar gel and Tacrolimus  
The expected duration study participation for each patient 
will be two (2) years. One year of ACTHar gel treatment 
alone or in combination with Tacrolimus and then one year 
for follow up off drug treatment. 
1) Complete remission: < 300 mg UP/Cr mg/gm
2) Partial Remission: > 50% reduction in UP/Cr from 
baseline values 

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Patient Identification 
& Recruitment 
Patient Pre-
Screening and 
HIPPA Release 
Patient Consenting 
3) Clinical Response: >30%-<50% in UP/Cr from baseline 
values 
Patient Identification & Recruitment: 
     Two major Renal pathology centers will be involved in the 
recruitment of newly diagnosed patients with Fibrillary 
glomerulopathy:  1) Arkana Laboratories and 2) Columbia 
University. New or repeat renal biopsies determined by  
Arkana Laboratories to be consistent with Fibrillary GN will 
be identified by the attending pathologist and referred to a 
clinical research coordinator affiliated with the Arkana 
Clinical Research Division. During the standard of care 
verbal review of the biopsy result, the attending pathologist 
will inquire whether the referring nephrologist would like to 
know more about the FACT Trial including his/her patients 
eligibility to participate in the study. If the referring 
Nephrologist expresses a desire to know more about the 
study, he/she will be given the option of being contacted by a 
member of the NephroNet study team.  
Once the primary nephrologist has communicated with a 
potential study patient and determined that he/she is 
interested in participating in the trial, the primary Attending 
will forward an IRB approved HIPPA release to the patient. 
After signing the HIPPA release, the potential study patients 
medical records will then be sent to the National PI AND the 
local site PI for screening and eligibility. If it is determined 
that the patient meets eligibility requirements, the patient will 
be provided transportation and lodging to the nearest FACT 
Trial site.  
The potential patient’s medical records will be reviewed by 
the National and Local PIs. If it is determined that the patient 
is a candidate, he/she will be and the FACT team has 
occurred, a preliminary review of the protocol and its 
objectives will be made with the attending physician. The 
attending physician will either contact the prospective patient 
directly or seek permission from the patient to be contacted 
by  the  FACT  team.  Patients expressing a desire to know 
more about the study will be contacted by Dr. Tumlin the 
Medical Director/Lead PI and the Site PI nearest to the 
patient’s location.  
Patients completing an initial screening assessment and who 
meet the clinical inclusion/exclusion criteria will be sent a 
copy of the study IRB approved Consent. A telephone 

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Number of total 
Clinic Visits 
FACT-Trial: Study 
Design 
conference call with the prospective patient will be arranged 
to discuss in details of the study; the risks/benefits of the 
study drug, as well as details regarding patient requirements 
and travel to and from the study site. The patient will be 
given time to review the consent with their families and other 
physicians.  
If is determined by the Medical Director and the FACT Site 
PI that the patient is a likely candidate for the study, a travel 
agent will contact patient and make arrangements for airfare 
and overnight accommodations to visit the FACT PI. Both 
the airfare and overnight accommodations will be provided 
by NephroNet. If a patient lives within approximately 4 hours 
of the FACT site, they will be reimbursed for mileage and 
hotel. There will be a total of 13 visits per patient per site. 
Patients agreeing to participate in the FACT sign consent at 
their first screening visit. 
Thirteen (13) visits for total study: 
Pre-screening visits- two (2) 
Study Drug Treatment visits- six (6) 
Post Study Drug Treatment visits- five (5) 
Study Design: This study will be a multi-center, prospective, 
randomized, open-labeled intervention trial of 34 patients 
randomized to 52 weeks of ACTHar gel alone or ACTHar gel 
plus oral Tacrolimus. 
Drug Dosing: 
Group-1: ACTHar gel alone-patients will be receive 80 units 
SQ Q 2X/week for 52 weeks 
Group-2: ACTH gel 80 units 2X per week plus oral 
Tacrolimus (1.0 mg BID) titrating to a trough level of 4-6 
ng/ml for 52 weeks 
Note: Patient with type II diabetes will be allowed to dose at 
24 units/day (0.3 mls SQ Q day) to reduce glucose 
fluctuations and simplify management of diabetes at the 
discretion of the PI. 
Protocol-Schedule and Follow Up: Clinic Visits: 

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x Visit 
1: 
Pre-Randomization 
Screening 
& 
Consenting Visit: Patients that have gone through 
the Pre-screening review and considered to be 
eligible for study participation will seen by the local 
site PI for formal consenting two months prior to study 
randomization.  The patient will then be see the FACT 
trial site PI who will perform a complete physical exam 
and obtain routine laboratory testing including a urine 
to protein Cr ratio.  
Pre-Randomization Screening & Consenting Visit 
(V1): Blood and Urine Study Samples: Blood 
samples (5 mls) for serum and plasma will be 
obtained at each visit. Blood samples will be 
centrifuged at 3000 RPM for 5 minutes and 250 ul of 
plasma or serum will be transferred to an O-ring 
sealed cryovials and frozen at -80oC until analyzed. 
Each 10-ml sample of urine will be added to 100 ul of 
Thermo Scientific HALT proteinase inhibitor solution 
and then centrifuged at 3,000 rpm for 10 minutes at 
4°C. Then, 250 μL of the urine supernatant will be 
transferred to an O-ring sealed cryovials and frozen at 
-80oC until analyzed.
x Visit 
2: 
Pre-Randomization 
Screening 
#2) 
“Optimization & Run-In Phase”: After the initial pre-
screening visit, the prospective patients will enter a 4-
week “optimization and run-in phase” during which 
patients will have their blood pressure optimized to a 
“pre-randomization” target level of 140/90. During the 
“run-in phase”, RAAS blockers will not be modified 
and target blood pressure will be achieved using 
antihypertensive agents that do not alter urinary 
protein excretion (e.g. Nifedipine Hydralazine).   
x Visit 3:  Randomization/Baseline: After the 4-week 
run-in phase, patient will be flown back to the FACT 
trial 
site 
where 
they 
will 
undergo 
formal 
randomization. When the site PI determines that the 
patient has met all inclusion and exclusion criteria, 
they contact Dr. Tumlin and the NephroNet data 
coordinating center for randomization. Each patient 
will then undergo a physical exam and routine blood 
and urine laboratory studies. The UP/Cr from the pre-

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screening and randomization visits will be averaged 
and this value will be considered the “baseline UP/Cr” 
for that patient. 
Note: If the pre-screen and randomization UP/Cr 
values differ by more than 50%, the patient will be 
allowed to collect a third UP/Cr ratio one week later. 
The average of those 3 UP/Cr ratios will be recorded 
as the patient’s baseline proteinuria.  
Baseline- Blood and Urine Study Samples: Blood 
samples (5 mls) for serum and plasma will be 
obtained at each visit. Blood samples will be 
centrifuged at 3000 RPM for 5 minutes and 250 ul of 
plasma or serum will be transferred to an O-ring 
sealed cryovials and frozen at -80oC until analyzed. A 
10-ml sample of urine will be centrifuged at 3,000 rpm
for 10 minutes at 4°C. Then, 250 μL of the
supernatant will be transferred to an O-ring sealed
cryovials and frozen at -80oC until analyzed
x Visit 4:  14 Days Post Randomization Visit:  14 
Days Post Randomization (Visit 4) will be optional for 
patients traveling from long distances.  Would request 
that patient visit nephrologist in home town if any 
adverse events of concern are reported.  
x Visits 5 – 7:  Study Visits-Months 3 (V5), 6(V6) & 
9(V7) : We will be conducted in like manner to 
Randomization visit. Each patient will get a complete 
physical exam. Standard blood and urine studies will 
be performed as well as plasma, serum and urine 
study sample collections.  Tacrolimus Trough Levels 
will be drawn for those patients randomized to the 
Tacrolimus arm. 
x Visit 8:  Month 12:  Primary Endpoint Evaluation: 
All patients completing of 52 weeks of ACTHar gel 
therapy alone or in combination with Tacrolimus will 
be examined for their change in UP/Cr as compared 
to their baseline levels of urinary protein. Patients will 
be asked to bring 2 first morning voids of urine. These 
two samples will be averaged and used for 

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determination of the percentage of patients 
achieving the primary endpoint.    
Complete Responders: < 300 mg/gm UP/Cr ratio 
Patients that have reached this milestone will be 
weaned off ACTHar Gel with or without Tacrolimus 
over the subsequent 14 days.
Sites will start the ACTHar Gel wean at 40 units and 
reduce over a 2 week taper period at the discretion of 
the principal investigator of each site.
Non-or Partial Responders: > 50% Reduction in 
UP/Cr ratio to minimum value of 2000 mg/gm: 
Patients will follow the same weaning protocol as the 
complete responders described above.
x Visit 9:  ACTHar Washout Visit: 
14 Days Post End of Treatment (Visit 9) will be 
optional for patients traveling from long distances 
and will occur after the post treatment taper.  
The Study Staff will request that the patient visit 
a Nephrologist in the patient's home town if any 
adverse events of concern are reported. 
x Visits 10 -12:  Follow-Up Visits-Months 15 (V10), 
18(V11) & 9(V12): We will be conducted in like 
manner to Randomization visit. Each patient will be 
get a complete physical exam. Standard blood and 
urine studies will be performed as well as plasma, 
serum and urine study sample collections.  
x Visit 13:  Month 24 Visit: Secondary Endpoint 
Evaluation: 
Patients completing 104 weeks of study participation 
will be evaluated for the following: 
1) Percentage of Complete Responder patients
weaned off ACTHar gel and Tacrolimus that
developed a relapse after 12 months of no therapy.
2) Percentage of patients in the ACTHar gel alone
group that demonstrated additional reduction in UP/Cr

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ratio following the addition of Tacrolimus at Week 52.  
Hyperkalemia: Patient developing hyperkalemia defined as 
> 5.5 meq/L will undergo the following interventions:
Intervention #1: Review dietary sources of potassium and 
assess patient compliance with prescribed dietary 
restrictions. 
Intervention #2: Adding or increasing dose of a loop diuretic. 
If they patient was already taking a diuretic as part of their 
standard of care regimen, the dose or frequency will be 
increased according to the discretion of the Site PI.   
Intervention #3: For patients with continued hyperkalemia 
following intervention 1 & 2, the Site PI can consider adding 
a Thiazide diuretic (HCTZ or Metolazone) to the current loop 
diuretic.   
Intervention #4: For patients with continued hyperkalemia 
following intervention 1 & 2 & 3, the dose of Tacrolimus can 
be reduced to 0.5 mg BID. 
Combining Thiazide and Loop diuretic therapy to AM-PM 
doses 
Intervention #5: For patients with continued hyperkalemia 
following intervention 1 & 2, 3, & 4, the patient can 
discontinued from Tacrolimus.    
Note: Any Site PI that chooses to treat a study patient’s 
hyperkalemia with Patiromer may do and keep the patient in 
the study. Any decision to use Patiromer is solely at the 
discretion of the Site PI. 
Hyperglycemia: 
Patients 
developing 
intractable 
hyperglycemia defined as > 400 mg/dl can have their current 
diabetic medications modified. For patients with continued 
hyperglycemia despite increases in diabetic therapy, the 
dose of ACTHar gel can be reduced by 50%. Patients with 
persistent hyperglycemia can be withdrawn from the study at 
the discretion of the Site PI.  
Note: Any Site PI choosing to use of Insulin to treat a study 
patient’s hyperglycemia can do and keep the patient in the 

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study. Any decision to use institute Insulin therapy is solely 
at the discretion of the Site PI. 
Lower Extremity Edema: Patients developing increasing 
lower extremity edema can have their diuretic regimen 
increased by either dose or frequency. Patients continuing to 
have edema with maximal Loop diuretics can be treated with 
dual Loop and Thiazide diuretic therapy. All decisions as the 
management of lower extremity edema will be left to the 
discretion of the Site PI.  
Statistical Analysis Sample Size and Power. 
     The sample size was calculated to detect a 40% 
difference in the mean UP/Cr ratio after 12 -month of 
ACTHar gel therapy alone or with oral Tacrolimus. Analysis 
will be intention to treat for all patient receiving at least one 
week of drug therapy.  Based on the estimated variability of 
30% for the change in UP/Cr ratio (CV) a sample size of 17 
patients per arm (total-34) will be needed to provide 80% 
power to see a difference with a P value of < 0.05.  A Fisher 
exact test will be applied for comparisons of adverse event 
frequencies. All tests were two-tailed with a P value-0.05 
considered significant. 
References: 
1) Laser Microdissection and Proteomic Analysis of
Amyloidosis, Cryoglobulinemic GN, Fibrillary GN, and
Immunotactoid Glomerulopathy Sanjeev Sethi,* Jason
D. Theis,* Julie A. Vrana,* Fernando C. Fervenza,†
Anjali Sethi,‡ Qi Qian,† Patrick Quint,* Nelson
Leung,* Ahmet Dogan,* and Samih H. Nasr* Clin J
Am Soc Nephrol 8: 915–921, 2013.
2) Fibrillary Glomerulonephritis: A Report of 66 Cases
from a Single Institution Samih H. Nasr,* Anthony M.
Valeri,† Lynn D. Cornell,* Mary E. Fidler,* Sanjeev
Sethi,* Nelson Leung,‡ and Fernando C. Fervenza‡
Clin J Am Soc Nephrol 6: 775–784, 2011.
3) Fibrillary Glomerulonephritis and Immunotactoid
Glomerulopathy Charles E. Alpers and Jolanta
Kowalewska. J Am Soc Nephrol 19: 34–37, 2008.
4) Plasmapheresis leading to remission of refractory

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nephrotic syndrome due to fibrillary 
glomerulonephritis: a case report Rainer U Pliquett1*, 
Peter Mohr1, Badr El Din Mukhtar2, Matthias Girndt1 
and Silke Markau1 Journal of Medical Case Reports 
2012, 6:116 
5) Rituximab treatment for fibrillary glomerulonephritis
Jonathan Hogan, Michaela Restivo, Pietro A. Canetta,
Leal C. Herlitz, Jai Radhakrishnan, Gerald B. Appel
and Andrew S. Bomback Nephrol Dial Transplant
(2014) 0: 1–7
6) Rituximab Treatment of Fibrillary Glomerulonephritis
Michael Collins, DO,1 Sankar D. Navaneethan, MD,2
Miriam Chung, MD,3 James Sloand, MD,2
Bruce Goldman, MD,2 Gerald Appel, MD,3 and Brad
H. Rovin, MD1 Am J
Kidney Dis 52:1158-1162, 2008
7) The Occurrence or Fibrillary Glomerulonephritis in
Patients with Diabetes Mellitus May Not Be
Coincidental: A Report of Four Cases Fayna
González-Cabrera,1 Fernando Henríquez-Palop,1
Ana Ramírez-Puga,2 Raquel Santana-Estupiñán,1
Celia Plaza-Toledano,1 Gloria Antón-Pérez,1 Silvia
Marrero-Robayna,1 Davinia Ramírez-Medina,1
Roberto Gallego-Samper,1 Nicanor Vega-Díaz,1
Rafael Camacho-Galan,3 and José C. Rodríguez-
Pérez1 Case Reports in Medicine Volume 2013,
Article ID 935172.
8) J. A. Tumlin,1,2 C. M. Galphin,2 and B. H. Rovin3
Advanced Diabetic Nephropathy with Nephrotic
Range Proteinuria: A Pilot Study of the Long-Term
Efficacy of Subcutaneous ACTH Gel on Proteinuria,
Progression of CKD, and Urinary Levels of VEGF and
MCP-1. Journal of Diabetes Research Article ID
489869, 8 pages, 2013
9) Stephen M. Korbet,* Melvin M. Schwartz,† and
Edmund J. Lewis* Immuotactoid Glomerulopathy
(Fibrillary Glomerulonephritis) Clin J Am Soc Nephrol
1: 1351–1356, 2006

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Pre-Screen
V3_Randomization & 
Baseline
Visit 4
Study Visit 5, 6, & 7
EOT- V8
Optional- V9
F/U- V10, 11 & 12
Visit 13-          
End of Study 
Cycle (Days or Months)
-2 Months
-1 Month
Baseline
(14 Days
Post Rand **3)
3, 6 & 9 Months
12 Months
2 Weeks Post EOT**4     
(54 Weeks)
15, 18 & 21 Months
24 Months
Window (weeks)
+/- 2 Wks
+/- 2 Wks
+/- 2 Wks
+/- 1 Wk
+/- 2 Wks
+/- 2 Wks
+/- 1 Wk
+/- 2 Wks
+/- 2 Wks
HIPPA Release
X**1
Informed Consent
X
Full H&P
X
X
X
X
Limited H&P
X
X
X
X
X
Blood 
X
X
X
X
X
X
X
X
X
Pressure
Study Drug Administration
X
X
Stable
X
X
X
X
X
X
X
X
X
ACE or ARB
AE/SAE Events
X
X
X
X
X
X
X
CBC
X
X
X
X
X
X
X
CMP
X
X
X
X
X
X
X
UA
X
X
X
X
X
X
X
UP/Cr
X
X
X
X
X
X
X
HgbA1c **2
X
X
X
X
Tracrolimus 
Trough Levels (if in 
Tacrolimus Group)
X
X
Urinary 
X
X
X
X
X
X
X
VEGF
Urinary 
X
X
X
X
X
X
X
MCP-1
Urinary
X
X
X
X
X
X
X
TGF-beta
Urinary
X
X
X
X
X
X
X
Synapto
Urinary
X
X
X
X
X
X
X
Future Proteins
**1:  National PI & Local PI to review patient records for study eligibility prior to Pre-Randomization Visit 1
**3:  14 Days Post Randomization (Visit 4) will be optional for patients traveling from long distances.  Would request that patient visit nephrologist in home town if any adverse events of concern are reported.
**4:  14 Days Post End of Treatment (Visit 9) will be optional for patients traveling from long distances.  Would request that patient visit nephrologist in home town if any adverse events of concern are reported.
Pre-Screen_Randomization       
(V1 & V2)
**2:  HgbA1c will be optional for diabetic patients left to discretion of the site PI
Laboratory Assessments
Exploratory Laboratory Assessments