Conditions: C3 Glomerulopathy C3 Glomerulonephritis Dense Deposit Disease
Keywords: factor D fD Alternative pathway Complement mediated disease Membranoproliferative Glomerulonephritis Primary MPGN MPGN Mesangiocapillary Glomerulonephritis Idiopathic MPGN DDD C3GN
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 13
Healthy volunteers: no

Brief summary:
The primary purpose of this proof-of-concept clinical study was to evaluate the efficacy and safety of the study drug, ACH-0144471 (also known as danicopan and ALXN2040), in participants with C3G who also had significant proteinuria attributable to C3G.

Detailed description:

Arms:
arm 1: Danicopan was administered at a starting dose of 100 milligrams (mg) 3 times daily (TID) for the first 2 weeks, then dosage was to be increased to 200 mg TID for the remainder of the 6-month treatment period.

All participants who completed the double-blind treatment period were enrolled in the open-label extension period and were to receive danicopan 200 mg TID. arm 2: Placebo was administered TID during the 6-month treatment period.

All participants who completed the double-blind treatment period were enrolled in the open-label extension period and were to receive danicopan 200 mg TID.

Interventions: intervention 1: Danicopan intervention 2: Placebo
Intervention descriptions: intervention 1: Danicopan was administered as an oral tablet. intervention 2: Matching placebo was administered as an oral tablet.

Protocol document:
Prot_000.pdf: 
A Phase 2, Proof-of-Concept, Randomized, Double-Blinded, 
Placebo-Controlled Study of ACH-0144471 Treatment for 6 
Months in Patients with C3 Glomerulopathy (C3G), with an 
Open-Label Extension 
 
Unique Protocol ID: 
ACH471-204 
NCT Number: 
NCT03369236 
EudraCT Number:  
2017-000663-33 
Date of Protocol:  
15 May 2020 
 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 1 of 86 
CLINICAL TRIAL PROTOCOL 
ACH471-204 
Study Title: 
A Phase 2, Proof-of-Concept, Randomized, Double-Blinded, Placebo-
Controlled Study of ACH-0144471 Treatment for 6 Months in Patients 
with C3 Glomerulopathy (C3G), with an Open-Label Extension 
Study Number: 
ACH471-204 
Study Phase: 
2 
Product Name: 
ACH-0144471 Tablets 
Regulatory 
Agency and 
Registry 
Identification 
Numbers: 
 
IND: 129,916 
EudraCT: 2017-000663-33 
ClinicalTrials.gov: NCT03369236 
WHO UTN: U1111-1203-9076 
Indication: 
C3 Glomerulopathy (C3G) 
Investigators: 
 
Sponsor: 
Achillion Pharmaceuticals, Inc. (a subsidiary of Alexion 
Pharmaceuticals, Inc.) 
Medical Monitor: 
 
 
Direct 
 Mobile 
 
 
 
Date 
Original Protocol: 
25 August 2017 (Version 1.0) 
Amendment 1: 
25 October 2017 (Version 2.0) 
Amendment 2: 
12 December 2017 (Version 3.0) 
Amendment 3: 
07 March 2018 (Version 4.0) 
Amendment 4: 
02 November 2018 (Version 5.0) 
Amendment 5: 
15 February 2019 (Version 6.0) 
Amendment 6: 
19 June 2019 (Version 7.0) 
Amendment 7: 
15 May 2020 (Version 8.0) 
 
Confidentiality Statement 
The information contained in this document, particularly unpublished data, is the property or under the control of 
Achillion Pharmaceuticals, Inc. (a subsidiary of Alexion Pharmaceuticals, Inc.), and is provided to you in confidence 
as an investigator, potential investigator, or consultant for review by you, your staff and an applicable 
Institutional Review Board and/or Independent Ethics Committee. The information is only to be used by you and 
in connection with authorized clinical studies of the investigational drug described in the protocol. You will not 
disclose any of the information to others without written authorization from Achillion Pharmaceuticals, except to 
the extent necessary to obtain informed consent from those persons to whom the drug may be administered. 
PPD
PPD
PPD


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ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 3 of 86 
INVESTIGATOR’S SIGNATURE(S) 
Study Title: 
A Phase 2, Proof-of-Concept, Randomized, Double-Blinded, 
Placebo-Controlled Study of ACH-0144471 Treatment for 6 Months 
in Patients with C3 Glomerulopathy (C3G), with an Open-Label 
Extension  
Study Number: 
ACH471-204 
Protocol Version and 
Date 
15 May 2020 (Version 8.0) 
I have read the protocol described above. I agree to comply with all applicable regulations and to 
conduct the study as described in the protocol. 
 
 
<Name and Credentials/Title> 
<Affiliation/Company> 
<Address> 
<Address> 
<Phone Number> 
Date 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 4 of 86 
SYNOPSIS 
Sponsor 
Achillion Pharmaceuticals, Inc. (a subsidiary of Alexion Pharmaceuticals, Inc.) 
121 Seaport Blvd 
Boston, MA 02210 
Phone: 
 
Name of Finished 
Product 
ACH-0144471 Tablet: 50 and 100 mg  
Placebo for ACH-0144471 Tablet: 50, and 100 mg  
Name of Active 
Ingredient 
ACH-0144471 
Name of Inactive 
Ingredient 
ACH-0144471 Tablet: Lactose, Microcrystalline Cellulose, Croscarmellose Sodium, 
Sodium Lauryl Sulphate, Magnesium Stearate, Colloidal Silicon Dioxide, and 
Hypromellose Acetate Succinate. The coating components are: polyvinyl alcohol, 
titanium dioxide, macrogol/polyethylene glycol, and talc 
Placebo Tablet: Lactose, Microcrystalline Cellulose, Croscarmellose Sodium, Sodium 
Lauryl Sulphate, Magnesium Stearate, Colloidal Silicon Dioxide, and Hypromellose 
Acetate Succinate. The coating components are: polyvinyl alcohol, titanium dioxide, 
macrogol/polyethylene glycol, and talc 
Study Title 
A Phase 2, Proof-of-Concept, Randomized, Double-Blinded, Placebo-Controlled Study of 
ACH-0144471 Treatment for 6 Months in Patients with C3 Glomerulopathy (C3G), with 
an Open-Label Extension  
Study Number 
ACH471-204 
Study Phase 
Phase 2 
Primary Objective 
• 
To evaluate the efficacy, relative to placebo, of 6 months of oral ACH-0144471 in 
participants with C3G based on histologic scoring and proteinuria 
Secondary 
Objectives 
• 
To evaluate the clinical effect, relative to placebo, of 6 months of oral ACH-0144471 
in participants with C3G based on improvement in slope of estimated glomerular 
filtration rate (eGFR) relative to baseline over time  
• 
To evaluate for improvement in eGFR following treatment with ACH-0144471, 
relative to placebo 
• 
Where available, evaluate the change in measured (m) GFR relative to baseline at 
end of 6 months study drug treatment 
• 
To evaluate the safety and tolerability of ACH-0144471 in participants with C3G by 
assessing serious adverse events (SAEs) 
Study Design 
This is a randomized, placebo-controlled, double-blinded study with 6 months of dosing, 
followed by a 6-month open-label extended treatment period and up to an additional 21 
months long-term follow-up period. The study will include approximately 20 subjects. 
Participants enrolled a will be randomized 1:1 to ACH-0144471 or placebo, stratified by 
the disease diagnosis (dense deposit disease [DDD] or C3 glomerulonephritis [C3GN]) 
and renal function at study entry (eGFR ≥60 mL/min/1.73 m2 or <60 mL/min/1.73 m2). 
For all participants, eligibility will be confirmed based on the results from screening 
eligibility assessments. Once eligibility is confirmed, arrangements can be made for a 
renal biopsy and/or vaccination, as discussed below. 
PPD


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 5 of 86 
The initial screening visit must occur no more than 75 days before the first dose date. 
All participants should be vaccinated against Haemophilus influenzae (H. influenzae), 
Streptococcus pneumoniae (S. pneumoniae), and Neisseria meningitidis (N. meningitidis) 
to minimize the risk of serious infection with an encapsulated organism.  Vaccinations 
should be administered at least 2 weeks before the start of dosing with ACH-014447 
according to Advisory Committee on Immunization Practices (ACIP) guidelines, as 
described in Section 6.4, unless otherwise recommended by national and/or local 
vaccination guidelines or precluded by licenses or availability. The PI may institute 
additional prophylactic measures, including the use of prophylactic antibiotics, if deemed 
appropriate by local clinical practice and/or guidelines for treatment with a complement 
inhibitor. 
The starting dosage of ACH-0144471 will be 100 mg three times daily (TID), a total 
daily dose of 300 mg. After 2 weeks of treatment, dosing will be escalated to 200 mg 
TID. Additional dosage regimens may be investigated if supported by emerging data 
from this and other clinical studies. Upon treatment discontinuation, regardless of the 
timing or reasons for discontinuation, a 6-day taper period is required unless the PI 
determines this taper period poses a risk to the participant. The taper period is in place to 
prevent the theoretical risk of marked increase or rebound in complement activity, as 
described in Section 5.2.1. 
Because C3G is a serious and chronic disease, this study includes an extended treatment 
period.  All participants entering the Extended Treatment Period will receive 
ACH-0144471; those on active treatment will continue to receive daily treatment with 
ACH-0144471 and safety and efficacy monitoring, while those on placebo treatment will 
transition to active treatment with appropriate safety and efficacy monitoring. 
Study Visit 
Schedule 
On Day 1, the required pre-dose assessments will be obtained, followed by administration 
of the first dose of study drug. Additional outpatient clinic visits will occur as described 
in the Schedule of Assessments (Appendix 1) for the rest of the Blinded Treatment Period 
(to Week 28).  
At each visit, safety and efficacy will be assessed. Safety assessments may include 
physical examination, vital signs, electrocardiogram (ECG) measurements, and safety 
laboratory testing. Samples will be collected for measurement of complement biomarkers 
at selected visits as specified in the Schedule of Assessments (Appendix 1). Quality of 
Life and Patient Reported Outcomes assessments will occur according to the Schedule of 
Assessments (Appendix 1). 
Upon completion of the Blinded Treatment Period, participants may continue in the open-
label Extended Treatment Period in which all participants will receive active treatment.  
The 6-month Open Label Extension will end at Week 52, participants may continue to the 
Long-Term Follow-up period for up to an additional 21 months. Participants will 
continue on ACH-0144471 until up to Week 143. 
At the end of treatment, a 6-day taper will occur to allow gradual return of complement 
activity to baseline. If a participant discontinues from the study early, study participation 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 6 of 86 
is not necessarily immediately terminated. Instead, whenever possible, dosing of 
ACH-0144471 should be tapered over 6 days. Whether dosing is tapered or not, all 
participants should return for two follow-up visits, 2 and 4 weeks after the last dose of 
study drug 
Treatment Groups: 
There will be two treatment groups, with participants randomized 1:1 to either active 
treatment with ACH-0144471 or to placebo, stratified by disease diagnosis (DDD or 
C3GN) and renal function at study entry (eGFR ≥60 mL/min/1.73 m2 or 
<60 mL/min/1.73 m2).  
Study Population 
Participants must have biopsy-confirmed DDD or C3GN, have not undergone renal 
transplant, and have significant proteinuria  
Number of 
Participants 
20  
Inclusion Criteria 
Each participant must meet all of the following criteria to be enrolled in this study: 
1. Must have biopsy-confirmed primary C3G 
2. Must be 17 years of age or older and capable of swallowing tablets 
3. Must have clinical evidence of ongoing disease based on significant proteinuria 
(defined as ≥500 mg/day of protein in a 24-hour urine or equivalent on spot 
urine) attributable to C3G disease in the opinion of the PI, and present prior to 
study entry and confirmed during Screening 
4. If on corticosteroids, anti-hypertensive medications, anti-proteinuric medications 
(e.g., ACE inhibitors or angiotensin receptor blockers [ARBs]), or 
mycophenolate mofetil (MMF), must be on a stable dose for at least 2 weeks 
prior to screening 
5. Female participants of childbearing potential must agree to use an acceptable 
method of contraception (as defined in Section 5.5.4) from the date of signing 
the informed consent to the first day of dosing (Day 1), and must agree to use a 
highly effective form of contraception (as defined in Section 5.5.4) from the first 
day of dosing to 30 days after their last dose of study drug. Female participants 
of childbearing potential must also have a negative serum pregnancy test during 
Screening and negative urine pregnancy test on Day 1. Female participants of 
non-childbearing potential need not employ a method of contraception 
6. Non-sterile male participants must agree to use a highly effective form of 
contraception (as defined in Section 5.5.4) with their partner(s) of childbearing 
potential from the first day of dosing to 90 days after their last dose of study 
drug. 
Male participants who are surgically sterile need not employ additional 
contraception. 
Male participants must agree not to donate sperm while enrolled in this study 
and for 90 days after their last dose of study drug. 
7. Adult participants must be capable of providing written informed consent and 
adolescent participants must be capable of providing written assent. All 
participants must be willing and able to comply with the requirements and 
restrictions listed in the consent form and with all procedures in the protocol, 
including, the visit schedule, the treatment plan, the schedule for laboratory 
testing, and other study procedures 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 7 of 86 
8. Must be up-to-date on routine vaccinations, or willing to be brought up-to-date, 
based on local guidelines 
9. Must have access to emergency medical care 
Exclusion Criteria 
Participants who meet any of the following criteria will be excluded from the study. 
1. Have a history or presence of any clinically relevant co-morbidities that would 
make the participant inappropriate for the study (for example, a comorbidity 
which is likely to result in deterioration of the participant’s condition, affect the 
participant’s safety during the study, or confound the results of the study), in the 
opinion of the PI 
2. Have ever received ACH-0144471 
3. Have a pre-treatment renal biopsy, or a recent historical biopsy available for 
review, which shows more than 50% global fibrosis or more than 50% of 
glomeruli with cellular crescents 
4. Have an estimated GFR <30 mL/min/1.73 m2 at the time of screening or at any 
time over the preceding four weeks 
5. Is a renal transplant recipient or receiving renal replacement therapy 
6. Have a history of a major organ transplant (e.g., heart, lung, kidney, liver) or 
hematopoietic stem cell/marrow transplant  
7. Have evidence of monoclonal gammopathy of unclear significance (MGUS), 
infections, malignancy, autoimmune diseases, or other conditions to which C3G 
is secondary 
8. Have other renal diseases that would interfere with interpretation of the study  
9. Have been diagnosed with or show evidence of hepatobiliary cholestasis  
10. Females who are pregnant, nursing, or planning to become pregnant during the 
study or within 90 days of study drug administration  
11. Have a history of febrile illness, a body temperature >38°C, or other evidence of 
a clinically significant active infection, within 14 days prior to study drug 
administration 
12. Have evidence of human immunodeficiency virus (HIV), hepatitis B infection, 
or active hepatitis C infection at Screening 
13. Have a history of meningococcal infection within the prior year 
14. Have a history of hypersensitivity reactions to commonly used antibacterial 
agents, including beta-lactams, penicillin, aminopenicillins, fluoroquinolones, 
cephalosporins, and carbapenems, which, in the opinion of the investigator 
and/or an appropriately qualified immunology or infectious disease expert, 
would make it difficult to properly provide either empiric antibiotic therapy or 
treat an active infection. 
15. Have participated in a clinical study in which an investigational drug was given 
within 30 days, or within 5 half-lives of the investigational drug, whichever is 
longer, prior to the first dose of study drug  
16. Have received eculizumab at any dose or interval within the past 50 days prior 
to the first dose of study drug 
17. Have received tacrolimus or cyclosporine within 2 weeks of the first dose of 
study drug 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 8 of 86 
18. Have any of the following laboratory abnormalities at screening:  
• 
Alanine transaminase (ALT) > upper limit of normal (ULN) 
• 
Aspartate aminotransferase (AST) > ULN 
• 
Absolute neutrophil counts (ANC) <1,000/μL 
• 
Total bilirubin >1.5× ULN 
• 
Indirect bilirubin > ULN 
• 
Any laboratory abnormality that, in the opinion of the PI, would make the 
participant inappropriate for the study 
19. Are unwilling or unable to comply with the study protocol for any reason 
Stopping Rules for 
Individual 
Participants 
Any individual participant who meets any of the following criteria may be discontinued 
from further dosing: 
• 
The participant experiences a SUSAR 
• 
The PI believes that participant continuation in the study is not advisable, or the 
participant withdraws from the study or meets one of the conditions described in 
Section 6.21, including, but not limited to: 
o The participant becomes pregnant 
o Intercurrent illness that would, in the judgment of the investigator, affect 
assessments of clinical status to a significant degree 
o Participant requests to discontinue for any reason 
Discontinuation of treatment should also be considered if:  
• 
ALT or AST >8× ULN  
• 
ALT or AST >5× ULN for more than 2 weeks  
• 
ALT or AST >3× ULN and concomitant total bilirubin >2× ULN and/or 
International Normalized Ratio [INR]* >1.5 
• 
ALT or AST >3× ULN with the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%) 
• 
If there is a marked prolongation of the QT/QTc interval during treatment with the 
study drug, especially if the measurement is obtained from more than one ECG 
* Participants, particularly those with nephrotic syndrome, may be receiving ongoing 
warfarin, resulting in increased INR values. The PI should evaluate INR in the context of 
any concomitant medications to determine if any observed increases are due to an effect 
on liver function or are secondary to anticoagulation. 
Upon dosing termination, a participant will be expected to complete the study, if possible, 
by complying with the schedule for the Taper Period (if relevant) and Follow Up Period. 
Of note, additional visits beyond those specified in the protocol may be required if 
needed to ensure adequate safety monitoring. 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 9 of 86 
Duration of 
Treatment, 
Confinement, and 
Total Study 
Participation 
Screening is up to 75 days. Treatment in the Blinded Treatment Period is 6 months with 
an additional 6 months of open- label treatment period and up to a 21-month long-term 
extension. The study is up to 33 months long, and follow-up may be an additional 
28 days if not going into an extension study. Therefore, a participant’s participation will 
up to 37 months. 
Safety 
Assessments: 
Safety assessments will include assessment of AEs, clinical laboratory tests, physical 
examination findings, vital signs measurements, and 12-lead ECG recordings at 
screening, baseline, and at various time points during the study as listed in the schedule of 
assessments (Appendix 1). 
Pharmacodynamic 
and Efficacy 
Assessments 
Pharmacodynamics will be evaluated using serum, plasma, and/or urine collected at the 
time points listed in the Schedule of Assessments (Appendix 1). 
Samples will be collected and retained for non-genetic complement-associated biomarker 
testing. 
Patient-Reported 
Outcomes 
Assessments 
Patient-reported outcome (PRO) questionnaires will be administered at various time 
points as specified in the Schedule of Assessments in Appendix 1, to assess participants’ 
health-related quality of life, fatigue, and kidney-related symptoms, and to determine 
health states value over the course of treatment with ACH-0144471/placebo.  The 
questionnaires are: 
Adult participants: 
• 
KDQOL-SF v1.3 questionnaire 
• 
FACIT-Fatigue scale version 4.0 
• 
EQ-5D-3L questionnaire 
Statistical 
Methods:  
Primary efficacy endpoints: 
• 
Change from baseline in biopsy, based on a score incorporating changes in both the 
activity index and C3 staining, at the end of 6 months of treatment 
• 
Number and percent of participants with reduction in proteinuria relative to baseline 
at the end of 6 months of treatment 
Secondary efficacy endpoints: 
• 
Change and percent change from baseline in proteinuria over the 6 months of 
treatment 
• 
Change and percent change from baseline in eGFR over the 6 months of treatment  
• 
Number and percent of patients with significant improvement relative to baseline in 
eGFR at the end of 6 months of treatment  
• 
Descriptive analysis of slope of GFR from baseline to 6 months 
• 
Descriptive analysis of slope of GFR after 12 months of ACH-0144471 therapy 
 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 10 of 86 
 
 
TABLE OF CONTENTS 
SPONSOR SIGNATURE(S) ...........................................................................................................2 
INVESTIGATOR’S SIGNATURE(S) ............................................................................................3 
SYNOPSIS ......................................................................................................................................4 
TABLE OF CONTENTS ...............................................................................................................10 
LIST OF TABLES .........................................................................................................................14 
LIST OF FIGURES .......................................................................................................................15 
LIST OF APPENDICES ................................................................................................................15 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ................................................16 
1. 
INTRODUCTION ......................................................................................................19 
1.1. 
Previous Experience with ACH-0144471 ..................................................................19 
1.2. 
Background .................................................................................................................19 
1.2.1. 
Complement Factor D .................................................................................................19 
1.2.2. 
C3 Glomerulopathy ....................................................................................................20 
2. 
STUDY OBJECTIVES ..............................................................................................22 
2.1. 
Primary Objective .......................................................................................................22 
2.2. 
Secondary Objectives .................................................................................................22 
2.3. 
Exploratory Objectives ...............................................................................................22 
2.3.1. 
Quality of Life Objectives ..........................................................................................22 
3. 
INVESTIGATIONAL PLAN .....................................................................................23 
3.1. 
Overall Study Design and Plan ...................................................................................23 
3.2. 
Rationale for Study Design .........................................................................................24 
3.2.1. 
Justification of Design ................................................................................................24 
3.2.1.1. 
Participant Population .................................................................................................25 
3.2.1.2. 
Endpoints ....................................................................................................................25 
3.2.1.3. 
Duration of Treatment ................................................................................................27 
3.2.1.4. 
Safety Monitoring Plan ...............................................................................................28 
3.2.2. 
Justification of Dose ...................................................................................................29 
3.2.3. 
Stopping Criteria and End-of-Study Definition ..........................................................29 
3.2.3.1. 
Study Stopping Rules .................................................................................................29 
3.2.3.2. 
Stopping Rules for Individual Participants .................................................................29 
4. 
STUDY POPULATION SELECTION ......................................................................31 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 11 of 86 
4.1. 
Study Population .........................................................................................................31 
4.2. 
Inclusion Criteria ........................................................................................................31 
4.3. 
Exclusion Criteria .......................................................................................................32 
5. 
STUDY TREATMENT(S) .........................................................................................34 
5.1. 
Description of Treatment(s) ........................................................................................34 
5.1.1. 
Study Drug ..................................................................................................................34 
5.1.2. 
ACH-0144471 .............................................................................................................34 
5.1.3. 
Placebo ........................................................................................................................34 
5.2. 
Treatment(s) Administered .........................................................................................34 
5.2.1. 
ACH-0144471 or Placebo ...........................................................................................34 
5.2.2. 
Vaccines ......................................................................................................................35 
5.2.3. 
Prophylactic Antibiotics .............................................................................................35 
5.3. 
Selection of Timing and Dose for Each Participant ...................................................35 
5.3.1. 
Clinic Visit Dose Administration Instructions ...........................................................35 
5.3.2. 
Home Dose Administration Instructions ....................................................................36 
5.3.3. 
Dose Adjustment ........................................................................................................36 
5.4. 
Method of Assigning Participants to Treatment Groups ............................................36 
5.5. 
Restrictions .................................................................................................................37 
5.5.1. 
Prior and Concomitant Therapy ..................................................................................37 
5.5.2. 
Fluid and Food Intake .................................................................................................38 
5.5.3. 
Participant Activity and Other Restrictions ................................................................38 
5.5.4. 
Contraception ..............................................................................................................38 
5.5.4.1. 
Contraception for Male Participants ...........................................................................38 
5.5.4.2. 
Contraception for Female Participants .......................................................................39 
5.6. 
Treatment Compliance ................................................................................................40 
5.7. 
Packaging and Labeling ..............................................................................................40 
5.8. 
Storage and Accountability .........................................................................................41 
5.9. 
Investigational Product Retention at Study Site .........................................................41 
6. 
STUDY PROCEDURES ............................................................................................42 
6.1. 
Informed Consent .......................................................................................................42 
6.2. 
Medical History ..........................................................................................................42 
6.3. 
Percutaneous Renal Biopsy ........................................................................................42 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 12 of 86 
6.3.1. 
Renal Biopsy ...............................................................................................................43 
6.4. 
Vaccination .................................................................................................................43 
6.5. 
Prophylactic Antibiotics .............................................................................................43 
6.6. 
Urine Collection ..........................................................................................................44 
6.6.1. 
24-Hour Urine Collection ...........................................................................................44 
6.6.2. 
First Morning Urine Collection ..................................................................................44 
6.7. 
Physical Examination .................................................................................................44 
6.8. 
Vital Signs ..................................................................................................................45 
6.9. 
Body Temperature ......................................................................................................45 
6.10. 
Electrocardiography ....................................................................................................46 
6.11. 
Clinical Laboratory Tests ...........................................................................................46 
6.12. 
Pregnancy Testing ......................................................................................................48 
6.13. 
Sample Collection, Storage, and Shipping .................................................................48 
6.13.1. 
Blood and Urine Collection for Complement Assays ................................................48 
6.13.2. 
Blood Collection for Genetic Complement-Associated Biomarker Testing ..............49 
6.13.3. 
Blood Volumes ...........................................................................................................49 
6.14. 
Dispensing Study Drug ...............................................................................................50 
6.15. 
Safety Assessments .....................................................................................................50 
6.16. 
Pharmacodynamic Assessments .................................................................................50 
6.17. 
Patient-Reported Outcomes Assessments ...................................................................51 
6.17.1. 
Quality of Life Questionnaires ...................................................................................51 
6.18. 
Adverse Events Assessments ......................................................................................51 
6.18.1. 
Definitions ..................................................................................................................51 
6.18.2. 
Criteria for Assessing Seriousness ..............................................................................53 
6.18.3. 
Documentation and Reporting of Adverse Events .....................................................53 
6.18.4. 
Treatment and Follow-Up of Adverse Events ............................................................54 
6.18.5. 
Timeframe for Collection of Adverse Events .............................................................54 
6.18.6. 
Severity and Grading of Adverse Events ....................................................................54 
6.18.7. 
Assessment of Causality .............................................................................................55 
6.18.8. 
Pregnancy ...................................................................................................................55 
6.18.9. 
Reporting Serious Adverse Events .............................................................................56 
6.18.10. 
Investigator Reporting Requirements for SAEs .........................................................57 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 13 of 86 
6.19. 
Concomitant Medication Assessments .......................................................................57 
6.20. 
Monitoring Participant Safety .....................................................................................57 
6.21. 
Removal of Participants from the Trial or Study Drug ..............................................57 
6.22. 
Study Assessments When Clinic Visits are Not Possible due to the COVID-
19 Pandemic ................................................................................................................58 
6.23. 
Study Drug Compliance and Supply When Clinic Visits are Not Possible ...............59 
6.24. 
Renal Biopsies When Clinic Visits are Not Possible .................................................59 
7. 
STUDY ACTIVITIES ................................................................................................60 
7.1. 
Screening Period (Days –75 to -1) ..............................................................................60 
7.1.1. 
Screening and Pre-Treatment Renal Biopsy ...............................................................60 
7.1.2. 
Vaccination .................................................................................................................61 
7.2. 
Blinded Treatment Period ...........................................................................................61 
7.3. 
Extended Treatment Period ........................................................................................61 
7.4. 
21- Month Long-Term Follow-up ..............................................................................62 
7.5. 
Taper Period ................................................................................................................62 
7.6. 
Follow-Up Period .......................................................................................................63 
7.7. 
Early Termination from the Study ..............................................................................63 
7.8. 
Unscheduled Visits .....................................................................................................63 
8. 
QUALITY CONTROL AND ASSURANCE ............................................................64 
8.1. 
Routine Monitoring ....................................................................................................64 
8.2. 
Site Audits ..................................................................................................................64 
9. 
PLANNED STATISTICAL METHODS ...................................................................65 
9.1. 
General Considerations ...............................................................................................65 
9.2. 
Determination of Sample Size ....................................................................................65 
9.3. 
Analysis Populations ..................................................................................................65 
9.4. 
Demographics and Baseline Characteristics ...............................................................65 
9.5. 
Efficacy, including Pharmacodynamics Analysis ......................................................66 
9.6. 
Safety Analysis ...........................................................................................................67 
10. 
ADMINISTRATIVE CONSIDERATIONS ..............................................................68 
10.1. 
Investigators and Study Administrative Structure ......................................................68 
10.2. 
Institutional Review Board (IRB) or Independent Ethics Committee (IEC) 
and Regulatory Approval ............................................................................................68 
10.2.1. 
Ethical Approval .........................................................................................................68 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 14 of 86 
10.2.2. 
Regulatory Approval ..................................................................................................68 
10.2.3. 
Amendments ...............................................................................................................68 
10.3. 
Ethical Conduct of the Study ......................................................................................68 
10.4. 
Participant Information and Consent ..........................................................................69 
10.5. 
Participant Confidentiality ..........................................................................................69 
10.6. 
Study Monitoring ........................................................................................................69 
10.6.1. 
Access to Information for Monitoring ........................................................................69 
10.6.2. 
Access to Information for Auditing or Inspections ....................................................69 
10.7. 
Case Report Forms and Study Records ......................................................................70 
10.7.1. 
Recording of Data .......................................................................................................70 
10.7.2. 
Source Documentation and Medical/Study Records ..................................................70 
10.8. 
Protocol Deviations ....................................................................................................70 
10.9. 
Access to Source Documentation ...............................................................................70 
10.10. 
Data Generation and Analysis ....................................................................................71 
10.11. 
Retention of Data ........................................................................................................71 
10.12. 
Study and Site Closure ................................................................................................71 
10.13. 
Final Report, Publication and Disclosure Policy ........................................................72 
11. 
REFERENCES ...........................................................................................................73 
12. 
APPENDICES ............................................................................................................76 
 
LIST OF TABLES 
Table 1. 
ACH-0144471 Taper Schedule ..............................................................................35 
Table 2. 
Clinical Laboratory Tests .......................................................................................47 
Table 3. 
Approximate Total Blood Volumes .......................................................................50 
Table 4. 
Schedule of Assessments – Screening through Week 8 ........................................76 
Table 5. 
Schedule of Assessments – Week 10 through Week 28 ........................................79 
Table 6. 
Schedule of Assessments – Extended Treatment Period .......................................81 
Table 7. 
Schedule of Assessments – 21 Month Long-Term Follow-up, with Taper and 
Follow-up ...............................................................................................................83 
 
 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 15 of 86 
LIST OF FIGURES 
 Figure 1. 
Study Schematic.....................................................................................................24 
LIST OF APPENDICES 
Appendix 1. 
Schedule of Assessments .......................................................................................76 
Appendix 2. 
Fever Management Plan ........................................................................................85 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 16 of 86 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Definition 
Ab 
Antibody 
ACE 
Angiotensin converting enzyme 
AE 
Adverse event 
ALP 
Alkaline phosphatase 
ALT 
Alanine transaminase 
ANC 
Absolute neutrophil count 
AP 
Alternative Pathway (of complement)  
ARBs 
Angiotensin receptor blockers 
AST 
Aspartate aminotransferase 
AUC  
Area under the curve 
BA 
Bioavailability 
Ba 
Ba fragment of complement factor B 
Bb 
Bb fragment of complement factor B 
BID 
“bis in die” or twice daily 
BMI 
Body mass index 
BP 
Blood pressure 
°C 
Degrees Celsius 
C3 
C3 complement protein 
C3a 
Complement cleavage fraction of C3 
C4 
C4 complement protein 
C5 
C5 complement protein 
C5a 
Complement cleavage fraction of C5 
C6 
C6 complement protein 
CFHR-5 
Complement Factor H Related – 5 gene 
C3G 
C3 glomerulopathy 
C3GN 
C3 glomerulonephritis 
CFU 
Colony-forming unit 
CKD 
Chronic kidney disease 
CKD-EPI 
Chronic kidney disease - Epidemiology collaboration 
Cmax 
Maximum plasma concentration 
CP 
Classical pathway (of complement) 
CRF 
Case report form 
CT 
Computed tomography  
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP 
Cytochrome P450 
DDD 
Dense deposit disease 
DDI 
Drug-drug interaction 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
eGFR 
Estimated glomerular filtration rate 
ELISA 
Enzyme-linked immunosorbent assay 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 17 of 86 
Abbreviation 
Definition 
EM 
Electron microscopy 
EQ-5D-3L 
Three-level version of EuroQol 5 Dimensions questionnaire 
ESRD 
End stage renal disease 
FACIT-Fatigue 
Functional Assessment of Chronic Illness Therapy-Fatigue scale version 4.0 
fB 
(Complement) Factor B 
fD 
(Complement) Factor D 
FDA 
Food and Drug Administration 
fH 
(Complement) Factor H 
fI 
(Complement) Factor I 
FSH  
Follicle stimulating hormone 
GCP 
Good Clinical Practice 
HbsAg 
Hepatitis B surface antigen 
Hct 
Hematocrit 
HCV 
Hepatitis C virus 
Hgb 
Hemoglobin  
H&E 
Hematoxylin & eosin stain 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HIV 
Human immunodeficiency virus 
HRQOL 
Health-related quality of life 
HR 
Heart rate 
iC3b 
Complement cleavage fragment of C3b 
IC-MPGN 
Immune-Complex Membranoproliferative Glomerulonephritis  
ICH 
International Conference on Harmonisation 
IEC  
Independent Ethics Committee 
INR 
International normalized ratio 
IRB 
Institutional review board 
IUD 
Intrauterine device 
IUS 
Intrauterine hormone-releasing system 
kDa 
Kilodalton 
KDQOL-SF 
v1.3 
Kidney Disease Quality of Life short form questionnaire version 1.3 
LFC 
Liquid filled capsule 
LLN 
Lower limit of normal 
LP 
Lectin pathway (of complement) 
MAD 
Multiple-ascending dose 
MCP 
Membrane Co-Factor Protein 
MDRD 
Modification of Diet in Renal Disease 
MedDRA 
Medical Dictionary for Regulatory Activities 
MenB 
Meningococcal B 
MGUS 
Monoclonal gammopathy of unclear significance 
MM 
Medical monitor 
MMF 
Mycophenolate mofetil 
MPA 
Mycophenolic acid 
msec 
Millisecond 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 18 of 86 
Abbreviation 
Definition 
NIH 
National Institute of Health (US) 
NOAEL 
No observed adverse effect level 
PAS 
Periodic acid-Schiff 
PD 
Pharmacodynamic(s) 
PI 
Principal investigator 
PK 
Pharmacokinetic(s) 
POC 
Proof of Concept 
PR interval 
Period that extends from the beginning of the P wave until the beginning of the QRS complex 
PRO 
Patient-reported outcome 
PT 
Prothrombin time 
PTT 
Partial thromboplastin time 
QRS 
Group of electrocardiogram waves comprising the Q, R, and S waves 
QT 
Period (in milliseconds) from the beginning of the QRS complex until the end of the T wave 
QTcF 
QT interval Fridericia Correction Formula  
RBC  
Red blood cells 
Relative BA 
Relative bioavailability study 
RR 
Respiration rate 
SAD 
Single-ascending dose 
SAE  
Serious adverse event 
SAP  
Statistical Analysis Plan 
sC5b-9 
Soluble terminal complement complex  
SD 
Standard deviation 
SLE 
Systemic lupus erythematosus 
SUSAR 
Serious, unexpected suspected adverse reaction 
TEAE 
Treatment-emergent adverse event 
THBD 
Thrombomodulin 
tmax 
Time after administration of a drug when the maximum plasma concentration is reached 
UGT 
UDP-gluronosyltransferase 
ULN 
Upper limit of normal 
WBC  
White blood cells 
Wk 
Week 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 19 of 86 
1. 
INTRODUCTION 
ACH-0144471, a small molecule, orally administered, factor D (fD) inhibitor, is in development 
by Achillion Pharmaceuticals, Inc. (“Achillion”, or the sponsor), a subsidiary of Alexion 
Pharmaceuticals, Inc., for the treatment of complement-related diseases, such as paroxysmal 
nocturnal hemoglobinuria (PNH) and C3 glomerulopathy (C3G). Factor D is a serine protease 
that catalyzes the cleavage of factor B, a rate-limiting step in the alternative pathway (AP) of 
complement. By inhibiting fD, ACH-0144471 potently and specifically inhibits AP activity. 
Because C3G is a disease of AP hyperactivity, ACH-0144471 represents an ideal therapeutic 
approach to C3G, as it has the potential to reverse the underlying pathophysiology of the disease. 
Other renal diseases, such as primary immunoglobulin-associated membranoproliferative 
glomerulonephritis (MPGN), in which complement also likely plays a key role, may also be 
attractive as future therapeutic targets. 
This protocol is a randomized, placebo-controlled, double-blinded study in which participants 
with C3G will receive ACH-0144471 or placebo for approximately 6 months, followed by an 
open-label extension of an additional 6 months and up to an additional 21 months long-term 
follow-up. In preceding studies, it has been demonstrated that ACH-0144471 inhibits AP 
activity. This study will assess whether inhibition of AP activity by ACH-0144471 results in 
improvements in the clinical manifestations of C3G. Doses for this study were selected based on 
available data from the completed and ongoing studies in healthy volunteers, and from 
paroxysmal nocturnal hemoglobinuria (PNH) participants and C3G patients treated in other 
clinical studies. 
1.1. 
Previous Experience with ACH-0144471 
A detailed description of the chemistry, pharmacology, efficacy, and safety of ACH-0144471 is 
provided in the Investigator’s Brochure [1]. 
1.2. 
Background 
1.2.1. 
Complement Factor D 
Factor D is one of nine serine proteases in the complement system. It is a highly specific enzyme 
with only one known substrate, fB. Of all the complement proteins, it has the lowest abundance 
in serum with a concentration of approximately 2 µg/mL and is the rate-limiting step of AP 
activation [2, 3]. It is a low molecular weight protein (24 kDa) that is primarily produced by 
adipocytes, but can also be produced and secreted by monocytes/macrophages and astrocytes in 
humans [2, 3]. Due to its small size, it is freely filtered at the glomerulus, and then taken up by 
the proximal tubule cell where it is catabolized with an estimated fractional catabolic rate of 60% 
per hour. It is this rapid catabolism that is responsible for maintaining low circulating fD levels. 
As a result, renal dysfunction is associated with elevated fD levels, which may lead to increased 
alternative pathway activity and inflammation [4, 5]. The biochemical, physiological, and 
functional features of fD make it an attractive target for pharmacological inhibition as this may 
prove useful in the treatment of a wide spectrum of complement-mediated diseases, including 
C3G. 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
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1.2.2. 
C3 Glomerulopathy  
C3 glomerulopathy (C3G) is an ultra-rare disease with an incidence rate of approximately 2 per 
million people worldwide [6, 7].  It is widely accepted that C3G is attributable to excessive 
alternative pathway (AP) activity [8]. Although the disease is typically diagnosed during early 
adulthood in a majority of patients, the manifestations of glomerular C3 deposition can be 
detected in childhood and thus, it may be clinically meaningful to treat patients as young as 12 
years of age [7, 9, 10]. The clinical course of C3G is characterized by variable amounts of 
proteinuria, hematuria, hypertension, and decreased renal function, with approximately 30% to 
50% of patients reaching end-stage renal disease (ESRD) within 10 years of diagnosis [7, 11, 12, 
13].  The diagnosis is based on predominant deposition of C3 in the glomerulus on renal biopsy 
along with clinical evidence of AP hyperactivity. C3G can be further subdivided into two 
separate entities, dense deposit disease (DDD) and C3 glomerulonephritis (C3GN), based on 
electron microscopic features of the renal pathology [8]. Although the two disorders have similar 
clinical features, DDD tends to present earlier in life than C3GN. However, both diseases can 
present in either childhood or adulthood [13]. 
Unfortunately, no specific therapy has proven effective for the treatment of C3G. Care is 
therefore largely non-specific and supportive. Given the lack of available therapeutic options, 
immunosuppressive and plasma infusion/exchange therapy are often attempted, as a subset of 
patients may benefit [13, 14]. Treatment is otherwise focused on management of hypertension, 
proteinuria and the manifestations of chronic kidney disease. 
The overall prognosis of C3G is poor, with approximately 30% to 50% of patients progressing to 
ESRD within 10 years of diagnosis. Dialysis and renal transplantation are options available for 
patients who reach ESRD; however, disease recurrence is frequent after transplantation, 
occurring in more than 50% of patients. Only about 50% of patients have a functioning graft 5 
years after transplantation, which is significantly lower than renal graft survival in other settings 
[13, 14, 15]. 
Studies in animal models have indicated that the pathophysiology of C3G strongly relates to an 
excessive AP activity at the level of the C3 convertase. Specifically, mouse factor H-deficient 
animals have evidence of uncontrolled alternative pathway activation, with low plasma levels of 
intact C3, high levels of C3 breakdown product and renal pathology consistent with C3G; yet, in 
mice deficient in both factor H (fH) and fD (knock-out mice), serum C3 levels were similar to 
wild-type and dense deposits were not present in the kidneys [16, 17]. These studies confirmed 
that removal of fD prevented the renal pathogenesis of C3G in the factor H-deficient mice. 
Given that the pathophysiology of C3G derives from excessive C3 activation through the AP, 
treatment of the disease with an AP complement inhibitor is logical. Eculizumab, the only 
commercially available complement inhibitor, has been tested in patients with C3G, even though 
its mechanism of action (targeting the terminal complement pathway) would not be expected to 
affect C3 activation. Based on the published results of an open-label trial in 20 patients, the 
general consensus is that only a subset of patients appears to benefit from eculizumab therapy; 
however, identification of these patients prior to treatment remains a challenge [8, 13, 14, 18].  It 
has been suggested that response to eculizumab may be more likely in those patients with 
elevated soluble C5b-9 levels, indicative of excessive terminal pathway activity, although this 
hypothesis remains to be established [18]. 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 21 of 86 
A fD inhibitor like ACH-0144471, which inhibits directly at the level of the AP C3 convertase 
formation, provides a more targeted rationale for efficacy than existing complement inhibitors 
that target the terminal complement pathway. This hypothesis is supported by animal data in 
which the renal disease observed with factor H deficiency, which is similar to human C3G, was 
completely prevented in the setting of simultaneous fD or fB deficiency [16, 17]. In contrast C5 
deficiency only ameliorated, but did not prevent, renal disease. Furthermore, C6 deficiency had 
no effect on the renal disease in fH deficient mice. Taken together, the data from the C5 and C6 
deficient mice provide evidence that the membrane attack complex itself plays little role in renal 
pathogenesis of C3G in the setting of fH deficiency, but that C5a production may be a factor 
contributing to disease [13, 19]. 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 22 of 86 
2. 
STUDY OBJECTIVES 
2.1. 
Primary Objective 
The primary objective of this study is to evaluate the efficacy, relative to placebo, of 6 months of 
oral treatment with ACH-0144471 in participants with C3G. 
Evaluation of efficacy will be based on improvement in histologic scoring and proteinuria 
relative to baseline. 
2.2. 
Secondary Objectives 
The secondary objectives of this study are: 
• To evaluate the clinical effect relative to placebo, of 6 months of oral ACH-0144471 in 
participants with C3G based on improvement in slope of estimated glomerular filtration rate 
(eGFR) relative to baseline over time 
• To evaluate the clinical effect, relative to placebo, of 6 months of oral ACH-0144471 in 
participants with C3G based on improvement in estimated glomerular filtration rate (eGFR) 
relative to baseline over time  
• Where available, evaluate the change in measured (m) GFR relative to baseline at end of 
6 months study drug treatment. 
• To evaluate the safety and tolerability of 6 months of oral treatment with ACH-0144471 in 
participants with C3G by assessing serious adverse events (SAEs). 
2.3. 
Exploratory Objectives 
Complement Biomarkers 
• To evaluate the change in Complement proteins C3, Bb and Ba (split products) relative to 
baseline and compare these changes as they relate to clinical outcomes described in primary 
and secondary objectives. 
• To evaluate the PK measures as they relate to complement biomarkers and alternative 
pathway inhibition assays (AP Weislab and AP Hemolysis) 
• To evaluate the effect of -4471 therapy on complement biomarkers compared with placebo at 
6 months relative to baseline 
2.3.1. 
Quality of Life Objectives 
The quality of life (QoL) objectives of the study are: 
• To evaluate kidney disease and health-related quality of life instruments in participants 
with C3G, over the course of ACH-0144471/placebo treatment 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 23 of 86 
3. 
INVESTIGATIONAL PLAN 
3.1. 
Overall Study Design and Plan 
This is a randomized, placebo-controlled, double-blinded study with 6 months of dosing, 
followed by a 6-month open-label extended treatment period and up to an additional 21-month 
long-term follow-up. The study will include approximately 20 participants with C3 
glomerulopathy. Participants enrolled to the protocol will be randomized 1:1 to ACH-0144471 or 
placebo, stratified by the disease diagnosis (DDD or C3GN) and renal function at study entry 
(eGFR ≥60 mL/min/1.73 m2 or <60 mL/min/1.73 m2). 
Participants must have a biopsy-confirmed diagnosis of C3G (C3GN or DDD, the 2 types of 
C3G). The initial diagnosis should have been made at least 3 months prior to dosing, unless 
otherwise approved by the sponsor. Participants must also have significant proteinuria (defined 
as ≥500 mg/day of protein in a 24-hour urine) that is attributable to C3G in the opinion of the 
principal investigator (PI). 
For all participants, eligibility will be confirmed based on the results from the screening 
eligibility assessments. Once eligibility is confirmed, arrangements can be made for the 
“baseline” renal biopsy and/or vaccinations. The initial screening visit should occur no more than 
75 days before the first dose date.  
All participants should be vaccinated against Haemophilus influenzae (H. influenzae), 
Streptococcus pneumoniae (S. pneumoniae), and Neisseria meningitidis (N. meningitidis) to 
minimize the risk of serious infection with an encapsulated organism.  Vaccinations should be 
administered at least 2 weeks before the start of dosing with ACH‑0144471 according to 
Advisory Committee on Immunization Practices (ACIP) guidelines, as described in Section 6.3, 
unless otherwise recommended by national and/or local vaccination guidelines or precluded by 
licenses or availability. The PI may institute additional prophylactic measures, including the use 
of prophylactic antibiotics if deemed appropriate by local clinical practice and/or guidelines for 
treatment with a complement inhibitor.  
The starting dosage of ACH-0144471 will be 100 mg TID, a total daily dose of 300 mg. After 
2 weeks of treatment, dosing will be escalated to 200 mg TID. Additional dosage regimens may 
be investigated if supported by emerging data from this and other clinical studies, as described in 
Section 5.3.3. If treatment is discontinued, regardless of the timing or reasons for 
discontinuation, a 6-day taper period of the study medication is required unless the PI determines 
this taper period poses a risk to the participant. The taper period is in place to prevent the 
theoretical risk of marked increase or rebound in complement activity, as described in 
Section 5.2.1. 
Because C3G is a serious and chronic disease, this study includes an extended treatment period 
which will allow participants to continue dosing for an additional 6 months or, for participants 
randomized to placebo for the Blinded Treatment Period, will provide the opportunity to receive 
ACH-0144471. All participants entering the Extended Treatment Period will receive 
ACH-0144471; those on active treatment will continue to receive daily treatment with 
ACH-0144471 and safety and efficacy monitoring, while those on placebo treatment will 
transition to active treatment with appropriate safety and efficacy monitoring.  


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 24 of 86 
This is a placebo-controlled and blinded study to the patient and site. The Sponsor and Safety 
team is unblinded therefore a data safety monitoring board (DSMB) is not necessary. 
Patient-reported outcome (PRO) questionnaires will be administered to participants at various 
time points as specified in the Schedule of Assessments (Appendix 1), to assess their health-
related quality of life (HRQOL), fatigue, and kidney-related fears and worries (e.g., kidney 
failure, dialysis, kidney transplant), and to determine health states value, over the course of 
treatment with ACH-0144471 or placebo.  Figure 1 provides the study schematic. 
 Figure 1. 
Study Schematic 
3.2. 
Rationale for Study Design 
3.2.1. 
Justification of Design 
This therapeutic trial for ACH-0144471 in C3G aims to demonstrate that factor D inhibition can 
reduce AP hyperactivity, and thereby halt, and possibly even reverse, progression of C3G 
disease. Disease progression and activity will be assessed using evaluation of clinical 
manifestations of the disease, namely proteinuria and abnormal eGFR and the sponsor will 
attempt to correlate any such improvements in clinical manifestations with changes in 
histopathology, to the extent biopsy data is available. A placebo-controlled, randomized, double-
blinded trial was selected as a rigorous study design that minimizes the introduction of bias and 
misinterpretation of randomly occurring events. Further rationale is provided below for the 
participant population selected, the endpoints to be evaluated, the duration of treatment, and the 
safety monitoring plan. Rationale for dose selection and dose adjustment parameters are detailed 
in Section 3.2.2. 
Population: Patients
with biopsy - confirmed 
DDD or C3GN who have 
not undergone renal 
transplant, and have 
significant proteinuria 
N = 20 
ACH-0144471 
or 
Placebo 
R 
Taper
Follow
-up
ACH-0144471 
Open- Label 
Extended 
Treatment 
6 - Month 
Blinded Treatment 
Period 
R = Randomization
Participants will be
randomized 1:1 to
either ACH- 0144471 or 
placebo
Long-Term 
Follow-up 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
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3.2.1.1. 
Participant Population 
The participant population enrolled in this study will be patients with biopsy-confirmed C3G.  
Achillion hypothesizes that a fD inhibitor will reduce AP hyperactivity, halting deposition of 
complement by-products in the kidney. These complement by-products induce an inflammatory 
response that affects glomerular function, and over time this chronic inflammation can lead to 
irreversible scarring of the renal parenchyma. As discussed in Section 3.2.1.2.1, the primary 
clinical manifestations of these processes are proteinuria and/or abnormal eGFR, and 
intervention during the period of active inflammation is expected to reverse damage and yield 
improvements in the clinical manifestations of the disease. In contrast, intervention once the 
kidney is irreversibly damaged may only provide minimal benefit, and even in non-ESRD 
participants, there is likely to be some component of irreversible renal damage that could limit 
the maximal response to a fD inhibitor. Therefore, we aim to enrich the population for those 
participants with the greatest likelihood for significant improvements by targeting participants 
with enough reversible renal disease to enable a detectable response to a fD inhibitor (proteinuria 
of at least 500 mg/day) but who do not have ESRD.  
With the above in mind, we are excluding participants with an estimated GFR 
≤30 mL/min/1.73 m2, and participants with more than 50% global fibrosis or more than 50% of 
glomeruli with cellular crescents on renal biopsy. Furthermore, to avoid inadvertent inclusion of 
participants with renal disease secondary to another underlying condition, or with post-infectious 
glomerulonephritis or another self-resolving condition that could confound interpretation of 
study results, participants must not have another condition to which their C3G disease is likely to 
be secondary.  
Taken together, these criteria ensure that the appropriate population is enrolled based on the 
available supporting data from the clinical and nonclinical programs for ACH-0144471 at the 
time of study conduct. 
3.2.1.2. 
Endpoints 
Demonstrating definitive efficacy with well-established endpoints for renal diseases, such as 
time to end-stage renal disease or doubling of serum creatinine, is impractical in clinical trials for 
an ultra-rare disease such as C3G where these endpoints typically occur over many years, and 
unfortunately, there are no existing validated surrogate endpoints for progression of C3G. 
Achillion is therefore working with health authorities, including the FDA, to identify surrogate 
endpoints that are likely to predict improvement in relevant long-term outcomes. In the absence 
of validated surrogate endpoints, proteinuria and reduced eGFR are mechanistically important 
markers for glomerular loss and inflammation, as discussed in Section 3.2.1.2.1, and as such will 
be endpoints measured in this study.  
In patients with reversible renal disease due to C3G, successful treatment should be marked by 
improvement in the clinical, pathologic, and laboratory evidence of the disease, namely 
improvements in proteinuria and/or eGFR (clinical), improvements in complement deposits and 
glomerular inflammation (pathologic), and correction of AP hyperactivity reflected by 
improvements in systemic C3 levels, as well as changes in factor B breakdown products (Bb and 
Ba), and other complement components (laboratory). Histology will be examined for effect of 
drug and changes in context of clinical improvements or stabilization of renal disease, in general 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
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Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 26 of 86 
and will be correlated to signs of clinical improvement. As no other precedent exists for 
surrogate endpoints that reasonably predicts outcome, a co-primary endpoint of change in 
histology and proteinuria relative to baseline was chosen. 
3.2.1.2.1. Clinically-Based Endpoints  
Achillion has considered meaningful clinical endpoints that would be indicative of 
improvements in disease, based on currently available information for C3G and other primary 
glomerular diseases. Based on two large case series, clinical features of C3G at the time of 
biopsy diagnosis included proteinuria >3.5 g/day and/or nephrotic syndrome in 26.8% to 44.0%, 
microscopic hematuria in 64.3% to 76%, and high blood pressure in 20.7% to 44% of patients. It 
should be noted that at the time of diagnosis, many patients were on steroids and/or other 
immunosuppressive agents as well as treatment with angiotensin converting enzyme (ACE) 
inhibitors or angiotensin receptor blockers (ARBs), which confounds interpretation of the 
frequency and extent of both proteinuria and high blood pressure. Regarding blood pressure, 
there is little additional data in the literature on the extent of high blood pressure, or its 
responsiveness to anti-hypertensive therapy and management, either at presentation or during the 
disease course. Up to 50% of patients may also have an abnormal creatinine/eGFR at time of the 
biopsy diagnosis. Of note, the disease can present with acute kidney injury and/or as a rapidly 
progressive glomerulonephritis, although these represent a minority of cases [6, 9, 20, 21, 22, 23, 
24]. 
Considering that the primary clinical manifestations of C3G are proteinuria and/or abnormal 
eGFR, and that current treatment strategies heavily focus on management of these clinical 
features, Achillion has focused its attention on these two parameters. It is well-accepted within 
the nephrology community that for glomerular diseases, especially glomerulonephritis, the 
following earlier changes will translate to long-term clinical benefit, including renal survival: 
conversion of nephrotic to non-nephrotic proteinuria, decreasing proteinuria (assuming baseline 
proteinuria is significant [≥500 mg/day]), eliminating proteinuria or reducing it to less than 
300 mg/day, normalizing serum creatinine if abnormal at baseline, and/or improving or 
stabilizing eGFR relative to baseline if abnormal at baseline [25, 26, 27, 28]. Further data in the 
literature supports a relationship between reduction in proteinuria and improved renal survival 
across chronic kidney disease (CKD), and especially across multiple different primary 
glomerular diseases with multiple different types of interventions [29, 30, 31, 32]. Therefore, it is 
reasonable to expect that improvement in these clinical markers of C3G (proteinuria and/or 
eGFR) would be indicative of reduced glomerular injury and inflammation and would translate 
to improved renal survival. 
As the clinical presentation and course of C3G is quite heterogeneous, patients with C3G are 
likely to have only a subset of the possible clinical manifestations. Given the small number of 
participants, it is not practical to create multiple stratified response criteria (e.g., as often done in 
trials for SLE nephritis) [27, 28]. Instead, the study will focus on decreasing proteinuria relative 
to baseline, which is expected to translate to clinical benefit. As such, the inclusion criteria 
require that a participant have proteinuria attributable to C3G. The study will also evaluate 
changes in GFR, both estimated and, where available, measured relative to baseline as a 
secondary endpoint. 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
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Clinical Protocol ACH471-204, Amendment 7 
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Confidential Property of Achillion Pharmaceuticals, Inc. 
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3.2.1.2.2. Pathology-Based Endpoints  
Renal biopsy scoring is a proximal and direct measure of renal disease. An improvement in 
disease activity scoring by renal histopathology is expected to translate into observed 
improvements in clinical manifestations, and hopefully into improvements in long-term renal 
outcomes. There has been no formal assessment correlating histologic features and outcomes in 
C3G, however, there are some data showing that the presence of crescents and more tubular 
atrophy in the initial biopsy are associated with worse outcomes [10, 33, 34]. In addition, the 
extent of C3c staining will be a key feature for biopsy analysis for this disease and considering 
the mechanism of action for ACH-0144471. Achillion is therefore asking for pre- and post- 
treatment biopsies to evaluate the effects of ACH-0144471 on renal pathology, as described in 
Section 6.3.1. 
The pathology assessments will be described in more detail in a Pathology Manual, and the 
specific analysis of pathology endpoints for this study will be described in the Statistical 
Analysis Plan. 
3.2.1.2.3. PRO-Based endpoints 
Findings from the analysis of qualitative interviews conducted with C3G patients (n = 10) and 
with key opinion leaders (n = 7; clinicians and patient advocacy group leaders) have shown that 
C3G has a detrimental impact on patients’ everyday lives. The C3G population appeared highly 
heterogeneous in terms of disease symptomatology, occurrence and evolution of symptoms, and 
level of impact on patients’ lives. However, fatigue and lack of energy are the symptoms most 
frequently reported. In addition, patients expressed their fear and worries, mainly due to the 
likelihood of kidney failure, dialysis and/or transplant. In turn, this significantly affects their 
everyday lives and quality of life. These symptoms and impacts were salient in C3G patient 
testimonials during the 04 August 2017 FDA Patient-Focused Drug Development Meeting that 
was organized by the National Kidney Foundation. Therefore, the PRO strategy for this study 
will include questionnaires selected to focus on these facets of patients’ lives. In particular, 
participants will complete PRO questionnaires (participants will complete the KDQOL-SF v1.3; 
FACIT-Fatigue and EQ-5D-3L questionnaires) at various time points as specified in Appendix 1, 
to assess their HRQOL, fatigue, and kidney-related fears and worries (e.g., kidney failure, 
dialysis, kidney transplant), and to determine health states value, over the course of treatment 
with ACH-0144471.  
3.2.1.3. 
Duration of Treatment 
Unfortunately, there is no precedent available for this disease to guide our decision about the 
length of therapy required to see improvements in clinical manifestations of renal disease (e.g., 
proteinuria and/or eGFR). A 6-month Blinded Treatment Period was selected following 
consultation with multiple C3G experts as a feasible timeframe for changes in proteinuria, eGFR 
and/or histopathology. Achillion is evaluating the time course of response in this investigational 
population, and longer dosing may be necessary; the Extended Treatment Period will therefore 
allow participants to continue dosing for an additional 6 months or, for participants randomized 
to placebo for the Blinded Treatment Period, will provide the opportunity to receive 
ACH-0144471 after 28 weeks. Patients may be treated for up to an additional 21 months in the 
long-term open-label extension.  


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
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Confidential Property of Achillion Pharmaceuticals, Inc. 
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3.2.1.4. 
Safety Monitoring Plan 
The primary focus of the safety monitoring plan will be to regularly monitor safety including any 
adverse events, safety laboratory measurements including liver function test and serum 
creatinine, and the urine albumin creatinine ratio. In addition, there are specific safety monitoring 
plans for the potential risk of infection (Appendix 2) and elevation in liver function tests 
(Section 3.2.3.2). 
3.2.1.4.1. Infection 
Since one of the primary functions of the complement system is to fight infections, 
pharmacologic inhibition of the complement system could theoretically result in an increased 
rate or severity of infections. However, high doses of C1 esterase inhibitor in transplant patients 
with rejection did not show a signal for infection [35]. Thus, it remains unclear as to whether fD 
inhibition would increase risk for infection. 
In vitro work was done to understand potential infection risk, especially meningococcal infection 
risk that is associated with AP inhibition. As summarized in Sections 4.1.2 and 6.5.1 of the 
Investigator's Brochure [1], ACH-0144471 showed minimal inhibition of protective bactericidal 
and opsonophagocytic activities in studies that included several strains of the clinically important 
pathogen N. meningitidis and blood samples from immunized individuals, suggesting that 
vaccination should provide protection from meningococcal infections in participants receiving 
ACH-0144471.  
Nonetheless, this study takes steps to minimize the risk of serious infection. Participants should 
be vaccinated according to applicable national and/or local guidelines or local clinical practice 
for N. meningitidis, H. influenza, and S. pneumonia (see Section 6.4), and antibiotic prophylaxis 
is permitted if deemed appropriate by local clinical practice and/or guidelines, as described in 
Section 6.5. Achillion will also create and distribute a wallet card for outpatient studies with 
warning signs and symptoms of serious infection, and appropriate steps of action for all 
participants. Finally, a fever management plan has been incorporated into the study protocol (see 
Appendix 2). 
3.2.1.4.2. Hepatic Injury 
Hepatobiliary cholestasis has been observed in dog toxicology studies at exposures higher than 
those intended for clinical use, and higher than those planned for this study. Based on clinical 
observations, the cholestasis is reversible and can be monitored with hepatic safety biomarkers. 
Elevations of transaminases have occurred clinically with ACH-0144471. Grade 3 or Grade 4 
liver enzyme elevations occurred in 2 active phase 1 study participants receiving higher doses of 
ACH-0144471 (500 and 800 mg twice daily [BID]), although these elevations occurred after 
dosing was completed (3 days and 7 days after last dose). Elevated transaminases associated with 
breakthrough hemolysis have been reported in PNH studies. All abnormal transaminase findings 
were transient, were not associated with evidence of hepatic decompensation, and resolved 
within a short time period. Transaminases will be monitored in this study.  


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
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Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
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Stopping criteria have been included ensuring prompt discontinuation of any participant with 
evidence of unexplained liver injury. Finally, participants with evidence of active hepatic or 
hepatobiliary disease will be excluded. 
3.2.2. 
Justification of Dose 
The starting dosage will be 100 mg TID for all participants. This dose has been demonstrated to 
inhibit the alternative pathway in PNH patients and in C3G patients, and dosing regimens with 
similar exposures (e.g., 200 mg BID) have demonstrated AP inhibition in healthy volunteers. 
Early data shows some clinically relevant reduction in proteinuria associated with AP inhibition, 
and ACH-0144471 has been well tolerated in participants with C3G. In order to maximize 
inhibition of the AP, the dosage will be escalated after 2 weeks, unless the participant has not 
tolerated treatment, or the investigator feels escalation would not be in the participant’s interest.  
Further, because renal impairment increases factor D levels, participants with impaired renal 
function may require higher levels of ACH-0144471 in order to inhibit AP activity. If 
appropriate, additional dosage regimens may be investigated, as described in Section 5.3.3. 
All parties except the sponsor will remain blinded as to whether the participant is receiving 
ACH-0144471 or placebo in the Blinded Treatment Period. 
Based on adult pharmacokinetic data, a PBPK (physiologically based pharmacokinetics) model 
was developed and validated to determine a dose of ACH-0144471 in adolescents equivalent to 
the starting dose of 100 mg TID in adults. 
3.2.3. 
Stopping Criteria and End-of-Study Definition 
The Sponsor reserves the right to close a study site or terminate the study at any time for any 
reason at the sole discretion of the Sponsor. 
A participant is considered to have completed the study if he/she has completed all phases of the 
study including the last scheduled procedure shown in the Schedule of Assessments. 
3.2.3.1. 
Study Stopping Rules 
If dosing is terminated in the study, all participants will be expected to complete the early 
termination activities described in Section 7.7, and comply with the schedule for the Taper 
Period (if relevant) and Follow-Up Period as described in Appendix 1. Of note, additional visits 
beyond those specified in the protocol may be required if needed to ensure adequate safety 
monitoring. 
3.2.3.2. 
Stopping Rules for Individual Participants 
Any individual participant who meets any of the following criteria may be discontinued from 
further dosing: 
• The participant experiences a SUSAR  
• The PI believes that participant continuation in the study is not advisable, or the participant 
withdraws from the study or meets one of the conditions described in Section 6.21, including, 
but not limited to: 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
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Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
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− The participant becomes pregnant 
− Intercurrent illness that would, in the judgment of the investigator, affect assessments of 
clinical status to a significant degree 
− Participant requests to discontinue for any reason 
Discontinuation of treatment should also be considered for:  
• ALT or AST >8× ULN  
• ALT or AST >5× ULN for more than 2 weeks  
• ALT or AST >3× ULN and concomitant total bilirubin >2× ULN and/or International 
Normalized Ratio [INR]* >1.5 
• ALT or AST >3× ULN with the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%) 
• If there is a marked prolongation of the QT/QTc interval during treatment with the study 
drug, especially if the measurement is obtained from more than one ECG  
* Participants, particularly those with nephrotic syndrome, may be receiving ongoing warfarin, 
resulting in increased INR values. The PI should evaluate INR in the context of any concomitant 
medications to determine if any observed increases are due to an effect on liver function or are 
secondary to anticoagulation. 
The PI may stop dosing or reduce dosing in any participant who meets an Individual Stopping 
Rule; however, the Achillion Medical Monitor (MM) should be notified immediately, and if 
possible, before dosing is reduced or terminated. When dosing is stopped in an individual 
participant, the PI should consider whether it is in the best interest of the participant to 
discontinue dosing immediately or to taper (as described in Section 5.2). Whenever possible, the 
taper decision should also be discussed with the Achillion MM prior to dosing termination. 
Further continuation in the study should be discussed with the Achillion MM. 
Upon dosing termination and study discontinuation, a participant will be expected to complete 
the early termination activities described in Section 7.7, and comply with the schedule for the 
Taper Period (if relevant) and Follow-Up Period as described in Appendix 1. Of note, additional 
visits beyond those specified in the protocol may be required if needed to ensure adequate safety 
monitoring. 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 31 of 86 
4. 
STUDY POPULATION SELECTION 
4.1. 
Study Population 
This study will be conducted in approximately 20 participants, with biopsy-confirmed DDD or 
C3GN who have not undergone renal transplant, and who have significant proteinuria (defined as 
≥500 mg/day of protein in a 24-hour urine) and an eGFR >30 mL/min/1.73 m2. 
4.2. 
Inclusion Criteria 
Each participant must meet all the following criteria to be enrolled in this study. 
1. Must have biopsy-confirmed primary C3G 
2. Must be 17 years of age or older and capable of swallowing tablets 
3. Must have clinical evidence of ongoing disease based on significant proteinuria (defined 
as ≥500 mg/day of protein in a 24-hour urine or equivalent on spot urine) attributable to 
C3G disease in the opinion of the PI, and present prior to study entry and confirmed 
during Screening 
4. If on corticosteroids, anti-hypertensive medications, anti-proteinuric medications (e.g., 
ACE inhibitors or angiotensin receptor blockers [ARBs]), or mycophenolate mofetil 
(MMF), must be on a stable dose for at least 2 weeks prior to screening 
5. Female participants of childbearing potential must agree to use an acceptable method of 
contraception (as defined in Section 5.5.4) from the date of signing the informed consent 
to the first day of dosing (Day 1), and must agree to use a highly effective form of 
contraception (as defined in Section 5.5.4) from the first day of dosing to 30 days after 
their last dose of study drug. Female participants of childbearing potential must also have 
a negative serum pregnancy test during Screening and negative urine pregnancy test on 
Day 1. Female participants of non-childbearing potential need not employ a method of 
contraception 
6. Non-sterile male participants must agree to use a highly effective form of contraception 
(as defined in Section 5.5.4) with their partner(s) of childbearing potential from the first 
day of dosing to 90 days after their last dose of study drug. 
Male participants who are surgically sterile need not employ additional contraception. 
Male participants must agree not to donate sperm while enrolled in this study and for 
90 days after their last dose of study drug. 
7. Adult participants must be capable of providing written informed consent and adolescent 
participants must be capable of providing written assent. All participants must be willing 
and able to comply with the requirements and restrictions listed in the consent form and 
with all procedures in the protocol, including, the visit schedule, the treatment plan, the 
schedule for laboratory testing, and other study procedures 
8. Must be up-to-date on routine vaccinations, or willing to be brought up-to-date, based on 
local guidelines 
9. Must have access to emergency medical care. 


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Clinical Protocol ACH471-204, Amendment 7 
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4.3. 
Exclusion Criteria 
Participants who meet any of the following criteria will be excluded from the study. 
1. Have a history or presence of any clinically relevant co-morbidities that would make the 
participant inappropriate for the study (for example, a comorbidity which is likely to 
result in deterioration of the participant’s condition, affect the participant’s confound the 
results of the study), in the opinion of the PI 
2. Have ever received ACH-0144471 
3. Have a pre-treatment renal biopsy, or a biopsy collected within approximately 6 months 
of the start of dosing and available for review, which shows more than 50% global 
fibrosis or more than 50% of glomeruli with cellular crescents 
4. Have an estimated GFR <30 mL/min/1.73 m2 at the time of screening or at any time over 
the preceding four weeks 
5. Is a renal transplant recipient or receiving renal replacement therapy 
6. Have a history of a major organ transplant (e.g., heart, lung, kidney, liver) or 
hematopoietic stem cell/marrow transplant.  
7. Have evidence of monoclonal gammopathy of unclear significance (MGUS), infections, 
malignancy, autoimmune diseases, or other conditions to which C3G is secondary 
8. Have other renal diseases that would interfere with interpretation of the study  
9. Have been diagnosed with or show evidence of hepatobiliary cholestasis  
10. Females who are pregnant, nursing, or planning to become pregnant during the study or 
within 90 days of study drug administration  
11. Have a history of febrile illness, a body temperature >38°C, or other evidence of a 
clinically significant active infection, within 14 days prior to study drug administration 
12. Have evidence of human immunodeficiency virus (HIV), hepatitis B infection, or active 
hepatitis C infection at Screening  
13. Have a history of meningococcal infection within the prior year 
14. Have a history of hypersensitivity reactions to commonly used antibacterial agents, 
including beta-lactams, penicillin, aminopenicillins, fluoroquinolones, cephalosporins, 
and carbapenems, which, in the opinion of the investigator and/or an appropriately 
qualified immunology or infectious disease expert, would make it difficult to properly 
provide either empiric antibiotic therapy or treat an active infection. 
15. Have participated in a clinical study in which an investigational drug was given within 
30 days, or within 5 half-lives of the investigational drug, whichever is longer, prior to 
the first dose of study drug  
16. Have received eculizumab at any dose or interval within the past 50 days prior to the first 
dose of study drug 
17. Have received tacrolimus or cyclosporine within 2 weeks of the first dose of study drug 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
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Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 33 of 86 
18. Have any of the following laboratory abnormalities at screening:  
▪ Alanine transaminase (ALT) > upper limit of normal (ULN)  
▪ Aspartate aminotransferase (AST) > ULN  
▪ Absolute neutrophil counts (ANC) <1,000/μL 
▪ Total bilirubin >1.5× ULN 
▪ Indirect bilirubin > ULN 
▪ Any laboratory abnormality that, in the opinion of the PI, would make the participant 
inappropriate for the study 
19. Are unwilling or unable to comply with the study protocol for any reason 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
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Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
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5. 
STUDY TREATMENT(S) 
5.1. 
Description of Treatment(s) 
5.1.1. 
Study Drug 
Throughout this protocol, “study drug” should be understood to refer to the treatment being 
evaluated. During the Blinded Treatment Period, this may be either ACH-0144471 or placebo, 
but neither the participants or the investigators, will know which an individual participant is 
receiving. During the Extended Treatment Period, “study drug” will be ACH-0144471. 
5.1.2. 
ACH-0144471 
ACH-0144471 will be dosed orally as a tablet formulation containing the drug substance, 
lactose, microcrystalline cellulose, croscarmellose sodium, sodium lauryl sulphate, magnesium 
stearate, colloidal silicon dioxide, and hypromellose acetate succinate. The coating components 
are polyvinyl alcohol, titanium dioxide, macrogol/polyethylene glycol, and talc. Tablets will be 
provided in 50, and 100-mg strengths. 
5.1.3. 
Placebo 
Matching placebo tablets will contain lactose, microcrystalline cellulose, croscarmellose sodium, 
sodium lauryl sulphate, magnesium stearate, colloidal silicon dioxide, and hypromellose acetate 
succinate. The coating components are polyvinyl alcohol, titanium dioxide, 
macrogol/polyethylene glycol, and talc. 
5.2. 
Treatment(s) Administered 
5.2.1. 
ACH-0144471 or Placebo 
ACH-0144471 or matching placebo tablets will be administered at a starting dosage of 100 mg 
TID on Day 1. After 2 weeks of treatment, dosing will be escalated to 200 mg TID, as for an 
additional 26 weeks (Blinded Treatment Period). On completion of the Blinded Treatment 
Period, participants may continue in the Extended Treatment Period, and Long-Term Follow-up 
Period during which all participants will receive ACH-0144471 as described in Section 5.3. If 
there is a gap prior to starting the Extended Treatment Period, Long-Term Follow-up Period or if 
dosing is discontinued, the dose should be tapered over approximately 6 days to minimize the 
potential adverse effects of a rapid surge in complement activity following drug withdrawal. 
Dosing taper regimens are described in Table 1. If a dosing regimen not specified in the Table 1 
is used, then the taper regimen will be defined by the Achillion MM prior to dosing termination.  
In addition, the taper regimen may be adjusted if the sponsor or investigator feels it would be 
appropriate to do so (e.g., to allow for slower taper in a participant who is not tolerating 
discontinuation of drug, or for other reasons). 


ACH-0144471 
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Table 1. 
ACH-0144471 Taper Schedule 
Dose at Termination 
Taper Period 1 
(Taper Days 1-3) 
And Taper Period 2 
(Taper Days 4-6) 
100 mg TID 
100 mg BID 
0 mg BID 
200 mg TID 
100 mg TID 
100 mg BID 
5.2.2. 
Vaccines 
Depending on the participant’s vaccination history, the vaccines described in Section 6.4 may 
need to be administered to participants according ACIP guidelines, unless otherwise 
recommended national and/or local vaccination guidelines or precluded by licenses or 
availability. Because these are commercially available products, information about the specific 
vaccines can be found on the package inserts/product labels for those products. Full identifying 
information for any administered vaccines, including the brand, should be recorded in the 
participant’s CRF. 
5.2.3. 
Prophylactic Antibiotics 
As described in Section 6.5, antibiotic prophylaxis is not mandated but allowed if deemed 
necessary by local clinical practice and/or guidelines for treatment with a complement inhibitor. 
Because commercially available products will be used, information about any specific antibiotics 
administered can be found on the package inserts/product labels for those products. 
For any antibiotics given as part of this study, full identifying information, including the brand, 
should be recorded in the participant’s CRF. 
5.3. 
Selection of Timing and Dose for Each Participant 
For the starting dose, participants will take one 100-mg ACH-0144471 or matching placebo 
tablet three times daily (TID): a dose in the morning, a second dose 8 hours later, and a third 
dose 8 hours after the second dose. Doses should be taken at approximately the same time each 
day and as close as possible to 8 hours apart. All doses should be taken approximately 15 to 
30 minutes after completion of a meal. Water intake is not restricted. If a dose is missed, it 
should be taken within 4 hours of the originally scheduled time. After 4 hours, the missed dose 
should be skipped. In either case, the next dose should be taken according to the original dosing 
schedule. 
If a dosing interval other than TID is used during the study, then interval between doses should 
be equally distributed over a 24-hour period, and dosing should otherwise comply with the 
guidelines provided for a TID interval. 
All participants will receive ACH-0144471 in the Extended Treatment Period. While the blinded 
portion of the study is ongoing, the treatment assignment for a given participant will not be 
known. In order to maintain the overall blind, all participants will start the Extended Treatment 
Period. The timing, intervals, and makeup of the doses will follow the above instructions. 
5.3.1. 
Clinic Visit Dose Administration Instructions 
Participants will be instructed to fast for at least 8 hours before their clinic visit, and to drink 
enough water to ensure they are adequately hydrated. Participants must abstain from taking their 


ACH-0144471 
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Clinical Protocol ACH471-204, Amendment 7 
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Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
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study medication on the mornings of their study visits so that they can be dosed in the clinic 
following safety and pharmacokinetic assessments. All doses should be taken approximately 15 
to 30 minutes after completion of a meal. Participants will be required to bring back their study 
drug at each visit so that study site personnel may perform drug accountability. If morning clinic 
visits are not possible, participant visits may be scheduled so that safety and pharmacokinetic 
assessments can be made before the second daily dose. The 8-hour interval between doses should 
be maintained, as should the relative timing of dosing and all study-related activities. 
5.3.2. 
Home Dose Administration Instructions 
Participants should be instructed to finish a meal or snack approximately 15 to 30 minutes prior 
to dosing. Doses should be taken at approximately the same time each day and as close as 
possible to 8 hours apart (or the relevant interval in the event of a non-TID schedule). 
Participants should be instructed to keep their study medications at room temperature. 
5.3.3. 
Dose Adjustment 
After 2 weeks of treatment, dosing will be escalated to 200 mg TID unless the participant has not 
tolerated treatment, as determined by the medical monitor. While the intent is to maintain a 
steady dose for the duration of the study, additional dose adjustments are permitted if it is felt to 
be in the participant’s interest. Further, because renal impairment increases factor D levels, 
participants with impaired renal function may require higher levels of ACH-0144471 in order to 
inhibit AP activity. If supported by emerging data from this and other clinical studies, additional 
dosage regimens may be investigated. Dosing may be adjusted by the MM (or designee) in 
consultation with the PI within the parameters provided below.  
• Dose adjustments can include changes in dose amount (e.g., change from 100 to 200 mg per 
dose) or in dose frequency (e.g., change from TID to BID or QID). 
• While treatment is blinded, the decision to dose escalate will be made without breaking the 
treatment blind. 
• Dose increases should be such that the new total daily dose is no more than 2× the prior total 
daily dose. 
5.4. 
Method of Assigning Participants to Treatment Groups 
Participants enrolled will be randomized 1:1 to either active treatment (ACH-0144471) or 
placebo, stratified by disease diagnosis (DDD or C3GN) and renal function at study entry (eGFR 
≥60 mL/min/1.73 m2 or <60 mL/min/1.73 m2). 
A centralized Interactive Web Response System (IWRS) will be used to generate a 
randomization scheme to provide treatment assignment of either ACH-0144471 or placebo to 
each participant in a 1:1 ratio. The randomization will be stratified by renal function at study 
entry and disease diagnosis as stated above. The randomization block design will be utilized 
within each stratum. The process of obtaining blinded treatment assignment for each participant 
will be documented in the laboratory manual. 


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If it is necessary to unblind a study participant due to an emergency requiring knowledge of the 
participant’s treatment group for medical management, the investigator may perform the 
unblinding via the IWRS by entering the participant’s identifiers. The PI does not need prior 
approval from the Sponsor in order to unblind; however, the PI should notify the medical 
monitor as soon as possible regarding the unblinding decision and rationale. 
Although all participants will receive active drug during the open-label Extended Treatment 
Period, the first portion of the study will not be unblinded until all participants have completed 
the Blinded Treatment Period.  
5.5. 
Restrictions 
5.5.1. 
Prior and Concomitant Therapy 
Participants may not have received another investigational agent within 30 days or 5 half-lives of 
the investigational agent prior to the first dose of study drug, whichever is greater. Participants 
may not have received eculizumab within 50 days prior to the first dose of study drug. 
Participants may not have received tacrolimus or cyclosporine within 2 weeks prior to the first 
dose of study drug. 
Based on in vitro data, ACH-0144471 has the potential to interact with several CYP enzymes as 
well as some transporters as a perpetrator but not as a victim drug. In vitro results for various 
CYP enzymes and transporters are described in the Investigator’s Brochure [1].  
A drug-drug interaction study with ACH-0144471 has been conducted to determine the potential 
for ACH-0144471 to affect the PK of midazolam (substrate for CYP3A), fexofenadine (substrate 
for P-gp), and mycophenolic acid (substrate of UGT). Preliminary results indicate that ACH-
0144471 is a weak inhibitor of CYP3A, a moderate inhibitor of P-gp, and had no effect on UGT.  
Use of specific concomitant medications will be considered on a case-by-case basis, with 
decisions made jointly between the PI and Sponsor, based on available and emerging knowledge 
of ACH-0144471 as well as the characteristics of the potential concomitant medication. Details 
of all concomitant medication use, including all medications administered for the treatment of 
AEs, must be recorded in the participant’s case report form (CRF). The following are some 
general guidelines for concomitant medication use based on currently available data:  
• Concomitant administration of cyclosporine and tacrolimus are not allowed and must be 
stopped at least two weeks prior to study drug administration. 
• Concomitant administration of corticosteroids is permitted if on stable doses for at least 
2 weeks prior to the first screening visit. Doses should be maintained at the same dose 
throughout the study, whenever possible, unless the PI deems it necessary to do otherwise. 
• Concomitant administration of mycophenolate mofetil (MMF) is allowed if on stable doses 
for at least 2 weeks prior to the first screening visit. Doses should be maintained at the same 
dose throughout the study, whenever possible, and unless the PI deems it necessary to do 
otherwise. 
• Concomitant administration of warfarin or low molecular weight heparin is permitted. 


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• Oral, injectable, implantable, transdermal, or intravaginal hormonal therapies are allowed for 
either contraception or hormonal replacement therapy. 
• Concomitant administration of anti-proteinuric medications (e.g., ACE inhibitors or ARBs) 
or anti-hypertensive medications is permitted if on stable doses for at least 2 weeks prior to 
the first screening visit. Doses should be maintained at the same dose throughout the study, 
whenever possible, unless the PI deems it necessary to do otherwise. 
• If it is necessary to treat a fever (see Appendix 2), or any minor ailment occurring while on 
study, ibuprofen (maximum 400 mg/day and up to 1200 mg/week) and/or acetaminophen 
(maximum 1000 mg/day) are permitted without prior approval. 
• Antibiotic prophylaxis is allowed if deemed appropriate by local clinical practice and/or 
guidelines for treatment with a complement inhibitor. 
No new therapy should be added during the study unless the participant’s condition deteriorates 
to the extent that the PI deems it in the best interest of the participant to do so. In addition, doses 
of medications for C3G (e.g., immunosuppressive agents, ACE inhibitors, etc.), should be 
maintained at the same dose throughout the study, whenever possible, and unless the PI deems it 
necessary to do otherwise. 
5.5.2. 
Fluid and Food Intake 
Participants should be instructed to take each dose of study drug within 15 to 30 minutes of 
finishing a meal or snack. 
Water or other non-alcoholic fluid intake is not restricted. 
5.5.3. 
Participant Activity and Other Restrictions 
Participants should refrain from heavy exercise 24 hours prior to and after having blood drawn 
for safety laboratory evaluations. Walking and light exercise are acceptable. 
5.5.4. 
Contraception 
5.5.4.1. 
Contraception for Male Participants 
All non-sterile male participants must use highly effective or acceptable contraception with their 
partner(s) of childbearing potential from the first day of dosing (Day 1) through 90 days after 
their last dose of study drug. 
Sterile is defined as having bilateral orchiectomy. 
Highly effective contraception for males is defined as any of the following:  
• Vasectomy with confirmed medical assessment of surgical success 
• Condom plus use of one of the following by partner(s) of child-bearing potential: 
▪ Oral, intravaginal, or transdermal combined (estrogen and progestogen containing) 
hormonal contraception associated with inhibition of ovulation 


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▪ Oral, injectable, or implantable progestogen-only hormonal contraception associated 
with inhibition of ovulation 
▪ Intrauterine device (IUD) or Intrauterine hormone-releasing system (IUS) 
▪ Bilateral tubal occlusion (including bilateral tubal ligation) 
• Sexual abstinence, defined as refraining from heterosexual intercourse during the entire 
period from the first day of dosing (Day 1) through 90 days after their last dose of study 
drug. Periodic abstinence (e.g., calendar, symptothermal, post-ovulation methods) is not 
an acceptable method of contraception. The reliability of sexual abstinence needs to be 
evaluated in relation to the duration of the clinical trial and the preferred and usual 
lifestyle of the participant. If a participant is usually not sexually active but becomes 
active, they, with their partner(s), must comply with the contraceptive requirements 
described in this section. 
Acceptable contraception for males or female partner of childbearing potential is defined as any 
of the following:  
• 
Progestin-only oral hormonal contraception, where inhibition of ovulation is not the 
primary mode of action 
• 
Male or female condom with or without spermicide 
• 
Cap, diaphragm, or sponge with spermicide 
• 
Combinations of male condom with either cap, diaphragm, or sponge with spermicide 
(double-barrier methods) 
Male participants must agree to refrain from sperm donation from the date of screening until 90 
days after their last dose of study drug.  
5.5.4.2. 
Contraception for Female Participants 
Female participants of child-bearing potential and/or their male partners must use a highly 
effective or acceptable method of contraception from the date of signing the informed consent to 
the first day of dosing (Day 1), through 30 days after their last dose of study drug. 
Highly effective contraception for females is defined as any of the following: 
• Oral, intravaginal, or transdermal combined (estrogen and progestogen containing) hormonal 
contraception associated with inhibition of ovulation 
• Oral, injectable, or implantable progestogen-only hormonal contraception associated with 
inhibition of ovulation 
• Intrauterine device (IUD) or Intrauterine hormone-releasing system (IUS) 
• Bilateral tubal occlusion (including bilateral tubal ligation) 
• Vasectomised partner(s) with confirmed medical assessment of surgical success 
• Sterile partner(s) (bi-lateral orchiectomy) 


ACH-0144471 
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• Sexual abstinence, defined as refraining from heterosexual intercourse during the entire 
period from the first day of dosing (Day 1) through 30 days after their last dose of study 
drug. Periodic abstinence (e.g., calendar, symptothermal, post-ovulation methods) is not an 
acceptable method of contraception. The reliability of sexual abstinence needs to be 
evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle 
of the participant. If a participant is usually not sexually active but becomes active, they, with 
their partner(s), must comply with the contraceptive requirements described in this section. 
Acceptable contraception for females is defined as any of the following: 
• Progestin-only oral hormonal contraception, where inhibition of ovulation is not the primary 
mode of action 
• Male or female condom with or without spermicide. 
• Cap, diaphragm or sponge with spermicide 
• Combinations of male condom with either cap, diaphragm, or sponge with spermicide 
(double-barrier methods) 
Female participants of childbearing potential must have a negative serum pregnancy test at 
screening and a negative urine pregnancy test at baseline in order to enter the study, and must 
have urine pregnancy tests throughout the study at the intervals defined in the Schedule of 
Assessments (Appendix 1). 
Female participants of non-childbearing potential, as defined by one of the following, need not 
employ a method of contraception: 
• Surgical sterilization by hysterectomy, bilateral salpingectomy, or bilateral oophorectomy 
• Postmenopausal with amenorrhea for at least 1 year prior to dosing and FSH serum levels 
consistent with postmenopausal status 
5.6. 
Treatment Compliance 
Treatment compliance assessments shall be performed at each visit. Participants will be required 
to bring their supply of study drug to each visit so that study site personnel may perform drug 
accountability. Site personnel will keep a record of all drug dispensed and returned at each visit. 
Drug dispensing records will be updated at each visit. 
Participants will be asked to record the time they take each daily dose of study drug and may 
receive automated reminders (e.g., via SMS text or phone call) in an effort to ensure compliance. 
The site will receive notification of any non-response or non-compliance to follow up and 
address with the participant directly.  
5.7. 
Packaging and Labeling 
Labels for ACH-0144471 and placebo tablets will include, at a minimum, the following 
information, in English: 
• Clinical Study Number 
• Sponsor Name and Address 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
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Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
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• Product Name and Strength 
• Dosage Form and Route of Administration 
• Direction for Use 
• Contents (Number of Tablets) 
• Randomization Number 
• Storage Instructions 
• Caution statement to keep out of the reach of children 
• Caution Statements such as “For Clinical Trial Use Only” or “Caution: New Drug-Limited 
by Federal (or United States) law to investigation use” or similar statements 
5.8. 
Storage and Accountability 
At the pharmacy, the ACH-0144471 and placebo tablets must be stored as provided at controlled 
room temperature (20°C to 25°C), with allowed excursion of 15°C to 30°C. Participants should 
be instructed to keep their study medications in the original container at room temperature. 
Participants will be required to bring back their study drug at each clinic visit so that study site 
personnel may perform drug accountability. 
The PI or designee (e.g., pharmacist) is responsible for ensuring storage as per the label on the 
drug product at the site and adequate accountability of all used and unused study drug. This 
includes acknowledgment of receipt of each shipment of study drug (quantity and condition) and 
participant dispensing records and returned or destroyed drug. Dispensing records will document 
quantities received from Achillion Pharmaceuticals (or designee) and quantities dispensed to 
participants, including lot number, date dispensed, participant identifier number, participant 
initials, and the initials of the person dispensing the medication. All drug supplies and associated 
documentation will be periodically reviewed and verified by the Study Monitor over the course 
of the study. 
5.9. 
Investigational Product Retention at Study Site 
At study initiation, the Study Monitor will evaluate the site’s Standard Operating Procedure for 
study drug disposal/destruction in order to ensure that it complies with Achillion 
Pharmaceuticals requirements. Drug may be returned to the Sponsor (or designee) or destroyed 
on an ongoing basis during the study, if appropriate, after drug accountability has been verified 
by the Study Monitor. At the end of the study, following final drug inventory reconciliation by 
the Study Monitor, the study site will dispose of and/or destroy all unused study drug supplies, 
including empty containers, according to these procedures. If the site cannot meet Achillion 
Pharmaceuticals requirements for disposal, arrangements will be made between the site and 
Achillion Pharmaceuticals or its representative, for destruction or return of unused study drug 
supplies. 


ACH-0144471 
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Clinical Protocol ACH471-204, Amendment 7 
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Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
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6. 
STUDY PROCEDURES 
The required study procedures are detailed in this section. The timeline for these procedures may 
be found in Appendix 1. 
6.1. 
Informed Consent  
The PI or designee is responsible for administering and obtaining freely given consent, in 
writing, before the participant enters into the study and any study-related procedures are 
performed. Each adult participant will sign an Ethics Committee (EC) or Institutional Review 
Board (IRB)-approved written informed consent form (ICF). This may include additional 
consent forms for HIV testing or other procedures which may be performed prior to participants 
being accepted into the study. 
6.2. 
Medical History 
At Screening, the PI or designee will interview each participant and obtain a complete medical 
and medication history to determine whether the participant meets the eligibility criteria. The 
history should include the specific type of C3 glomerulopathy (C3GN or DDD), date of initial 
C3G diagnosis, family history of renal disease, all surgeries and past medical procedures, all past 
significant illnesses or current chronic conditions, all medication use currently and within the 
past 90 days (including over the counter medications, and use of herbal and nutrient 
supplements), any prior use of alcohol, illicit drugs and/or controlled substances, and any other 
relevant information. Other relevant information should include all available GFR or eGFR 
values for the past year, and any extrarenal manifestations of C3G, including ophthalmic 
manifestations such as drusen. If any ophthalmic exams are performed (including any exams 
performed for reasons unrelated to the conduct of this study), then every effort will be made to 
include an anonymized copy of the exam results in the participants’ source documents. The 
history should also include the results of any genetic testing related to the disease, and a full 
vaccination history. The medical history must be recorded in the participant’s source documents 
and in the participant’s CRF. 
6.3. 
Percutaneous Renal Biopsy 
Percutaneous renal biopsies should be performed according to local practices for this procedure, 
including appropriate pre-biopsy evaluation, biopsy technique, choice of imaging technique (e.g., 
ultrasound-guided, CT-guided, or other), anesthesia, and post-biopsy care. All biopsies will be 
reviewed by the designated central pathology laboratory, and will be evaluated by light 
microscopy, electron microscopy and immunofluorescence. 
Details on the processing of the biopsy sample and discussion of the final renal pathology 
assessment and scoring for this study will be provided in the Pathology Manual, and the method 
for analyzing the pathology data will be provided in the Statistical Analysis Plan. However, the 
approach will be like that described for lupus in that it will assess features that indicate active 
glomerular inflammation, and those that indicate chronic fibrotic irreversible injury. Each of 
these will be quantitated and may be combined into a composite scoring system. If a composite 
scoring system is not used, the score of each feature at baseline and post-treatment can be 
compared. 


ACH-0144471 
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(a subsidiary of Alexion Pharmaceuticals, Inc.)  
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If, for any reason, any additional renal biopsies are performed (e.g., for a clinical indication), 
then every effort will be made to make these biopsy samples and results available to the central 
pathology laboratory for evaluation. 
6.3.1. 
Renal Biopsy 
Participants should have a renal biopsy before the first dose of ACH-0144471 to establish a 
baseline histology score. Only one biopsy will be obtained prior to dosing; if a biopsy is required 
to confirm the diagnosis of C3G.it will be considered the pre-treatment biopsy. If a participant 
has had a recent renal biopsy it may not be clinically reasonable to repeat the procedure, and in 
this situation, a biopsy collected within approximately 6 months of the first dose of study drug 
may be accepted in lieu of a biopsy during screening if it meets the requirements for analysis, 
and with written sponsor approval prior to study enrolment. 
For all subjects, a biopsy should be obtained at the end of the Blinded Treatment Period 
(approximately Week 28), as defined in Appendix 1, to allow evaluation of changes in renal 
pathology. If not contraindicated, an additional biopsy may be obtained at the end of the 
Extended Treatment Period. 
A sub-study is being conducted to evaluate the effects of ACH-0144471 on renal pathology; 
participation in this sub-study is not required. A separate informed consent will be required for 
participation.  
Participants who choose to participate in the sub-study should have a renal biopsy at Week 52 
and 104 as detailed on the Schedule of Assessments.  
6.4. 
Vaccination 
Information regarding the risk of infection can be found in Section 6.5.1 of the Investigator's 
Brochure [1]. 
As discussed in Section 6.2, a full vaccination history will be gathered.  Based on the vaccination 
history, the need for vaccinations against N. meningitidis, S. pneumoniae, and H. influenzae in 
this study will be evaluated. Study participants who do not have a sufficient history for some or 
all of these vaccines should receive vaccinations at least 2 weeks before the start of dosing with 
ACH-0144471 as recommended in the Advisory Committee on Immunization Practices (ACIP) 
guidelines, unless otherwise recommended by national and/or local guidelines or local clinical 
practice. If local and/or national guidelines do not exist or do not fully address vaccination 
against these organisms, investigators should consider consulting the ACIP guidelines (available 
at https://www.cdc.gov/vaccines/acip/index.html).  
Full identifying information for any vaccines given as part of this study, including the brand, 
should be recorded in the participant’s CRF.  
6.5. 
Prophylactic Antibiotics 
As described in Section 6.4, Achillion expects that participants will be vaccinated according to 
ACIP guidelines at least 2 weeks prior to dosing with ACH-0144471 and believes that this will 
provide sufficient protection against these organisms. However, this is a global study and 
Achillion recognizes that some vaccines may not be available in all countries, and that guidelines 


ACH-0144471 
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Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
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Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
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and clinical practices differ by region and may include the use of prophylactic antibiotics in 
some instances. Antibiotic prophylaxis is therefore allowed if deemed appropriate by the PI or 
local clinical practice and/or guidelines for treatment with a complement inhibitor. 
Full identifying information for any antibiotics given as part of this study, including the brand, 
dosage, and times of administration should be recorded in the participant’s CRF. 
6.6. 
Urine Collection 
6.6.1. 
24-Hour Urine Collection 
Collection of urine over 24 hours will occur according to the Schedule of Assessments 
(Appendix 1). Urine collected will be assayed as described in Table 2 for total protein 
concentration, albumin and creatinine concentrations, albumin:creatinine ratio, total 
protein:creatinine ratio, and total volume. Complement components may also be assessed using 
urine, as described in Section 6.13.1. 
The 24-hour urine collection period may be at any time during screening, but if it is to occur 
after a renal biopsy, it must be at least 7 days after the biopsy procedure. If clinic visits are not 
possible during the COVID-19 global pandemic, urine samples may be collected during home 
healthcare visits or delivered to a local laboratory. 
Specific instructions for urine collection, processing, and shipping will be provided in the 
laboratory manual. 
6.6.2. 
First Morning Urine Collection 
Collection of urine will occur according to the Schedule of Assessments (Appendix 1). Urine 
collected will be assayed as described in Table 2; in addition to standard urinalysis, urine 
collected will be assayed for total protein concentration, albumin and creatinine concentrations, 
and the protein:creatinine and albumin:creatinine ratios. Complement components may also be 
assessed, as described in Section 6.13.1.  
Participants will be given a collection container to collect their first morning void. Specific 
instructions for urine collection, processing, and shipping will be provided in a separate 
laboratory manual. If the first morning urine collection coincides with a renal biopsy, collection 
must be completed before or at least 7 days after the biopsy procedure. If clinic visits are not 
possible during the COVID-19 global pandemic, urine samples may be collected during home 
healthcare visits or delivered to a local laboratory.  
6.7. 
Physical Examination 
A complete physical examination will be conducted by the PI (or designee) at the times specified 
in the Schedule of Assessments (Appendix 1). This will include an examination of all major 
body/organ systems (including skin, head, eyes, ears, nose, throat, neck, thyroid, lungs, heart, 
abdomen, lymph nodes, and extremities), height, weight and calculation for BMI. Measurements 
of height and weight should be taken with the participants in light clothing or underwear and 
without shoes. Assessment of edema is part of the complete physical exam. If edema is present, 


ACH-0144471 
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Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
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then assessment of edema should be performed at each subsequent visit, even when a physical 
exam is not required.  
Brief physical examinations, to include general appearance and examination of cardiovascular 
and respiratory systems, abdomen, extremities, and skin will be performed by the PI (or 
designee) at the times specified in the Schedule of Assessments (Appendix 1). Assessment of 
edema is part of the brief physical exam. If edema is present, then assessment of edema should 
be performed at each subsequent visit, even when a physical exam is not required. Additional 
complete, brief or targeted physical exams (e.g., targeted to any new signs or symptoms) may be 
performed at any time at the discretion of the Investigator or designee, for example to evaluate 
an AE. All clinically significant physical examination findings that are new or worsened since 
the last physical examination must be recorded in the participant’s source documents and in the 
participant’s CRF as an adverse event. 
6.8. 
Vital Signs 
The PI or designee will obtain blood pressure (BP), heart rate (HR), and respiration rate (RR) at 
the visits indicated in the Schedule of Assessments (Appendix 1). Vital signs will be measured in 
the supine position following a 5-minute rest. All blood pressure measurements should be taken 
on the same arm throughout the study. Vital signs may be measured using an automated vital 
sign monitor, although manual measurements of blood pressure are preferred. All vital sign 
measurements must be done using a calibrated instrument. For each participant, the same method 
of measurement should be used at all visits. All vital sign values, including whether measured 
manually or via an automated monitor, will be recorded in the participant’s source documents 
and in the participant’s CRF. 
6.9. 
Body Temperature 
The PI or designee will obtain body temperature using an oral thermometer at the visits indicated 
in the Schedule of Assessments (Appendix 1). Prior to discharge from the clinic on Day 1, the 
participant will: 
1. Be educated and counseled by site staff regarding the potential for serious, rapidly 
progressive bacterial infections which may be life threatening and therefore understand 
the need to identify fever rapidly and seek emergency medical evaluation without delay 
2. Be educated and counseled by site staff regarding high risk behaviors, which include 
drinking from the same beverage containers, sharing eating utensils with others, avoiding 
large crowds, and smoking (including second-hand exposure) 
3. Be provided a thermometer and taught how to use it. All participants need to take these 
thermometers with them at all times. They need to be able to take their temperature if 
feeling warm or unwell 
4. Be instructed to contact the investigator immediately and/or seek emergency medical 
attention for any temperature >38.0°C /100.4°F 
5. Be advised not to wait for site staff to return their phone call before seeking emergency 
medical attention but should go to the nearest emergency or urgent care medical facility 
for evaluation. 


ACH-0144471 
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Clinical Protocol ACH471-204, Amendment 7 
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(a subsidiary of Alexion Pharmaceuticals, Inc.)  
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6. Be taught to be alert to the signs of possible serious infections, which are often flu-like 
symptoms 
7. At all times, have immediate access to transportation and telephone, and be within 
reasonable proximity to emergency medical care 
8. Be provided with a study contact card and instructed to carry this with them at all times. 
The study contact card should be provided to the emergency medical personnel who 
should be asked to contact the study site 
All abnormal body temperature measurements must be recorded or stored in the participant’s 
source documents and CRF. Any clinically significant finding must be reported as an adverse 
event. Any temperature measurement ≥38.0°C, measured either at the clinic or by the participant 
outside the clinic, requires action as outlined in the Fever Management Plan (Appendix 2). 
6.10. 
Electrocardiography 
The PI or designee will obtain a screening ECG measurement, as indicated in Appendix 1. All 
ECG recordings should be 12-lead, and should be performed after the participant has rested 
quietly for at least 5 minutes in a supine position prior to dosing and before blood is drawn 
(whenever possible). The following parameters and intervals will be assessed: HR, RR, PR, 
QRS, QT, and QTcF. The occurrence of depolarization or repolarization disorders, arrhythmic 
disorders or other abnormalities will be noted. A designation of clinical significance shall also be 
noted. 
In some cases, it may be appropriate to repeat an abnormal ECG to rule out improper lead 
placement as contributing to the ECG abnormality. It is important that the leads are placed in 
approximately the same positions each time in order to achieve precise ECG recordings. 
All ECGs must be read by the PI or designee. The PI/designee needs to evaluate the finding of 
ECG abnormalities promptly (refer to Section 6.18.1 for a discussion of the circumstances under 
which ECG findings are to be reported as AEs). 
All ECG parameters and assessments must be recorded or stored in the participant’s source 
documents and in the participant’s CRF. Any clinically significant finding must be reported as an 
adverse event. 
6.11. 
Clinical Laboratory Tests 
Blood and urine samples will be collected for safety and PD laboratory evaluation as listed in 
Table 2, at the times in Appendix 1. Participants will be in a seated or supine position during the 
blood collection. Specific instructions for sample collection, processing, and shipping will be 
provided in a separate laboratory manual. 
In addition to the calculation of eGFR, some investigators may choose to measure GFR based on 
iohexol clearance. Measurement of GFR is at the discretion of the investigator, but if performed, 
these measurements should be taken, at a minimum, in accordance with the Schedule of 
Assessments. Additional measurements may also be done at the discretion of the investigator. 
 


ACH-0144471 
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Clinical Protocol ACH471-204, Amendment 7 
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Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
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Table 2. 
Clinical Laboratory Tests  
Hematology 
Chemistry 
Urinalysis 
Additional 
Tests at 
Screening Only 
Other 
Assessments 
Complete blood count 
(CBC), including: 
- Red blood cell 
(RBC) count 
- White blood cell 
(WBC) count 
- WBC differential 
(absolute and 
percent): 
- neutrophils 
- lymphocytes 
- monocytes 
- eosinophils 
- basophils 
- Hematocrit (Hct) 
- Hemoglobin 
(Hgb) 
- Mean corpuscular 
volume (MCV)  
- Mean corpuscular 
hemoglobin 
(MCH) 
- Mean corpuscular 
hemoglobin 
concentration 
(MCHC)  
- Mean platelet 
volume (MPV) 
- Platelet count 
- Red cell 
distribution width 
(RDW) 
- Reticulocyte 
count 
Alanine 
aminotransferase 
(ALT) 
Albumin 
Alkaline phosphatase 
Aspartate 
aminotransferase 
(AST) 
Bicarbonate (HCO3) 
Bilirubin 
(fractionated)1 
Blood urea nitrogen 
(BUN) 
Calcium 
Calculated eGFR2 
Chloride 
Creatinine 
Cystatin C 
Gamma-glutamyl 
transferase (GGT) 
Glucose3 
GFR (iohexol 
clearance)4 
Lipid Profile including: 
- Cholesterol/HDL 
ratio 
- High-density 
lipoprotein 
cholesterol (HDL-
C) 
- Low-density 
lipoprotein 
cholesterol (LDL-
C) 
- Non-HDL-C 
- Total cholesterol 
- Triglycerides 
- Very low-density 
lipoprotein 
cholesterol 
(VLDL-C) 
Phosphate 
Potassium 
Sodium 
Total protein 
Uric acid 
Dipstick Analysis 
including: 
- Bilirubin 
- Color 
- Glucose 
- Ketones 
- Leukocytes 
- Nitrite 
- Occult blood 
- pH 
- Protein 
- Specific gravity 
- Urobilinogen 
Microscopic 
examination of 
sediment5 
Spot Urine and 
24-Hour Urine 
samples6: 
- Total protein  
- Albumin 
- Creatinine 
- Albumin: 
creatinine ratio 
- Total protein/ 
creatinine ratio 
- Complement 
components 
HCV Ab7 
HbsAg 
HIV Ab 
FSH8 
Serum 
Pregnancy 
test9 
Urine drug 
screen10 
Sample for 
potential 
genetic 
biomarker 
testing (white 
blood cells) 
 
Serum/Plasma 
Complement 
Biomarkers: 
- C3 
Convertase 
- AP 
Hemolysis 
- AP Wieslab 
- Ba 
- Bb 
- C3 
- C4 
- CP activity 
- fD 
- sC5b-9 
- C3a 
- C5 
- Multiplex 
assay (fB, 
fH, 
properdin) 
- Auto-
antibodies to 
fH 
- C3 nephritic 
factor 
PT/PTT/INR 
Urine pregnancy 
test9 
 
Check the Schedule of Assessments (Appendix 1) for specific times when these tests should be done. 
1 
Fractionate and obtain measurements of direct and indirect bilirubin for all participants.  


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2 
Provide eGFR based on CKD-EPI creatinine equation (2009) for participants ≥19 years of age, and based on the 
“Bedside Schwartz” equation (2009) for participants <19 years of age. 
3 
If glucose is > ULN, reflexively test HbA1c 
4 
Optional, at the discretion of the investigator.  
5 
Only if occult blood, protein, or leukocytes present on dipstick analysis. 
6 
The spot urine sample should be a first-morning void.  
7 
If positive, HCV RNA levels should be measured. Participants with detectable HCV RNA will be excluded.  
8 
FSH for postmenopausal women at screening only. 
9 
Serum pregnancy test at Screening Visit 1 and urine pregnancy tests at other times as per the schedule in 
Appendix 1 for women of childbearing potential only. Any positive urine pregnancy test will be confirmed by a 
serum pregnancy test. 
10 Urine drug screen will be measured at Screening Visit 1. For all participants, the urine drug test should include, 
at a minimum, cotinine, amphetamines, barbiturates, cocaine metabolites, opiates, benzodiazepines, and 
cannabinoids. 
6.12. 
Pregnancy Testing 
All females of childbearing potential (as determined at screening) will have a serum pregnancy 
test during screening, and urine pregnancy tests for the duration of the study including follow-up 
as indicated in the Schedule of Assessments (Appendix 1). On Day 1, the urine pregnancy test 
must be done before dosing and must be negative to begin dosing. 
Female participants of childbearing potential who require vaccinations (see Section 6.3) must 
also have a negative urine pregnancy test before any vaccine or booster is administered.  
Any positive urine pregnancy test will be confirmed by a serum pregnancy test. 
6.13. 
Sample Collection, Storage, and Shipping 
6.13.1. 
Blood and Urine Collection for Complement Assays 
Serum/plasma samples will be collected at the time points indicated in the Schedule of 
Assessments (Appendix 1). It is important that samples for PD testing be collected, prepared, and 
shipped in a way that ensures minimum freeze-thaw cycles and avoids potential in vitro 
complement activation before testing. Whole blood will be collected and processed to obtain 
cell-free serum or plasma which will be aliquotted into cryovials, frozen on dry ice, stored in a -
80°C freezer and shipped frozen to the designated laboratories for testing.  
Urine samples will be collected at the time points indicated in the Schedule of Assessments 
(Appendix 1) and stored for potential assessment of the concentrations of selected complement 
proteins in urine.  
Specific instructions for sample collection, processing, and shipping will be provided in a 
separate laboratory manual. 
Biological samples, such as serum, plasma and urine, may be kept for up to 3 years after 
completion of the Clinical Study Report and then will be destroyed by internationally accepted 
means (e.g., incineration). 


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6.13.2. 
Blood Collection for Genetic Complement-Associated Biomarker Testing  
Subject to participant consent, a sample will also be collected at screening for potential genetic 
analysis. Genetic analyses may be conducted if a participant does not respond to the investigative 
drug, to better understand a potential drug-related toxicity, or to further characterize the 
underlying disease. Genes which may be sequenced include (but are not limited to): 
• Complement component C3 
• Complement factor H-related proteins (CFHR1, CFHR3, CFHR4, CFHR5) 
• Complement factor B 
• Complement factor D 
• Complement factor H 
• Complement factor I 
• Membrane Co-Factor Protein (MCP/CD46) 
• Thrombomodulin (THBD) 
All genetic samples will be stored for a maximum of 3 years after completion of the Clinical 
Study Report. During that time, samples may be retested if other mutations are discovered that 
may be associated with C3G. Participants may withdraw their consent for genetic testing and 
withdraw their samples from further genetic testing at any time by notifying the study 
investigator verbally and in writing. After the 3-year storage period defined above, or once the 
sponsor is informed of withdrawal of consent for further analysis, the sample will be destroyed 
consistent with accepted laboratory standards and no further testing or analysis will be 
completed. Any data already generated from the sample may continue to be used for the 
purposes of this study and future research. 
6.13.3. 
Blood Volumes 
Approximate blood volumes to be drawn are detailed in Table 3 below. The maximum planned 
blood volume to be collected from each participant over the course of the study (approximately 
143 weeks, including Screening, the 6-month Blinded Treatment Period, the 6-month Extended 
Treatment Period, Long-Term Follow-up Period, Taper, and Follow-up) is approximately 
519 mL. The individual visit with the largest blood draws is expected to be the Screening visit 
(51 mL), and the maximum blood volume to be drawn in an 8-week window is 102 mL, from 
Day 1 to Week 8 (Day 56), inclusive. This does not include discarded blood from pre-collection 
used to flush catheters. The discarded volume is not expected to exceed 40 mL. Unanticipated 
additional blood may be collected throughout the study for such things as safety monitoring and 
additional PD assessments, if necessary, and if there are blood samples collected during any 
unscheduled visits. 


ACH-0144471 
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Table 3. 
Approximate Total Blood Volumes 
Period 
Blood Volume (mL) 
Screening 
Treatment Periods 
Taper 
Follow-
Up 
Total 
Blinded 
(Weeks 1 to 
28) 
Extended 
(Weeks 29 to 
52) 
Long-Term 
(Weeks 53 to 
143) 
TOTALS 
51 
190 
65 
139 
37 
37 
519 
The maximum volume drawn in an 8-week window is 102 mL, from Day 1 to Week 8 (Day 56), inclusive. 
6.14. 
Dispensing Study Drug 
ACH-0144471 will be supplied as 50 and 100 mg tablets. At each visit, the site will dispense 
study drug as required to provide participants with sufficient study drug for dosing until their 
next clinic visit. If a clinic visit is not possible during the COVID-19 pandemic, study drug will 
be sent directly to participant’s home (Section 6.23).  
6.15. 
Safety Assessments 
Safety will be evaluated by monitoring and assessment of AEs, clinical laboratory tests, physical 
examination findings, and vital signs measurements at Screening, Baseline, and at various time 
points during the study as described in Section 7 and the Schedule of Assessments (Appendix 1). 
6.16. 
Pharmacodynamic Assessments 
PD markers monitor biological effects and are used in early drug development to assist in future 
decision making. Pharmacodynamics will be evaluated using serum, plasma, and urine collected 
during the study. Additional information on sample collection and shipping instructions will be 
provided in a separate laboratory manual. 
Pharmacodynamics will be evaluated by assessment of Bb levels in plasma samples collected 
during the study, which should provide a direct readout of AP inhibition in vivo. In addition, the 
CP activity assay is a functional assay to qualitatively evaluate the effect of ACH-0144471 on 
total CP activity. 
Inhibition of AP activity will also be evaluated with the AP Wieslab ELISA, AP hemolysis, and 
C3 convertase activity, the presence of autoantibodies to complement components or regulators, 
and the concentrations of multiple complement components and their split and terminal products 
in serum, plasma, and/or urine may be explored to understand their association with the 
underlying disease and any changes in response to ACH-0144471 treatment. 
White blood cells will be collected and stored for possible genetic profiling of selected 
complement components and regulators (see Section 6.13.2) for possible exploration of the 
understanding of the underlining etiology of C3G and any correlation with participants’ response 
to ACH-0144471. 


ACH-0144471 
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6.17. 
Patient-Reported Outcomes Assessments 
6.17.1. 
Quality of Life Questionnaires 
All participants enrolled in the trial will self-administer questionnaires for the FACIT-Fatigue 
(version 4), KDQOL version 1.3, and EQ-5D-3L scales at the times specified in Appendix 1 to 
assess their HRQOL, fatigue, and kidney-related fears and worries (e.g., kidney failure, dialysis, 
kidney transplant), and to determine health states value, over the course of treatment with ACH-
0144471. Local language versions of each of the tools will be provided separately. 
6.18. 
Adverse Events Assessments 
6.18.1. 
Definitions 
Adverse events (AEs) must be assessed for the investigational products in this study. An 
investigational product is defined as a pharmaceutical form of an active ingredient or placebo 
being tested or used as a reference in the study, whether blinded or unblinded. The term “adverse 
event” is defined as any untoward medical occurrence associated with the use of a drug in 
humans, whether or not considered drug related. An AE can arise with any use of the drug (e.g., 
off-label use, use in combination with another drug) and with any route of administration, 
formulation, or dose, including an overdose. 
Medical occurrences, including pregnancies, that begin before the start of study intervention but 
after obtaining informed consent will be recorded on the Medical History/Current Medical 
Conditions section of the CRF, not the AE section. This does not include pre- or post-treatment 
complications that occur as a result of protocol-mandated procedures (e.g., invasive procedures, 
such as venipuncture or biopsy), which should be reported as AEs. While pregnancy itself is not 
considered an AE, for the purposes of tracking, a pregnancy occurring after the start of study 
intervention should be captured as an AE as well as reported on the pregnancy forms. 
A treatment-emergent adverse event (TEAE) is defined as an AE that emerges during treatment, 
having been absent prior to treatment, or worsens relative to the pretreatment state. In this study, 
any AE first assessed after receipt of the first dose of ACH-0144471 until 28 days after the last 
dose of study drug will be considered treatment-emergent, as defined in Section 6.18.5. All 
TEAEs will be recorded and reported. 
An AE (including a TEAE) can be one or more of the following: 
• Any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or 
disease temporally associated with the use of a drug, and does not imply any judgment about 
causality. 
• Any new disease or exacerbation of an existing disease. 
• Recurrence of an intermittent medical condition (e.g., headache) not present at baseline. 
• Any case of abuse of alcohol, illicit drugs, or prescription drugs; abuse of study drug(s) or 
protocol-specified drug(s); addiction. 
• A pregnancy that occurs or becomes confirmed during a clinical study (see Section 6.18.8). 


ACH-0144471 
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• Laboratory test or other clinical test (e.g., ECG or X-ray) with a clinically significant 
abnormality (as defined below). 
• An effect of the study medication, including comparator. 
• Any dose of medication (study drug or other concomitant medication) that is taken at a dose 
higher than the prescribed dose (i.e., an overdose). Overdose should be reported as an AE 
whether or not it is associated with any symptoms or signs. 
 
The following are not considered to be AEs: 
• Medical or surgical procedures (e.g., surgery, endoscopies, tooth extraction, transfusion, etc.) 
- the condition which leads to the procedure is the AE; 
• Preexisting diseases or conditions or laboratory abnormalities present or detected prior to the 
screening evaluation that do not worsen; 
• Situations where an untoward medical occurrence has not occurred (e.g., hospitalization for 
elective surgery, social and/or convenience admissions, etc.) 
 
Clinically significant changes in objective findings (e.g., laboratory, ECG, physical examination) 
should be considered AEs only if they meet one or more of the following criteria: 
• Associated with accompanying symptoms;  
• Require medical/surgical intervention;  
• Lead to a change in study drug dosing or discontinuation from the study;  
• Lead to significant additional concomitant drug treatment, or other therapy;  
• Lead to any of the outcomes included in the definition of a serious adverse event; 
• Are considered clinically significant by the investigator. 
 
Whenever possible, the etiology of the abnormal finding (rather than the abnormal finding itself) 
should be documented as the adverse event. Repeated additional tests and/or other evaluations 
required to establish the significance and etiology of an abnormal result should be obtained when 
clinically indicated. 
Any abnormal test result that is determined to be an error does not require reporting as an AE. 
Surgical procedures themselves are not AEs but are therapeutic measures for conditions that 
require surgery. The condition for which the surgery is required may be an adverse event, if it 
occurs or is detected during the study period. Planned surgical measures permitted by the clinical 
study protocol (if any) and the condition(s) leading to these measures are not AEs, if the 
condition(s) was (were) known before the start of the study treatment and documented in the 
participant’s medical record. In the latter case, the condition should be reported as medical 
history. 


ACH-0144471 
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All participants who have AEs, whether considered to be associated with the use of the 
investigational product or not, must be monitored to determine the outcome of the event(s). The 
clinical course of the AE will be followed according to accepted standards of medical practice, 
even after the end of the period of observation, until a satisfactory explanation is found, or the 
investigator considers it medically justifiable to terminate follow-up. 
6.18.2. 
Criteria for Assessing Seriousness 
All AEs must be evaluated as potential SAEs. If an event is not an AE per definition above, then 
it cannot be an SAE even if serious conditions are met. An SAE is any untoward medical 
occurrence that occurs at any dose and meets at least one of the following criteria: 
• 
Results in death 
• 
Is life-threatening i.e., the participant was at immediate risk of death from the AE as it 
occurred. (This does not include an event that, had it occurred in a more severe form or 
was allowed to continue, might have caused death.) 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization for the AE 
▪ The following types of hospitalizations are not considered SAEs for regulatory 
reporting purposes: 
− Hospitalization(s) for planned (pre-scheduled) medical procedures known at the 
time of screening 
− Protocol-specific hospital admission 
− Respite care 
− Admission for the treatment of pre-existing condition (known at the time of 
screening) not associated with the development of a new AE or with the 
worsening of the pre-existing condition 
− Observation/same day/ambulatory procedure 
• 
Is a persistent or significant disability/incapacity or substantial disruption of the ability to 
conduct normal life functions 
• 
Is a congenital anomaly/birth defect (in the child of a participant who was exposed to the 
study drug) 
• 
Is an important medical event or reaction 
6.18.3. 
Documentation and Reporting of Adverse Events 
AEs, including TEAEs, may be spontaneously reported by a participant or his/her representative, 
or elicited during questioning and examination of a participant. All AEs will be assessed by the 
Investigator and documented regardless of apparent causality from use of the study treatment(s). 
For each AE, the investigator will evaluate and report the date of onset and resolution, outcome, 
severity, relationship to study treatment(s), action taken, additional treatments required to 
manage the event, and determination of seriousness. All identified AEs occurring during the trial 
and follow-up period must be fully recorded and described on the appropriate CRF page. The AE 


ACH-0144471 
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should be reported in standard medical terminology. Whenever possible, the AE should be 
evaluated and reported as a diagnosis, rather than as individual signs or symptoms. A cluster of 
signs and symptoms that results from a single cause should be reported as a single AE (e.g., 
fever, elevated WBC, cough, abnormal chest X-ray, etc. can all be reported as “pneumonia”). 
If a definitive diagnosis is not possible, the individual symptoms and signs should be recorded.  
Documentation must be supported by an entry in the participant’s medical record. The 
relationship to study drug or study procedures should be assessed using the definitions in 
Section 6.18.7. 
6.18.4. 
Treatment and Follow-Up of Adverse Events 
All AEs should be followed up (including obtaining relevant laboratory tests) until they have 
returned to baseline status or stabilized. If a clear explanation is established, it should be 
recorded. Follow-up of AEs will continue through the last day on study (including the follow-up 
period) or until the events have resolved or stabilized to the satisfaction of the PI and the 
Achillion Pharmaceuticals Medical Monitor (or designee). Achillion Pharmaceuticals may 
request that certain AEs be followed until resolution or stabilization. 
6.18.5. 
Timeframe for Collection of Adverse Events 
AEs include events that have appeared or worsened during the course of the clinical trial. AEs 
may also include pre- or post-treatment complications that occur as a result of protocol-mandated 
procedures (e.g., invasive procedures, such as venipuncture, biopsy, etc.). 
Any AE (i.e., a new event or an exacerbation of a preexisting condition) with an onset date after 
the participant provides informed consent through the 28 days following the participant’s last 
study drug dose will be recorded as an AE on the appropriate CRF page(s). 
All SAEs, regardless of cause or relationship, occurring within 28 days of last study drug dose 
must be documented and reported. 
Follow-up of SAEs will continue through the last day on study or until the event has resolved or 
stabilized to the satisfaction of the PI and the Achillion Pharmaceuticals Medical Monitor (or 
designee). Investigators are not obligated to actively seek out SAEs beyond the follow-up period. 
However, if the PI (or designee) learns of an SAE occurring after completion of the final follow-
up visit, and the SAE is deemed by the PI (or designee) to be related to the study drug (s), the PI 
(or designee) should promptly document and report the event to Achillion Pharmaceuticals. 
6.18.6. 
Severity and Grading of Adverse Events 
The severity of an adverse event will be graded according to the Common Terminology Criteria 
for Adverse Events (CTCAE) v4.03 [36]. The PI (or designee) should determine the severity of 
the AE (mild, moderate or severe) based on the overall clinical importance or significance of the 
finding for that individual participant.   
If an AE that was reported during the study increases or decreases in severity, then that AE is 
given a resolution date and time and a new record initiated with the new severity. If the severity 
of an AE remains the same, the AE will be kept open through to resolution. 


ACH-0144471 
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Clinical Protocol ACH471-204, Amendment 7 
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6.18.7. 
Assessment of Causality 
The investigator must assess the likelihood that the study drug caused or contributed to each AE, 
and document this assessment assigning one of the following relatedness criteria to each AE: 
• 
Unrelated: In the opinion of the investigator, there is no association between the study drug 
and the AE. 
• 
Unlikely: In the opinion of the investigator, it is unlikely that there is an association between 
the study drug and the reported event. 
• 
Possible: In the opinion of the investigator, treatment with the study drug may have caused 
or contributed to the AE but could also have been produced by other factors (i.e., the event 
follows a reasonable temporal sequence from the time of drug administration and/or follows 
a known response pattern to the study drug, but is also known to be caused by other factors). 
• 
Probable: In the opinion of the investigator, it is likely that the study drug caused or 
contributed to the AE based on a reasonable temporal sequence of the event with drug 
administration and, the known pharmacologic action and/or adverse reactions of the drug (or 
class of drugs) or the investigator’s clinical judgment. 
• 
Definite: In the opinion of the investigator, it is definite that the study drug caused or 
contributed to an AE, and other conditions (e.g., concurrent illness, progression/expression of 
disease state, or concurrent medication reaction) do not explain the event. 
 
For the purposes of determining expedited reporting status to Health Authorities, Achillion 
considers the assessments of ‘unrelated’ and ‘unlikely’ as unrelated to study drug and ‘possible’, 
‘probable’, and ‘definite’ as related to study drug. 
In addition, for any analyses of AE data in which only two categories of ‘related’ and ‘unrelated’ 
are used, the assessments of ‘unrelated’ and ‘unlikely’ will be combined into the category of 
‘unrelated’, and the assessments of ‘possible’ and ‘probable’ and ‘definite’ will be combined into 
the category of ‘related’. 
6.18.8. 
Pregnancy 
Any pregnancy, including in a female partner of a male participant, that occurs or becomes 
confirmed during a clinical study (time frames outlined in Section 6.18.5) must be reported to 
Achillion (or designee) within one business day of first knowledge of the pregnancy. The report 
should be provided on the pregnancy form. While pregnancy itself is not considered an AE, for 
the purposes of tracking, it should be captured as an AE as well as reported on the pregnancy 
forms. 
All pregnancies temporally related to study drug should be followed and discussed with the 
medical monitor as follows: 
• 
The investigator will follow up with the participant or the participant’s female partner 
approximately every 3 months throughout the pregnancy and report to Achillion (or 
designee) using the pregnancy forms. Generally, follow up will not be required for longer 
than 6-8 weeks beyond the estimated delivery date.  


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
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Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
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• 
The investigator will report any information on the status of the pregnancy to Achillion 
(or designee) using the pregnancy forms. 
• 
The outcome of the pregnancy will be reported to Achillion (or designee) using the 
pregnancy forms. Any termination of pregnancy will be reported, regardless of fetal 
status (i.e., presence or absence of anomalies) or indication for the procedure.  
Any SAEs related to the pregnancy (see below), or occurring during the participant’s pregnancy, 
or after delivery, must be documented and reported to Achillion (or designee) on both the SAE 
Form and the pregnancy forms. SAEs occurring in the child (e.g., congenital anomalies or other 
conditions present at birth, whether genetically inherited or occurring in utero) must also be 
documented on both the SAE form and the pregnancy forms. 
Reportable SAEs associated with pregnancy include, but are not limited to: 
• 
Pregnancy losses (e.g., spontaneous abortion, late fetal death, elective termination) 
• 
Life-threatening developments (e.g., placental abruption, fetal distress) 
• 
Congenital anomalies 
• 
Neonatal or maternal death, or 
• 
Any event resulting in maternal or neonatal hospitalization/prolonged hospitalization. 
6.18.9. 
Reporting Serious Adverse Events 
Achillion Pharmaceuticals has requirements for the expedited reporting of safety events meeting 
specific requirements to worldwide regulatory authorities; therefore, Achillion Pharmaceuticals 
must be notified immediately regarding the occurrence of any SAE and/or pregnancy that occurs 
during the study (time frames outlined in Section 6.18.5).  
The procedures for reporting all SAEs and/or pregnancies, regardless of causal relationship, are 
as follows: 
SAE 
• 
Record the SAE within 24 hours of becoming aware of the event by logging into the EDC 
system (Fusion) and completing an initial SAE report. 
• 
This will trigger an email notification to the Axiom and Achillion Pharmaceuticals 
distribution lists. 
Pregnancy 
• 
Record the pregnancy into the EDC system (Fusion) and completing the pregnancy form. 
• 
This will trigger an email notification to the Axiom and Achillion Pharmaceuticals 
distribution lists. 
Contact information is provided below. 


ACH-0144471 
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Clinical Protocol ACH471-204, Amendment 7 
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Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
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SAE CONTACT 
SAE Telephone Number: 
In the event of System failure, or for questions about completing the forms in EDC: 
 
Axiom Real-Time Metrics 
 
  
  
For fatal or life-threatening events, provide copies of hospital discharge reports, autopsy reports, 
and other documents, as applicable.  Achillion Pharmaceuticals may request additional 
information from the PI to ensure the timely completion of accurate safety reports. 
In the case of a medical emergency, please use the contact provided on the title page of the 
protocol. 
6.18.10. 
Investigator Reporting Requirements for SAEs 
Achillion is responsible for ensuring that Investigators and central ECs/IRBs are notified of all 
AEs that are serious, unexpected and considered related, probably related, or possibly related to 
the investigational product. A CRO may be designated to perform this notification. This 
notification will be in the form of a MedWatch/CIOMS report. The PI will notify the local ECs 
or IRBs as per EC or IRB requirements. Upon receiving such notices, the PI must review and 
retain the notice. The Sponsor, investigator, and EC or IRB will determine if the informed 
consent requires revision. The PI should also comply with EC or IRB procedures for reporting 
any other safety information. 
6.19. 
Concomitant Medication Assessments 
Details of all prior (within 90 days of the screening evaluation) and concomitant medication use, 
including all medications administered for the treatment of AEs, will be recorded in the 
participant’s CRF at each study visit. 
6.20. 
Monitoring Participant Safety 
The safety of participants will be monitored by Investigators and by a medical monitor (or 
designee) at Achillion Pharmaceuticals on an ongoing basis while participants are receiving 
ACH-0144471. A Fever Management Plan (Appendix 2) has been developed for this study to 
enable rapid assessment, detection and treatment of any potential serious infection. 
6.21. 
Removal of Participants from the Trial or Study Drug 
A participant is free to withdraw from the study at any time without jeopardizing future medical 
care. The PI (or designee) may decide, for reasons of medical prudence or participant 
noncompliance, to discontinue dosing in a participant. The PI should also stop dosing in any 
participant who meets an individual stopping rule (Section 3.2.3.2). In either case, whenever 
possible, the Achillion MM should be notified immediately, and if possible, before dosing is 
terminated.  
PPD


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 58 of 86 
If dosing is to be terminated, it may be done so immediately, or a taper can be implemented as 
described in Section 5.2.1, whichever is considered to be in the best interest of the participant. 
When dosing is terminated, study participation is not necessarily immediately terminated. 
Instead, whenever possible, the participant should complete all activities in the Taper and 
Follow-Up periods (if tapered) or in the Follow-Up period (if discontinued immediately), as 
described in Appendix 1. 
Reasons for participant withdrawal include (but are not limited to): 
• One or more of the stopping criteria described in Section 3.2.3 is met 
• Intercurrent illness that would, in the judgment of the investigator, affect assessments of 
clinical status to a significant degree 
• Unacceptable toxicity (including a clinically significant laboratory abnormality) 
necessitating discontinuation of study or that, in the judgment of the investigator, 
compromises the ability to continue study-specific procedures, or it is considered not to 
be in the participant’s best interest to continue the study  
• Participant request to discontinue for any reason 
• A female participant becomes pregnant or wishes to become pregnant 
• Participant noncompliance 
• Discontinuation of the study at the request of Achillion Pharmaceuticals, regulatory 
agency, or Ethics Committee or IRB 
• Any other condition or circumstance that would jeopardize the welfare of the participant 
if s/he were to continue in the trial 
The reason for any participant’s discontinuation and the date of withdrawal will be recorded in 
the participant’s CRF. The participant’s CRF, which will be completed up to the point of 
withdrawal, will be retained for the Sponsor. 
6.22. 
Study Assessments When Clinic Visits are Not Possible due to the 
COVID-19 Pandemic 
If a study participant is unable to get to a clinic visit, study data collection may still occur: 
Option 1 (preferred option) 
• Home Healthcare Visits: At these home visits, nurses may collect 24-hour urine, first 
morning urine, and safety labs, including pregnancy testing, for shipment to the central 
laboratory. Serum/plasma biomarker laboratory assessments, and serum C3 and C4 
assessments cannot be collected at home visits, due to the stringent storage and handling 
requirements of these specimens. Other assessments will include adverse events, vital 
signs, concomitant medications, and study drug accountability. Physical examinations, 
weights, and patient-reported outcomes will not be collected at home health visits.  


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 59 of 86 
Option 2 (if Option 1 is not possible) 
 Telephone visits: If home visits are not possible, participants may have telephone visits 
with the PI or designee. Data collection should include adverse events and concomitant 
medications. Physical examinations cannot be performed during a telephone visit. 
Patients will be asked about study drug compliance.  
o Local Laboratories: If home visits are not possible, the participant should go to a 
local laboratory to drop off 24-hour urine collections and for safety laboratory 
testing, including pregnancy testing (if applicable), to be performed. 
6.23. 
Study Drug Compliance and Supply When Clinic Visits are Not 
Possible 
If a study participant is unable to get to a clinic visit during the COVID-19 global pandemic, 
study drug may be shipped to the participant’s home.  
Treatment compliance assessments shall be made at each home visit or telephone visit. 
Participants will be asked about their supply of study drug so that study drug compliance may be 
assessed. Study staff will address any non-compliance issues with the participant.  
6.24. 
Renal Biopsies When Clinic Visits are Not Possible 
If a study participant is unable to get to a clinic visit during the COVID-19 global pandemic, 
optional renal biopsies at Week 52 and Week 104 should be performed when possible, even if 
the biopsy is done outside the visit window of ±7 days. In addition, an unscheduled 24-hour 
urine collection should be obtained at the same time as the optional biopsies at Week 52 and 
Week 104. If the collection of 24-hour urine is to occur after a renal biopsy, it must be done at 
least 7 days after the biopsy procedure.  


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 60 of 86 
7. 
STUDY ACTIVITIES 
Activities for each visit are provided in the Schedule of Assessments (Appendix 1). Additional 
details for the various activities are provided in Section 6. 
During the periods when multiple assessments occur at the same time, ECGs and vital signs 
should be recorded prior to blood sampling.  
The actual times of procedures and sample collections will be recorded in the participant’s CRF. 
7.1. 
Screening Period (Days –75 to -1) 
For each participant, informed consent or assent will be obtained as described in Section 6.1 
before the participant enters into the study and any study-related procedures are performed. 
Participant eligibility will be determined according to the criteria specified in this protocol. All 
screening eligibility assessments listed in the Schedule of Assessments (Appendix 1) should be 
performed and documented prior to dosing. This should include a review of the inclusion and 
exclusion criteria, and a review of the study restrictions, as defined in Section 5.5. The 
participant’s medical history should be reviewed as described in Section 6.2, and a complete 
physical examination should be conducted as described in Section 6.7. A 24-hour urine sample 
should be collected as described in Section 6.6.1 and a first morning urine sample should be 
collected as described in Section 6.6.2; participants may be provided with collection containers 
and may bring their samples to the clinic.  
If the participant remains eligible, then arrangements can be made for any required vaccinations 
(see Section 7.1.2). If required, vaccinations should be at least 2 weeks before the first dose of 
study drug unless otherwise recommended by national and/or local guidelines or local clinical 
practice. Participants who meet all eligibility criteria will be educated about the restrictions on 
concomitant medication usage and other substances. 
Each adult participant will complete the KDQOL-SF v1.3, FACIT-Fatigue, and EQ-5D-3L 
questionnaires during the screening period, prior to study treatment administration. 
All evaluations required for determination of eligibility must be completed before the participant 
is randomized into the study. 
If the participant is unable to receive study drug within 75 days of screening the participant may 
be re-screened once (for all assessments except the renal biopsy). 
The repeating of individual screening laboratory results that fall outside the protocol-required 
range may be permitted on a case-by-case basis with the written pre-approval of the Achillion 
Pharmaceuticals Medical Monitor (or designee). 
7.1.1. 
Screening and Pre-Treatment Renal Biopsy  
If necessary to confirm eligibility (as discussed in Section 6.3.1) or as a pre-treatment (baseline) 
biopsy  a renal biopsy should be performed during screening according to the procedures 
described in Section 6.3. When obtained to confirm eligibility, the results must be available and 
reviewed prior to dosing. Given that the renal biopsy is an invasive procedure, a participant 
should be confirmed as eligible by all other criteria before the renal biopsy is performed.  


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 61 of 86 
Biopsies will not be obtained from participants less than 18 years of age (unless they are 
determined to be clinically indicated by the treating provider), or from participants for whom a 
biopsy is contraindicated. 
7.1.2. 
Vaccination  
As part of the screening process, participants will be evaluated to determine whether vaccination 
against N. meningitidis, S. pneumoniae, or H. influenzae is to be performed, as described in 
Section 6.3. Female participants of childbearing potential must have a negative urine pregnancy 
test on the day of vaccination, before any vaccine or booster is administered.  
7.2. 
Blinded Treatment Period 
During the Blinded Treatment Period, physical examinations, assessment of vital signs, all 
required safety laboratory testing, and collection of blood and urine samples for PD evaluation 
will be performed at various time points as specified in Appendix 1. 
Participants should be instructed to fast prior to coming to a clinic visit; however, they may drink 
water or other non-alcoholic beverages. Participants should be instructed to bring their study 
drug with them for administration at the site. 
At clinic visits, participants should be instructed how to take their medication at home, as 
described in Section 5.3, and record the time they took it. 
Participants should be instructed to store their study drug at room temperature, as described in 
Section 5.8. 
In-clinic visits will be scheduled as listed in the Schedule of Assessments (Appendix 1). The 
final visit in the Blinded Treatment Period will be at Week 28.  
The assessments listed in the Schedule of Assessments (Appendix 1) should be performed prior 
to the administration of the first daily dose of study drug.  
As indicated in the Schedule of Assessments (Appendix 1), participants will be asked to 
complete the QoL assessments at Week 28. Each adult participant will be asked to complete the 
KDQOL-SF v1.3 questionnaire, the FACIT-Fatigue scale, and the EQ-5D-3L.  
The visits on Weeks 3, 5, 6, 7, 10, 14, 18, 22,24, 26, 32, 40, and 48 can be conducted by phone 
7.3. 
Extended Treatment Period 
During the Extended Treatment Period, physical examinations, assessment of vital signs, and all 
required safety laboratory testing, and collection of blood and urine samples PD evaluation will 
be performed at various time points as specified in Appendix 1. 
Participants should bring their study drug with them for administration at the site. 
At clinic visits, participants should be instructed how to take their medication at home, as 
described in Section 5.3, and record the time they took it. 
Participants should be instructed to store their study drug at room temperature, as described in 
Section 5.8. 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 62 of 86 
As listed in the Schedule of Assessments (Appendix 1), outpatient clinic visits will be scheduled 
on Weeks 29, 30, 32, 36, 44, and 52. Visits at Week 40 and 48 can be done by phone call. Some 
participants will be transitioning from placebo to ACH-0144471 after Week 28, and investigators 
and participants may not know the treatment assignments due to the study being blind. The 
assessments listed in the Schedule of Assessments (Appendix 1), including measurement of the 
listed complement markers should be performed prior to the administration of the first daily 
dose.  
As indicated in the Schedule of Assessments (Appendix 1), participants will be asked to 
complete the QoL assessments at Week 52.  Each adult participant will be asked to complete 
KDQOL-SF v1.3 questionnaire, EQ-5D-3L, and the FACIT-Fatigue scale. 
7.4. 
21- Month Long-Term Follow-up 
During the 21-Month Long-Term Follow-up Period, quarterly visits will be completed in clinic. 
The visits will include physical examinations, assessment of vital signs, all required safety 
laboratory testing, and collection of blood and urine samples and complement biomarker 
evaluation to be performed as specified in Appendix 1. 
Participants should bring their study drug with them for administration at the site. 
At clinic visits, participants should be instructed how to take their medication at home, as 
described in Section 5.3.  
Participants should be instructed to store their study drug at room temperature, as described in 
Section 5.8. 
7.5. 
Taper Period 
It is recommended that participants who discontinue ACH-0144471 have study drug tapered over 
3-6 days, as described in Section 5.2. If a participant meets an Individual Stopping Rule 
(Section 3.2.3.2) and dosing is stopped, the PI should consider whether it is in the best interest of 
the participant to discontinue dosing immediately or to taper (as described in Section 5.2.1). 
Whenever possible, the taper decision should also be discussed with the Achillion MM prior to 
dosing termination. If a Group Stopping Rule is met and dosing is terminated in the study, the 
Achillion MM in consultation with the PI will decide whether or not the taper should be 
implemented. When dosing is terminated, study participation is not necessarily immediately 
terminated. Instead, whenever possible, the participant should advance to the Taper and/or 
Follow-Up Periods, as relevant, and complete all activities in those periods as described in 
Appendix 1. Participants who are completing the taper will have assessments indicated in 
Appendix 1 performed on Days 3 (T3) and 6 (T6) of the taper period. 
Participants will be instructed to bring their study drug with them for administration at the site. 
Participants will continue taking their medication at home in the same way as previously 
described (see Section 5.2). 
Participants will be instructed to store their study drug at room temperature, as described in 
Section 5.8. 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 63 of 86 
Participants should be instructed how to take their medication at home, as described in 
Section 5.3, and record the time they took it.   
7.6. 
Follow-Up Period 
During the Follow-Up Period, physical examinations, assessment of vital signs, all required 
safety laboratory testing, and collection of blood and urine samples for PD evaluation will be 
performed at various time points as specified in Appendix 1. 
As listed in the Schedule of Assessments (Appendix 1), participants will be evaluated at the 
clinical site 2 weeks after the last dose of study drug, and again 4 weeks after the last dose of 
study drug during the Follow-up Period. Participants should arrive at the clinic at the time 
designated by site personnel. If necessary, clinic visits during the Follow-Up Period may occur 
up to 2 days earlier or later than scheduled. Unless the PI feels a clinic visit is required, the 4-
week follow up may be conducted by a phone call  
7.7. 
Early Termination from the Study 
A participant who discontinues dosing does not necessarily discontinue from the protocol, and 
whenever possible, should continue with the Taper and/or Follow-Up Periods, as relevant, and 
complete all activities in those periods as described in Appendix 1. If this is not possible, a 
participant who withdraws from this study should at a minimum have the assessments listed for 
the second follow up visit in the Schedule of Assessments (Appendix 1). 
7.8. 
Unscheduled Visits 
Additional clinic visits may be added if deemed necessary by the Investigator. Activities at these 
visits will be directed by the circumstances, but should include at a minimum: 
• Assess for compliance with protocol restrictions 
• Assess for AEs and SAEs 
• Record concomitant medications 
• Measure body temperature 
• Additional tests or procedures as appropriate 
 
The reason for the visit and the results of any tests or procedures must be recorded in the 
participant’s CRF. 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 64 of 86 
8. 
QUALITY CONTROL AND ASSURANCE 
8.1. 
Routine Monitoring 
The PI is responsible for the validity of all data collected at the clinical site and must accept the 
various monitoring procedures employed by the Sponsor. The purpose of monitoring is to verify 
that the rights and well-being of human participants are protected; that trial data are accurate, 
complete, and verifiable with source data; that the trial is conducted in compliance with the 
protocol, GCP, and the applicable regulatory requirements. 
A monitor assigned by the Sponsor will conduct regular site visits for the purpose of monitoring 
various aspects of the study. Visits will take place usually within a predetermined interval, but 
this may vary during the course of the study. The PI must agree to allow the study monitor and 
authorized representatives of the Sponsor to inspect all CRFs and corresponding source 
documents, e.g., original medical records, participant records and laboratory raw data, access to 
the clinical supplies, dispensing, and storage areas and agree to assist with their activities if 
requested. The PI should provide adequate time and space for monitoring visits. 
The monitor will query any missing or spurious data with the PI (or designee), which should be 
resolved in a timely manner. A monitoring log will be maintained recording each visit, the 
reason for the visit, the monitor’s signature, and PI or designee’s confirmation signature. 
8.2. 
Site Audits 
For the purpose of compliance with GCP and regulatory agency guidelines, it may be necessary 
for Sponsor authorized Quality Assurance personnel and/or authorized personnel from an 
external regulatory agency to conduct an audit/inspection of an investigational site. The purpose 
of an audit is to assess the quality of data with regard to accuracy, adequacy, and consistency, 
and to assure that studies are in accordance with GCP, and Regulatory Agency guidelines. 
Having the highest quality data from studies is an essential aspect of drug development. 
The PI will be given sufficient notice to prepare for such visits, which are planned to take usually 
between one and two days and may be conducted at any stage during the study. The audit will 
involve the review of all study related documentation, which is required by GCP to be 
maintained by each site, review of drug storage, dispensing, and return, review of all study 
related supplies and review of source documents against the CRFs to assure the adequacy and 
accuracy of the information that has been recorded, including the verification of any AEs that 
have occurred. 
In the event of the site being notified of a regulatory inspection, the Sponsor will help with the 
preparation and it is essential that they be notified of the inspection as soon as possible. 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 65 of 86 
9. 
PLANNED STATISTICAL METHODS 
9.1. 
General Considerations 
The planned statistical analysis methodologies will apply to the data collected both during 
Blinded Treatment Period and open-label Extended Treatment Period, wherever appropriate. 
Summary statistics will be provided for efficacy and safety parameters by the treatment group, 
ACH-0144471 and placebo. 
To summarize continuous data, descriptive statistics will include: number of participants, mean, 
standard deviation, median, minimum, and maximum. To summarize categorical data, frequency 
counts and percentages will be presented.  
Longitudinal summaries of efficacy and safety parameters use pre-defined visit week as 
described in Appendix 1, Schedule of Assessments. Laboratory measures will be summarized 
using standard values and units. 
Participant listings will be provided for all efficacy (including PD) and safety parameters. 
A statistical analysis plan (SAP) will be developed and finalized prior to database lock. The SAP 
will provide details of the data analysis procedures and presentations, including relevant 
subgroup analysis. Analysis procedures for addressing exploratory objectives, including those 
based on QoL measures, will also be included in the SAP.  
9.2. 
Determination of Sample Size 
The sample size is determined based on limited clinical cases of C3G to evaluate the 
effectiveness of ACH-0144471. 
9.3. 
Analysis Populations 
All participants receiving at least one dose of study drug, ACH-0144471 or placebo, will be 
included in the efficacy, safety, and pharmacodynamic analyses.  
9.4. 
Demographics and Baseline Characteristics 
The following will be summarized by treatment group and overall for treated participants: 
• demographics: age, gender, race, country / geographic region 
• disease characteristics at baseline: disease diagnosis, duration of the disease, biopsy 
results 
• physical measurement at baseline: height, weight, BMI 
• laboratory tests at baseline 
• prior medications. 
Additional baseline characteristics may also be summarized as clinically indicated. 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 66 of 86 
9.5. 
Efficacy, including Pharmacodynamics Analysis 
The primary efficacy endpoint is: 
• 
Change from baseline in biopsy, based on a score incorporating changes in both the 
activity index and C3 staining at the end of 6 months of treatment. 
• 
Number and percent of participants with reduction in proteinuria relative to baseline at 
the end of 6 months of treatment 
The secondary efficacy endpoints are: 
• 
Change and percent change from baseline in proteinuria over 6 months of treatment 
• 
Change and percent change from baseline in eGFR over 6 months of treatment  
• 
Number and percent of participants with significant improvement relative to baseline in 
eGFR at the end of 6 months of treatment. 
• 
Descriptive analysis of slope of GFR from baseline to 6 months 
• 
Descriptive analysis of slope of GFR after 12 months of ACH-0144471 therapy 
eGFR will be provided using the following formulas: 
• 
For participants 19 years old and older the CKD-EPI creatinine equation (2009) will be 
used for inclusion/exclusion and primary endpoint analysis. However, cystatin C will also 
be measured and as exploratory analysis, eGFR will be calculated by the CKD-EPI 
creatinine-cystatin equation (2012), the CKD-EPI cystatin C equation (2012), and the 
MDRD equation. 
• 
For participants <19 years old the creatinine-based “Bedside Schwartz” equation (2009) 
will be used for inclusion/exclusion and primary endpoint analysis. However, cystatin C 
will also be measured and as exploratory analyses, eGFR will be calculated by the 
cystatin C-based equation (2012) and the creatinine-cystatin C-based CKiD equation 
(2012)  
Cystatin C will be measured to allow use of formulas requiring this parameter. Note that 
calculation details of eGFR will be in detail in the laboratory manual. 
When possible, proteinuria will be evaluated in 24-hour urine collections, but if a 24-hour urine 
is not available, a calculated equivalent will be derived from albumin:creatinine and/or total 
protein:creatinine ratios, obtained from spot urine samples. The process for deriving this 
calculated equivalent will be described in detail in the laboratory manual. 
For changes and percent changes at end of 6 months of treatment, 95%confidence intervals will 
be provided for the mean differences between ACH-0144471 and placebo. Fisher’s Exact 
statistics will be used to compare the two treatment groups for the categorical efficacy 
parameters / response rates. 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 67 of 86 
9.6. 
Safety Analysis 
Treatment-emergent AEs (TEAEs) will be summarized and listed by system-organ-class and 
preferred term using the most current version of the Medical Dictionary for Regulatory Activities 
(MedDRA®). All SAEs and discontinuation due to AEs will be listed in tabulated format. 
All clinical laboratory data (hematology, serum chemistry, and urinalysis) with normal ranges, 
out-of-range flags, and toxicity grades will be listed by participant. Descriptive summary 
statistics may be provided for selected lab tests. 
Data on physical exam, vital signs, and ECG will be examined either through participant listings 
or by summary statistics of selected parameters. 
Other exploratory techniques, e.g., graphic presentations, may also be employed to facilitate 
clinical interpretations of the safety results. 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 68 of 86 
10. 
ADMINISTRATIVE CONSIDERATIONS 
10.1. 
Investigators and Study Administrative Structure 
The PI must maintain a screening log of all participants seen and considered for the study. For 
those participants who are not eligible to participate in the study, the reason for their exclusion 
should be recorded. 
10.2. 
Institutional Review Board (IRB) or Independent Ethics Committee 
(IEC) and Regulatory Approval 
10.2.1. 
Ethical Approval 
The study protocol, participant information and consent and assent forms, the Investigator 
Brochure, available safety information, participant recruitment procedures (e.g., advertisements), 
information about payments and compensation available to the participants and documentation 
evidencing the investigator’s qualifications should be submitted by the investigator to the EC or 
IRB for ethical review and approval according to local regulations, prior to the start of the study. 
The written approval should identify all documents reviewed by name, version, and the date on 
which the committee met and granted the approval. 
Any modifications to EC or IRB approved documents must also be submitted to the EC or IRB 
for approval before implementation. 
10.2.2. 
Regulatory Approval 
As required by local regulations, the Sponsor’s (or designee’s) Regulatory Affairs group will 
ensure all legal aspects are covered, and approval of the appropriate regulatory bodies obtained, 
prior to study initiation. 
10.2.3. 
Amendments 
Any change to the protocol will be affected by means of a protocol amendment. Any changes, 
which affect participant safety or welfare, will be submitted to the EC or IRB and regulatory 
authority (where applicable) for approval prior to implementation. The investigator, EC, and 
Sponsor must agree on all amendments. No amendment will be implemented until it is approved 
and signed by the investigator and Sponsor. Exceptions to this are when the investigator 
considers that the participant’s safety is compromised. Protocol amendments detailing minor 
administrative changes should be submitted by the investigator (or designee) to the EC or IRB 
for notification. 
10.3. 
Ethical Conduct of the Study 
This study will be performed in accordance with: 1) the principles of ICH Guideline E6 for Good 
Clinical Practice (CPMP/ICH/135/95 January 1997); 2) European Directive 2001/20/EC, 3) 
standard operating procedures and/or guidelines, 4) the U.S. Food and Drug Administration 
(FDA) regulations, 5) the Declaration of Helsinki, and 6) all applicable federal, state, and local 
laws, rules and regulations relating to the conduct of the clinical study. 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 69 of 86 
10.4. 
Participant Information and Consent 
In obtaining and documenting informed consent or assent, the investigator should comply with 
the applicable regulatory requirements and should adhere to ICH GCP (E6). Each participant 
must be adequately informed in a language that they can understand and read of the aims, 
methods, anticipated benefits, potential hazards and the discomfort the study may entail, as well 
as their right to abstain from participating in the study and to withdraw their consent at any time 
without affecting their medical care. If important new information is incorporated in the ICF and 
approved by the EC, all participants still actively participating in the study must be re-consented. 
Written informed consent for adult participants should be documented by the participant’s 
personally dated signature and the personally dated signature of the investigator or designee who 
conducted the informed consent discussion. The investigator or designee should supply all 
enrolled participants with a copy of their signed informed consent. The monitor will inspect the 
original forms for all participants. 
10.5. 
Participant Confidentiality 
The investigators and Sponsor and its designees will preserve the confidentiality of all 
participants taking part in the study, in accordance with GCP, local regulations and, to the extent 
applicable, the Health Insurance Portability and Accountability Act of 1996 (“HIPAA”). Subject 
to the requirement for source data verification by the study personnel by reference to the 
participant’s notes, confidentiality of all participant identities will be maintained. Only 
participant initials, date of birth, and study number will be used on the CRF and in all study 
correspondence, as permitted. No material bearing a participant’s name will be kept on file by 
the Sponsor. 
10.6. 
Study Monitoring 
10.6.1. 
Access to Information for Monitoring 
In accordance with ICH-GCP guidelines, the Study Monitor must have direct access to the 
investigator’s source documentation in order to verify the consistency of the data recorded in the 
CRFs. 
The Study Monitor is responsible for routine review of the CRFs at regular intervals throughout 
the study, to verify adherence to the protocol, and the completeness, consistency, and accuracy of 
the data being entered. The Study monitor should have access to any participant records needed 
to verify the entries on the CRFs. The investigator agrees to cooperate with the Study Monitor to 
ensure that any problems detected in the course of these monitoring visits are resolved. 
10.6.2. 
Access to Information for Auditing or Inspections 
Representatives of regulatory authorities or Achillion Pharmaceuticals may conduct inspections 
or audits of the clinical study. If the investigator is notified of an inspection by a regulatory 
authority, the investigator agrees to notify the Achillion Pharmaceuticals Medical Monitor 
immediately. The investigator agrees to provide to representatives of a regulatory agency or 
Achillion Pharmaceuticals access to records, facilities, and personnel for the effective conduct of 
any inspection or audit. 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 70 of 86 
10.7. 
Case Report Forms and Study Records 
10.7.1. 
Recording of Data 
All data collected during the study will be recorded in individual, participant-specific electronic 
case report forms (eCRFs). All eCRFs should be completed by the investigator (or designee), 
who should be identified and agreed upon with the Sponsor before the start of the study. A 
signature log identifying personnel who can enter data and/or sign off an eCRF will be 
maintained. Instructions for data entry will be provided. 
A CRF must be completed for each participant who signs a consent form and is admitted to the 
study. Corrections to the data on the CRF will only be made by the investigator (or designee). 
CRFs should be kept current to enable the study monitor to review the participant status 
throughout the course of the study. CRFs will be completed within 5 days of the last participant 
visit. 
10.7.2. 
Source Documentation and Medical/Study Records 
The participant’s number and date of entry into the study, along with the study code, should be 
recorded in the participant’s medical/study records by the investigator (or designee). The 
investigator (or designee) should also record, in the medical/study records, confirmation of 
written and oral consent, the participant’s clinical status/disease being treated, date of every 
study visit, date study drug started and stopped, concomitant medications, copies of all relevant 
reports and laboratory tests, comments on results and reference to any AEs. 
10.8. 
Protocol Deviations 
Protocol deviations will be assessed on a case-by-case basis. Withdrawal of consent for one or 
more activities within the protocol will not necessarily be considered to be a protocol deviation, 
and will not necessarily result in the removal of the participant from further study activities. The 
available data from any such participants will be included in analyses as appropriate. Significant 
protocol deviations will be reported to the Ethics Committee or IRB according to local 
regulations. 
10.9. 
Access to Source Documentation 
The investigator and staff must agree to allow the study monitor and authorized representatives 
of the Sponsor to inspect all eCRFs and corresponding source documents, e.g., original medical 
records, participant records, and laboratory raw data; to have access to the clinical supplies, and 
dispensing and storage areas; and to agree to assist with their activities if requested. The 
investigator and staff should provide adequate time and space for monitoring visits. 
Participants will have access to safety laboratory results upon request but should be aware that 
these typically are not immediately available. The results of the baseline biopsy evaluation can 
be provided to the investigator, who may share them with the participant. Evaluation of the end 
of treatment renal biopsy, and any other results which might compromise blinding of the study 
will not be available until after all study analysis is completed. 


ACH-0144471 
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10.10. 
Data Generation and Analysis 
Data generation and analysis will be specified and detailed in the SAP. 
10.11. 
Retention of Data 
The investigator (or designee) must maintain adequate and accurate records to enable the 
conduct of the study to be fully documented and the study data to be subsequently verified. 
These documents should be classified into at least two separate categories as follows: 
• 
Investigator study file, and 
• 
Participant clinical source documents 
 
The investigator study file will contain the protocol/amendments, CRF and query forms, EC or 
IRB and governmental approval with correspondence, informed consent, drug records, staff 
curricula vitae and authorization forms, and other appropriate documents and correspondence. 
Participant clinical source documents (usually defined by the protocol-specified procedures and 
data collection requirements in advance to record key efficacy/safety parameters independent of 
the CRFs) include, but are not limited to, participant hospital/clinic records, physician and nurse 
notes, appointment book, original laboratory reports, ECG and/or EEG tracings, pathology and 
special assessment reports, consultant letters, screening and enrollment logs. 
All clinical study documents must be retained by the investigator for at least 2 years after the last 
approval of a marketing application in an ICH region (i.e., United States, Europe, or Japan) and 
until there are no pending or contemplated marketing applications in an ICH region; or, if no 
application is filed or if the application is not approved for such indication, until 2 years after the 
investigation is discontinued and regulatory authorities have been notified. Investigators may be 
required to retain documents longer if required by applicable regulatory requirements, by local 
regulations, or by an agreement with Achillion Pharmaceuticals. The investigator (or designee) 
must contact Achillion Pharmaceuticals prior to destroying any records associated with the 
study. Achillion Pharmaceuticals will notify the PI when the trial records are no longer needed. 
If the investigator withdraws from the study (e.g., relocates, retires, or dies), the records shall be 
transferred to a mutually agreed upon designee (e.g., another investigator, EC). Notice of such 
transfer will be given in writing to Achillion Pharmaceuticals. If the investigator cannot 
guarantee this archiving requirement at the study site for any or all of the documents, special 
arrangement must be made between the PI and Achillion Pharmaceuticals. to store these in 
sealed containers outside of the site, so that they can be returned sealed to the PI in case of a 
regulatory audit. Where source documents are required for the continued care of the participant, 
appropriate copies should be made for storage outside of the site. 
10.12. 
Study and Site Closure 
The sponsor reserves the right to close the study site or terminate the study at any time for any 
reason at the sole discretion of the sponsor. Study sites will be closed upon study completion.  A 
study site is considered closed when all required documents and study supplies have been 
collected and a study-site closure visit has been performed. 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
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Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
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The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to: 
• Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC or 
local health authorities, the sponsor's procedures, or GCP guidelines 
• Inadequate recruitment of participants by the investigator 
• Discontinuation of further study intervention development 
10.13. 
Final Report, Publication and Disclosure Policy 
All information contained in this protocol and the trial results are considered to be confidential. 
The investigator agrees to use this information for purposes of conducting this trial. It is 
understood that Achillion Pharmaceuticals may use data derived from this trial for the purpose of 
research and development. The data may be disclosed by Achillion Pharmaceuticals to other 
investigators, the FDA, other government agencies, or foreign drug regulatory authorities, or to 
the public. No publication of trial design or results is permitted without specific Achillion 
Pharmaceuticals approval. To gain approval, a copy of the manuscript for review must, therefore, 
be sent to Achillion Pharmaceuticals 60 days before submission for publication. 
It is the intent of Achillion Pharmaceuticals to present the results of this study at future scientific 
meetings. Additionally, it is the intent of Achillion Pharmaceuticals to publish the results of this 
study in leading scientific journals. The investigator of each investigative site will be invited to 
be an author in conjunction with the investigator(s) from Achillion Pharmaceuticals. Achillion 
Pharmaceuticals will determine additional authors. Presentations and manuscripts will be 
provided and agreed to by the authors and Achillion Pharmaceuticals. 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
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11. 
REFERENCES 
1. 
 ACH-0144471 Investigator’s Brochure Version 7.0. New Haven (CT): 
Achillion Pharmaceuticals, Inc.; Aug 2018. 92 p. 
2. 
Volanakis JE, Narayana SV. Complement factor D, a novel serine protease. Protein 
Science. 1996;5(4):553-64. 
3. 
Figueroa JE, Densen P. Infectious diseases associated with complement deficiencies. 
Clinical microbiology reviews. 1991;4(3):359-95. 
4. 
Miyata T, Inagi R, Oda O, et al. Deterioration of immune complex solubilization activity 
of serum by increased concentration of factor D. Nephron. 1991;59(3):409-15. 
5. 
Kobayakawa H, Miyata T, Inagi R, et al. Effects of excess factor D on early- and late-
phase activation of the complement cascade. Nihon Jinzo Gakkai Shi. 1992;34(1):103-6. 
6. 
Medjeral-Thomas NR, O’Shaughnessy MM, O’Regan JA, et al. C3 Glomerulopathy: 
clinicopathologic features and predictors of outcome. Clin J Am Soc Nephrol. 2014 
Jan;9(1):46-53. 
7. 
Servais A, Noël LH, Roumenina LT, et al. Acquired and genetic complement 
abnormalities play a critical role in dense deposit disease and other C3 glomerulopathies. 
Kidney Int. 2012 Aug;82(4):454-64. 
8. 
Pickering MC, D'Agati VD, Nester CM, et al. C3 glomerulopathy: consensus report. 
Kidney Int. 2013 Dec;84(6):1079-89. 
9. 
Nasr SH, Valeri AM, Appel GB, et al. Dense deposit disease: clinicopathologic study of 32 
pediatric and adult patients. Clin J Am Soc Nephrol. 2009 Jan;4(1):22-32. doi: 
10.2215/CJN.03480708. Epub 2008 Oct 29.  
10. 
Medjeral-Thomas N, Malik TH, Patel MP, et al. A novel CFHR5 fusion protein causes C3 
glomerulopathy in a family without Cypriot ancestry. Kidney Int. 2014 Apr;85(4):933-7. 
11. 
Lu DF, Moon M, Lanning LD, et al. Clinical features and outcomes of 98 children and 
adults with dense deposit disease. Pediatr Nephrol. 2012 May;27(5):773-81. 
12. 
Smith RJ, Alexander J, Barlow PN, et al. New approaches to the treatment of dense deposit 
disease. J Am Soc Nephrol. 2007 Sep;18(9):2447-56.  
13. 
Barbour TD, Pickering MC, Cook HT. Dense deposit disease and C3 glomerulopathy. 
Semin Nephrol. 2013 Nov;33(6):493-507 
 
PPD


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
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Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
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14. 
De Vriese AS, Sethi S, Van Praet J, et al. Kidney disease caused by dysregulation of the 
complement alternative pathway: an etiologic approach. J Am Soc Nephrol. 2015 
Dec;26(12):2917-29. 
15. 
Achillion White Paper. The Natural History of C3G. May 5, 2017 
16. 
Pickering MC, Cook HT, Warren J, et al. Uncontrolled C3 activation causes 
membranoproliferative glomerulonephritis in mice deficient in complement factor H. Nat 
Genet. 2002 Aug;31(4):424-8. 
17. 
Abrera Abeleda, Maria Asuncion. The role of the alternative pathway of the complement 
system in the development of dense deposit disease. University of Iowa, Iowa Research 
Online, Thesis and Dissertations, 2010. 
18. 
Bomback AS, Smith RJ, Barile GR, et al. Eculizumab for dense deposit disease and C3 
glomerulonephritis. Clin J Am Soc Nephrol. 2012 May;7(5):748-56. 
19. 
Pickering MC, Warren J, Rose KL, et al. Prevention of C5 activation ameliorates 
spontaneous and experimental glomerulonephritis in factor H-deficient mice. Proc Natl 
Acad Sci U S A. 2006 Jun 20;103(25):9649-54. 
20. 
National Organization for Rare Disorders (NORD). 2015. Available at: 
https://rarediseases.org/rare-diseases/c3-glomerulopathy-dense-deposit-disease-and-c3-
glomerulonephritis/.  
21. 
Sandhu G, Bansal A, Ranade A, et al. C3 glomerulopathy masquerading as acute 
postinfectious glomerulonephritis. Am J Kidney Dis. 2012 Dec;60(6):1039-43. doi: 
10.1053/j.ajkd.2012.04.032. Epub 2012 Jul 6.  
22. 
Vernon KA, Goicoechea de Jorge E, Hall AE, et al. Acute presentation and persistent 
glomerulonephritis following streptococcal infection in a patient with heterozygous 
complement factor H-related protein 5 deficiency. Am J Kidney Dis. 2012 Jul;60(1):121-5. 
doi: 10.1053/j.ajkd.2012.02.329. Epub 2012 Apr 13.  
23. 
Fervenza FC, Smith RJ, Sethi S. Association of a novel complement factor H mutation 
with severe crescentic and necrotizing glomerulonephritis. Am J Kidney Dis. 2012 
Jul;60(1):126-32. doi: 10.1053/j.ajkd.2012.03.007. Epub 2012 Apr 26. 
24. 
Krmar RT, Holtbäck U, Linné T, et al. Acute renal failure in dense deposit disease: 
complete recovery after combination therapy with immunosuppressant and plasma 
exchange. Clin Nephrol. 2011 Feb;75 Suppl 1:4-10.  
25. 
Hladunewich MA, Cattran D, Beck LH, et al. A pilot study to determine the dose and 
effectiveness of adrenocorticotrophic hormone (H.P. Acthar® Gel) in nephrotic syndrome 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc. 
(a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 75 of 86 
 
due to idiopathic membranous nephropathy. Nephrol Dial Transplant. 2014 
Aug;29(8):1570-7. 
26. 
Stevens LA, Greene T, Levey AS. Surrogate End Points for Clinical Trials of Kidney 
Disease Progression. Clin J Am Soc Nephrol. 2006 Jul;1(4):874-84. 
27. 
Corapi KM, Dooley MA, Pendergraft WF. Comparison and evaluation of lupus nephritis 
response criteria in lupus activity indices and clinical trials. Arthritis Res Ther. 
2015;17(1):110. 
28. 
Renal Disease Subcommittee of the American College of Rheumatology Ad Hoc 
Committee on Systemic Lupus Erythematosus Response Criteria. The American College 
of Rheumatology response criteria for proliferative and membranous renal disease in 
systemic lupus erythematosus clinical trials. Arthritis Rheum 2006 Feb;54(2):421–32. 
29. 
Inker LA, Levey AS, Pandya K, et al, Early Change in Proteinuria as a Surrogate Endpoint 
for Kidney Disease Progression: An Individual Patient Meta-analysis. Am J Kidney Dis. 
2014 Jul;64(1):74-85. 
30. 
Lambers Heerspink HJ, Gansevoort RT. Albuminuria Is an Appropriate Therapeutic Target 
in Patients with CKD: The Pro View. Clin J Am Soc Nephrol. 2015 Jun 5;10(6):1079-88. 
31. 
Inker LA, Mondal H, Greene T, et al. Early Change in Urine Protein as a Surrogate End 
Point in Studies of IgA Nephropathy: An Individual-Patient Meta-analysis. Am J Kidney 
Dis. 2016 Sep;68(3):392-401. 
32. 
Thompson A, Cattran DC, Blank M, Nachman PH. Complete and Partial Remission as 
Surrogate End Points in Membranous Nephropathy. J Am Soc Nephrol. 2015 
Dec;26(12):2930-7. 
33. 
Little MA, Dupont P, Campbell E, et al. Severity of primary MPGN, rather than MPGN 
type, determines renal survival and post-transplantation recurrence risk. Kidney Int. 2006 
Feb;69(3):504-11. 
34. 
Cameron JS, Turner DR, Heaton J, et al. Idiopathic mesangiocapillary glomerulonephritis. 
Comparison of types I and II in children and adults and long-term prognosis. Am J Med. 
1983 Feb;74(2):175-92. 
35. 
Montgomery RA, Orandi BJ, Racusen L, et al. Plasma-Derived C1 Esterase Inhibitor for 
Acute Antibody-Mediated Rejection Following Kidney Transplantation: Results of a 
Randomized Double-Blind Placebo-Controlled Pilot Study. Am J Transplant. 2016 
Dec;16(12):3468-78.  
36. 
U.S. Department of Health and Human Services, National Institutes of Health, National 
Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE), Version 
4.03. [CTCAE 4.03 June 2010]. Available online at: 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
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Confidential Property of Achillion Pharmaceuticals, Inc.  
a subsidiary of Alexion Pharmaceuticals, Inc.) 
 Page 76 of 86 
12. 
APPENDICES 
Appendix 1. 
Schedule of Assessments 
Table  4. 
Schedule of Assessments – Screening through Week 8 
Study Period 
Screening1 
Blinded Treatment 
Study Week 
Wk  
1 
Wk  
2 
Wk  
3 
Wk  
4 
Wk  
5 
Wk  
6 
Wk  
7 
Wk  
8 
Study Day2 
Day -75 to Day -1 
1 
3 
7 
14 
21 
28 
35 
42 
49 
56 
Required Clinic Visit 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
Phone Visit 
 
 
 
 
 
 
X 
 
X 
 
X 
 
Screening Assessments 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/ Exclusion Criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
X 
 
 
 
 
 
 
 
 
 
FSH3 
X 
 
 
 
 
 
 
 
 
 
 
 
Urine Drug screen4 
X 
 
 
 
 
 
 
 
 
 
 
 
Vaccinations 
 
X5 
 
 
 
 
 
 
 
 
 
 
Sample for potential genetic 
assessment of complement 
genes 
X 
 
 
 
 
 
 
 
 
 
 
 
Study Drug Dispensing 
 
 
X 
 
 
X 
 
X 
 
 
 
X 
AE/SAE/Protocol 
Restrictions/Con Meds 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Patient-Reported Outcomes Assessments 
FACIT-Fatigue  
X 
 
 
 
 
 
 
 
 
 
 
 
KDQOL  
X 
 
 
 
 
 
 
 
 
 
 
 
EQ-5D-3L  
X 
 
 
 
 
 
 
 
 
 
 
 
Clinical Assessments 
Complete Physical Exam  
X 
 
X 
 
 
 
 
 
 
 
 
 
Brief Physical Exam6 
 
 
 
 
 
X 
 
 
 
 
 
X 
Weight 
X 
X 
X7 
X7 
X7 
X7 
 
X7 
 
X7 
 
X7 
Vital Signs8 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
12-Lead ECG (single) 
X 
 
X7 
 
 
 
 
 
 
 
 
 
Other Assessments 
Renal Biopsy  
 
X9 
 
 
 
 
 
 
 
 
 
 


ACH-0144471 
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Confidential Property of Achillion Pharmaceuticals, Inc.  
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Table  4. 
Schedule of Assessments – Screening through Week 8 (Continued)
Study Period 
Screening1 
Blinded Treatment 
Study Week 
Wk  
1 
Wk  
2 
Wk  
3 
Wk  
4 
Wk  
5 
Wk  
6 
Wk  
7 
Wk  
8 
Study Day2 
Day -75 to Day -1 
1 
3 
7 
14 
21 
28 
35 
42 
49 
56 
Required Clinic Visit 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
Phone Visit 
 
 
 
 
 
 
X 
 
X 
 
X 
 
Standard Laboratory Assessments10 
Safety Labs: Chemistry11 
X 
 
X 
X 
X 
X 
 
X 
 
 
 
X 
Safety Labs: Hematology11 
X 
 
X 
X 
X 
X 
 
X 
 
 
 
X 
Serum C3 and C4 
X 
 
X7 
 
 
X 
 
 
 
 
 
 
First Morning Urine12 
X 
 
X7 
 
 
X 
 
X 
 
 
 
X 
24-Hour Urine Collection13 
 
X13 
 
 
 
 
 
 
 
 
 
 
Pregnancy Test14 
X 
X 
X 
 
 
X 
 
X 
 
 
 
X 
Complement Biomarkers10 
X 
 
X7 
 
 
X 
 
 
 
 
 
 
AE = Adverse event; AP = Alternative pathway; BMI = Body mass index; Con Meds = concomitant medications; ECG = Electrocardiogram; fD = Factor D; 
SAE = Serious adverse event 
1 
Screening assessments do not need to all occur on the same day. 
2 
Visits should be on the specified day during Weeks 1-3.  Starting with the Week 4 visit, visits may be ± 2 days. Unless the PI feels a clinic visit is required, 
the visits on Weeks 3, 5 and 7 should be conducted by phone. 
3 
FSH for postmenopausal women in screening only. 
4 
Urine drug screen should include, at a minimum, amphetamines, barbiturates, cotinine, cocaine metabolites, opiates, benzodiazepines, and cannabinoids. 
5 
Patients should be confirmed to be eligible based on all other inclusion and exclusion criteria, except the renal biopsy, before being vaccinated.  
6 
Conduct as described in Section 6.7; exam should be prior to dosing. Assessment of edema is part of the brief physical exam. If edema is present, then 
assessment of edema should be performed at each visit, even when a physical exam is not required.  
7 
Prior to dosing. 
8 
Vital signs include body temperature, blood pressure in triplicate, heart rate and respiratory rate. Manual measurement of blood pressure is preferred; all 
other vital signs may be measured using an automated instrument. During the treatment periods, assessments should be collected prior to dosing.  Not 
required for visits conducted by phone.  
9 
Renal biopsies should be performed as described in Section 6.3. If obtained during screening to confirm eligibility, the results must be available and 
reviewed prior to dosing. 
10 
During the treatment periods, blood draws and urine collection should be done prior to dosing as detailed in Table 2 
11 
As listed in Section 6.11, Table 2. 
12 
Should be a first morning void, and will be collected and analyzed as described in Section 6.6.2. Participants should be given a collection container before 
the visit. If the first morning urine collection coincides with a renal biopsy, collection must be completed before or at least 7 days after the biopsy procedure. 


ACH-0144471 
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Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc.  
a subsidiary of Alexion Pharmaceuticals, Inc.) 
 Page 78 of 86 
13 
The 24 hour urine will be collected and analyzed as described in Section 6.6.1. The screening 24-hour urine collection period may be at any time during 
screening, but if it is to occur after the renal biopsy, it must be at least 7 days after the biopsy procedure. 
14 
Serum pregnancy test at the initial screening visit and urine pregnancy tests at other time points for women of childbearing potential only. On Day 1, urine 
pregnancy test must be confirmed as negative prior to administration of the first dose of study drug. Any positive urine pregnancy test will be confirmed by a 
serum pregnancy test. Female participants of childbearing potential must have a urine pregnancy test on the day of any vaccination, and the result must be 
confirmed as negative prior to vaccine administration. 
 


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a subsidiary of Alexion Pharmaceuticals, Inc.) 
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Table 5. 
Schedule of Assessments – Week 10 through Week 28 
Study Period 
Blinded Treatment1 
Study Week 
Wk 10 
Wk 12 
Wk 14 
Wk 16 
Wk 18 
Wk 20 
Wk 22 
Wk 24 
Wk 26 
Wk 28 
Study Day 
70 
84 
98 
112 
126 
140 
154 
168 
182 
196 
Required Clinic Visit 
 
X 
 
X 
 
X 
 
 
 
X 
Phone Visit 
X 
 
X 
 
X 
 
X 
X 
X 
 
Study Drug Dispensing 
 
X 
 
 
 
X 
 
 
 
X 
AE/SAE/Protocol 
Restrictions/Con Meds 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Patient-Reported Outcomes Assessments 
FACIT-Fatigue  
 
 
 
 
 
 
 
 
 
X 
KDQOL 
 
 
 
 
 
 
 
 
 
X 
EQ-5D-3L  
 
 
 
 
 
 
 
 
 
X 
Clinical Assessments 
Complete Physical Exam2 
 
 
 
 
 
 
 
 
 
X 
Brief Physical Exam2 
 
X 
 
 
 
X 
 
 
 
 
Weight 
 
X3 
 
X3 
 
X3 
 
 
 
X3 
Vital Signs4 
 
X 
 
X 
 
X 
 
 
 
X 
Other Assessments 
Renal Biopsy  
 
 
 
 
 
 
 
 
X5 
Standard Laboratory Assessments6 
Safety labs: Chemistry 
 
X 
 
X 
 
X 
 
 
 
X 
Safety labs: Hematology 
 
X 
 
X 
 
X 
 
 
 
X 
Serum C3 and C4 
 
X 
 
 
 
 
 
 
 
X 
First Morning Urine7 
 
X 
 
 
 
X 
 
 
 
X 
24-Hour urine collection8 
 
X 
 
 
 
 
 
 
 
X 
Pregnancy Test9 
 
X 
 
 
 
X 
 
 
 
X 
Complement Biomarkers6 
 
X 
 
 
 
 
 
 
 
X 
AE = Adverse event; AP = Alternative pathway; BMI = Body mass index; Con Med = concomitant medications; fD = Factor D; SAE = Serious adverse event 
1 
Visits may take place within a window of ±2 days relative to the specified day.  
2 
Conduct as described in Section 6.7; during the treatment periods, exam should be prior to dosing. Assessment of edema is part of the brief physical exam. If 
edema is present, then assessment of edema should be performed at each visit, even when a physical exam is not required. 
3 
Prior to dosing.  
4 
Vital signs include body temperature, blood pressure in triplicate, heart rate and respiratory rate. Manual measurement of blood pressure is preferred; all 
other vital signs may be measured using an automated instrument. During the treatment periods, assessments should be done prior to dosing. 
5 
The post treatment biopsy should be done prior to the Week 28 dose. 


ACH-0144471 
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6 
During the treatment periods, blood draws and urine collection should be done prior to dosing. As listed in Section 6.11, Table 2. 
7 
Should be a first morning void and will be collected and analyzed as described in Section 6.6.2. Participants should be given a collection container before the 
visit. If the first morning urine collection coincides with a renal biopsy, collection should be completed before or at least 7 days after the biopsy procedure. 
8 
The 24-hour urine will be collected and analyzed as described in Section 6.6.1. The 24-hour urine collection should be within a window of ± approximately 
1 week relative to the specified day. If the 24-hour urine collection period is to occur after a renal biopsy, it must be at least 7 days after the biopsy 
procedure. 
9 
Urine pregnancy tests for women of childbearing potential only. Any positive urine pregnancy test will be confirmed by a serum pregnancy test. Pregnancy 
tests should be done monthly. 
 


ACH-0144471 
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Table 6. 
Schedule of Assessments – Extended Treatment Period 
Study Period 
Extended Treatment1 
Study Week 
Wk 29 
Wk 30 
Wk 32 
Wk 36 
Wk 40 
Wk 44 
Wk 48 
Wk 52 
Clinic Visits1 
X 
X 
 
X 
 
X 
 
X 
Phone Call 
 
 
X 
 
X 
 
X 
 
Study Drug Dispensing 
 
X 
 
X 
 
X 
 
X 
AE/SAE/Protocol Restrictions/Con Meds 
X 
X 
X 
X 
X 
X 
 
X 
Patient-Reported Outcomes Assessments 
FACIT-Fatigue 
 
 
 
 
 
 
 
X 
KDQOL 
 
 
 
 
 
 
 
X 
EQ-5D-3L  
 
 
 
 
 
 
 
X 
Clinical Assessments 
Complete Physical Exam2 
 
 
 
 
 
 
 
X 
Brief Physical Exam2 
 
X 
 
 
 
 
 
 
Weight 
X 
X 
 
X 
 
X 
 
X 
Vital Signs3 
X 
X 
 
X 
 
X 
 
X 
OtherAssessments 
Renal Biopsy  
 
 
 
 
 
 
 
X4 
Standard Laboratory Assessments5 
Safety labs: Chemistry 
X 
X 
 
X 
 
X 
 
X 
Safety labs: Hematology 
X 
X 
 
X 
 
X 
 
X 
Serum C3 and C4 
 
 
 
 
 
 
 
X 
First Morning Urine6 
 
X 
 
X 
 
 
 
X 
24-Hour Urine7 
 
 
 
 
 
 
 
X 
Pregnancy Test8 
 
X 
 
X 
 
 
 
X 
Complement Biomarkers5 
 
 
 
 
 
 
 
X 
AE = Adverse Event; F/U = Follow-up Visit; QoL = Quality of Life; SAE = Serious Adverse Event  
1 
Clinic visits may take place within a window of ±2 days relative to the specified day for the Weeks 29-32 and ±7 days relative to the specified day for the 
remainder of the study, except as noted for the Taper, Follow-Up, and Dose Escalation visits.  Unless the PI feels a clinic visit is required, the visits on 
Weeks 32, 40, and 48 may be conducted by phone call. If a patient is unable to get to a clinic visit during the COVID-19 global pandemic (Section 6.22), 
study data collection should still occur. The preferred option is home healthcare visits; nurses may collect 24-hour urine, first morning urine, and safety 
labs, including pregnancy testing. Additional assessments should include AEs, vital signs, and concomitant medications. Nurses will perform study drug 
accountability. If a home healthcare visit is not possible, patients may have telephone visits with the PI or designee. Data collection will include AEs and 
concomitant medications, and patients will be asked about study drug compliance.   


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc.  
a subsidiary of Alexion Pharmaceuticals, Inc.) 
 Page 82 of 86 
2 
Conduct as described in Section 6.7; during the treatment periods, exam should be prior to dosing.  Assessment of edema is part of the brief physical exam. 
If edema is present, then assessment of edema should be performed at each visit, even when a physical exam is not required. 
3 
Vital signs include body temperature, blood pressure in triplicate, heart rate and respiratory rate; manual measurement of blood pressure is preferred. All 
other vital signs may be measured using an automated instrument. During the treatment periods, assessments should be done prior to dosing. 
4 
As part of the Biopsy sub-study, a renal biopsy may be obtained at approximately Week 52, if not contraindicated. If clinic visits are not possible during the 
COVID-19 global pandemic, the Week 52 biopsy should be done when safe to do so, even if the biopsy is unable to be done within 7 days of the target date. 
In addition, an unscheduled 24-hour urine collection should be obtained at the same time as the Week 52 renal biopsy (Section 6.24). If the collection of 24-
hour urine is to occur after a renal biopsy, it must be done at least 7 days after the biopsy procedure.  
5 
During the treatment periods, blood draws and urine collection should be done prior to dosing, as detailed in Section 6.11, Table 2. Blood collection for 
biomarkers will not be done at home health visits or at local laboratories. If a home visit occurs but laboratory samples cannot be shipped to the central 
laboratory by the nurse conducting home visits, the nurse should go to a local laboratory to drop off all laboratory samples, including 24-hour urine 
collections and safety labs. If home visits are not possible, the participant should go to a local laboratory to drop off 24-hour urine collections and for safety 
laboratory testing, including pregnancy testing (if applicable), to be performed.  
6 
Should be a first morning void, and will be collected and analyzed as described in Section 6.6.2. Participants should be given a collection container before 
the visit.  If the first morning urine collection coincides with a renal biopsy, collection should be completed before or at least 7 days after the biopsy 
procedure. 
7 
The 24-hour urine will be collected and analyzed as described in Section 6.6.1. The 24-hour urine collection should be within a window of ± approximately 
1 week relative to the specified day. If the 24-hour urine collection period is to occur after a renal biopsy, it must be at least 7 days after the biopsy 
procedure. If a clinic visit is not possible and a home healthcare visit is done, the home healthcare nurse will collect the 24-hour urine sample. If a telephone 
visit is done instead, the patient should take the 24-hour urine to the local laboratory, if possible. 
8 
Urine pregnancy tests for women of childbearing potential only.  Any positive urine pregnancy test will be confirmed by a serum pregnancy test.  Pregnancy 
tests should be done monthly. 
 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc.  
a subsidiary of Alexion Pharmaceuticals, Inc.) 
 Page 83 of 86 
Table 7. 
Schedule of Assessments – 21 Month Long-Term Follow-up, with Taper and Follow-up 
Study Period 
Long-Term Follow-up 
Taper2 
Follow-up3 
 
Study Week 
Wk 65 
Wk 117 
Wk 78 
Wk 130 
Wk 91 
Wk 143 
Wk 104 
T3 
T6 
F/U 1 
F/U 2 
Clinic Visits1 
X 
X 
X 
X 
X 
 
X 
 
Phone Call 
 
 
 
 
 
X 
 
X 
Study Drug Dispensing 
X 
X 
X 
X 
X 
 
 
 
AE/SAE/Protocol Restrictions/Con Meds 
X 
X 
X 
X 
X 
X 
X 
X 
Patient-Reported Outcomes Assessments 
FACIT-Fatigue 
 
 
 
X 
 
 
X 
 
KDQOL 
 
 
 
X 
 
 
X 
 
EQ-5D-3L  
 
 
 
X 
 
 
X 
 
Clinical Assessments 
Complete Physical Exam4 
 
 
 
X 
 
 
 
 
Brief Physical Exam4 
 
X 
 
 
X 
 
X 
 
Weight 
X 
X 
X 
X 
X 
 
X 
 
Vital Signs5 
X 
X 
X 
X 
X 
 
X 
 
Histology 
Renal Biopsy  
 
 
 
X6 
 
 
 
 
Standard Laboratory Assessments7 
Safety labs: Chemistry 
X 
X 
X 
X 
X 
 
X 
 
Safety labs: Hematology 
X 
X 
X 
X 
X 
 
X 
 
Serum C3 and C4 
 
X 
 
X 
X 
 
X 
 
First Morning Urine8 
 
X 
 
X 
X 
 
X 
 
24-Hour Urine9 
 
 
 
X 
 
 
 
 
Pregnancy Test10 
 
X 
 
X 
 
 
X 
 
Complement Biomarkers7 
 
X 
 
X 
X 
 
X 
 
AE = Adverse Event; F/U = Follow-up Visit; QoL = Quality of Life; SAE = Serious Adverse Event; T3 = Day 3 of the taper; T6 = Day 6 of the taper; Wk = 
Weeks 
1 
Clinic visits may take place within a window of ± 2 days relative to the specified day for the Weeks 29-32 and ±7 days relative to the specified day for the 
remainder of the study, except as noted for the Taper, Follow-Up, and Dose Escalation visits.  If a patient is unable to get to a clinic visit during the 
COVID-19 global pandemic (Section 6.22), study data collection should still occur. The preferred option is home healthcare visits; nurses may collect 
24-hour urine, first morning urine, and safety labs, including pregnancy testing. Additional assessments should include AEs, vital signs, and concomitant 
medications. Nurses will perform study drug accountability. If a home healthcare visit is not possible, patients may have telephone visits with the PI or 
designee. Data collection will include AEs and concomitant medications, and patients will be asked about study drug compliance.  


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
Confidential Property of Achillion Pharmaceuticals, Inc.  
a subsidiary of Alexion Pharmaceuticals, Inc.) 
 Page 84 of 86 
2 
Participants should gradually decrease the daily total dose of ACH-0144471 during the taper.  Visits should be on the 3rd (T3) and 6th (T6) day of the taper.  
3 
Follow-up visits should be conducted 2 and 4 weeks after the last dose of ACH-0144471 (including the taper, if applicable), within a window of ±2 days. 
4 
Conduct as described in Section 6.7 ; during the treatment periods, exam should be prior to dosing.  Assessment of edema is part of the brief physical exam.  
If edema is present, then assessment of edema should be performed at each visit, even when a physical exam is not required. 
5 
Vital signs include body temperature, blood pressure in triplicate, heart rate and respiratory rate; manual measurement of blood pressure is preferred.  All 
other vital signs may be measured using an automated instrument.  During the treatment periods, assessments should be done prior to dosing. 
6 
As part of the Biopsy sub-study, a renal biopsy may be obtained at approximately Week 104, if not contraindicated. If clinic visits are not possible during the 
COVID-19 global pandemic, the optional Week 104 biopsy should be done when safe to do so, even if the biopsy is unable to be done within 7 days of the 
target date. In addition, an unscheduled 24-hour urine collection should be obtained at the same time as the Week 104 renal biopsy (Section 6.24). If the 
collection of 24-hour urine is to occur after a renal biopsy, it must be done at least 7 days after the biopsy procedure. 
7 
During the treatment periods, blood draws and urine collection should be done prior to dosing, as detailed in Section 6.11, Table 2. Blood collection for 
biomarkers will not be done at home health visits or at local labs. If a home visit occurs but laboratory samples cannot be shipped to the central laboratory by 
the nurse conducting home visits, the nurse should go to a local laboratory to drop off all laboratory samples, including 24-hour urine collections and safety 
labs. If home visits are not possible, the participant should go to a local laboratory to drop off 24-hour urine collections and for safety laboratory testing, 
including pregnancy testing (if applicable), to be performed. 
8 
Should be a first morning void, and will be collected and analyzed as described in Section 6.6.2. Participants should be given a collection container before 
the visit.  If the first morning urine collection coincides with a renal biopsy, collection should be completed before or at least 7 days after the biopsy 
procedure. 
9 
The 24-hour urine will be collected and analyzed as described in Section 6.6.1. The 24-hour urine collection should be within a window of ± approximately 
1 week relative to the specified day. If the 24-hour urine collection period is to occur after a renal biopsy, it must be at least 7 days after the biopsy 
procedure.  
10 
Urine pregnancy tests for women of childbearing potential only. Any positive urine pregnancy test will be confirmed by a serum pregnancy test. Pregnancy 
tests should be done monthly.  
 
 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
 
Confidential Property of Achillion Pharmaceuticals, Inc.  
a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 85 of 86 
Appendix 2. 
Fever Management Plan 
Treatment with complement inhibitors may lead to an increased lifetime risk of acute 
meningococcal disease, or other encapsulated bacterial infection. Because of this risk, it is 
essential to monitor participants for signs and symptoms of infection. 
Minimum Requirements 
The points mentioned below are to be considered as a minimum diagnostic and management 
procedure. These are not meant to replace or bypass a systematic and thorough assessment of the 
participant; instead, they are intended to facilitate rapid initiation of assessment and management 
of fever. 
General Management for Any Fever Detected in the Clinic  
For any fever, the site must: 
1. Assess for symptoms - consider meningococcal disease as a diagnosis.  When 
meningococcal disease is suspected, early treatment is critical 
2. Repeat and confirm all temperature measurements >38.0°C 
3. Notify the PI and Sponsor for all confirmed temperature measurements >38.0°C 
4. Consider if referring to an emergency medical facility is appropriate. If so, refer. 
Otherwise: 
a. PI or designee to perform a complete physical examination (including assessing if 
fever is accompanied by a severe headache, stiff neck, or other signs of meningeal 
irritation, shortness of breath, skin rashes, or other unusual signs or symptoms), 
document a plan based on her/his clinical judgment, and possibly an ID consult 
depending on assessment 
b. CBC (if not done in the last 12 hours) and blood culture  
c. Treat any suspicion of meningococcal infection aggressively; consider initiation of 
empirical antimicrobial therapy (assuming there are no other obvious sources of 
fever) at least until culture results become available and/or an alternative etiology is 
found 
d. Infectious disease consult is required once the PI or designee initiates empiric 
antibiotic treatment 
e. Measure temperature hourly until <38.0°C 
f. All cases of fever will be assessed by the Investigator, regardless of apparent 
causality from use of the study treatment(s) 
g. All activities performed as part of the Fever Management Plan should be documented 
 
Acute Meningococcal Disease 
If acute meningococcal disease is diagnosed, immediate medical and antibiotic management by 
local physician must be initiated documented and reported to the sponsor’s medical monitor 
immediately, but not more than 24 hours from diagnosis. 
Normal body temperature varies over the course of the day. The normal daily temperature 
variation is typically 0.5°C (0.9°F). During a febrile illness, daily low and high temperature 


ACH-0144471 
Achillion Pharmaceuticals, Inc. (a subsidiary of 
 
Alexion Pharmaceuticals, Inc.) 
Clinical Protocol ACH471-204, Amendment 7 
15 May 2020 (Version 8)  
 
 
Confidential Property of Achillion Pharmaceuticals, Inc.  
a subsidiary of Alexion Pharmaceuticals, Inc.)  
Page 86 of 86 
readings are maintained but at higher levels. However, this daily variation can be as high as 
1.0°C in some individuals recovering from a febrile illness. 

SAP_001.pdf: 
A P h ase 2, Pr o of -of -C o n ce pt, R a n d o mize d,  D o u ble -Bli n d e d, 
Pl a ce b o -C o nt r olle d St u d y of A C H -0 1 4 4 4 7 1 Tre at me nt f o r 
6 M o nt hs i n P atie nts wit h C 3 Gl o mer ul o p at h y ( C 3 G),  wit h  
a n O p e n -L a b el E xt e nsi o n  
 
 
 
 
U ni q ue Pr ot oc ol I D:  
A C H 4 7 1 -2 0 4  
N C T N u m ber:  
N C T 0 3 3 6 9 2 3 6  
E u dr a C T N u m ber:  
2 0 1 7 -0 0 0 6 6 3 -3 3  
D at e of S A P:  
3 0 Oct o ber 2 0 2 0  
 


Alexion Pbannaceuticals 
ACH471-204: 15 May2020 (Version 8) 
LEXl□N 
Statistical Analysis Plan 
30 October 2020, Version 5
STATISTICAL ANALYSIS PLAN 
PROTOCOL NUMBER: ACH471-204
A PHASE 2, PROOF-OF-CONCEPT, RANDOMIZED, DOUBLE­
BLINDED, PLACEBO-CONTROLLED STUDY OF ACH-0144471 
TREATMENT FOR 6 MONTHS IN PATIENTS WITH C3 
GLOMERULOPATHY (C3G), WITH AN OPEN-LABEL 
EXTENSION 
Author: ____ _, 
Date: 30 October 2020 
Version: 5.0 
Confidential 
Page I of33 
STATISTICAL ANALYSIS PLAN 
PROTOCOL NUMBER: ACH471-204
A PHASE 2, PROOF-OF-CONCEPT, RANDOMIZED, DOUBLE­
BLINDED, PLACEBO-CONTROLLED STUDY OF ACH-0144471 
TREATMENT FOR 6 MONTHS IN PATIENTS WITH C3 
GLOMERULOPATHY (C3G), WITH AN OPEN-LABEL 
EXTENSION 
Author:PPD ---
Date: 30 October 2020 
Version: 5.0 
STATISTICAL ANALYSIS PLAN 
PROTOCOL NUMBER: ACH471-204
A PHASE 2, PROOF-OF-CONCEPT, RANDOMIZED, DOUBLE­
BLINDED, PLACEBO-CONTROLLED STUDY OF ACH-0144471 
TREATMENT FOR 6 MONTHS IN PATIENTS WITH C3 
GLOMERULOPATHY (C3G), WITH AN OPEN-LABEL 
EXTENSION 
Author:PPD ---
Date: 30 October 2020 
Version: 5.0 


Ale xi o n P har mace uticals  
A C H 4 7 1 -2 0 4: 1 5 Ma y 2 0 2 0 ( Versi o n 8)  
Statistical A nal ysis Pla n  
3 0 Oct o ber 2 0 2 0, Versi o n 5  
 
 
 
C o nfi de ntial  
Pa ge 2  of 3 3  
 
 
1.     
A P P R O V A L SI G N A T U R E S  
   
 
   
Date d d M m m y y y y  
   
 
   
Date d d M m m y y y y  
   
 
   
 
   
 
   
Date d d M m m y y y y  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
0 6 - N o v - 2 0 2 0  |  0 9 : 0 9 : 2 0  E S T
0 6 - N o v - 2 0 2 0  |  0 9 : 2 4 : 1 2  E S T
0 6 - N o v - 2 0 2 0  |  1 0 : 1 5 : 1 4  E S T
P P D


Ale xi o n P har mace uticals  
A C H 4 7 1 -2 0 4: 1 5 Ma y 2 0 2 0 ( Versi o n 8)  
Statistical A nal ysis Pla n  
3 0 Oct o ber 2 0 2 0, Versi o n 5  
 
 
 
C o nfi de ntial  
Pa ge 3  of 3 3  
 
 
T a bl e of C o nt e nt s  
List of A p pe n dices  .......................................................................................................................................4  
List of A b bre viati o ns  ...................................................................................................................................5  
1  
O ver vie w  ..............................................................................................................................................7  
2  
O bjecti ve  ..............................................................................................................................................7  
2. 1  
Pri mar y O bjecti ves  ......................................................................................................................7  
2. 2  
Sec o n dar y O bjecti ves  ..................................................................................................................7  
2. 3  
E x pl orat or y O bjecti ves  ................................................................................................................8  
2. 4  
Q ualit y of Life O bjecti ves  ...........................................................................................................8  
3  
E n d p oi nts  ..............................................................................................................................................8  
3. 1  
Efficac y O utc o me Meas ures  ........................................................................................................8  
3. 1. 1  Brief Descri pti o n of Re nal Bi o ps y Sc ori n g S yste m  .................................................................8  
3. 1. 2  Pr otei n uria Defi niti o ns  ...........................................................................................................1 0  
3. 1. 3  Pri mar y Efficac y O utc o me Meas ures  .....................................................................................1 0  
3. 1. 4  Sec o n dar y Efficac y O utc o me Meas ures  .................................................................................1 0  
3. 1. 5  Ot her Effi cac y / P K / P D / Q ualit y of Life O utc o me Meas ures  .............................................1 0  
3. 2  
Safet y O utc o me Meas ures  .........................................................................................................1 1  
3. 3  
P har mac o ki netic ( P K) Para meters  .............................................................................................1 1  
4  
St u d y Descri pti o n  ...............................................................................................................................1 1  
4. 1  
St u d y Desi g n  ..............................................................................................................................1 1  
4. 2  
Treat me nt Assi g n me nt  ...............................................................................................................1 2  
4. 3  
Bli n di n g a n d U n bli n di n g  ...........................................................................................................1 2  
4. 4  
Pr ot oc ol A me n d me nts  ................................................................................................................1 3  
5  
Sa m ple Size  ........................................................................................................................................1 4  
6  
A nal ysis Sets  ......................................................................................................................................1 5  
6. 1  
Ra n d o mize d A nal ysis Set  ..........................................................................................................1 5  
6. 2  
F ull A nal ysis Set ( F A S)  .............................................................................................................1 5  
7  
Statistical A nal yses  .............................................................................................................................1 5  
7. 1  
Ge nera l Met h o ds ........................................................................................................................1 5  
7. 2  
St u d y P o p ulati o n  ........................................................................................................................1 6  
7. 2. 1  Patie nt Disc o nti n uati o n a n d Dis p ositi o n  ................................................................................1 6  
7. 2. 2  De m o gra p hic a n d Baseli ne C haracteristics  ............................................................................1 6  


Ale xi o n P har mace uticals  
A C H 4 7 1 -2 0 4: 1 5 Ma y 2 0 2 0 ( Versi o n 8)  
Statistical A nal ysis Pla n  
3 0 Oct o ber 2 0 2 0, Versi o n 5  
 
 
 
C o nfi de ntial  
Pa ge 4  of 3 3  
 
 
7. 2. 3  Me dical Hist or y  ......................................................................................................................1 7  
7. 3  
E xte nt of E x p os ure  ....................................................................................................................1 7  
7. 4  
C o nc o mita nt Me dicati o ns  ..........................................................................................................1 7  
7. 5  
Efficac y a n d P D Mar kers Assess me nt  .......................................................................................1 8  
7. 5. 1  A nal ysis of Pri mar y Efficac y O utc o me Meas ures  .................................................................1 8  
7. 5. 2  A nal ysis of Sec o n dar y Efficac y O utc o me Meas ures  .............................................................1 8  
7. 5. 3  A nal ysis of Ot her Efficac y O utc o me Meas ure a n d P D Mar kers  ...........................................1 9  
7. 6  
Patie nt Re p ort O utc o mes ( P R O)  ................................................................................................2 0  
7. 6. 1  K D Q O L -S F ™ versi o n 1. 3 ......................................................................................................2 0  
7. 6. 2  F A CI T Fati g ue Scale ( Versi o n 4)  ..........................................................................................2 1  
7. 6. 3  E Q -5 D -3 L  ...............................................................................................................................2 1  
7. 7  
Safet y Assess me nt  .....................................................................................................................2 2  
7. 7. 1  Treat me nt -E mer ge nt A d verse E ve nts ( T E A E)  .......................................................................2 2  
7. 7. 2  Cli nical La b orat or y Para meters  ..............................................................................................2 3  
7. 7. 3  1 2 -lea d E C G ...........................................................................................................................2 4  
7. 7. 4  Vital Si g ns a n d B o d y Wei g hts  ...............................................................................................2 5  
7. 7. 5  P h ysical E x a m  ........................................................................................................................2 5  
7. 8  
P har mac o ki netic ( P K) Assess me nts  ..........................................................................................2 5  
7. 8. 1  P K Para meters  ........................................................................................................................2 5  
7. 8. 2  P K A nal ysis  ............................................................................................................................2 6  
7. 8. 3  Pre -D ose C o nce ntrati o ns ( P K Tr o u g hs)  .................................................................................2 7  
8  
C ha n ges fr o m Pr ot oc ol S pecifie d A nal ysis  ........................................................................................2 7  
9  
D oc u me nt Hist or y  ..............................................................................................................................2 7  
 
Li st of A p p e n di c e s  
A p pe n di x 1.  Gra di n g t he Se verit y of La b orat or y Val ues  .......................................................................2 9  
A p pe n di x 2.  K D Q O L -S F Scale Sc ori n g Pr oce d ure  ...............................................................................3 2  
A p pe n di x 3.  F A CI T -Fati g ue Scale a n d Calc ulati o n of T otal Sc ore  .......................................................3 3  
 
 
 


Ale xi o n P har mace uticals  
A C H 4 7 1 -2 0 4: 1 5 Ma y 2 0 2 0 ( Versi o n 8)  
Statistical A nal ysis Pla n  
3 0 Oct o ber 2 0 2 0, Versi o n 5  
 
 
 
C o nfi de ntial  
Pa ge 5  of 3 3  
 
 
 
Li st of A b br e vi ati o n s  
A E  
A d verse e ve nt  
A P  
Alter nati ve Pat h wa y  ( C o m ple me nt) 
A U C ta u 
Area u n der t he plas ma c o nce ntrati o n -ti me c ur ve fr o m ti me of a d mi nistrati o n t o t he 
e n d of d osi n g i nter val  
B L Q  
B el o w t he l o wer li mit of q ua ntificati o n  
C 3 G  
C 3 gl o mer ul o pat h y  
C 3 G N  
C 3 gl o mer ul o ne p hritis  
C K D -E PI     
C hr o nic ki d ne y disease - E pi de mi ol o g y c olla b orati o n  
C L/ F  
A p pare nt oral dr u g cleara nce  
C ma x  
Ma xi m u m plas ma c o nce ntrati o n  
C V %  
C oefficie nt of variati o n  
D D D  
De nse de p osit disease  
E C G  
Electr ocar di o gra m  
E O T  
E n d of treat me nt  
E Q -5 D -3 L     
T hree -le vel versi o n of E ur o Q ol 5 Di me nsi o ns q uesti o n naire 
F A CI T -Fati g ue     
F u ncti o nal Assess me nt of C hr o nic Ill ness T hera p y -Fati g ue scale  
F A S  
F ull A nal ysis Set  
K D Q O L -S F     
Ki d ne y Disease Q ualit y of Life s h ort f or m q uesti o n naire  
L F T  
Li ver f u ncti o n test s 
Ma x  
Ma xi m u m  
Me d D R A     
Me dical Dicti o nar y f or Re g ulat or y Acti vities  
Mi n  
Mi ni m u m  
P D  
P har mac o d y na mic  
P K  
P har mac o ki netic  
Q T c F  
Q T i nter val c orrecte d usi n g Fri dericia’s f or m ula  


Ale xi o n P har mace uticals  
A C H 4 7 1 -2 0 4: 1 5 Ma y 2 0 2 0 ( Versi o n 8)  
Statistical A nal ysis Pla n  
3 0 Oct o ber 2 0 2 0, Versi o n 5  
 
 
 
C o nfi de ntial  
Pa ge 6  of 3 3  
 
 
S A P  
Statistical A nal ysis Pla n  
S D  
Sta n dar d de viati o n  
T E  
Treat me nt e mer ge nt  
T E A E  
Treat me nt -e mer ge nt a d verse e ve nt  
T ma x  
Ti me after a d mi nistrati o n of a dr u g w he n t he ma xi m u m plas ma c o nce ntrati o n is 
reac he d 
U L N  
U p per li mit n or mal  
V A S  
Vis ual a nal o g scale  
 
 
  


Alexion Pharmaceuticals 
ACH471-204: 15 May 2020 (Version 8) 
Statistical Analysis Plan 
30 October 2020, Version 5 
Confidential 
Page 7 of 33 
1 Overview 
This statistical analysis plan (SAP) describes in detail the statistical procedures and presentations to be 
implemented for the data analysis of Study ACH471-204.  This version of the SAP (V5.0) will be the 
final version.   
It is noted that changes in protocol amendments 4 and 5 included study objectives (both primary and 
secondary), study design to increase sample size, and inclusion of adolescents (12 years and older) 
which had major regulatory impact.  Protocol amendment 6 restores initial sample size projections and 
includes adult patients only, restoring the primary objectives to be the same as in Amendment 3 
  Protocol amendment 7 implements risk mitigations due to the COVID-19 global 
pandemic.  Section 4.4 below briefly summarizes the changes in each protocol amendment. 
As stated above, this study has completed enrollment of patients.  Twelve (12) patients have been treated 
which is about two-thirds of the planned sample size of 20.  Only descriptive statistical methodologies 
will be utilized.  Inferential comparisons between ALXN2040 (formerly ACH-0144471) and placebo 
will be considered if deemed meaningful and appropriate from a clinical perspective. 
Throughout this document, ‘6 months of treatment’ is synonymous with ‘at least 24 weeks of treatment’.  
2 Objective 
2.1 Primary Objectives 
The primary objective of this study is to evaluate the efficacy, relative to placebo, of six months of oral 
ALXN2040 in patients with C3G based on: 

Improvement in renal biopsy results

Improvement relative to baseline in proteinuria.
2.2 Secondary Objectives 
The secondary objectives of this study are: 

To evaluate the clinical effect relative to placebo, of six months of oral ALXN2040 in patients with
C3G based on slope of estimated glomerular filtration rate (eGFR) relative to baseline over time

To evaluate the clinical effect, relative to placebo, of six months of oral ALXN2040 in patients with
C3G based on change in estimated glomerular filtration rate (eGFR) relative to baseline over time

Where available, evaluate the change in measured (m) GFR relative to baseline at end of 6 months
study drug treatment.

To evaluate the safety and tolerability of six months of oral treatment with ALXN2040 in patients
with C3G by assessing serious adverse events (SAEs).
CCI


Ale xi o n P har mace uticals  
A C H 4 7 1 -2 0 4: 1 5 Ma y 2 0 2 0 ( Versi o n 8)  
Statistical A nal ysis Pla n  
3 0 Oct o ber 2 0 2 0, Versi o n 5  
 
 
 
C o nfi de ntial  
Pa ge 8  of 3 3  
 
 
2. 3  E x pl or at or y  O bj e cti v e s  
C o m ple me nt Bi o m ar kers  
 T o e val uate t he c ha n ge i n C o m ple me nt pr otei ns C 3, B b a n d Ba (s plit pr o d ucts) relati ve t o 
baseli ne a n d c o m p are t h ese c ha n ges as t he y relate t o cli nical o utc o mes descri be d i n pri mar y a n d 
sec o n dar y o bj ecti ves.  
 T o e val uate t he P K meas ures as t he y relate t o c o m ple me nt bi o mar kers a n d alter nati ve pat h wa y 
( A P) i n hi biti o n assa ys ( A P Wiesla b a n d A P He m ol ysis) 
 T o e val uate t he effect of A L X N 2 0 4 0  t hera p y o n c o m ple me nt bi o mar kers c o m pare d wit h place b o 
at 6 m o nt hs relati ve t o baseli ne  
2. 4  Q u alit y of Lif e O bj e cti v e s  
T he q ualit y of life ( Q o L) o bjecti ves of t he st u d y are:  
 T o e val uate ki d ne y dis ease a n d healt h -relate d q ualit y of life i nstr u me nts i n patie nt s wit h C 3 G, 
o ver t he c o urse of A L X N 2 0 4 0 / place b o treat me nt 
 
3  E n d p oi nt s  
T he f oll o wi n g s ecti o ns i nte n d t o pr o vi de a list of o utc o me meas ures fr o m d ata c ollecte d o n effi cac y, 
i ncl u di n g p har mac o d y na mics ( P D), safet y, a n d p har mac o ki netics ( P K) t o a d dress t he st u d y o bj ecti ves.  
T he res ult fr o m q ualitati ve  patie nt i nter vie ws will n ot be i ncl u de d i n t he st u d y cli nical data base, a n d 
t heref ore, is n ot liste d bel o w. 
N ote t hat t he o utc o me meas ures t o a d dress e x pl orat or y o bj ecti ves are dat a -de pe n de nt a n d are pr o vi de d 
as g ui de f or cli nical i nter pretati o ns.  
3. 1  Effi c a c y O ut c o m e M e a s ur e s  
3. 1. 1  Bri ef D e s cri pti o n of R e n al Bi o p s y S c ori n g S y st e m  
A ne w  preli mi nar y  re nal bi o ps y sc ori n g s yste m f or C 3 G disease has bee n de vel o pe d f or use i n t his pr o of 
of c o nce pt ( P O C)  st u d y.  A  si n gle bi o ps y c o m p osit e i n de x c o nsist i n g of t hree c o m p o ne nts : acti vit y 
i n de x, gl o mer ular C 3c st ai ni n g, a n d gl o mer ular macr o p ha ge i nfiltrati o n, will be use d as o ne of t he 
pri mar y efficac y o utc o me meas ures  i n t his st u d y.  T he c hr o nicit y i n de x  f or C 3 G disease will als o be 
e x pl ore d t o assess t he effecti ve ness of A L X N 2 0 4 0 . 
I n di vi d ual bi o ps y feat ures as descri be d bel o w are classifie d i nt o f o ur q ua ntifia ble cate g ories .  Se verit y 
sc ores of 0, 1, 2, a n d 3 are  assi g ne d t o t he c orres p o n di n g f o ur  cate g o ries f or eac h bi o ps y  feat ure. Sc ore 
of  0 i n dicat es t he n or mal  state ( 0 or e xtre mel y l o w q ua ntities) of a partic u lar feat ure. 


Ale xi o n P har mace uticals  
A C H 4 7 1 -2 0 4: 1 5 Ma y 2 0 2 0 ( Versi o n 8)  
Statistical A nal ysis Pla n  
3 0 Oct o ber 2 0 2 0, Versi o n 5  
 
 
 
C o nfi de ntial  
Pa ge 9  of 3 3  
 
 
T he acti vit y i n d e x i ncl u des fi ve feat ures of t he bi o ps y ass ess me nt , eac h wit h a p ossi ble sc ore of 0 t o 3, 
t hat are c o m bi ne d t o gi ve a n o verall acti vit y i n de x sc ore ra n gi n g fr o m 0 t o 1 5.   T he c orrecte d acti vit y 
sc ore was calc ulate d b y t he ce ntral pat h ol o gist b y assessi n g eac h of t he f oll o wi n g fi ve feat ures i n via ble 
gl o mer uli.  A via ble gl o mer ul us is o ne t hat d oes n ot s h o w gl o bal scler osis.   
 E n d oca pillar y h y percell ularit y –  defi ne d as t he prese nce of cells i n ca pillar y l o o ps wit h l o o p 
occl usi o n. Eac h via ble gl o mer ul us  is e val uate d f or t he perce nta ge of t he t uft t hat has e n d oca pillar y 
h y percell ularit y  a n d classifie d t he perce nta ges i nt o f o ur cat e g ories:  0, 1 -2 5 %, 2 6 -5 0 %, a n d > 5 0 % , 
c orres p o n di n g t o sc ores 0 -3 .  T he o verall sc ore is t he me dia n of sc ores of all via ble gl o mer uli 
i n v ol ve d.   
 Ne utr o p hils i n ca pillar y l u me ns - sc ore eac h via ble gl o mer ul us as 0, 1 -3, 4 -1 0, > 1 0 c orres p o n di n g t o 
sc ores of 0-3 . T he o verall sc ore is t he me dia n of sc ores of all via ble gl o mer uli i n v ol ve d.  
 Mesa n gial h y percell ularit y –  defi ne d as m ore t h a n 4 cells i n a mesa n gial area a wa y fr o m t he hil u m 
( % gl o mer uli). Sc ore as perce nt age of via ble gl o mer uli i n v ol ve d:  0, 1 -2 5 %, 2 6 -5 0 %, > 5 0 % 
c orres p o n di n g t o sc ores of 0 -3 . 
  Necr osis - defi ne d as disr u pti o n of t he gl o mer ular base me nt me m bra ne wit h fi bri n e x u dati o n a n d 
kar y orr he xis. At least t w o of t hese t hree lesi o ns nee d t o be prese nt t o meet t he criteria f or necr osis 
( % gl o mer uli). Sc ore as perce nt a ge of via ble gl o mer uli i n v ol ve d:  0, 1 -1 0 %, 1 1 -2 5 %, > 2 5 % 
c orres p o n di n g t o sc ores of 0 -3 . 
 Cell ular or fi br ocell ular cresce nts ( % gl o mer uli) –   Sc ore as perce nt a ge of via ble gl o mer uli i n v ol ve d : 
0,  1 -1 0 %, 1 1 -2 5 %, > 2 5 % c orres p o n di n g t o sc ores of 0 -3.  
Gl o mer ular C 3c stai ni n g  is sc ore d 0-3 base d o n t h e  sta n dar d se mi q ua ntitati ve sc ore i n w hi c h ne gati ve, 
1 +, 2 + a n d 3 + will c orres p o n d t o sc ores of 0 -3 . 
Gl o mer ular macr o p ha ge i nfiltrati o n  –  defi ne d as macr o p ha ge  c o u nts per gl o mer ul us i n a C D 6 8 
i m m u n ostai n.  T he c o u nts of eac h gl o mer ul us  will be assi g ne d t o  o ne of  f o ur cate g ories, 0 cell, 1 -3  cells, 
4 -1 0 cells, > 1 0 cells, c orres p o n di n g t o sc ores of 0 -3.   T he o verall sc ore is t he me dia n of sc ores of all 
g l o mer uli i n v ol ve d. 
T he sc ores  fr o m t he a b o ve t hree ele me nts (c orrect e d acti vit y i n d e x, gl o mer ular C 3c stai ni n g a n d 
gl o mer ular macr o p ha ge i nfiltrati o n) a d de d t o t o get her pr o vi de s a si n gle c o m p osite bi o ps y sc ore , 
ra n gi n g fr o m 0 t o 2 1, a n d ser ves as o n e of t he pri mar y efficac y meas ures.  
C hr o nicit y i n de x  i ncl u des assess me nt of f o ur lesi o n t y pes i n t he bi o ps y , eac h wit h a p ossi ble sc ore of 0 
t o 3; t heref ore, t h e t otal p ossi ble sc ores ra n ge fr o m 0 t o 1 2. 
 Gl o mer ular scler osis  –  defi ne d as % of gl o mer uli wit h se g me ntal or gl o bal scler osis.  Sc ores will be 
base d o n perce nta ge gl o mer uli affecte d: < 1 0 %, 1 0 -2 5 %, 2 6 -5 0 %, > 5 0 % c orres p o n di n g t o sc ores of 
0 -3 . 
 Fi br o us cresce nts  -- defi ne d as  % of gl o mer uli  wit h fi br o us cresce nts .  Sc ore s will be base d  o n  
perce nt a ge gl o mer uli affecte d: n o ne, < 2 5 %, 2 6 -5 0 %, > 5 0 % c orres p o n di n g t o sc ores of 0 -3.  
 T u b ular atr o p h y  –  F o ur cate g ories will be gi ve n t o assess t u b ular atr o p h y,  < 5 %,  6 -2 5 % , 2 6 -5 0 %, a n d  
> 5 0 % , c orres p o n di n g t o sc ores of 0, 1, 2, a n d 3. 


Ale xi o n P har mace uticals  
A C H 4 7 1 -2 0 4: 1 5 Ma y 2 0 2 0 ( Versi o n 8)  
Statistical A nal ysis Pla n  
3 0 Oct o ber 2 0 2 0, Versi o n 5  
 
 
 
C o nfi de ntial  
Pa ge 1 0  of 3 3  
 
 
 I nterstitial fi br osis -- F o ur cate g ories  will be gi ve n t o assess i nterstitial fi br osis , < 5 % , 6 -2 5 % , 2 6 -
5 0 % , a n d > 5 0 % , c orres p o n di n g sc ore of 0, 1, 2, a n d 3. 
 
3. 1. 2  Pr ot ei n uri a D efi niti o n s  
Q ua ntitati ve assess me nt of p r otei n uria will be base d o n t w o t y pes of uri ne c ollecti o n s o urces  i n t his 
st u d y, a n d usi n g b ot h t otal pr otei n a n d al b u mi n meas ure m e nts i n uri ne:  
1.  2 4 -h o ur uri ne c ollecti o n sa m ple s w hic h will be o btai ne d at Scree ni n g , M o nt h 6, M o nt h 1 2 , a n d 
M o nt h 2 4  visits;  
2.  S p ot  uri ne sa m ple s w hic h will be c ollecte d at pr ot oc ol s pecifie d visit ti me p oi nts . 
F or 2 4 -h o ur uri ne sa m ples, pr otei n uria will be assesse d  as t he meas ure me nts of t otal pr otei n ( m g/ d a y ) 
a n d al b u mi n (u m ol/ da y ). 
F or s p ot uri ne sa m ples, pr otei n uria will be assesse d  as t he ratio of t otal pr ot ei n/creati ni ne a n d t he rati o of 
al b u mi n/creati ni ne. 
F or c o m p aris o n  a n d q ualit y c o ntr ol of pr otei n meas ure me nts  f or 2 4 -h o ur uri ne sa m ples , rati os of  
pr otei n/creati ni ne a n d al b u mi n/creati ni ne will als o be calc ulate d f or t he sa m ples. 
3. 1. 3  Pri m ar y  E ffi c a c y O ut c o m e M e a s ur e s  
 C ha n ge  fr o m baseli ne i n bi o ps y, base d o n a sc ore i nc or p orati n g c ha n ges i n b ot h t he acti vit y i n de x 
a n d C 3 stai ni n g, at t he e n d of 6 m o nt hs of treat me nt 
 N u m ber a n d perce nt of patie nts wit h re d ucti o n i n pr otei n uria at t he e n d of 6 m o nt hs of treat me nt  
Re d ucti o n  is defi ne d as ≥3 0 % decrease i n pr otei n uria  (t otal pr otei n/ da y) rel ati ve t o baseli ne fr o m 2 4-
h o ur uri ne c ollecti o ns . 
3. 1. 4  S e c o n d ar y Effi c a c y O ut c o m e M e a s ur e s  
 C ha n ge a n d perce nt c ha n ge fr o m baseli ne i n pr otei n uria o ver 6 m o nt hs of tr eat me nt  
 C ha n ge a n d perce nt c ha n ge fr o m baseli ne i n e G F R o ver 6 m o nt hs of treat me nt  
 N u m ber a n d perce nt of patie nts wit h si g nifica nt i m pr o ve me nt relati ve t o baseli ne i n e G F R at t he e n d 
of 6 m o nt hs of treat me nt  
 Descri pti ve a nal ysis of  sl o pe of G F R fr o m baseli n e t o 6 m o nt hs 
 Descri pti ve a nal ysis of  sl o pe of G F R after 1 2 m o nt hs of A L X N 2 0 4 0  t hera p y 
 
3. 1. 5  Ot h er  Effi c a c y  / P K / P D  / Q u alit y of Lif e O ut c o m e M e a s ur e s  
 C ha n ges i n ki d ne y diseas e a n d healt h relate d q ualit y of life m eas ure me nts usi n g K D Q O L -S F v 1. 3 
a n d F A CI T -Fa ti g ue scale ( versi o n 4. 0) at 6 m o nt hs a n d 1 2 m o nt hs of treat me nt  


Ale xi o n P har mace uticals  
A C H 4 7 1 -2 0 4: 1 5 Ma y 2 0 2 0 ( Versi o n 8)  
Statistical A nal ysis Pla n  
3 0 Oct o ber 2 0 2 0, Versi o n 5  
 
 
 
C o nfi de ntial  
Pa ge 1 1  of 3 3  
 
 
 Deter mi nati o n of healt h state val ues usi n g t he 3 -le vel versi o n of t he E ur o Q ol 5 di me nsi o ns ( E Q-5 D -
3 L) q uesti o n naire  at 6 m o nt hs a n d 1 2 m o nt hs of treat me nt  
 C ha n ges i n t he f oll o wi n g bi o mar kers o ver t he 6 m o nt hs of treat me nt : A P  acti vit y, C P acti vit y, Fact or 
D, C 3,  C 4,  B b, s C 5 b-9 a n d ot her bi o mar ker meas ure me nts a vaila ble fr o m ce ntral la b orat ories.  
 Plas ma c o nce ntrati o ns a n d p har mac o ki netic ( P K) para meters o n data fr o m C 3 G patie nts rec ei vi n g 
A L X N 2 0 4 0  
 C ha n ge a n d perce nt c ha n ge fr o m baseli ne i n meas ure d G F R, base d o n i o he x ol cleara nce, o ver t he 
6  m o nt hs of treat me nt f or patie nts f or w h o m t his data is a vaila ble.  
 
3. 2  S af et y O ut c o m e M e a s ur e s  
 Fre q ue nc y of S A E  
 Fre q ue nc y of A Es lea di n g t o disc o nt i n uati o n of t he st u d y dr u g  
 Fre q ue nc y of A Es (relate d a n d re gar dless of relati o ns hi p t o st u d y dr u g ) 
 Fre q ue nc y of la b orat or y a b n or malities b y t o xicit y gra de  
 C ha n ge fr o m baseli ne o n selecte d la b orat or y test res ults o ver treat me nt d urati o n  
 C ha n ge fr o m baseli ne  o n para meters of vital si g ns a n d wei g ht o ver treat me nt d urati o n  
 Treat me nt e mer ge nt a b n or malities o n selecte d E C G para meters  
 C ha n ge fr o m baseli ne o n E C G para meters o ver treat me nt d urati o n  
 
3. 3  P h ar m a c o ki n eti c ( P K) P ar a m et er s  
 C ma x , A U C0 -ta u, a n d tma x  f or Da y  1 0  
 C tr o u g h c o nce ntrati o ns  f or ot her da ys 
 
4  St u d y D e s cri pti o n  
4. 1  St u d y D e si g n  
T his is a ra n d o mize d, place b o -c o ntr olle d, d o u ble -bli n de d (s p o ns or -o pe n) st u d y wit h si x m o nt hs  ( 2 4-2 8 
wee ks)  of  bli n de d  treat m e nt, f oll o we d b y 6 m o nt hs of o pe n-la bel treat me nt peri o d a nd u p t o a n 
a d diti o nal 2 1 -m o nt h l o n g ter m f oll o w u p .  T he st u d y was pla n ne d t o  i ncl u de a p pr o xi matel y 2 0 patie nts 
wit h C 3 gl o mer ul o pat h y  ( C 3 G) w h o ha ve n ot u n der g o ne re nal tra ns pl a nt.  Patie nts are ra n d o mize d 1: 1 
t o A L X N 2 0 4 0  or place b o, strat ifie d b y t h e dis ease dia g n osis: de nse de p osit disease ( D D D) a n d C 3 
gl o mer ul o ne p hritis ( C 3 G N).  
Patie nts m ust ha ve bi o ps y -c o nfir me d dia g n osis of eit her  D D D or C 3 G N  a n d si g nifica nt pr otei n uria, 
defi ne d as ≥5 0 0  m g/ da y of pr otei n i n a 2 4 -h o ur uri ne,  t hat is attri b uta ble t o C 3 G i n t he o pi ni on of t he 
pri nci pal i n vesti gat or . 


Ale xi o n P har mace uticals  
A C H 4 7 1 -2 0 4: 1 5 Ma y 2 0 2 0 ( Versi o n 8)  
Statistical A nal ysis Pla n  
3 0 Oct o ber 2 0 2 0, Versi o n 5  
 
 
 
C o nfi de ntial  
Pa ge 1 2  of 3 3  
 
 
St u d y eli gi bilit y re q uire s a n a de q uate re nal bi o ps y sa m ple f or e val uati o n b y all t hree sta n dar d 
m o dalities: li g ht micr osc o p y, el ectr o n micr osc o p y, a n d i m m u n ofl u oresce nce .  I n a d diti o n, patie nts m ust 
ha ve t he dia g n osis of D D D or C 3 G N f or at least 3 m o nt hs pri or t o d osi n g , u nless ot her wise a p pr o ve d b y 
t he s p o ns or. 
All patie nts m ust be vacci nate d a gai nst H ae m o p hil us i nfl ue nz ae  (H. i nfl ue nz ae ), Stre pt oc occ us 
p ne u m o ni ae (S. p ne u m o ni ae ), a n d Neisseri a me ni n giti dis  (N. me ni n giti dis ) acc or di n g t o nati o nal a n d/ or 
l ocal g ui d eli nes t o mi ni mize t he ris k of seri o us i nfecti o n wit h a n e nca ps ulat e d or ga nis m, u nless 
precl u de d b y l ocal vacci nati o n g ui deli nes, lice nses, or a vaila bilit y .  
T he start i n g d os e of A L X N 2 0 4 0  is 1 0 0 m g TI D , a t otal d ose of 3 0 0 m g per da y.  After t w o wee ks of 
treat me nt, d osi n g  is es cal ate d t o 2 0 0 m g TI D .  A d diti o nal  d os a ge re gi me ns ma y be i n vesti gate d if 
s u p p orte d b y e mer gi n g data fr o m t his a n d ot her cli nical st u dies.     
Safet y, effi cac y (i ncl u di n g bi o ps y res ults, P D bi o mar kers, a n d t hree ki d n e y disease a n d healt h relate d 
q ualit y of life i nstr u me nts), a n d P K assess me nts are carrie d o ut at pre-s pecifie d ti me p oi nts t hr o u g h o ut 
treat me nt a n d p ost-treat me nt f oll o w u p peri o d.  N ote t hat r e nal bi o ps y is perf or me d pre -treat me nt, at t he 
e n d of bli n de d d osi n g  peri o d  ( bet wee n Wee k 2 6 a n d Wee k 2 8), a n d o pti o nall y  at Wee k 5 2 a n d Wee k 
1 0 4 .  
I n a d diti o n, q ualitati ve e x pl orat or y i nter vie ws are c o n d ucte d b y i n de pe n de nt o utc o mes researc hers  
c h ose n b y t he S p o ns or wit h patie nts pri or t o i nitiati o n of st u d y treat me nt ( d uri n g t he scree ni n g peri o d) 
a n d at t he e n d of st u d y treat me nt a d mi nistrati o n ( Wee k 2 8) t o c ollect patie nts’ e x perie nce of t heir 
disease a n d treat me nt, its i m pact o n e ver y da y li ve s, a n d t he disease traject or y o ver t he c o urse of 
A L X N 2 0 4 0 / place b o treat me nt. 
T he pri mar y a nal ysis will occ ur after all patie nts c o m plete t he Wee k 2 8 visit  or wit h dra w fr o m t he st u d y 
earl y.  
4. 2  Tr e at m e nt A s si g n m e nt  
Patie nts are ra n d o mize d 1: 1 t o eit her acti ve treat me nt (A L X N 2 0 4 0 ) or place b o, stratifie d b y disease 
dia g n osis, D D D a n d C 3 G N.   
A we b -base d ce ntralize d ra n d o mizati o n sc he me, stratifie d b y disease dia g n osis, is use d t o pr o vi de 
treat me nt assi g n me nt of eit her A L X N 2 0 4 0  or place b o t o eac h patie nt.  Pri or t o ra n d o mizati o n, eac h 
patie nt is assi g ne d t o o ne of t he t w o disease dia g n oses, D D D or C 3 G N , base d o n t he bi o ps y res ults.  T he 
ra n d o mizati o n bl oc k desi g n is utilize d wit hi n eac h strat u m.  I n a d diti o n, t he ra n d o mizati o n sc he d ule ma y  
als o be pr o vi de d t o t he bi oa nal yti cal la b orat or y res p o nsi ble f or a nal ysis of P K sa m ples . 
4. 3  Bli n di n g a n d U n bli n di n g  
Ra n d o mize d treat me nt assi g n me nt will be d o u ble -bli n d a n d place b o -c o ntr olle d f or A L X N 2 0 4 0 . T he 
st u d y sites a n d t he patie nts  are bli n de d t o treat me nt assi g n me nt d uri n g t he bli n de d treat me nt peri o d . 
Alt h o u g h all patie nt s recei ve acti ve dr u g d uri n g t he o pe n-la bel exte n de d treat me nt p eri o d, t he first 
p orti o n of t he st u d y is n ot u n bli n de d u ntil all patie nt s ha ve c o m plete d t he b li n de d treat me nt p eri o d.  
D esi g nate d staff of Ac hilli o n P har mace uticals, I nc. will be u n bli n de d t o t he treat me nt assi g n me nts.  I n 


Ale xi o n P har mace uticals  
A C H 4 7 1 -2 0 4: 1 5 Ma y 2 0 2 0 ( Versi o n 8)  
Statistical A nal ysis Pla n  
3 0 Oct o ber 2 0 2 0, Versi o n 5  
 
 
 
C o nfi de ntial  
Pa ge 1 3  of 3 3  
 
 
a d diti o n, a me m ber ( or desi g nat e) of t he Bi oa nal ytical Scie nce secti o n will be u n bli n de d t o treat me nt 
assi g n me nts i n or der t o mi ni mize u n necessa r y a nal ysis of sa m ples fr o m patie nts  recei vi n g place b o. 
4. 4  Pr ot o c ol A m e n d m e nt s  
A me n d me nt 
N o.  
A me n d me nt 
D ate  
M ai n P ur p oses of A me n d me nt  
1  
2 5 -O C T -2 0 1 7  
 All o w visits o n Wee ks 1 4, 1 8, 2 2, a n d 2 6 t o be c o n d ucte d b y 
p h o ne rat her t ha n i n t he cli nic, at t he discreti o n of t he 
i n vesti gat or, i n or der t o re d uce t he b ur de n o n pati e nts i n t he 
st u d y. 
2  
1 2 -D E C -2 0 1 7  
 A ll o w i n vesti gat ors w h o wis h t o d o s o t o c ollect meas ure d G F R 
i n a d diti o n t o t he e xisti n g e G F R calc ulati o ns.  
  T he c o ntrace pti o n re q uire me nts are bei n g m o difie d t o ali g n wit h 
u p date d Ac hilli o n sta n dar d w or di n g, a n d S A E re p orti n g c o ntact 
i nf or mati o n is bei n g u p date d . 
3  
0 7 -M A R -2 0 1 8   C ha n ge i m pr o ve me nt i n e G F R fr o m a pri mar y t o a sec o n dar y 
o bjecti ve a n d t o ali g n e n d p oi nts wit h t his c ha n ge.  
 A dj ust i ncl usi o n/e xcl usi o n criteria relate d t o c o m ple me nt 
c o m p o ne nts i n or der t o facilitate e nr oll me nt of s uita ble patie nt s. 
 Re m o ve t he pla n ne d c oll ecti o n P K pr ofile sa m ples o n Da y 3 i n 
or der t o re d uce t he b ur de n o n patie nt s.   
 T he c o ntrace pti o n re q uire me nts are bei n g m o difie d t o ali g n wit h 
u p date d Ac hilli o n sta n dar d w or di n g.  
 Vacci n ati o n pr oce d ures are bei n g u p date d t o refer t o  nati o nal 
a n d/ or l ocal g ui deli nes, mi n or w or di n g c ha n ges are bei n g ma de 
f or clarit y. 
4  
0 2 -N O V -2 0 1 8  
 
A ll ows t he i ncl usi o n of a d olesce nts  
 E x pa n ds e nr oll me nt t o 4 5 patie nt s e nr olle d after a p pr o val of 
A me n d me nt 4, a n d c ha n ges t he ra n d o mizati o n t o 2: 1 A L X N 2 0 4 0  
or place b o  
 Ma kes t he c ollecti o n of re nal bi o ps y sa m ples o pti o nal, a n d 
c ha n ges t he i m pr o ve me nt i n bi o ps y sc ore fr o m a pri mar y t o a n 
e x pl orat or y o bjecti ve  
 Ma kes t he st u d y s p o ns or -bli n de d, i n a d diti o n t o t he patie nt s a n d 
i n vesti gat ors bei n g bli n de d 
 Ma kes c h a n ges t o t he i ncl usi o n a n d e xcl usi o n criteria t o better 
reflect t he i nte n de d patie nt p o p ulati o n a n d t o facilitate 
e nr oll me nt 
 Re d uces sa m ple c ollecti o n a n d a d ds fle xi bilit y t o t he c ollecti o n 
sc he d ule t o re d uce t he b ur de n o n patie nt s 
 A d ds a 6 -m o nt h o pe n -la bel treat me nt peri o d after t he bli n de d 
treat me nt peri o d 


Ale xi o n P har mace uticals  
A C H 4 7 1 -2 0 4: 1 5 Ma y 2 0 2 0 ( Versi o n 8)  
Statistical A nal ysis Pla n  
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C o nfi de ntial  
Pa ge 1 4  of 3 3  
 
 
A me n d me nt 
N o.  
A me n d me nt 
D ate  
M ai n P ur p oses of A me n d me nt  
5  
1 5 -F E B -2 0 1 9  
 Ma kes c ha n ges t o t he i ncl usi o n a n d e xcl usi o n criteria t o better 
reflect t he i nte n de d patie nt p o p ulati o n a n d t o facilitate 
e nr oll me nt 
 C ha n ges t h e d ose escalati o n strate g y, s o t hat all patie nt s will 
escalate after 2 wee ks  
 Re d uces sa m ple c ollecti o n a n d a d ds fle xi bilit y t o t he c ollecti o n 
sc he d ule t o re d uce t he b ur de n o n patie nt s (i ncl u di n g ma ki n g 
c ollecti o n of re nal bi o psies a n o pti o nal s u b -st u d y) 
6  
0 5 -J U N-2 0 1 9  
 Ma kes c ha n ges t o t he i ncl us i o n a n d e xcl usi o n criteria t o re m o v e 
t he all o wa nce of a d olesce nts i n t he st u d y p o p ulati o n 
 Re d uces sa m ple c ollecti o n a n d a d ds fle xi bilit y t o t he c ollecti o n 
sc he d ule t o re d uce t he b ur de n o n patie nt s  
 Re m o ves t he bi o ps y s u b -st u d y o pti o n (all patie nts ha d bi o ps y-
c o nfir me d dia g n osis)  
 E xte n ds t he st u d y t o Wee k 1 0 4 (a d diti o n of a 1 2 -m o nt h l o n g -
ter m f oll o w-u p peri o d)  
 Re m o ves D S M B si nce t h e st u d y is o nl y bli n de d t o t he 
I n vesti gat or, site staff a n d patie nt ( S p o ns or n ot bli n de d) 
 Re d uces t he n u m ber of i n -cli nic st u d y visits b y ha vi n g t he 
a bilit y t o d o visits as p h o ne calls  
 Re d uce t he n u m ber of e x pecte d patie nts t o 2 0  
7  
1 5 -M A Y -2 0 2 0   I ncreases d urati o n of st u d y treat me nt 
 All o ws h o me a n d tele p h o ne visits, l ocal la b orat or y testi n g, a n d 
st u d y dr u g t o be se nt directl y t o patie nt ’s h o me w he n cli nic 
visits are n ot p ossi ble d ue t o C O VI D -1 9 gl o bal pa n de mic  
 All o ws o pti o nal re nal bi o ps y at Wee k 5 2 a n d Wee k 1 0 4 t o be 
p ost p o ne d d ue t o C O VI D -1 9 gl o bal pa n de mic, a n d t o be 
perf or me d w he n p ossi ble  
 U p dates c o ntrace pti ve l a n g ua ge t o ali g n wit h m ost rece nt 
I n vesti gat or Br oc h ure 
 
5  S a m pl e Si z e  
T he pla n ne d sa m ple size of 2 0 patie nts, 1 0 eac h of A L X N 2 0 4 0  a n d place b o,  was  deter mi ne d base d o n 
ver y li mite d cli nical cases of C 3 G  patie nts  t o e val uate t he effecti ve ness of A L X N 2 0 4 0 . 
 


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6  A n al y si s S et s  
6. 1  R a n d o mi z e d A n al y si s S et  
All patie nts w h o are ra n d o mize d a n d are assi g ne d t o eit her A L X N 2 0 4 0  or place b o will be i ncl u de d i n 
t his a nal ysis data set. 
6. 2  F ull A n al y si s S et ( F A S)  
All  ra n d o mize d patie nts recei vi n g at least o n e d ose of st u d y dr u g, A L X N 2 0 4 0  or place b o, will be 
i ncl u de d i n t he f ull a nal ysis set.  Data fr o m patie nts i n F A S will be use d f or efficac y, safet y, a n d 
p har mac o d y na mic  ( P D) a nal ys es.  H o we ver, f or p har mac o ki netic  ( P K) a nal ysis, o nl y data fr o m patie nts 
recei vi n g A L X N 2 0 4 0  will be utilize d.  
7  St ati st i c al A n al y s e s 
Statistical a nal yses  a n d data pres e ntati o ns  are perf or me d usi n g t he usi n g St atistical A nal ysis S yste m ®  
( S A S® ) Versi o n 9. 4 or hi g her ( S A S I nstit ute I nc., Car y, N C, U S A) or ot her vali date d statistical s oft ware. 
 
7. 1  G e n er al M et h o d s  
Data will be s u m marize d se parat el y f or t he 6-M o nt h Bli n de d Treat me nt Peri o d a n d O pe n -La bel 
E xte nsi o n a n d L o n g -Ter m F oll o w -u p Peri o ds.  
Data listi n gs  b y patie nt  i de ntificati o n will be pr o vi de d f or all data, i ncl u di n g efficac y, safet y, P D , a n d 
P K  para meters.   
T o s u m marize c o nti n u o us data, descri pti ve statistics will i ncl u de : n u m ber of patie nt s, mea n , sta n dar d 
de viati o n, me dia n, mi ni m u m , a n d ma xi m u m.   F or t he calc ulati o n of s u m mar y statistics a n d a nal ysis, 
u nr o u n de d data will be use d.  
T o s u m marize  cate g orical data,  fre q ue nc y c o u nts a n d perce nta ges will be prese nte d.  
O nl y  des cri pti ve statistical pr oce d ures , i ncl u di n g gra p hic prese ntati o ns, will be perf or me d o n  t h e 
efficac y, safet y, a n d ot her o utc o me meas ures, u nless ot her wise s pecifie d.   N o statistical c o m paris o ns 
b et wee n A L X N 2 0 4 0  a n d place b o will be pr o vi de d.    
Missi n g data f or Q o L i nstr u me nts will be ha n dle d as s pecifie d i n t he i nstr ucti o ns f or eac h i nstr u me nt 
(see A p pe n di x ).  All ot her data will be s u m marize d f or o bser ve d cases, wit h n o i m p utati o n f or missi n g 
data.  
Alt h o u g h t he st u d y is ra n d o mize d b y stratificati o n fact or of dis ease dia g n osis, statistical a nal ysis 
pr oce d ures a n d prese ntati o ns will n ot ta ke i nt o c o nsi derati o n t he stratificati o n fact or.  D ue t o s mall 
sa m ple size of t his st u d y, t he stratifie d ra n d o mizati o n pr ocess is utilize d t o bala nce t h e treat me nt 
assi g n me nts acr oss t he t w o disease dia g n oses.  


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L o n git u di nal s u m maries of efficac y a n d safet y para m eters use pre-def i ne d visit Wee k  / Da y as descri be d 
i n A p pe n di x 1, sc he d ule of assess me nt, of t he pr ot oc ol.   It s h o ul d be n ote d t hat s o me patie nts e nr olle d 
usi n g later versi o ns of pr ot oc ol a me n d me nts will ha ve re d uce d sc he d ule d visits.  L o n git u di nal s u m mar y 
prese ntati o ns m a y ha ve differe nt n u m ber of patie nts at vari o us sc he d ule d visits.   
F or l o n git u di nal s u m maries of data, wi n d o ws ar o u n d pla n ne d meas ure me nt ti mes are base d o n t h e 
mi d p oi nt bet wee n pla n ne d st u d y visits u nless s pecifie d ot her wise.   If t here are m ulti ple meas ure me nts 
wit hi n t he sa me wi n d o w , use t he val ue i n t he visit wi n d o w cl osest t o t he da y of t he pl a n ne d visit f or 
eac h ti me p oi nt (as d eter mi ne d b y t he a bs ol ute differe nce i n da ys bet wee n t he pla n ne d visit a n d t he 
c ollecti o n date, a n d t he a bs ol ute differe nce i n  da ys bet wee n t he pla n ne d visit a n d t he assa y date).   
F or la b orat or y test res ults, w he n b ot h l ocal a n d ce ntral la b orat or y val ues are c ollecte d o n t he sa me date, 
t he ce ntral la b orat or y val ue will be use d.  
Baseli ne val ues f or effi cac y / P D a n d s afet y para m e ters are defi ne d as t he last meas ure me nt, i ncl u di n g 
u nsc he d ule d visits, pri or t o first d ose of st u d y dr u g .  
7. 2  St u d y P o p ul ati o n  
7. 2. 1  P ati e nt  Di s c o nti n u ati o n a n d Di s p o siti o n  
T he patie nt  dis p ositi o n s u m mar y ta ble(s) will i ncl u de t he f oll o wi n g:  
 N u m ber of patie nts ( ra n d o mize d /  treate d) 
 N u m ber of patie nts  w h o  c o m plete d 2 8 wee ks  of d osi n g  
 Reas o ns f or n ot c o m pleti n g 2 8 wee ks of d osi n g  
 F or patie nts e nt eri n g o pe n -la bel peri o d of t he st u d y:  
o  N u m ber of patie nts w h o ha ve reac he d Wee k 5 2  
o  Reas o ns f or n ot c o m pleti n g t he o pe n -la bel st u d y peri o d 
 F or patie nts e nt eri n g d os e ta peri n g p hase of t he st u d y:  
o  N u m ber of patie nts w h o c o m plete d d ose ta peri n g  
o  Reas o ns f or n ot c o m pleti n g d ose t a peri n g  
I n a d diti o n, a s u m mar y of st u d y visits will be pr o vi de d i ncl u di n g t he n u m ber of patie nts w h o c o m plet e 
eac h visit as pla n ne d a n d t he n u m ber of patie nts w h o c o m plete m o difie d st u d y visits.  A patie nt listi n g 
will detail t he reas o n f or m o difie d visit as well as t he assess me nts t hat were m o difie d a n d t he 
m o dificati o n.  
7. 2. 2  D e m o gr a p hi c a n d B a s eli n e C h a r a ct eri sti c s  
T he f oll o wi n g de m o gra p hic a n d baseli ne c ha racteristics will be s u m marize d b y A L X N 2 0 4 0  a n d 
place b o : 
 de m o gra p hics: a ge, ge n der, race, c o u ntr y  


Ale xi o n P har mace uticals  
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 p h ysical meas ure m e nt at baseli ne: hei g ht, wei g ht, B MI , B P 
 disease c haracteristics at baseli ne: diseas e dia g n osis, d urati o n of t he disease, bi o ps y res ults , 
pr otei n uria, e G F R  
 selecte d P D mar kers a n d la b orat or y tests at baseli ne : 2 4 -h o ur uri ne pr otei n, 2 4 -h o ur 
pr otei n/creati ni ne, 2 4 -h o ur al b u mi n/creati ni ne, s p ot uri ne pr otei n/creati ni ne, s p ot uri ne 
al b u mi n/creati ni ne, ser u m al b u mi n, a n d ser u m creati ni ne. 
 pri or me dicati o ns : use of A C E i n hi bit ors or A R B dr u gs or im m u n os u p pressi o n (I S) me dicati o ns . 
 
7. 2. 3  M e di c al Hi st or y  
Me dical hist or y will be c o de d wit h t he m ost c urre nt versi o n of Me dical Di cti o nar y f or Re g ul at or y 
A cti vities ( Me d D R A ®)  a n d will be  s u m marize d b y preferre d t er m a n d s yst e m or ga n class b y treat m e nt 
gr o u p of A L X N 2 0 4 0  a n d place b o . 
7. 3  E xt e nt of E x p o s ur e   
Treat me nt d urati o ns will be c o m p ute d f or eac h patie nt as (last date of d ose  –  first date of d ose + 1).  T he 
last date of d ose will be t he e n d date of 1 2 -m o nt h treat me nt peri o d.   
If patie nts e nter t he 7-da y d ose ta per sc he d ul e, d urati o n of ta peri n g d osi n g peri o d ma y als o be pr o vi de d  
as a se parate c o m p utati o n .  T he d urati o n will be calc ulate d si milarl y as (la st date of ta per d ose –  first 
date of ta per d ose + 1).  
Treat me nt d urati o n will be s u m marize d b y A L X N 2 0 4 0  a n d place b o.  
C o m plia nce wit h st u d y dr u g was c ollecte d as n u m ber of ta blets dis pe nse d a n d n u m ber of ta blets 
ret ur ne d be gi n ni n g i n J ul y 2 0 1 9, after patie nts ha d alrea d y bee n e nr olle d a n d c o m plete d st u d y visits. T he 
n u m ber of ta blets ta ke n d uri n g t his ti me peri o d will be deri ve d fr o m t he n u m ber rec or de d as dis pe nse d 
at t he c urre nt visit mi n us t he n u m ber rec or de d as ret ur ne d at t he ne xt c o nsec uti ve visit.  A patie nt listi n g 
of n u m ber of ta blets ta ke n b y visits d uri n g t his ti me peri o d will be pr o vi d e d b y treat me nt gr o u p.  A 
se parat e patie nt listi n g will be pr o vi de d i ncl u di n g st u d y dr u g c o m plia nce d uri n g t his ti me peri o d as 
deri ve d b y:  
    
C o m plia nce = ( # ta blets t a ke n / # ta blets assi g ne d) * 1 0 0.  
I n a d diti o n, a s u m mar y of misse d d oses d ue t o C O VI D-1 9 will be pr o vi d e d b y treat me nt gr o u p.  
7. 4  C o n c o mit a nt M e di c ati o n s  
C o nc o mita nt me dicat i o ns are s u m marize d b y A L X N 2 0 4 0  a n d place b o. T hese are me dicati o ns ta ke n a n y 
ti me o n or after t he first acti ve d ose of st u d y t hera p y. Me di cati o ns are prese nte d al p ha beticall y b y 
a nat o mic class, t hera pe utic class a n d ge neric na me usi n g t he  m ost rece nt versi o n of  W H O dicti o nar y.  
Se parate s u m mar y t a bles ma y be pr o vi de d f or all o wa ble c o nc o mita nt  me dicati o ns f or C 3 G patie nts.  


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7. 5  Effi c a c y  a n d P D M ar k er s  A s s e s s m e nt  
7. 5. 1  A n al y si s of Pri m ar y  Effi c a c y  O ut c o m e M e a s ur e s  
T he a nal ysis met h o ds descri be d bel o w utilize data fr o m patie nts i n F A S.  
 C o m p osite Bi o ps y Sc ore    
C ha n ge  a n d perce nt c ha n ge  fr o m baseli ne f or t he c o m p osite bi o ps y sc ore at t he e n d of 6 m o nt hs a n d 1 2 
m o nt hs of treat me nt will be c o m p ute d f or eac h patie nt.  
Differe nce i n m ea n c ha n ges  fr o m baseli ne bet wee n  A L X N 2 0 4 0  a n d place b o gr o u p  will be  prese nte d.  
Mea ns fr o m ori gi nal sc ores at baseli ne a n d eac h visit will als o be prese nte d . 
Pr otei n uri a  
N u m ber a n d perce nt of patie nts wit h re d ucti o n i n pr otei n u ria rel ati ve t o baseli ne as defi ne d i n s ecti o n 
3 . 1. 3 will be s u m marize d b y A L X N 2 0 4 0  a n d place b o.  
I n a d diti o n t o t he pri mar y a nal ysis of t he pri mar y efficac y e n d p oi nts, a se nsiti vit y a nal ysis will be 
perf or me d e xcl u di n g pati e nts w h o ha d m o difie d assess me nts d ue t o C O VI D -1 9 t o assess t he r o b ust ness 
of t he res ults.  
7. 5. 2  A n al y si s of S e c o n d ar y  Effi c a c y  O ut c o m e M e a s ur e s  
I n a d diti o n, cha n ge a n d perce nt c ha n ge fr o m baseli n e f or pr otei n uria fr o m a 2 4 -h o ur s peci me n  at eac h 
visit  will be c o m p ute d f or eac h patie nt  base d o n 2 4 h o ur uri ne pr otei n, 2 4 h o ur uri ne al b u mi n, 2 4 h o ur 
uri ne pr otei n/creati ni ne rati o, 2 4 h o ur uri ne al b u mi n/creati ni ne rati o, s p ot uri ne pr otei n/creati ni ne r ati o, 
a n d s p ot uri ne al b u mi n/creati ni ne rati o .   
Differe nce i n mea n c ha n ges fr o m baseli ne bet wee n A L X N 2 0 4 0  a n d place b o gr o u p will be prese nte d.  
Mea ns fr o m ori gi nal sc ores at baseli ne a n d eac h visit will als o be prese nte d.  
C ha n ge a n d perce nt c ha n ge fr o m ba seli ne f or e G F R at eac h pre-defi ne d ti me p oi nt will be c o m p ute d f or 
eac h patie nt.  
Differe nce i n mea n c ha n ges fr o m baseli ne bet wee n A L X N 2 0 4 0  a n d place b o gr o u p will  als o be 
prese nte d.  
N u m ber a n d perce nt of patie nts wit h si g nifica nt i m pr o ve me nt relati ve t o ba seli ne (ie, ≥2 0 % i n crease 
fr o m baseli ne) i n e G F R will be s u m marize d b y A L X N 2 0 4 0  a n d place b o f or eac h visit . 
As state d i n Secti o n 3. 1. 4, descri pti ve a nal ysis o n sl o pe of e G F R o ver 6-m o nt h bli n de d treat me nt peri o d 
w ill be perf or me d.  Gra p hic prese ntati o n o n e G F R meas ure me nts o ver ti me will be pr o vi de d t o o bser ve 
t he tre n d a n d pr ofile of t he effect of A L X N 2 0 4 0  o n c ha n ge of e G F R.  T he ti me -meas ure me nt gra p h will 
be pr o vi de d f or eac h pati e nt.  Mea n ti me -meas ure me nt gra p h b y treat me nt, A C H 0 1 4 4 4 7 1 a n d place b o, 
wil l als o be a vaila ble f or vis ual e xa mi nati o n a n d i nter pretati o n. 


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T he descri pti ve meas ure of sl o pe will be esti mate d usi n g a si m ple li near re gressi o n f or eac h patie nt wit h 
e G F R as t he de pe n de nt varia ble a n d ti me as t he i n de pe n de nt varia ble.  T he mea n sl o pe  ( m L/ mi n/ 1. 7 3 m 2 
per m o nt h)  will be s u m marize d descri pti vel y b y treat me nt gr o u p.  
I n a d diti o n, t he n u m ber a n d perce nt a ge of patie nts w h o ac hie ve t he f oll o wi n g res p o nse stat uses will be 
s u m marize d at t he e n d of 6 m o nt hs a n d at t he e n d of 1 2 m o nt hs b y A L X N 2 0 4 0  a n d place b o:  
 C o m plete res p o nse, defi ne d as pr otei n uria < 5 0 0 m g/ d base d o n 2 4 -h o ur uri ne sa m ples pl us sta ble 
e G F R (ie, l ess t ha n 2 5 % decrease fr o m baseli ne)   
 Partial res p o nse, defi ne d as ≥3 0 % decrease fr o m b aseli ne i n pr otei n uria  b ut n ot < 5 0 0 m g/ d base d o n 
2 4 -h o ur uri ne sa m ples pl us sta ble e G F R (ie, less t ha n 2 5 % decrease fr o m b aseli ne)  
 W orse ni n g, defi ne d as > 2 5 % decrease fr o m baseli ne i n e G F R or > 3 0 % i ncrease fr o m baseli ne i n 
pr otei n uria  base d o n 2 4 -h o ur uri ne sa m ples  
T he n u m ber a n d perce nta ge of patie nts w h o ac hie ve partial res p o nse base d o n 2 4 -h o ur uri ne 
pr otei n/creati ni ne rati o a n d s p ot uri ne/ pr otei n creati ni ne rati o, defi ne d as ≥3 0 % decrease fr o m baseli ne 
i n pr otei n uria pl us sta ble e G F R (ie, l ess t ha n 2 5 % decrease fr o m baseli ne), will als o be s u m marize d at 
eac h visit b y treat me nt gr o u p.  
T he n u m ber a n d perce nta ge of patie nts w h o ac hie ve w orse ni n g base d o n 2 4 -h o ur uri ne 
pr otei n/creati ni ne rati o a n d s p ot uri ne/ pr otei n creati ni ne rati o, defi ne d as > 2 5 % decrease fr o m base li ne 
i n e G F R or > 3 0 % i ncreas e fr o m baseli ne i n pr otei n uria, will als o be s u m marize d at eac h visit b y 
treat me nt gr o u p. 
7. 5. 3  A n al y si s of Ot h er Effi c a c y O ut c o m e M e a s ur e a n d P D M ar k er s  
Ori gi nal val ues a n d c ha n ge s fr o m baseli ne at eac h pre-defi ne d ti me p oi nt will be  c o m p ute d f or eac h 
patie nt  a n d will be s u m marize d b y A L X N 2 0 4 0  a n d place b o  f or t he f oll o wi n g o utc o me m eas ures as 
liste d i n Secti o n 3. 1. 5. 
 A P acti vit y  
 C P acti vit y  
 Fact or D  
 C 3  
 C 4  
 B b  
 s C 5 b-9   
 
F or Wiesla b test res ults  ( A P acti vit y), o nl y ori gi nal val ues will be use d f or s u m mar y ta bles.   
G ra p hic prese ntati o ns f or t he l o n git u di nal data ma y  als o be pr o vi de d  f or t he a b o ve o utc o me meas ures if 
cli nicall y dee me d mea ni n gf ul.  
T he patie nt re p ort o utc o mes  ( P R O) i nstr u me nts liste d i n secti o n 3 . 1.5  will be descri be d i n t he  ne xt 
secti o n.   


Ale xi o n P har mace uticals  
A C H 4 7 1 -2 0 4: 1 5 Ma y 2 0 2 0 ( Versi o n 8)  
Statistical A nal ysis Pla n  
3 0 Oct o ber 2 0 2 0, Versi o n 5  
 
 
 
C o nfi de ntial  
Pa ge 2 0  of 3 3  
 
 
Secti o n 7 . 8 bel o w descri bes i n detail o n P K data prese ntati o n a n d a nal ysis  met h o ds.   
7. 6  P ati e nt R e p ort O ut c o m e s ( P R O)  
T hree P R O i nstr u me nts are use d t o e val uate ki d ne y disease a n d healt h relate d q ualit y of life o n patie nts 
wit h C 3 G.   T he f oll o wi n g secti o ns briefl y descri be t he utilit y a n d i nter pret ati o n of t hese i nstr u me nts.  
Details of c o m p uti n g a n d s u m marizi n g t he sc ores a n d/ or scales ca n be f o u n d i n t he res pecti ve user 
ma n uals.   
T he P R O prese ntati o ns utilize data fr o m patie nts i n F A S.  
7. 6. 1  K D Q O L -S F ™ v er si o n 1. 3  
T he ki d ne y disease q ualit y of life s h ort f or m ( K D Q O L -S F ™) is a wi del y use d healt h -relate d q ualit y of 
life ( H R Q O L) meas ure f or patie nts wit h c hr o nic ki d ne y diseases.  T he q uesti o n naire c o nsists of t he 
ge neric S F -3 6 as well as 1 1 m ulti -ite m scales f oc use d o n q ualit y of life iss ues s pecific t o patie nts wit h 
ki d ne y disease. T w o of t he ele ve n ( 1 1) s u bscales of t he ki d ne y disease ( K D) tar get e d areas are f or 
patie nts re q uiri n g  ki d ne y dial ysis  a n d, t heref ore, are e xcl u de d fr o m q uesti o n naire f or t his st u d y.  T he 
re mai ni n g 9 K D tar gete d areas are:  
 s y m pt o ms/ pr o ble ms 
 effects of ki d ne y dis eas e  
 b ur de n of ki d ne y disease  
 w or k stat us  
 c o g niti ve f u ncti o n  
 q ualit y of s oci al i nteracti o n  
 se x ual f u ncti o n  
 slee p  
 s ocial s u p p ort 
 
T he ge neric 3 6 -ite m healt h s ur ve y, S F-3 6, c o nsists of t w o c o m p o ne nt s u m maries wit h  t heir res pecti ve 
d o mai ns.  
 P h ysical C o m p o ne nt S u m mar y ( P C S)  
o  P h ysical f u ncti o ni n g  
o  R ole -p h ysical  
o  Pai n  
o  Ge neral healt h  
 M e ntal C o m p o ne nt S u m mar y ( M C S)  


Ale xi o n P har mace uticals  
A C H 4 7 1 -2 0 4: 1 5 Ma y 2 0 2 0 ( Versi o n 8)  
Statistical A nal ysis Pla n  
3 0 Oct o ber 2 0 2 0, Versi o n 5  
 
 
 
C o nfi de ntial  
Pa ge 2 1  of 3 3  
 
 
o  E m oti o nal well -bei n g  
o  R ole -e moti o nal  
o  S ocial f u ncti o n  
o  E ner g y/fati g ue  
 
T he q uesti o n naire ite ms i ncl u de d i n eac h of S F -3 6 d o mai ns  a n d K D tar gete d areas are liste d i n 
A p pe n di x 2.  
T he sc ori n g pr oce d ure f or t he K D Q O L -S F ™ first tra nsf or ms t he ra w pre -c o de d n u meric val u es of ite ms 
t o a 0-1 0 0 p ossi ble ra n ge, wit h hi g her tra nsf or me d ‘scale sc ores’ al wa ys reflecti n g better q ualit y of life.   
Eac h ite m is p ut o n a 0  t o 1 0 0 ra n ge s o t hat t he l o west a n d hi g hest p ossi ble sc ores are set at 0  a n d 1 0 0, 
res pecti vely.  Details of tra nsf or mi n g eac h ite m sc ore t o c orres p o n di n g scal e are pr o vi de d i n t he 
K D Q O L -S F user ma n ual.  
Ori gi nal val ues a n d c ha n ge fr o m baseli ne val ues o ver ti me will be s u m marize d b y treat me nt gr o u p at 
pr ot oc ol -s pecifi e d ti me p oi nts. Patie nt  listi n gs o n sc ore scales will be pr o vi de d f or eac h of K D tar gete d 
areas a n d S F-3 6 d o m ai ns.   
7. 6. 2  F A CI T F ati g u e S c al e ( V er si o n 4)  
T here are 1 3 ite ms i n t he F A CI T Fati g ue scale q uesti o n naire.   Eac h ite m i ncl u des 5  p ossi ble  res p o nses, 
0 -4, wit h  0  bei n g “ N ot at all ” a n d 4 bei n g “ V er y m uc h”.  T otal sc ore fr o m t hese 1 3 ite ms will be 
pr o vi de d f or eac h patie nt at eac h pr ot oc ol pre -defi ne d ti me p oi nts.  
Ne gati vel y state d ite ms m ust be re verse d bef ore bei n g a d de d t o o btai n t he scale t otal sc ore.  T heref ore, 
t he ne gati vel y s tate d ite ms will be  re verse d b y s u btracti n g t h e res p o ns e fr o m “ 4”.  N ote t hat all ite ms, 
e xce pt f or ite ms # 7 a n d # 8, are ne gati vel y state d.  
T he F A CI T Fati g ue s cale a n d t he cal c ulati o n of t otal sc ore are prese nte d i n A p pe n di x 3  of t his 
d oc u me nt .  N ote t hat t he t otal sc ore ra n ge is 0 t o 5 2, wit h hi g her t otal sc ore d i n dicati n g better q ualit y of 
life. 
Ori gi nal val ues a n d c ha n ge fr o m baseli ne val ues o ver ti me will be s u m marize d b y treat me nt gr o u p at 
pr ot oc ol -s pecifi e d ti me p oi nts. Patie nt  listi n gs f or t otal sc ore a n d c ha n ge fr o m baseli ne i n t otal sc ore will 
be pr o vi de d f or pr ot oc ol -s pecifie d ti me p oi nts.  
7. 6. 3  E Q -5 D -3 L  
T he  self-re p orte d q uesti o n naire  E Q -5 D -3 L has t w o parts.   T he first part is a descri pti ve s yste m  wit h 5 
di me nsi o ns : m o bilit y, s elf-care, us ual acti vities, pai n / disc o mf ort, a n d a n xiet y / de pressi o n.  Eac h 
di me nsi o n has t hree res p o nse le vels, 1, 2, a n d 3, re prese nti n g “ n o pr o ble ms”, “s o me pr o ble ms”, a n d 
“e xtre me pr o ble ms”, res pecti vel y.   A  sc ori n g f u ncti o n ca n be use d t o c o n vert t he self -re p ort e d 
descri pti ve s yste m  t o a si n gle s u m mar y i n d e x ( E Q-5 D I n de x sc ore) t hr o u g h  a set of p o p ulati o n -base d 
prefere nce wei g hts.  


Ale xi o n P har mace uticals  
A C H 4 7 1 -2 0 4: 1 5 Ma y 2 0 2 0 ( Versi o n 8)  
Statistical A nal ysis Pla n  
3 0 Oct o ber 2 0 2 0, Versi o n 5  
 
 
 
C o nfi de ntial  
Pa ge 2 2  of 3 3  
 
 
T he sec o n d part is a vis ual a nal o g scal e ( V A S) w hic h rec or ds patie n t's self-rate d healt h stat us o n a 
gra d uate d ( 0 – 1 0 0) scale, wit h hi g her sc ores f or hi g her heat h relate d q ualit y of life .  T he E Q -5 D, 
t heref ore, pr o d uces t hree t y pes of data f or eac h patie nt:  
 a pr ofile i n dicati n g t he e xte nt of pr o ble ms o n eac h of t he fi ve di me nsi o ns;  
 a p o p ulati o n prefere nce -wei g ht e d healt h i n de x sc ore base d o n t h e descri pti ve s yste m;  
 a self-re p orte d assess me nt of healt h stat us base d o n t he E Q-V A S  
 
F or t his st u d y, t he U. S. p o p ulati o n wei g hts will be use d t o c o n vert t he descri pti ve s yste m t o a n E Q -5 D 
i n de x sc ore o n a scale w here 1. 0 = perfect healt h a n d 0 = deat h. 
Ori gi nal val ues a n d c ha n ge fr o m baseli ne val ues o ver ti me will be s u m marize d b y treat me nt gr o u p at 
pr ot oc ol -s pecifi e d ti me p oi nts. Patie nt  listi n gs will be pr o vi de d f or t he res p o nses of 5-di me nsi o n 
descri pti ve s yste m, E Q -5 D -V A S, a n d U. S. p o p ulati o n -base d E Q -5 D i n de x.  
7. 7   S af et y A s s e s s m e nt   
E val uati o n of safet y  i n cl u des assess me nt of t he f oll o wi n g cli nical para meters a n d will be descri be d i n 
det ail i n t he s u bse q ue nt s u bsecti o ns .  S afet y data c ollecte d  d uri n g bli n de d  treat me nt peri o d of t h e st u d y  
( u p t o a n d i ncl u de Wee k 2 8 visit) will be  s u m marize d se paratel y fr o m safet y dat a c ollecte d d uri n g t he 
o pe n -la bel treat me nt peri o d.  S electe d cli nical la borat or y  para meters  will be s u m marize d .  H o we ver, all 
la b orat or y test res ults will be i ncl u de d i n t he listi n gs. 
1.  Treat me nt e mer ge nt a d verse e ve nts  (t otal as well as as relate d v ers us u nrelate d) , i ncl u di n g 
disc o nti n uati o n s d ue t o a d verse e ve nt  
2.  Cli nical la b ora t or y para meters 
3.  1 2 -lea d E C G 
4.  Vital si g ns  
5.  B o d y wei g hts  
6.  P h ysical fi n di n gs  
 
I n a d diti o n, a listi n g of patie nts wit h k n o w n e x p os ure t o C O VI D-1 9 will be pr o vi de d.  
 
7. 7. 1  Tr e at m e nt -E m er g e nt A d v er s e E v e nt s ( T E A E)  
A d verse e ve nts ( A Es) will be c o de d wit h t he m ost c urre nt  versi o n of Me dical Dicti o nar y f or R e g ulat or y 
Acti vities ( Me d D R A ®).  
A treat me nt -e mer ge nt a d verse e ve nt ( T E A E) is defi ne d as a n A E t hat e mer ges d uri n g treat me nt  wit h 
A L X N 2 0 4 0  or place b o , ha vi n g bee n a bse nt pre-treat me nt, or w orse ns relati ve t o t he pre-treat me nt st ate.   


Ale xi o n P har mace uticals  
A C H 4 7 1 -2 0 4: 1 5 Ma y 2 0 2 0 ( Versi o n 8)  
Statistical A nal ysis Pla n  
3 0 Oct o ber 2 0 2 0, Versi o n 5  
 
 
 
C o nfi de ntial  
Pa ge 2 3  of 3 3  
 
 
If a n A E t hat was re p orte d d uri n g treat me nt i ncreases i n se verit y, t he n t hat A E is gi ve n a res ol uti o n date 
a n d ti me a n d a ne w rec or d i nitiate d wit h t he ne w se verit y.  If t he se verit y of a n A E re m ai ns t he sa me or 
decreases, t he A E will be ke pt o pe n t hr o u g h t o res ol uti o n , reflecti n g t he ma xi m u m se verit y.  
A Es will be liste d b y pati e nt  i ncl u di n g preferre d t er m, ver bati m ter m, s yste m or ga n class ( S O C), da ys 
fr o m first d os i n g date, o nset a n d res ol uti o n dates/ti mes, d urati o n, fre q ue nc y, se verit y, seri o us ness, 
o utc o me, acti o n ta ke n, a n d relati o ns hi p t o  st u d y dr u gs .  
T E A Es will be s u m marize d b y preferre d ter m a n d S O C b y treat me nt gr o u p f or t he n u m ber of patie nt s 
re p orti n g t he T E A E, t he n u m ber of T E A Es re p orte d, a n d t he n u m ber of e ve nts b y se verit y a n d 
relati o ns hi p t o st u d y dr u gs.  I n a d diti o n, T E A Es will be s u m marize d b y decreasi n g or der of fre q ue nc y .  
S u m maries of T E A Es i ncl u de b ot h n o n -seri o us a n d S A Es as defi ne d i n t he pr ot oc ol.  A d diti o nall y, all 
S A E s, re gar dless of treat me nt e mer ge nt or n ot, will be liste d i n ta b ulate d f or m.  S u m mar y of all S A Es, 
re gar dless of treat me nt e mer ge nt or n ot, will be pr o vi de d if necess ar y , f or ease of i nter pretati o n of t he 
data.   A Es wit h missi n g s e v erit y are i ncl u de d o nl y i n s u m maries of all se verit y gra des (relate d or 
re gar dless of rel ati o ns hi p t o st u d y dr u g).  If a patie nt  ha d a n A E wit h differe nt se verities d uri n g 
treat me nt, t he n o nl y t he greatest se verit y is re p orte d, u nless ot her wise s pecifie d. 
It is n ot a ntici pate d t o e nc o u nter A E wit h missi n g start date i n t his st u d y.  A n y A E wit h missi n g start 
date  will be treat e d as T E A E .   
All e ve nts ca pt ure d i n t he data bas e will be liste d i n b y -patie nt  data listi n gs.  H o we ver, o nl y T E A Es will 
be s u m marize d.   Se parat e patie nt  listi n gs will be pr o vi de d f or T E A Es a n d pre-treat me nt A Es.  If a n y 
patie nts re p ort k n o w n e x p os ure t o C O VI D -1 9 d uri n g t he st u d y, a listi n g of all a d verse e ve nts 
e x perie nce d b y t hese pati e nts will be pr o vi de d se paratel y.   
S h o ul d a n y seri o us a d verse e ve nts ( S A Es) or disc o nti n uati o n  of st u d y dr u g  d ue t o a d verse e ve nts ( T E A E 
or S A E) occ ur, patie nt  listi n gs f or s uc h a d verse e ve nts will be dis pla ye d i n a ta b ulate d f or mat a n d 
narrati ves will be i ncl u de d i n t he st u d y re p ort.  If n o s uc h e ve nt occ urs d uri n g t he st u d y, t he ta bles 
s h o ul d pr o vi de a state me nt clearl y i n dicati n g as s u c h, e. g. ‘ N o S A E  re p orte d’, ‘ N o T E A E le d t o 
disc o nti n uati o n  of st u d y dr u g ’. 
7. 7. 2  Cli ni c al L a b or at or y P ar a m et er s  
Descri pti ve statistics will be pr o vi de d, at a mi ni m u m, f or t he f o ll o wi n g l a b orat or y test res ults of 
he mat ol o g y, ser u m c he mistr y, uri nal ysis , a n d c oa g ulati o n tests  as liste d i n Ta ble 6  of t he pr ot oc ol. 
Descri pti ve statistics ma y be pr o vi de d f or a d diti o nal la b orat or y para meters, if cli nicall y warra nte d.  
 he mat ocrit ( Hct),  he m o gl o bi n ( H g b),  mea n c or p usc ular v ol u me ( M C V), platelet c o u nt,  a n d W B C 
c o u nt   
 all c he mistr y l a b orat or y t est res ults  
 p H, s pecific gra vit y  
 P T/ P T T/I N R  
 


Ale xi o n P har mace uticals  
A C H 4 7 1 -2 0 4: 1 5 Ma y 2 0 2 0 ( Versi o n 8)  
Statistical A nal ysis Pla n  
3 0 Oct o ber 2 0 2 0, Versi o n 5  
 
 
 
C o nfi de ntial  
Pa ge 2 4  of 3 3  
 
 
Le vels a n d c ha n ges fr o m baseli ne i n  t he la b orat or y meas ure me nts will  be  s u m marize d at baseli ne a n d at 
pre -defi ne d  visits  b y treat me nt gr o u p .  Baseli ne is t he last assess me nt bef ore  t he first d ose of st u d y dr u g, 
i ncl u di n g u nsc he d ul e d assess me nts.  
As n ote d i n Secti o n 7. 1, w he n b ot h l ocal a n d ce ntral la b orat or y val ues are c ollecte d o n t he sa m e dat e, 
t he ce ntral la b orat or y val ue will be use d.  La b orat or y para m eters are s u m m arize d base d o n  val u es a n d 
u nits  fr o m la b orat or y re p orts.  Selecte d la b para m eters ma y be c o n verte d t o SI or U S  sta n dar d u nits, as 
cli nicall y dee me d a p pr o priate .  La b orat or y a b n or malities ar e deter mi ne d fr o m la b orat or y meas ure me nts 
a nal yze d at t he ce ntral or l ocal la b orat or ies a n d are gra de d usi n g C o m m o n Ter mi n ol o g y Criteria f or 
A d verse E ve nts  ( C T C A E), as pres e nte d i n A p pe n di x 1 of t his d oc u me nt. 
F or la b orat or y tests wit h C T C A E  t o xicit y gra des a vaila ble, la b orat or y a b n or malities are s u m marize d b y 
w orst treat me nt -e mer ge nt gra de [treat me nt e mer ge nt ( T E) la b a b n or malities].  F or tests t hat ha ve 
C T C A E  t o xicit y gra des i n b ot h hi g h a n d l o w directi o ns, e. g. ser u m gl uc ose, etc., t he s u mmar y t a ble 
s h o ul d s pecif y se paratel y f or t he T E a b n or malities as bei n g hi g h or bei n g l o w i n t o xicit y gra des.  N ote 
t hat t he p ost-baseli ne la b orat or y val ue wit h t he hi g hest treat me nt -e m er ge nt t o xicit y gra de is re p orte d f or 
eac h test.  
S hift ta bles will be pr o vi de d f or li ver f u ncti o n test ( L F T) res ults a n d ot her selecte d la b orat or y test res ults 
base d o n C T C A E gra des.  I n a d diti o n, s hift ta bles base d o n m ulti ple of u p per li mit n or mal  (U L N ) will 
als o be pr o d uce d f or L F T meas ure me nts .  
La b orat or y a b n or malities d u ri n g treat me nt peri o d will be f urt her s u m marize d b y baseli ne t o xicit y gra de 
a n d treat me nt t hera p y (s hift ta bles) . 
E x pl orat or y gra p hi c pres e ntati o ns ma y be pr o vi de d w he n data i n dicate t hat s uc h a nal yses are 
a p pr o priate a n d cli nicall y mea ni n gf ul.  
7. 7. 3  1 2 -l e a d E C G 
Patie nt  listi n g will be pr o vi de d f or E C G para meters: H R, R R, P R i nter val, Q R S i nter val, Q T i nter val, 
a n d Q Tc F.  T he a b n or mal a n d cli nicall y si g nifica nt fi n di n gs will als o be i ncl u de d i n t he listi n g.  
Val ues a n d c ha n ges fr o m baseli ne i n E C G meas ure me nts are  s u m marize d at baseli ne a n d at eac h 
sc he d ule d ti me p oi nts f or t he t w o treat me nt gr o u ps.  Baseli ne E C G is t he last assess me nt bef ore first 
d ose of st u d y dr u g.  
E C G res ults will als o be classifie d as n or mal, a b n or mal ( n ot cli nicall y si g nifica nt), a n d a b n or mal  
(cli nicall y si g nifica nt).  S u m mar y ta ble will be pr o vi de d f or cli nicall y si g nifica nt a b n or malities b y 
treat me nt gr o u p.  If n o cli nicall y si g nifica nt a b n or malities are f o u n d, t he ta ble s h o ul d state ‘ N o cli nicall y 
si g nifica nt E C G a b n or malit y re p orte d’. 
T he treat me nt-e mer ge nt ( T E) E C G e ve nts i n dicat e t hat t he a b n or malit y / pr ol o n gati o ns were n ot prese nt 
at baseli ne.  T E a b n or malities will be s u m marize d f or t he f oll o wi n g para meters.  N ote t hat T E Q Tc F 
i nter val a b n or malities are base d o n m o difie d C T C A E criteria.  
 Treat me nt -e mer ge nt ( T E) P R i nter val  > 2 0 0 msec;  


Ale xi o n P har mace uticals  
A C H 4 7 1 -2 0 4: 1 5 Ma y 2 0 2 0 ( Versi o n 8)  
Statistical A nal ysis Pla n  
3 0 Oct o ber 2 0 2 0, Versi o n 5  
 
 
 
C o nfi de ntial  
Pa ge 2 5  of 3 3  
 
 
 T E Q Tc F i nter val:  
o  Gra de 1: 4 5 0 –  4 8 0 msec  
o  Gra de 2: 4 8 1 –  5 0 0 msec  
o  Gra de 3: ≥ 5 0 1 msec or > 6 0 msec c ha n ge fr o m baseli ne  
T he ma xi m u m i nter val ( or i ncrease fr o m b aseli ne) d uri n g bli n de d trea t me nt peri o d is re p orte d f or eac h 
E C G  para meter . 
 
7. 7. 4  Vit al Si g n s  a n d B o d y W ei g ht s  
Patie nt  listi n g will be pr o vi de d f or vital si g ns para meters: b o d y t e m perat ure, s yst olic a n d diast olic bl o o d 
press ures  i n tri plicate, heart rate, a n d res pirati o n rate.  F or s yst o lic a n d di ast olic bl o o d press ures, avera ge 
of  tri plicate rea di n gs will be c o m p ute d f or eac h ti me p oi nt.  
B o d y wei g hts  are ta ke n at t he sa me ti me p oi nts as vital si g ns a n d will be i n cl u de d i n t he listi n g.  
S u m mar y of c ha n ges fr o m baseli ne at i n di vi d ual ti me p oi nts will be pr o vi de d f or eac h para meter of vital 
si g ns a n d b o d y wei g ht.  Bl o o d press ures, b ot h s yst olic a n d diast olic, are of partic ular i nterest f or C 3 G 
patie nts.   A d diti o nal a nal ysis a n d prese ntati o ns ma y be re q uire d if cli nicall y dee me d mea ni n gf ul.   
7. 7. 5  P h y si c al E x a m  
Data c ollecte d fr o m p h ysical e xa ms, b ot h c o m plete a n d brief, will be liste d b y patie nt a n d b y ti me 
p oi nts, i ncl u di n g u nsc he d ule d visit ti me p oi nts.  
7. 8  P h ar m a c o ki n eti c ( P K) A s s e s s m e nt s  
P K assess me nts will be perf or me d o n pl as ma c o nce ntrati o ns fr o m patie nts  i ncl u de d i n P K a nal ysis set 
w h ose P K pr ofiles ca n be deter mi ne d.  
7. 8. 1  P K P ar a m et er s  
P K para meters fr o m plas ma c o nce ntrati o ns f or A L X N 2 0 4 0  will be calc ulate d usi n g a n o n -
c o m part me ntal a p pr oac h base d o n t he c o nce ntrati o n v ersus  ti me data. T he para meters liste d i n t he ta ble 
bel o w will be o btai ne d usi n g P h oe ni x Wi n N o nli n ® Versi o n 6. 4 or hi g her, as data per mit.   
Patie nt s f or w h o m t here is i ns ufficie nt data t o calc ulate t he P K para m eters will ha ve a vaila ble data 
i ncl u de d i n t he c o nce ntrati o n ta bles wit h descri pti ve statistics o nl y.  
F or t he calc ulati o n of t he P K para meters, c o nce ntrati o ns t hat are bel o w t h e l o wer li mit of q ua ntificati o n 
( B L Q) pri or t o t he T ma x will be set t o 0 a n d t h ose t hereafter as missi n g. C o nce ntrati o ns t hat are missi n g 
or n ot re p orta ble will be treate d as missi n g val ues. F or c o nce ntrati o n s u m mar y statistics, c o nce ntrati o ns 
t hat are B L Q will be set t o 0.  At least 3 ti me p oi nts wit h meas ura ble c o nce ntrati o n will be re q uire d f or 
t he calc ulati o n of A U C. 


Ale xi o n P har mace uticals  
A C H 4 7 1 -2 0 4: 1 5 Ma y 2 0 2 0 ( Versi o n 8)  
Statistical A nal ysis Pla n  
3 0 Oct o ber 2 0 2 0, Versi o n 5  
 
 
 
C o nfi de ntial  
Pa ge 2 6  of 3 3  
 
 
F or Da y 1 0 , t he f oll o wi n g P K para meters will be esti mate d: 
P ar a meter     
Defi niti o n/ C alc ul ati o n  
A U C ta u    
Area u n der t he plas ma c o nce ntrati o n -ti me c ur ve fr o m ti me of a d mi nistrati o n t o 
t he e n d of d osi n g i nter val , calc ulate d b y li near tra pez oi dal s u m mati o n 
C ma x  
Ma xi mal plas ma c o nce ntrati o n  
C tr o u g h 
Plas ma tr o u g h ( pre -d ose) c o nce ntrati o n o ver t he d osi n g i nter val f or t he first 
dail y d ose  
T ma x  
Ti me t o reac h t he ma xi mal plas ma c o nce ntrati o n  
C L/ F     
A p pare nt oral dr u g cleara nce d uri n g a d osi n g i nter val, calc ulate d as 
D ose/ A U C ta u 
 
A U C val ues will be esti mate d usi n g t he li near tra pez oi dal r ule. Act ual sa m pli n g ti mes relati ve t o d osi n g 
will be use d i n t he c o m p utati o n.  
U nless ot her wise s pecifie d bel o w, missi n g sa m pli n g or c o nce ntrati o n val ues s h o ul d n ot be i m p ute d, b ut 
left missi n g i n t he calc ulati o n of deri ve d P K para meters. If t he act ual sa m pli n g ti me is missi n g, b ut a 
vali d c o nce ntrati o n val ue has bee n meas ure d, t he sc he d ule d pr ot oc ol ti me will be use d f or t he 
calc ulati o n of deri ve d P K para meters.  
O n a cas e b y cas e basis, it m a y be necessar y t o e xcl u de i n di vi d ual P K c o nce ntrati o n val ues f or t he 
calc ulati o n of deri ve d P K para meters beca use t h e y are err o ne o us, a b n or mal or a p pear i m pla usi ble t o t he 
p har mac o ki neticist i n c har ge of t he a nal ysis. A n y e xcl u de d data will be fla g ge d i n t he i n di vi d ual data 
listi n gs. T he reas o n f or e xcl usi o n will als o be d oc u me nte d. If t he e xcl usi o n has a mea ni n gf ul i m pact o n 
t he o verall i nter pretati o n of t he res ults, t he n it will be disc usse d. 
Act ual p ost -d ose ti me will be use d i n calc ulati o n of P K para me t ers a n d i n t he ge nerati o n of i n di vi d ual 
c o nce ntrati o n -ti me pr ofiles. Sc he d ule d ( n o mi nal) sa m pli n g ti mes will be use d as a re place me nt f or 
u n k n o w n or missi n g act ual ti mes a n d will be use d f or t he pre -d ose val ues. N o mi nal sa m pli n g ti mes will 
be use d i n t he ge nerati o n of s u m mar y c o nce ntrati o n -ti me pr ofiles a n d the c o nce ntrati o n -ti me listi n gs. 
I n a d diti o n, t he tr o u g h c o nce ntrati o ns at pr ot oc ol s pecifie d visits  will be pr o vi de d.  
7. 8. 2  P K A n al y si s  
I n di vi d ual P K para meters will be liste d. Descri pti ve statistics ( n u m ber of n o n-missi n g o bser vati o ns ( N), 
arit h metic mea n, S D, me dia n, c oefficie nt of variati o n ( C V %), mi ni m u m, ma xi m u m, ge o metric mea n 
a n d ge o metric C V %) will be use d t o s u m marize t he calc ulat e d P K para meters of A L X N 2 0 4 0 . 
I n di vi d ual c o nce ntrati o n pr ofiles wit h act ual p ost-d ose ti me will be liste d. Descri pti ve s u m mar y 
statistics ( N, arit h metic mea n, S D, me dia n, C V %, mi ni m u m, ma xi m u m, ge o metric mea n a n d ge o m etric 
C V %) will be use d t o s u m marize t h e c o nce ntrati o n pr ofiles.  
I n di vi d ual ti me-c o nce ntrati o n gra p hs will be pr o vi de d f or eac h patie nt  i n b ot h li near a n d se mi-l o g 
scales. Mea n ti me-c o nce ntrati o n gra p hs will als o be pr o vi de d.  


Ale xi o n P har mace uticals  
A C H 4 7 1 -2 0 4: 1 5 Ma y 2 0 2 0 ( Versi o n 8)  
Statistical A nal ysis Pla n  
3 0 Oct o ber 2 0 2 0, Versi o n 5  
 
 
 
C o nfi de ntial  
Pa ge 2 7  of 3 3  
 
 
7. 8. 3  P r e-D o s e C o n c e ntr ati o n s ( P K Tr o u g h s)  
All i n di vi d ual pre -d ose plas ma c o nce ntrati o ns (tr o u g hs) will be liste d. Descri pti ve statistics ( n u m ber of 
n o n -missi n g o bser vati o ns ( N), arit h metic mea n, S D, me dia n, c oefficie nt of variati o n ( C V %), mi ni m u m, 
ma xi m u m, ge o metric mea n  a n d ge o metri c C V %) will be use d t o s u m marize t he se c o nce ntrati o ns of 
A L X N 2 0 4 0 . 
8  C h a n g e s fr o m Pr ot o c ol S p e cifi e d A n al y si s  
T he pr ot oc ol s pecifies usi n g t w o -sa m ple t-t est f or c o nti n u o us o utc o me meas ures a n d Fis her’s E xact test 
f or cat e g orical o utc o m e meas ures t o c o m pare t he differe nce bet wee n A L X N 2 0 4 0  a n d place b o.  N i n et y-
fi ve perce nt ( 9 5 %) c o nfi de nce i nter vals are als o p art of i nfere ntial statistical met h o d ol o gies t hat pr ot oc ol 
s pecifies.  As des cri be d i n Secti o n 1 O ver vie w a n d Secti o n 7. 1 Ge neral Met h o ds, o nl y a b o ut t w o -t hir ds 
of 2 0 patie nts are treat e d i n t his st u d y , s o descri pti ve statistics are s uffi cie nt a n d a p pr o priate  f or 
i nter preti n g t he st u d y res ults a n d o btai ni n g a reas o na ble cli nical u n dersta n di n g of C 3 G disease. 
9  D o c u m e nt Hi st or y  
Versi o n N o.  
A ut h or(s)  
Descri pti o n s 
1. 0     
J oa n na Ya n g  
Ori gi nal  versi o n  date d 1 8 S E P 2 0 1 7  
2. 0     
J oa n na Ya n g  
I nc or p orate t he f oll o wi n g c ha n ges ( date d 2 0 A P R 2 0 1 8) : 
  U p date  t he first para gra p h of Secti o n 1 O ver vie w;  
  M o dif y t he sec o n d b ullet of pri mar y o bjecti ves i n Secti o n 2. 1;  
  Ha ve re m o ve d t he first b ullet of sec o n dar y o bjecti ves i n Secti o n 2. 2;  
  A d d last b ullet of ot her o bjecti ves i n Secti o n 2. 3;  
  Si m plif y t he sc ore f or gl o mer ular scler osis of c hr o nicit y i n d e x i n Secti o n 3. 1. 1;  
  M o dif y a n d u p date t he pri mar y, sec o n dar y, a n d ot her efficac y o utc o me meas ures 
i n Secti o ns 3. 1. 3, 3. 1. 4, a n d 3. 1. 5 t o be c o nsiste nt wit h t he o bjecti ves of t he 
pr ot oc ol a me n d me nt 3;  
  M o dif y a n d u p date t he st u d y d esi g n Secti o n 4. 1 t o be c o nsist e nt wit h t he pr o t oc ol 
a me n d me nt 3;  
  C ha n ge t he place b o d ose a dj ust me nt al g orit h m fr o m Da y 3 a n d Da y 1 0 t o Da y 7 
a n d Da y 1 4 , res pecti vel y, (as i n dicate d i n t he Sc he d ule of Assess me nt of t he 
pr ot oc ol)  i n Secti o n 4. 3; 
  Descri be briefl y t he p ur p oses f or eac h pr ot oc ol a me n d me nt i n Secti o n 4. 4;  
  Re m o ve pr otei n uria a nal ysis set fr o m Secti o n 6;  
  M o dif y state me nts a n d w or di n g i n Secti o n 7. 5 t o ali g n wit h t he efficac y o utc o me 
meas ures i n Secti o ns 3. 1. 3 -5;  
  M o dif y t he treat me nt e mer ge nt a b n or malit y cate g ories f or E C G para meter Q T c F, 
f oll o wi n g t he C T C A E se verit y gra des, i n Secti o n 7. 7. 3;  
  U p date P K a nal ysis Secti o n 7. 8, re m o vi n g refere nces t o Da y 3.  
3 . 0    
J oa n na Ya n g  
I nc or p orate t he f oll o wi n g c ha n ges ( date d 2 1 N O V 2 0 1 9  a n d 0 9 D E C 2 0 1 9 ): 
  U p date S ecti o n 1 O ver vie w, e m p hasize t he S A P bei n g a p plica ble t o data c ollecte d 
d uri n g 6 m o nt hs of bli n de d treat me nt peri o d ; 
  M o dif y  a n d u p date t he f or mat a n d b ullet descri pti o n of Secti o ns 2. 2, 2. 3, a n d 2. 3 
t o ali g n wit h t he f or mat a n d b ullet c o nte nts wit h pr ot oc ol a me n d me nt 6; 
  M o dif y a n d u p date t he sec o n d ar y, a n d ot her efficac y o utc o me meas ures i n 
Secti o ns 3. 1. 3, 3. 1. 4, a n d 3. 1. 5 t o be c o nsiste nt wit h t he o bjecti ves of t he pr ot oc ol 
a me n d me nt 6 ; 


Ale xi o n P har mace uticals  
A C H 4 7 1 -2 0 4: 1 5 Ma y 2 0 2 0 ( Versi o n 8)  
Statistical A nal ysis Pla n  
3 0 Oct o ber 2 0 2 0, Versi o n 5  
 
 
 
C o nfi de ntial  
Pa ge 2 8  of 3 3  
 
 
Versi o n N o.  
A ut h or(s)  
Descri pti o n s 
  Secti o n 3. 1. 3, t he i m pr o ve me nt of pr otei n uria has bee n c ha n ge d fr o m 5 0 % t o 3 0 %;  
  A d d all bi o mar ker meas ure me nts a vaila ble fr o m ce ntral la b orat ories i n t he Secti o n 
3. 1. 5, t hir d b ullet;  
  M o dif y a n d u p date st u d y desi g n secti o n 4. 1 i n acc or da nce wit h a me n d me nt 6 ; 
  Descri be briefl y t he p ur p oses f or pr ot oc ol a me n d me nt s 4, 5, a n d 6 i n Secti o n 4. 4; 
  Re m o ve e G F R a nal ysis set fr o m Secti o n 6 ; 
  A d d E val ua ble a nal ysis set i n Secti o n 6;  
  Re m o ve  t he state me nt of i nfer e ntial statistical a nal ysis pr oce d ures f or selecte d  
efficac y o utc o mes  fr o m Secti o n 7. 1 ; 
  A d d descri pti o n o n visit wi n d o w defi niti o n i n t he t hir d para gra p h fr o m t he e n d of 
Secti o n 7. 1 ; 
  A d d t he list of baseli ne bi o mar ker a n d la b tests t o Secti o n 7. 2. 2; 
  A d d pri or me dicati o ns of i nter est t o C 3 G cli nical st u dies i n Secti o n 7. 2. 2 ; 
  Re m o ve para gra p hs stati n g statistical met h o ds of c o m pari n g t w o treat me nt gr o u ps 
i n Secti o n 7. 5; 
  U p date t he descri pti ve a nal ysis of sec o n dar y a n d e x pl orat or y o utc o me meas ures i n 
Secti o ns 7. 5. 2 a n d 7. 5. 3 ;  
  A d d Secti o n 7. 8. 3 Pre -D ose C o nce ntrati o ns ( P K Tr o u g hs) . 
4. 0     
Kara Rice  
  A d d clarit y ar o u n d ti mi n g of pri mar y a nal ysis  
  U p date bi o ps y sc ori n g details base d o n fi nal sc ori n g ma n ual 
  U p date d descri pti o n of e n d p oi nts t o matc h latest pr ot oc ol versi o n  
  Clarif y d urati o n of bli n di n g f or st u d y sites a n d patie nts per pr ot oc ol  
  U p date defi niti o n of per -pr ot oc ol set t o s pecif y e xcl u de d pr ot oc ol de viati o ns  
  Clarifie d a p pr oac h t o ha n dli n g missi n g data  
  Re m o ve d s u m mar y of treat me nt c o m plia nce f or i nteri m a nal ysis.  
  U p date d calc ulati o n of e G F R sl o pe t o i ncl u de all a vaila ble data  
  A d d s u m mar y of res p o nse stat uses base d o n c o m p osite defi niti o ns i ncl u di n g e G F R 
a n d pr otei n uria  
  Clarif y pla n ne d a nal yses f or P R O e n d p oi nts  
5. 0     
Kara Rice  
  U p date d t o i ncl u de a nal yses f or O pe n -La bel E xte nsi o n a n d L o n g -T er m F oll o w -u p 
Peri o ds  
  U p date d t o ali g n wit h Pr ot oc ol A me n d me nt 7  
  Re m o ve d per pr ot oc ol set gi ve n s mall sa m ple size  
  A d de d s u m maries of m o difie d st u d y visits a n d misse d d oses d ue t o C O VI D -1 9 
pa n de mic  
  A d de d s u m mar y of treat me nt c o m plia nce  
  A d de d se nsiti vit y a nal ysis f or pri mar y efficac y a n d safet y e n d p oi nts t o assess 
i m pact of C O VI D-1 9 pa n de mic  
 
 


Ale xi o n P har mace uticals  
A C H 4 7 1 -2 0 4: 1 5 Ma y 2 0 2 0 ( Versi o n 8)  
Statistical A nal ysis Pla n  
3 0 Oct o ber 2 0 2 0, Versi o n 5  
 
 
 
C o nfi de ntial  
Pa ge 2 9  of 3 3  
 
 
A p p e n di x 1 .   
Gr a di n g t h e S e v erit y of L a b or at or y V al u e s  
T he C o m m o n Ter mi n ol o g y Criteria f or A d verse E ve nts ( C T C A E), Versi o n 4. 0 ( v 4. 0 3: J u ne 1 4, 2 0 1 0)  
d oes n ot pr o vi de a se parate la b orat or y t o xicit y gra di n g ta ble .  All t he la b orat or y gra des are part of t h e 
descri pti o ns wit hi n vari o us s yste m or ga n classes ( S O C s).  T he f oll o wi n g ta ble has bee n create d as S A S 
pr o gra m mi n g s p ecificati o ns f or pr o d uci n g ta bles a n d listi n gs f or cli nical st u d y re p ort.  T he criteria f or 
eac h gra de are t h e sa me as i n C T C A E descri pti o ns.  
Gr a di n g t h e S e v erit y of L a b or at or y V al u es, U n m o difi e d fr o m C T C A E, V ersi o n 4. 0 ( v 4. 0 3: J u n e 1 4, 
2 0 1 0)  
P A R A M E T E R  
G R A D E 1  
MIL D  
G R A D E 2  
M O D E R A T E  
G R A D E 3  
S E V E R E  
G R A D E 4  
LI F E-T H R E A TI N G  
C H E MI S T RI E S  
Aci d osis  
p H < n or m al, b ut 
≥7. 3  
- 
p H < 7. 3  
Lif e-t hr e at e ni n g 
c o ns e q u e nc es  
Al b u mi n, L o w  
<LL N - 3 g/ dL; 
<LL N - 3 0 g/L  
< 3 - 2 g/ dL; < 3 0 - 
2 0 g/L  
< 2 g/ dL; < 2 0 g/L     
Lif e-t hr e at e ni n g 
c o ns e q u e nc es; 
ur g e nt 
i nt erv e nti o n 
i n dic at e d 
Al k ali n e P h os p h at as e, Hi g h  
> UL N - 2. 5 x UL N    
> 2. 5 - 5. 0 x UL N    
> 5. 0 - 2 0. 0 x UL N     
> 2 0. 0 x UL N  
Al k al osis  
p H > n or m al, b ut 
≤7. 5  
- 
p H > 7. 5  
Lif e-t hr e at e ni n g 
c o ns e q u e nc es  
AL T, Hi g h  
> UL N - 3. 0 x UL N    
> 3. 0 - 5. 0 x UL N    
> 5. 0 - 2 0. 0 x UL N     
> 2 0. 0 x UL N  
A myl as e, Hi g h  
> UL N –  1. 5 x UL N   
> 1. 5 –  2. 0 x UL N   
> 2. 0 –  5. 0 x UL N     
> 5. 0 x UL N  
A S T  
> UL N - 3. 0 x UL N    
> 3. 0 - 5. 0 x UL N    
> 5. 0 - 2 0. 0 x UL N     
> 2 0. 0 x UL N  
Bilir u bi n, Hi g h  
> UL N - 1. 5 x UL N    
> 1. 5 - 3. 0 x UL N    
> 3. 0 - 1 0. 0 x UL N     
> 1 0. 0 x UL N  
C alci u m, Hi g h  
C orr ect e d s er u m 
c alci u m of > UL N - 
1 1. 5 m g/ dL; > UL N 
- 2. 9 m m ol/L  
C orr ect e d s er u m 
c alci u m of > 1 1. 5 
- 1 2. 5 m g/ dL; 
> 2. 9 - 3. 1 
m m ol/L  
C orr ect e d s er u m 
c alci u m of > 1 2. 5 - 
1 3. 5 m g/ dL; > 3. 1 - 
3. 4 m m ol/L  
C orr ect e d s er u m 
c alci u m of > 1 3. 5 
m g/ dL; > 3. 4 
m m ol/L  
C alci u m (I o niz e d), Hi g h  
I o niz e d c alci u m 
> UL N - 1. 5 
m m ol/L  
I o niz e d c alci u m 
> 1. 5 - 1. 6 
m m ol/L  
I o niz e d c alci u m 
> 1. 6 - 1. 8 m m ol/L  
I o niz e d c alci u m 
> 1. 8 m m ol/L  
C alci u m, L o w  
C orr ect e d s er u m 
c alci u m of <LL N - 
8. 0 m g/ dL; <LL N - 
2. 0 m m ol/L  
C orr ect e d s er u m 
c alci u m of < 8. 0 - 
7. 0 m g/ dL; < 2. 0 - 
1. 7 5 m m ol/L  
C orr ect e d s er u m 
c alci u m of < 7. 0 - 
6. 0 m g/ dL; < 1. 7 5 - 
1. 5 m m ol/L  
C orr ect e d s er u m 
c alci u m of < 6. 0 
m g/ dL; < 1. 5 
m m ol/L  
C alci u m (I o niz e d), L o w 
I o niz e d c alci u m 
<LL N - 1. 0 m m ol/L  
I o niz e d c alci u m 
< 1. 0 - 0. 9 
m m ol/L  
I o niz e d c alci u m 
< 0. 9 - 0. 8 m m ol/L  
I o niz e d c alci u m 
< 0. 8 m m ol/L  
Cr e ati n e Ki n as e, Hi g h  
> UL N - 2. 5 x UL N    
> 2. 5 x UL N - 5 x 
UL N  
> 5 x UL N - 1 0 x 
UL N  
> 1 0 x UL N  
Cr e ati ni n e, Hi g h  
> 1  - 1. 5 x 
b as eli n e; > UL N - 
1. 5 x UL N  
> 1. 5 - 3. 0 x 
b as eli n e; > 1. 5 - 
3. 0 x UL N  
> 3. 0 b as eli n e; > 3. 0 
- 6. 0 x UL N  
> 6. 0 x UL N  


Ale xi o n P har mace uticals  
A C H 4 7 1 -2 0 4: 1 5 Ma y 2 0 2 0 ( Versi o n 8)  
Statistical A nal ysis Pla n  
3 0 Oct o ber 2 0 2 0, Versi o n 5  
 
 
 
C o nfi de ntial  
Pa ge 3 0  of 3 3  
 
 
P A R A M E T E R  
G R A D E 1  
MIL D  
G R A D E 2  
M O D E R A T E  
G R A D E 3  
S E V E R E  
G R A D E 4  
LI F E-T H R E A TI N G  
e G F R or Cr Cl  
<LL N - 6 0 
ml/ mi n/ 1. 7 3 m
2 
or pr ot ei n uri a 2 + 
pr es e nt; uri n e 
pr ot ei n/cr e ati ni n e 
> 0. 5  
5 9 - 3 0 
ml/ mi n/ 1. 7 3 m
2 
e G F R or Cr Cl 2 9 - 
1 5 ml/ mi n/ 1. 7 3 
m 2 
e G F R or Cr Cl 
< 1 5 
ml/ mi n/ 1. 7 3 m
2 
Gl uc os e,  
   F asti n g , Hi g h  
> UL N - 1 6 0 
m g/ dL; > UL N - 8. 9 
m m ol/L  
> 1 6 0 - 2 5 0 
m g/ dL; > 8. 9 - 
1 3. 9 m m ol/L  
> 2 5 0 - 5 0 0 m g/ dL; 
> 1 3. 9 - 2 7. 8 
m m ol/L;  
> 5 0 0 m g/ dL; 
> 2 7. 8 m m ol/L  
Gl uc os e, L o w  
<LL N - 5 5 m g/ dL; 
<LL N - 3. 0 m m ol/L  
< 5 5 - 4 0 m g/ dL; 
< 3. 0 - 2. 2 
m m ol/L  
< 4 0 - 3 0 m g/ dL; 
< 2. 2 - 1. 7 m m ol/L  
< 3 0 m g/ dL; < 1. 7 
m m ol/L  
G G T, Hi g h  
> UL N - 2. 5 x UL N    
> 2. 5 - 5. 0 x UL N    
> 5. 0 - 2 0. 0 x UL N     
> 2 0. 0 x UL N  
Li p as e, Hi g h 
> UL N –  1. 5 x UL N   
> 1. 5 –  2. 0 x UL N   
> 2. 0 –  5. 0 x UL N     
> 5. 0 x UL N  
Li pi d Dis or d ers, 
    C h ol est er ol, Hi g h  
> UL N - 3 0 0 
m g/ dL; > UL N - 
7. 7 5 m m ol/L  
> 3 0 0 - 4 0 0 
m g/ dL; > 7. 7 5 - 
1 0. 3 4 m m ol/L  
> 4 0 0 - 5 0 0 m g/ dL; 
> 1 0. 3 4 - 1 2. 9 2 
m m ol/L  
> 5 0 0 m g/ dL; 
> 1 2. 9 2 m m ol/L  
    Tri glyc eri d es, Hi g h  
1 5 0 m g/ dL - 3 0 0 
m g/ dL; 1. 7 1 
m m ol/L - 3. 4 2 
m m ol/L  
> 3 0 0 m g/ dL - 
5 0 0 m g/ dL; 
> 3. 4 2 m m ol/L - 
5. 7 m m ol/L  
> 5 0 0 m g/ dL - 1 0 0 0 
m g/ dL; > 5. 7 
m m ol/L - 1 1. 4 
m m ol/L  
> 1 0 0 0 m g/ dL; 
> 1 1. 4 m m ol/L  
M a g n esi u m, Hi g h  
> UL N - 3. 0 m g/ dL; 
> UL N - 1. 2 3  
m m ol/L  
- 
> 3. 0 - 8. 0 m g/ dL; 
> 1. 2 3 - 3. 3 0  
m m ol/L  
> 8. 0 m g/ dL; > 3. 3 0 
m m ol/L  
M a g n esi u m, L o w  
<LL N - 1. 2 m g/ dL; 
<LL N - 0. 5  
m m ol/L  
< 1. 2 - 0. 9 m g/ dL; 
< 0. 5 - 0. 4  
m m ol/L  
< 0. 9 - 0. 7 m g/ dL; 
< 0. 4 - 0. 3  
m m ol/L  
< 0. 7 m g/ dL; < 0. 3 
m m ol/L  
P h os p h at e, L o w  
<LL N - 2. 5 m g/ dL; 
<LL N - 0. 8  
m m ol/L  
< 2. 5 - 2. 0 m g/ dL; 
< 0. 8 - 0. 6  
m m ol/L  
< 2. 0 - 1. 0 m g/ dL; 
< 0. 6 - 0. 3  
m m ol/L  
< 1. 0 m g/ dL; < 0. 3 
m m ol/L;  
P ot assi u m, Hi g h  
> UL N - 5. 5 
m m ol/L  
> 5. 5 - 6. 0 
m m ol/L  
> 6. 0 - 7. 0 m m ol/L    > 7. 0 m m ol/L  
P ot assi u m, L o w  
<LL N - 3. 0 m m ol/L  
- 
< 3. 0 - 2. 5 m m ol/L;  < 2. 5 m m ol/L  
S O DI U M, Hi g h  
> UL N - 1 5 0 
m m ol/L  
> 1 5 0 - 1 5 5 
m m ol/L  
> 1 5 5 - 1 6 0 
m m ol/L  
> 1 6 0 m m ol/L  
S O DI U M, L o w  
<LL N - 1 3 0 
m m ol/L  
 -      
< 1 3 0 - 1 2 0 
m m ol/L  
< 1 2 0 m m ol/L  
U RI C A CI D  
> UL N - 1 0 m g/ dL 
( 0. 5 9 m m ol/L)  
 -      
- 
> 1 0 m g/ dL; > 0. 5 9 
m m ol/L  
H E M A T OL O G Y  
C D 4 L y m p h ocyt es  d ecr e as e d     
<LL N - 5 0 0/ m m 3; 
<LL N - 0. 5 x 1 0 9 /L 
< 5 0 0 - 2 0 0/ m m 3; 
< 0. 5 - 0. 2 x 1 0 9 
/L 
< 2 0 0 - 5 0/ m m 3; 
< 0. 2 - 0. 0 5 x 1 0 9 /L 
< 5 0/ m m 3; < 0. 0 5 x 
1 0 9 /L 


Ale xi o n P har mace uticals  
A C H 4 7 1 -2 0 4: 1 5 Ma y 2 0 2 0 ( Versi o n 8)  
Statistical A nal ysis Pla n  
3 0 Oct o ber 2 0 2 0, Versi o n 5  
 
 
 
C o nfi de ntial  
Pa ge 3 1  of 3 3  
 
 
P A R A M E T E R  
G R A D E 1  
MIL D  
G R A D E 2  
M O D E R A T E  
G R A D E 3  
S E V E R E  
G R A D E 4  
LI F E-T H R E A TI N G  
( A bs ol ut e) L y m p h ocyt e C o u nt, l o w    
<LL N - 8 0 0/ m m 3; 
<LL N - 0. 8 x 1 0 9 /L 
< 8 0 0 - 5 0 0/ m m 3; 
< 0. 8 - 0. 5 x 1 0 9 
/L 
< 5 0 0 - 2 0 0/ m m 3; 
< 0. 5 - 0. 2 x 1 0 9 /L 
< 2 0 0/ m m 3; < 0. 2 x 
1 0 9 /L 
A bs ol ut e N e utr o p hil C o u nt ( A N C), l o w  
<LL N - 1 5 0 0/ m m 3; 
<LL N - 1. 5 x 1 0 9 /L 
< 1 5 0 0 - 
1 0 0 0/ m m 3; < 1. 5 
–  1. 0 x 1 0 9 /L 
< 1 0 0 0 - 5 0 0/ m m 3; 
< 1. 0 - 0. 5 x 1 0 9 /L 
< 5 0 0/ m m 3; < 0. 5 x 
1 0 9 /L 
Fi bri n o g e n, D ecr e as e d  
< 1. 0 –  0. 7 5 x LL N 
or < 2 5 % d ecr e as e 
fr o m b as eli n e 
< 0. 7 5 –  0. 5 x LL N 
or  2 5 - < 5 0 % 
d ecr e as e fr o m 
b as eli n e  
< 0. 5 –  0. 2 5 x LL N 
or 5 0 - < 7 5 % 
d ecr e as e fr o m 
b as eli n e  
< 0. 2 5 x LL N or 
7 5 % d ecr e as e 
fr o m b as eli n e or 
a bs ol ut e v al u e 
< 5 0 m g/ dL  
H e m o gl o bi n, L o w  
H g b <LL N - 1 0. 0  
g/ dL; <LL N - 6. 2 
m m ol/L; <LL N - 
1 0 0 g/L  
H g b < 1 0. 0 - 8. 0 
g/ dL; < 6. 2  - 4. 9  
m m ol/L; < 1 0 0 - 
8 0 g/L  
H g b < 8. 0 g/ dL; 
< 4. 9 m m ol/L;  
< 8 0 g/L; 
tr a nsf usi o n 
i n dic at e d 
 Lif e-t hr e at e ni n g 
c o ns e q u e nc es; 
ur g e nt 
i nt erv e nti o n 
i n dic at e d 
I N R, Hi g h 
( n ot o n a ntic o a g ul ati o n t h er a p y) 
> 1 - 1. 5 x UL N;     
> 1. 5 - 2. 5 x UL N;  
> 2. 5 x UL N; > 2. 5     
 -      
I N R, Hi g h 
( o n a ntic o a g ul ati o n t h er a p y) 
> 1 - 1. 5 ti m es 
a b ov e b as eli n e  
> 1. 5 - 2. 5 ti m es 
a b ov e b as eli n e  
> 2. 5 ti m es a b ov e 
b as eli n e  
 -      
Pl at el ets, D ecr e as e d  
<LL N - 
7 5, 0 0 0/ m m 3; 
<LL N -7 5. 0 x 1 0 9 
/L 
< 7 5, 0 0 0 - 
5 0, 0 0 0/ m m 3; 
< 7 5. 0 -5 0. 0 x 1 0 9 
/L 
< 5 0, 0 0 0 - 
2 5, 0 0 0/ m m 3; 
< 5 0. 0 -2 5. 0 x 1 0 9 
/L 
< 2 5, 0 0 0/ m m 3; 
< 2 5. 0 x 1 0 9 /L 
W B C, D ecr e as e d  
<LL N - 3 0 0 0/ m m 3; 
<LL N - 3. 0 x 1 0 9 /L 
< 3 0 0 0 - 
2 0 0 0/ m m 3; < 3. 0 
- 2. 0 x 1 0 9 /L 
< 2 0 0 0 - 
1 0 0 0/ m m 3; < 2. 0 - 
1. 0 x 1 0 9 /L 
< 1 0 0 0/ m m 3; < 1. 0 
x 1 0 9 /L 
A P T T or P T T  
> UL N - 1. 5 x UL N    
> 1. 5 - 2. 5 x UL N    
> 2. 5 x UL N;     
 -      
Pr ot ei n uri a  
( Di pstic k) 
1 +  
 
2 +  
 
- 
- 
Pr ot ei n uri a  
( 2 4-h o ur uri n e)  
< 1. 0 g/ 2 4 hrs     
1. 0 - 3. 4 g/ 2 4 hrs  
> = 3. 5 g/ 2 4 hrs     
- 
 
 
 
 
 
 


Ale xi o n P har mace uticals  
A C H 4 7 1 -2 0 4: 1 5 Ma y 2 0 2 0 ( Versi o n 8)  
Statistical A nal ysis Pla n  
3 0 Oct o ber 2 0 2 0, Versi o n 5  
 
 
 
C o nfi de ntial  
Pa ge 3 2  of 3 3  
 
 
A p p e n di x 2 .   
K D Q O L -S F S c al e S c ori n g Pr o c e d ur e  
 
S c al e  
N u m b e r of It e m s  
Aft e r R e c o di n g , A v e r a g e t h e 
F oll o wi n g It e m s  
 
Ki d n e y dis e as e t a r g et e d a r e as  
 
 
S y m pt o m / pr o bl e m list  
1 2  
1 4 a -k  
Eff ects of ki d n e y dis e as e  
8  
1 5 a -h  
B ur d e n of ki d n e y dis e as e  
4  
1 2 a -d  
       W or k st at us  
2  
2 0, 2 1  
       C o g niti v e f u ncti o n  
3  
1 3 b, d, f  
     Q u alit y of s oci al i nt er acti o n  
3  
1 3 a, c, e  
       S e x u al f u ncti o n  
2  
1 6 a, b  
        Sl e e p  
4  
1 7, 1 8 a -c 
        S oci al s u p p ort  
2  
1 9 a, b  
 
3 6 -it e m h e alt h s u r v e y_ ( S F-3 6)  
 
 
P h ysic al f u ncti o ni n g  
1 0  
3 a -j 
           R ol e --p h ysic al  
4  
4 a -d  
            P ai n  
2  
7, 8  
            G e n er al h e alt h  
5  
1, 1l a -d  
E m oti o n al w ell -b ei n g  
5  
9 b, c, d, f, h  
           R ol e --e m oti o n al  
3  
5 a -c  
           S o ci al f u ncti o n  
2  
6, 1 0  
           E n er g y /f ati g u e  
4  
9 a, e, g, i  
N ot e:  T h e S F -3 6 c h a n g e i n h e alt h a n d t h e 0 -1 0 o v er all h e alt h  r ati n g it e ms ar e sc or e d as si n gl e 
it e ms. 
 


Ale xi o n P har mace uticals  
A C H 4 7 1 -2 0 4: 1 5 Ma y 2 0 2 0 ( Versi o n 8)  
Statistical A nal ysis Pla n  
3 0 Oct o ber 2 0 2 0, Versi o n 5  
 
 
 
C o nfi de ntial  
Pa ge 3 3  of 3 3  
 
 
A p p e n di x 3 .   
F A CI T -F ati g u e S c al e a n d C al c ul ati o n of T ot al S c or e  
Bel o w  is a list of  state me nts t hat ot her  pe o ple  wit h  y o ur  ill ness ha ve  sai d are i m p orta nt. Please  circle or  mar k  
o ne  n u m ber  per  li ne t o i n dicate y o ur  res p o nse as it a p plies t o t he past  7  da ys . 
   
 
N ot At All    
A Littl e Bit     
S o m e w h at  
Q uit e a Bit  
V er y M u c h  
1     
I f e el f ati g u e d 
0  
1  
2  
3  
4  
2     
I f e el w e a k all o v er 
0  
1  
2  
3  
4  
3     
I f e el listl ess (“ w as h e d o ut”) 
0  
1  
2  
3  
4  
4     
I f e el tir e d 
0  
1  
2  
3  
4  
5     
I h a v e tr o u bl e st arti n g t hi n gs 
 
0  
 
1  
 
2  
 
3  
 
4  
b ec a us e I a m tir e d  
6     
I h a v e tr o u bl e fi nis hi n g t hi n gs 
 
0  
 
1  
 
2  
 
3  
 
4  
b ec a us e I a m tir e d  
7     
I h a v e e n er g y 
0  
1  
2  
3  
4  
8     
I a m a bl e t o d o m y us u al acti viti es 
0  
1  
2  
3  
4  
9     
I n e e d t o sl e e p d uri n g t h e d a y 
0  
1  
2  
3  
4  
1 0    I a m t o o tir e d t o e at 
0  
1  
2  
3  
4  
1 1    I n e e d h el p d oi n g m y us u al acti viti es 
0  
1  
2  
3  
4  
1 2    I a m fr ustr at e d b y b ei n g t o o tir e d 
 
0  
 
1  
 
2  
 
3  
 
4  
t o d o t h e t hi n gs I w a nt t o d o 
1 3    I h a v e t o li mit m y s oci al acti vit y 
 
0  
 
1  
 
2  
 
3  
 
4  
b ec a us e I a m tir e d  
 
Sc ori n g: It e ms are s c ore d as f oll o ws: 4 = N ot At All; 3 = A Little Bit; 2 = S o me w hat; 1 = Q uite A Bit; 
0 = Ver y M u c h, E X C E P T ite ms # 7 a n d  # 8  w hic h  are re verse d sc ore d. Total s c ore ra n ge 0 -5 2.  
It e m N u m b er 
R e v ers e It e m?  
 
It e m R es p o ns e 
It e m S c or e  
1  
4  
- 
 
=  
2  
4  
- 
 
=  
3  
4  
- 
 
=  
4  
4  
- 
 
=  
5  
4  
- 
 
=  
6  
4  
- 
 
=  
7  
0  
+  
 
=  
8  
0  
+  
 
=  
9  
4  
- 
 
=  
1 0  
4  
- 
 
=  
1 1  
4  
- 
 
=  
1 2  
4  
- 
 
=  
1 3  
4  
- 
 
=  
 
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