Clinical trial NCT04730804
Conditions: Healthy
Keywords: ALXN1830 Autoimmune Disease Pharmacokinetics Pharmacodynamics
Sponsor: Alexion Pharmaceuticals, Inc.
Start date: 2021-03-17; Completion date: 2022-01-04
Enrollment: 34 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This trial will study the effects of single and multiple doses of ALXN1830 in healthy adult participants.

Detailed description:
This is a Phase 1 study in healthy adult participants. The study will consist of 2 single ascending dose (Cohorts 1 and 2) and 4 multiple ascending dose cohorts (Cohorts 3 to 6). Participants will be randomly assigned to each of the 6 cohorts to receive either single or multiple doses of ALXN1830 subcutaneous (SC) or single or multiple doses of placebo SC. Cohort 6 will enroll only healthy participants of Japanese descent who will be dosed according to the highest tolerated dose (HTD) established in the non-Japanese cohorts.

Arms: arm 1: Participants will receive a single SC dose of ALXN1830 or placebo. arm 2: Participants will receive a single SC dose of ALXN1830 or placebo. arm 3: Participants will receive multiple SC doses of ALXN1830 or placebo. arm 4: Participants will receive multiple SC doses of ALXN1830 or placebo. arm 5: Participants will receive multiple SC doses of ALXN1830 or placebo. arm 6: Japanese participants will receive multiple SC doses of ALXN1830 (HTD) or placebo.
Interventions: intervention 1: ALXN1830 intervention 2: Placebo
Intervention descriptions: intervention 1: ALXN1830 will be administered as SC infusion(s). intervention 2: Placebo will be administered as SC infusion(s).

Protocol documents:
Prot_000.pdf: 
Protocol Amendment 4 
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Protocol Title: 
TITLE PAGE 
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending 
Dose Study of Subcutaneous ALXN1830 in Healthy Participants 
Protocol Number: ALXN1830-HV-108 
Amendment Number:4 
Replaces Amendment 3 (08 Feb 2021) 
Compound: ALXN1830 
Study Phase: Phase 1 
Short Title: Safety, Pharmacokinetic and Pharmacodynamic Study of Subcutaneous ALXN1830 
in Healthy Adult Participants 
Sponsor Name: Alexion Pharmaceuticals, Inc. 
Legal Registered Address: 
121 Seaport Boulevard 
Boston MA 02210 
USA 
Regulatory Agency Identifier Number(s) 
EudraCT: 2020-001081-11 
Approval Date: 25 Jun 2021 
Sponsor Signatory: 
 
Date 
Medical Monitor Contact Information will be provided separately. 
NCT #: NCT04730804


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INVESTIGATOR’S AGREEMENT 
I have read the study protocol amendment and agree to conduct the study in accordance with this 
protocol amendment, all applicable government regulations, the principles of the ICH E6 
Guidelines for Good Clinical Practice, and the principles of the World Medical Association 
Declaration of Helsinki. I also agree to maintain the confidentiality of all information received or 
developed in connection with this protocol amendment. 
 
 
 
 
 
 
 
 
 
 
Printed Name of Investigator 
 
 
 
Signature of Investigator 
 
 
 
Date 


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PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Amendment 4 (25 Jun 2021) 
Replaces Amendment 3 (08 Feb 2021) 
Overall Rationale for the Amendment: 
This amendment has been prepared to add pregnancy follow-up testing for female participants of 
childbearing potential approximately monthly for 3 months after the last dose of study drug to be 
consistent with the Investigator’s Brochure. In addition, changes made in Administrative Letters 
2, 3, and 4 have been incorporated into this amendment. Minor editorial updates were made for 
clarification and consistency. 
 
Section # and Name 
Description of Change 
Brief Rationale 
Throughout the protocol 
Updated amendment 
number and approval date. 
Administrative change. 
Section 1.3 Schedule of Activities, Tables 2, 4, 
5, 6, 7, 8, 10, and 11 
Added footnote to clarify 
that the timing for postdose 
evaluations at the 2-, 4-, 
12-, and 24-hour 
timepoints ( as applicable) 
is relative to the start of 
infusion time, and to 
clarify the order of study 
activities when multiple 
procedures are scheduled 
to occur at the same time. 
To clarify that the timing for 
post-dose samples through the 
24-hour timepoint is based on 
the start of infusion time. 
Section 1.3 Schedule of Activities, Tables 2, 4, 
5, 6, 7, 8, 9, 10, 11, and 12 
Added footnote to indicate 
that visit windows 
specified in hours are not 
applicable for urinalysis. 
To allow flexibility in the 
timing of urine sample 
collection for urinalysis. 
Section 1.3 Schedule of Activities, Table 3 
(Cohorts 1 and 2) 
Added footnote to clarify 
that the pregnancy test at 
Day 64/ET for the SAD 
cohorts may be either 
serum or urine, and to 
specify that urine 
pregnancy test kits should 
be dispensed for monthly 
pregnancy testing post 
Day 64/ET. 
To clarify that either serum or 
urine pregnancy tests may be 
performed at Day 64/ET for the 
SAD cohorts and to ensure 
urine pregnancy test kits are 
dispensed as needed. 
Section 1.3 Schedule of Activities, Table 3 
(Cohorts 1 and 2) 
For SAD cohorts, added a 
Day 92 Follow-up Phone 
Call to capture the 
collection of pregnancy 
test results, along with AEs 
and concomitant 
medications, at Day 92 or 
for 3 months after the last 
dose; revised the footnote 
to clarify collection of 
these results. 
To add the process for 
collection of follow-up 
pregnancy test results. 


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Section # and Name 
Description of Change 
Brief Rationale 
Section 1.3 Schedule of Activities, Table 9 
(Cohort 3) 
Added a footnote to 
specify that at Day 141/ET, 
urine pregnancy test kits 
should be dispensed for 
monthly pregnancy testing 
post Day 141/ET. 
To ensure that urine pregnancy 
test kits are dispensed as 
needed for follow-up pregnancy 
testing. 
Section 1.3 Schedule of Activities, Table 9 
(Cohort 3) 
Added a Day 169 
Follow-up Phone Call to 
capture the collection of 
pregnancy test results, 
along with AEs and 
concomitant medications, 
at Day 169 or for 3 months 
after the last dose; added a 
footnote to clarify 
collection of these results. 
To add the process for 
collection of follow-up 
pregnancy test results. 
Section 1.3 Schedule of Activities, Table 12 
(Cohorts 4 to 6) 
Added pregnancy test at 
Day 50; added footnote to 
specify that urine 
pregnancy test kits should 
be dispensed for monthly 
pregnancy testing post 
Day 85/ET. 
To perform pregnancy testing 
approximately every 28 days; 
to ensure urine pregnancy test 
kits are dispensed as needed. 
Section 1.3 Schedule of Activities, Table 12 
(Cohorts 4 to 6) 
Added a Day 113 
Follow-up Phone Call to 
capture the collection of 
pregnancy test results, 
along with AEs and 
concomitant medications, 
at Day 113 or for 3 months 
after the last dose. 
To add the process for 
collection of follow-up 
pregnancy test results. 
Section 5.1 Inclusion Criteria 
Revised inclusion 
criterion 5 to allow 
participants with IgA or 
IgM levels above the lower 
limit of normal to enter the 
study. 
Based on available data, IgA or 
IgM reduction is not expected 
with ALXN1830 
administration; therefore, 
participants with IgA or IgM 
above the lower limit of normal 
may be enrolled. 
Section 6.1 Study Interventions Administered 
Revised description of the 
use of different 
compositions. 
To clarify that different 
compositions of ALXN1830 
may be used for the SAD and 
MAD cohorts. 
Section 6.2 
Preparation/Handling/Storage/Accountability 
Changed “The Investigator 
must confirm appropriate 
temperature 
conditions…study drug” to 
“The Investigator or 
designee must confirm 
appropriate temperature 
conditions…study drug.” 
To enhance clarity. 


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Section # and Name 
Description of Change 
Brief Rationale 
Section 7.2.1 Immunoglobulin Stopping Rules 
Added text to specify that a 
participant for whom IgA 
or IgM falls below the 
normal limit and is 
associated with clinical 
signs and symptoms will 
be discontinued from 
further dosing. 
To clarify that participants with 
IgA or IgM below the normal 
range and clinical signs and 
symptoms will be discontinued 
from dosing. 
Throughout the document 
Minor grammatical, 
editorial, and document 
formatting revisions. 
To enhance clarity. 
Abbreviations: AE = adverse event; ET = early termination; FcRn occupancy = neonatal crystallizable fragment 
receptor; Ig = immunoglobulin; MAD = multiple ascending dose; SAD = single-ascending dose 


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TABLE OF CONTENTS 
TITLE PAGE ................................................................................................................................... 1 
INVESTIGATOR’S AGREEMENT ............................................................................................... 2 
PROTOCOL AMENDMENT SUMMARY OF CHANGES ........................................................... 3 
TABLE OF CONTENTS ................................................................................................................. 6 
LIST OF TABLES ......................................................................................................................... 10 
LIST OF FIGURES ........................................................................................................................ 10 
1. 
PROTOCOL SUMMARY .......................................................................................... 11 
1.1. 
Synopsis ...................................................................................................................... 11 
1.2. 
Schema ........................................................................................................................ 14 
1.3. 
Schedule of Activities (SoA) ...................................................................................... 15 
2. 
INTRODUCTION....................................................................................................... 36 
2.1. 
Study Rationale ........................................................................................................... 37 
2.2. 
Background ................................................................................................................. 38 
2.3. 
Benefit/Risk Assessment ............................................................................................. 38 
2.3.1. 
Risk Assessment ......................................................................................................... 39 
2.3.2. 
Benefit Assessment ..................................................................................................... 39 
2.3.3. 
Overall Benefit: Risk Conclusion ................................................................................ 39 
3. 
OBJECTIVES AND ENDPOINTS ............................................................................. 41 
4. 
STUDY DESIGN ........................................................................................................ 42 
4.1. 
Overall Design ............................................................................................................ 42 
4.2. 
Scientific Rationale for Study Design ......................................................................... 45 
4.3. 
Justification for Dose................................................................................................... 46 
4.4. 
End of Study Definition .............................................................................................. 48 
5. 
STUDY POPULATION ............................................................................................. 49 
5.1. 
Inclusion Criteria......................................................................................................... 49 
5.2. 
Exclusion Criteria ....................................................................................................... 50 
5.3. 
Lifestyle Considerations .............................................................................................. 52 
5.3.1. 
Meals and Dietary Restrictions ................................................................................... 52 
5.3.2. 
Caffeine, Alcohol, and Tobacco ................................................................................. 52 
5.3.3. 
Activity........................................................................................................................ 52 
5.4. 
Screen Failures ............................................................................................................ 52 


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6. 
STUDY INTERVENTION ......................................................................................... 53 
6.1. 
Study Interventions Administered ............................................................................... 53 
6.2. 
Preparation/Handling/Storage/Accountability ............................................................. 53 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................................ 54 
6.4. 
Study Intervention Compliance................................................................................... 55 
6.5. 
Concomitant Therapy .................................................................................................. 56 
6.5.1. 
Hydration .................................................................................................................... 56 
6.5.2. 
Supportive/Symptomatic Care .................................................................................... 56 
6.5.3. 
Vaccinations ................................................................................................................ 56 
6.5.4. 
Antibiotics Use ............................................................................................................ 57 
6.5.5. 
Disallowed Medication ............................................................................................... 57 
6.6. 
Dose Modification ....................................................................................................... 57 
6.7. 
Intervention After the End of the Study ...................................................................... 57 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL ........................................ 58 
7.1. 
Discontinuation of Study Intervention ........................................................................ 58 
7.2. 
Stopping Criteria ......................................................................................................... 58 
7.2.1. 
Immunoglobulin Stopping Rules ................................................................................ 58 
7.2.2. 
Safety Stopping Rules (Individual, Cohort and Study Level Stopping Rules) ........... 59 
7.3. 
Participant Discontinuation/Withdrawal from the Study ............................................ 60 
7.4. 
Lost to Follow-up ........................................................................................................ 60 
8. 
STUDY ASSESSMENTS AND PROCEDURES ...................................................... 62 
8.1. 
Efficacy Assessments .................................................................................................. 62 
8.2. 
Safety Assessments ..................................................................................................... 62 
8.2.1. 
Physical Examinations ................................................................................................ 62 
8.2.2. 
Vital Signs ................................................................................................................... 62 
8.2.3. 
Electrocardiograms ...................................................................................................... 63 
8.2.4. 
Clinical Safety Laboratory Assessments ..................................................................... 63 
8.2.5. 
Virus Serology ............................................................................................................ 64 
8.2.6. 
Vaccination ................................................................................................................. 64 
8.2.7. 
Drug and Alcohol Screen ............................................................................................ 64 
8.2.8. 
Pregnancy .................................................................................................................... 64 
8.2.9. 
Infusion Site Evaluation .............................................................................................. 64 


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8.3. 
Adverse Events and Serious Adverse Events ..............................................................64 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE Information .......................65 
8.3.2. 
Method of Detecting AEs and SAEs ...........................................................................65 
8.3.3. 
Follow-up of AEs and SAEs .......................................................................................65 
8.3.4. 
Regulatory Reporting Requirements for SAEs ...........................................................65 
8.3.5. 
Adverse Events of Special Interest .............................................................................66 
8.3.5.1. 
Infusion-Related Reaction...........................................................................................66 
8.3.5.2. 
Non-acute Hypersensitivity Reaction ..........................................................................66 
8.4. 
Treatment of Overdose................................................................................................67 
8.5. 
Pharmacokinetics ........................................................................................................67 
8.6. 
Pharmacodynamics ......................................................................................................67 
8.7. 
Genetics .......................................................................................................................68 
8.8. 
Biomarkers ..................................................................................................................68 
8.9. 
Immunogenicity Assessments .....................................................................................68 
8.10. 
Medical Resource Utilization ......................................................................................68 
9. 
STATISTICAL CONSIDERATIONS ........................................................................69 
9.1. 
Statistical Hypotheses .................................................................................................69 
9.2. 
Sample Size Determination .........................................................................................69 
9.3. 
Populations for Analyses ............................................................................................69 
9.4. 
Statistical Analyses .....................................................................................................69 
9.4.1. 
Safety Analyses ...........................................................................................................70 
9.4.2. 
Other Analyses ............................................................................................................71 
9.4.2.1. 
Pharmacokinetic Analyses ..........................................................................................71 
9.4.2.2. 
Pharmacodynamic Analyses .......................................................................................71 
9.5. 
Interim Analyses .........................................................................................................72 
9.6. 
Safety Review Committee (SRC) ...............................................................................72 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................73 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations .....................73 
10.1.1. 
Regulatory and Ethical Considerations .......................................................................73 
10.1.2. 
Financial Disclosure ....................................................................................................73 
10.1.3. 
Informed Consent Process ..........................................................................................74 
10.1.4. 
Data Protection ............................................................................................................75 


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10.1.5. 
Committees Structure .................................................................................................. 75 
10.1.6. 
Dissemination of Clinical Study Data ......................................................................... 75 
10.1.7. 
Data Quality Assurance .............................................................................................. 75 
10.1.8. 
Source Documents ...................................................................................................... 76 
10.1.9. 
Study and Site Start and Closure................................................................................. 76 
10.1.10. 
Publication Policy ....................................................................................................... 77 
10.2. 
Appendix 2: Clinical Laboratory Tests ....................................................................... 78 
10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ........................................................................ 80 
10.3.1. 
Definition of AE ......................................................................................................... 80 
10.3.2. 
Definition of SAE ....................................................................................................... 81 
10.3.3. 
Recording and Follow-Up of AE and/or SAE ............................................................ 82 
10.3.4. 
Reporting of SAEs ...................................................................................................... 84 
10.4. 
Appendix 4: Guidelines for Grading and Management of Allergic or 
Infusion-Related Reactions ......................................................................................... 85 
10.5. 
Appendix 5: Contraceptive Guidance and Collection of Pregnancy 
Information .................................................................................................................. 87 
10.5.1. 
Definitions ................................................................................................................... 87 
10.5.2. 
Contraception Guidance .............................................................................................. 88 
10.5.2.1. 
Guidance for Female Participants ............................................................................... 88 
10.5.2.2. 
Guidance for Male Participants ................................................................................... 89 
10.5.3. 
Collection of Pregnancy Information .......................................................................... 89 
10.5.3.1. 
Male Participants With Partners Who Become Pregnant............................................ 90 
10.5.3.2. 
Female Participants who become pregnant ................................................................. 90 
10.6. 
Appendix 6: Biomarkers ............................................................................................. 91 
10.7. 
Appendix 7: Justification for Protective Measures ..................................................... 91 
10.7.1. 
IgG Lowering and the Potential Risk of Infection ...................................................... 91 
10.7.1.1. 
IgG Level Stopping Rule ............................................................................................ 92 
10.7.1.2. 
Evidence of Immunity/Vaccination ............................................................................. 93 
10.7.2. 
Hydration .................................................................................................................... 93 
10.8. 
Appendix 11: Abbreviations ....................................................................................... 94 
10.9. 
Protocol Amendment History ..................................................................................... 96 
11. 
REFERENCES ............................................................................................................ 97 


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LIST OF TABLES 
Table 1: 
Planned Dose and Dose Regimens in Healthy Participants ........................................13 
Table 2: 
SoA – Screening Through Day 8 for Single-Dose Cohorts 1 and 2 ...........................16 
Table 3: 
SoA – Day 12 Through Day 64/ET for Single-Dose Cohorts 1 and 2 ........................18 
Table 4: 
SoA – Screening Through Day 9 for Multiple-Dose Cohort 3 ...................................19 
Table 5: 
SoA – Day 14 through 28 for Multiple-Dose Cohort 3...............................................21 
Table 6: 
SoA – Day 29 Through Day 44 for Multiple-Dose Cohort 3......................................23 
Table 7: 
SoA – Day 49 Through Day 65 for Multiple-Dose Cohort 3......................................25 
Table 8: 
SoA – Day 70 Through Day 79 for Multiple-Dose Cohort 3......................................27 
Table 9: 
SoA – Day 80 Through Day 141 for Multiple-Dose Cohort 3....................................29 
Table 10: SoA – Screening Through Day 7 for Multiple-Dose Cohorts 4 to 6...........................30 
Table 11: SoA – Day 8 Through Day 23 for Multiple-Dose Cohorts 4 to 6 ...............................32 
Table 12: SoA – Day 24 Through Day 85 for Multiple-Dose Cohorts 4 to 6 .............................34 
Table 13: Risk Assessment for ALXN1830 ................................................................................39 
Table 14: Planned Dose and Dose Regimens of ALXN1830 in Healthy Participants ................43 
Table 15: Minimum Data Requirements for Dose Escalation .....................................................44 
Table 16: Predicted ALXN1830 Exposure, Safety Margin, and Immunoglobulin G 
Reduction after Subcutaneous Administration ............................................................47 
Table 17: Study Drug ..................................................................................................................53 
Table 18: Populations for Analyses ............................................................................................69 
Table 19: Protocol-Required Safety Laboratory Assessments ....................................................79 
Table 20: Grading and Management of Allergic or Infusion-Related Reactions ........................86 
 
 
LIST OF FIGURES 
Figure 1 
Study Schematic Diagram ...........................................................................................14 


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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple 
Ascending Dose Study of Subcutaneous ALXN1830 in Healthy Participants 
Short Title: Safety, Pharmacokinetic and Pharmacodynamic Study of Subcutaneous ALXN1830 
in Healthy Adult Participants 
Rationale: 
ALXN1830, an anti-neonatal crystallizable fragment receptor (FcRn) monoclonal antibody 
(mAb), has the potential to reduce the level of pathogenic immunoglobulin G (IgG) involved in 
certain autoimmune disorders. The purpose of this Phase 1 study in healthy adult participants is 
to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and 
immunogenicity of single ascending doses (SAD) and multiple ascending doses (MAD) of 
ALXN1830 administered subcutaneously (SC) and to compare safety, tolerability, PK, PD, and 
immunogenicity of ALXN1830 in Japanese participants with non-Japanese participants. Data 
from this study are anticipated to help design future studies in patients with IgG-mediated 
diseases. 
Objectives and Endpoints 
 
Objectives 
Endpoints 
Primary 
• To assess the safety and tolerability 
of single and multiple doses of 
ALXN1830 SC 
• Safety assessed by the incidence and relatedness of TEAEs, SAEs, 
AESIs, physical examination, vital sign measurements, clinical 
laboratory, and ECG results 
Secondary 
• To assess the PK of single and 
multiple doses of ALXN1830 SC 
• To explore the PD effects of single 
and multiple doses of ALXN1830 SC 
• To assess the immunogenicity of 
ALXN1830 SC 
• To compare safety and tolerability, 
PK, PD, and immunogenicity of 
ALXN1830 SC between Japanese 
and non-Japanese healthy 
participants 
• Serum ALXN1830 concentration profiles and single- and 
multiple-dose PK parameters 
• Change in serum IgG levels over time; FcRn saturation as 
measured by receptor occupancy 
• Incidence of antidrug antibodies and neutralizing antibodies to 
ALXN1830 
• Quantitative assessment of safety, PK parameters, PD parameters, 
and immunogenicity between Japanese and non-Japanese healthy 
participants 
Abbreviations: AESI = adverse events of special interest; ECG = electrocardiogram; FcRn = neonatal crystallizable 
fragment receptor; IgG = immunoglobulin G; PD = pharmacodynamics; PK = pharmacokinetics; SAE = serious 
adverse event; SC = subcutaneous; TEAE = treatment-emergent adverse event. 


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Overall Design 
This is a Phase 1 study in up to 48 healthy adult participants (36 on active treatment, 12 on 
placebo [PBO]). The study will consist of 2 SAD (Cohorts 1 and 2) and 4 MAD cohorts 
(Cohorts 3 to 6). Cohort 6 will enroll only Japanese1 participants). Eight participants will be 
randomly assigned in a 6:2 ratio to each of the 6 cohorts to receive either single or multiple doses 
of ALXN1830 SC (n = 6 per cohort) or single or multiple doses of PBO (n = 2 per cohort). 
Initially, the first 4 participants randomized to each cohort will be dosed, 3 participants with 
ALXN1830 and 1 participant with PBO. The dosing will be staggered, with an interval of at least 
3 days for the SAD cohorts and at least 7 days for the MAD cohorts, before dosing the rest of the 
participants in the cohort. The shorter interval of staggered dosing for the SAD cohorts compared 
to the MAD cohorts is considered appropriate as the expected PK exposure of the ALXN1830 
SC doses will be a fraction of that of the intravenous (IV) dose demonstrated to be safe and well 
tolerated in previous IV studies. The reduction of IgG after a single SC dose will be similar to 
the observed IgG reduction in previous IV studies; and in general, there will be low risk of 
immunogenicity and infusion related reactions after a single dose. All participants will be 
observed during the infusion and for 2 hours following the end of infusion for safety and 
participants will be encouraged to report any discomfort immediately, especially within 24 hours 
post dosing. At no time will more than 4 participants per cohort be dosed on a given day. 
Progression to the next dosing cohort will be gated by review of initial dosing data by a Safety 
Review Committee (SRC). At Alexion’s discretion, and after consultation with the SRC, 
additional participants may be enrolled as replacement participants only if a participant 
discontinues within 3 weeks of the last dose for reasons other than drug-related adverse events. 
Disclosure Statement: This is a sequential treatment study with 6 cohorts that is participant and 
Investigator blinded. 
Number of Participants: 
A maximum of 48 participants will be randomized such that approximately 8 evaluable 
participants per each of 6 cohorts complete the study. The number of participants was chosen 
based on feasibility and was considered adequate to meet the study objectives. 
Study Cohorts and Study Duration: 
Participants will be randomly assigned in a 6:2 ratio to each of the 6 cohorts to receive either 
single or multiple doses of ALXN1830 SC (n = 6 per cohort) or single or multiple doses of PBO 
(n = 2 per cohort). The planned dose and dose regimens are shown in Table 1. The planned study 
duration is approximately 124 days for Cohorts 1 and 2: up to 60 days for screening and 
 
 
 
 
 
 
 
1Japanese descent is defined as: 
• 
First generation (born to 2 Japanese parents and 4 Japanese grandparents) 
• 
Participant must have been born in Japan, and not have lived outside Japan for greater than 10 years 
• 
Lifestyle, including diet, must not have significantly changed since leaving Japan 


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approximately 64 days for dosing and follow-up; 201 days for Cohort 3: up to 60 days for 
screening and approximately 141 days for dosing and follow-up; and 148 days for Cohorts 
4 to 6: 60 days for screening and approximately 88 days for dosing and follow-up. Participants 
will be admitted to an inpatient facility during the dosing and follow-up period as shown in the 
schedule of activities (SoA). The study schematic is presented in Figure 1. 
Table 1:    Planned Dose and Dose Regimens in Healthy Participants 
 
Cohort No. 
Regimen/Route of Administration 
Study Drug (N) 
1 
Single dose SC 
Placebo (n = 2) or 
ALXN1830 1500 mg (n = 6) 
2 
Single dose SC 
Placebo (n = 2) or 
ALXN1830 2250 mg (n = 6) 
3 
Multiple dose (12 doses qw) SC 
Placebo (n = 2) or 
ALXN1830 750 mg (n = 6) 
4 
Multiple dose (4 doses qw) SC 
Placebo (n = 2) or 
ALXN1830 1500 mg (n = 6) 
5 
Multiple dose (4 doses qw) SC 
Placebo (n = 2) or 
ALXN1830 2250 mg (n = 6) 
6a 
Multiple dose (4 doses qw) SC 
Japanese healthy participants 
Placebo (n = 2) or 
ALXN1830 HTD (n = 6) 
a Healthy, Japanese participants enrolled in Cohort 6 will be dosed according to the HTD established in the 
non-Japanese cohorts. 
Abbreviations: qw = weekly; SC = subcutaneous; HTD = highest tolerated dose. 
Safety Review Committee: Progression to the next dosing cohort will be gated by review of 
initial dosing data by an SRC consisting of the Investigator, and Alexion Safety Physician, 
Medical Monitor, Study Statistician, and Clinical Pharmacologist. 


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1.2. 
Schema 
Figure 1 
Study Schematic Diagram 
 
 
Note: The SRC meeting dates are approximate. 
Abbreviations: D = day; HTD = highest tolerated dose; MAD = multiple ascending dose; PBO = placebo; qw = weekly; SAD = single ascending dose; 
SC = subcutaneous; SRC = Safety Review Committee 
 
 
 
 
 
 
 
 
 
 
 
 


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1.3. 
Schedule of Activities (SoA) 
The SoA for SAD Cohorts 1 and 2 (Table 2 and Table 3), MAD Cohort 3 (Table 4, Table 5, 
Table 6, Table 7, Table 8, and Table 9), and MAD Cohorts 4 to 6 (Table 10, Table 11, and 
Table 12) are presented below. 
Note: When multiple procedures are scheduled to occur at the same time, the following order of 
events should be strictly adhered to whenever possible: ECG, vital signs, blood sampling, study 
intervention administration. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Table 2: 
SoA – Screening Through Day 8 for Single-Dose Cohorts 1 and 2 
 
Study Day 
Screening 
Day -1 
---------------- Day 1 (Dosing Day)----------- 
Day 2 
Day 3 
Day 4 
Day 
5 
Day 6 
Day 7 
Day 8a 
Assessments 
Day –60 
to Day –2 
Admit 
Predose 
EOI 
2 hb 
4 hb 
12 hb 
24 hb 
48 h 
72 h 
96 h 
120 h 
144 h 
168 h 
Window (hours) 
NA 
+0.25 
±0.25 
±0.5 
±0.5 
±1 
±1 
±1 
±1 
±1 
±1 
±1 
Status (OP or CRU) 
OP 
Admit 
CRU 
Informed consent 
X 
Inclusion/exclusion criteria 
X 
X 
Serum pregnancy test (WOCBP) 
X 
X 
FSH test (postmenopausal women) 
X 
Alcohol breath test 
X 
X 
Urine drug screen 
X 
X 
Hepatitis B and C screen 
X 
Evidence of vaccinationc 
X 
X 
HIV (types 1 and 2) screen 
X 
Medical history and demographics 
X 
X 
Physical examinationd 
X 
X 
X 
X 
Height, weight, and BMIe 
X 
X 
Randomization 
X 
Study drug administration 
X 
PK blood sampling 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PD blood sampling - IgA, IgM, IgG 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PD blood sampling - IgG subtypes 1-4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PD blood sampling – CIC 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Immunogenicity blood sampling - ADA 
X 
FcRn occupancy 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Biochemistryf, hematology, coagulation 
X 
X 
X 
X 
X 
Exploratory biomarker sample 
X 
X 
X 
X 
Urinalysisg 
X 
X 
X 
X 
X 
Vital signsh 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG (triplicate) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Infusion site evaluationi 
X 
X 
X 
X 
Xj 
Concomitant medications 
←Monitor continuously (after ICF is signed at Screening)→ 
Adverse events 
←Monitor continuously (after ICF is signed at Screening)→ 
a Participant will be discharged from the CRU after completing all Day 8 assessments. 


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b Postdose evaluations at the 2-hour, 4-hour, 12-hour, and 24-hour timepoints are to be completed based on the start of infusion time. When multiple procedures 
are scheduled to occur at the same time, the following order of events should be strictly adhered to whenever possible: ECG, vital signs, blood sampling, and 
study intervention administration. 
c All participants must be vaccinated as described in Section 6.5.3. 
d Full PE at screening and symptom directed PE thereafter. 
e Height and BMI at Screening only. 
f Fasting, due to lipid panel. Note: lipid panel is not performed at Screening. 
g Visit window (hours) is not applicable for urinalysis. 
h Including temperature, respiratory rate, and pulse oximetry. 
i In the event of an IRR, it is recommended to collect a blood sample for assessment of tryptase, histamine, CRP, cytokines, and complement as soon as the IRR 
is observed (prior to administering any IRR medication), and 2 hours, 24 hours, and 7 days (prior to the next dose of study drug) after onset of the IRR; a blood 
sample for PK/PD and ADAs may be collected if there is no predefined sample collection on the same day. 
j IRR evaluation will continue until the reaction is fully resolved. 
Abbreviations: ADA = antidrug antibodies; BMI = body mass index; CIC = circulating immune complexes; CRP = C-reactive protein; CRU = Clinical Research 
Unit; ECG = electrocardiogram; EOI = end of infusion; FcRn = neonatal crystallizable fragment receptor; HIV = human immunodeficiency virus; 
ICF = informed consent form; Ig = immunoglobulin; IRR = infusion related reaction; NA = not applicable; OP = outpatient; PD = pharmacodynamic(s); 
PE = physical examination; PK = pharmacokinetic(s); WOCBP = women of childbearing potential. 


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Table 3: 
SoA – Day 12 Through Day 64/ET for Single-Dose Cohorts 1 and 2 
 
Assessments/ Study Day 
Day 12 
Day 15 
Day 22 
Day 29 
Day 36 
Day 43 
Day 50 
Day 57 
Day 64/ET 
Day 92 
Follow-up 
Phone Call 
Window (days) 
±1 
±1 
±1 
±1 
±1 
±1 
±1 
±1 
±1 
±3 
Status (OP or CRU) 
OP 
Pregnancy test 
Xa 
Xb 
Xc 
Physical examinationd 
X 
X 
PK blood sampling 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PD blood sampling - IgA, IgM, IgG 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PD blood sampling - IgG subtypes 1-4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PD blood sampling – CIC 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Immunogenicity blood sampling - ADA 
X 
X 
X 
Xe 
FcRn occupancy 
X 
X 
X 
Biochemistryf, hematology, coagulation 
X 
X 
X 
X 
Exploratory biomarker sample 
X 
X 
X 
X 
Urinalysis 
X 
X 
X 
X 
Vital signsg 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG (triplicate) 
X 
X 
X 
X 
Concomitant medications 
←Monitor continuously (after ICF is signed at Screening)→ 
Adverse events 
←Monitor continuously (after ICF is signed at Screening)→ 
a Serum pregnancy test. 
b May be serum or urine pregnancy test. For the Day 64 Visit, dispense a urine pregnancy test kit for the Day 92 Follow-up Phone Call. For an ET Visit, dispense 
urine pregnancy test kit to allow monthly testing for 3 months after the last dose. 
c Participants will be requested to take a urine pregnancy test at home at approximately Day 92, or, if ET, monthly for 3 months after the last dose; the site will 
solicit pregnancy test results, along with adverse events and concomitant medications, via phone call. 
d Symptom directed PE. 
e Participants who are ADA positive at Day 64/ET will be followed for up to 1 year (from the study drug administration) or until ADA titers return to baseline 
levels (whichever occurs first, see Section 8.9 for more details). 
f Fasting, due to lipid panel. Note: lipid panel is not performed at Screening. 
g Including temperature, respiratory rate, and pulse oximetry. 
Abbreviations: ADA = antidrug antibodies; CIC = circulating immune complexes; CRU = Clinical Research Unit; ECG = electrocardiogram; ET = early 
termination; FcRn = neonatal crystallizable fragment receptor; ICF = informed consent form; Ig = immunoglobulin; OP = outpatient; 
PD = pharmacodynamic(s); PE = physical examination; PK = pharmacokinetic(s); WOCBP = women of childbearing potential. 


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Table 4: 
SoA – Screening Through Day 9 for Multiple-Dose Cohort 3 
Page 19 of 98 
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Study Day 
Screen- 
ing 
-1 
1 
2 
3 
4 
5 
6 
7 
8 
9a 
Assessments 
Day -60 
to 
Day -2 
Admit 
Pre- 
dose 
EOI 
2 hb 
4 hb 
12 hb 
24 hb 
48 h 
72 h 
96 h 
120 h 
144 h 
Pre- 
dose 
EOI 
2 hb 
24 hb 
Window (hours) 
NA 
+0.25 
±0.25 
±0.5 
±0.5 
±1 
±1 
±1 
±1 
±1 
±1 
NA 
+0.25 
±0.25 
±1 
Status (OP or CRU) 
OP 
CRU 
Informed consent 
X 
Inclusion/exclusion criteria 
X 
Xc 
Pregnancy test (WOCBP)d 
X 
X 
FSH test (postmenopausal 
women) 
X 
Alcohol breath test 
X 
X 
Urine drug screen 
X 
X 
Hepatitis B and C screen 
X 
Evidence of vaccinatione 
X 
Xc 
HIV (types 1 and 2) screen 
X 
Medical history and 
demographics 
X 
Xc 
Physical examinationf 
X 
X 
X 
X 
Height, weight, and BMIg 
X 
X 
Randomization 
X 
Study drug administration 
X 
X 
PK blood sampling 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PD blood sampling - IgA, IgM, 
IgG 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PD blood sampling - IgG 
subtypes 1-4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PD blood sampling – CIC 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Immunogenicity blood 
sampling - ADA 
X 
FcRn occupancy 
X 
X 
X 
X 
X 
X 
X 
X 
Biochemistryh 
X 
X 
X 
X 
Coagulation 
X 
X 
X 
Hematology 
X 
X 
X 
X 
X 
Exploratory biomarker sample 
X 
X 
Urinalysisi 
X 
X 
X 
X 
Vital signsj 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


Protocol Amendment 4 
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ALXN1830-HV-108 
Table 4: 
SoA – Screening Through Day 9 for Multiple-Dose Cohort 3 
Page 20 of 98 
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Study Day 
Screen- 
ing 
-1 
1 
2 
3 
4 
5 
6 
7 
8 
9a 
Assessments 
Day -60 
to 
Day -2 
Admit 
Pre- 
dose 
EOI 
2 hb 
4 hb 
12 hb 
24 hb 
48 h 
72 h 
96 h 
120 h 
144 h 
Pre- 
dose 
EOI 
2 hb 
24 hb 
Window (hours) 
NA 
+0.25 
±0.25 
±0.5 
±0.5 
±1 
±1 
±1 
±1 
±1 
±1 
NA 
+0.25 
±0.25 
±1 
Status (OP or CRU) 
OP 
CRU 
12-lead ECG (triplicate) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Infusion site evaluationk 
X 
X 
X 
X 
Xl 
X 
X 
Xl 
Concomitant medications 
←Monitor continuously (after ICF is signed at Screening)→ 
Adverse events 
←Monitor continuously (after ICF is signed at Screening)→ 
a Participant will be discharged from the CRU after completing all Day 9, 16, 30, 37, 44, 51, 58, 65, 72, and 85 assessments. 
b Postdose evaluations at the 2-hour, 4-hour, 12-hour, and 24-hour timepoints are to be completed based on the start of infusion time. When multiple procedures 
are scheduled to occur at the same time, the following order of events should be strictly adhered to whenever possible: ECG, vital signs, blood sampling, and 
study intervention administration. 
c Activities will be performed on Day -1 only. 
d Serum pregnancy test at Screening and Day -1 and urine pregnancy test for all other timepoints in CRU. 
e All participants must be vaccinated as described in Section 6.5.3. 
f Full PE at screening and symptom directed PE thereafter. 
g Height and BMI at Screening only. 
h Fasting, due to lipid panel. Note: lipid panel is not performed at Screening. 
i Visit window (hours) is not applicable for urinalysis. 
j Including temperature, respiratory rate, and pulse oximetry. 
k In the event of an IRR, it is recommended to collect a blood sample for assessment of tryptase, histamine, CRP, cytokines, and complement as soon as the IRR 
is observed (prior to administering any IRR medication), and 2 hours, 24 hours, and 7 days (prior to the next dose of study drug) after onset of the IRR; a 
sample for PK/PD and ADAs may be collected if there is no predefined sample collection on the same day. 
l IRR evaluation will continue until the reaction is fully resolved. 
Abbreviations: ADA = antidrug antibodies; BMI = body mass index; CIC = circulating immune complexes; CRP = C-reactive protein; CRU = Clinical Research 
Unit; ECG = electrocardiogram; EOI = end of infusion; FcRn = neonatal crystallizable fragment receptor; HIV = human immunodeficiency virus; 
ICF = informed consent form; Ig = immunoglobulin; IRR = infusion related reaction; NA = not applicable; OP = outpatient; PD = pharmacodynamic(s); 
PE = physical examination; PK = pharmacokinetic(s); WOCBP = women of childbearing potential. 


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Table 5: 
SoA – Day 14 through 28 for Multiple-Dose Cohort 3 
 
Study Day 
14 
15 
16a 
21 
22 
23 
24 
25 
26 
27 
28 
Assessments 
Admit 
Pre- 
dose 
EOI 
2 hb 
24 hb 
Admit 
Pre- 
dose 
EOI 
2 hb 
4 hb 
12 hb 
24 hb 
48 h 
72 h 
96 h 
120 h 
144 h 
Window (hours) 
NA 
+0.25 
±0.25 
±1 
NA 
+0.25 
±0.25 
±0.5 
±0.5 
±1 
±1 
±1 
±1 
±1 
±1 
Status (OP or CRU) 
CRU 
Pregnancy test 
(WOCBP)c 
X 
X 
Alcohol breath test 
X 
X 
Urine drug screen 
X 
X 
Physical examinationd 
X 
X 
X 
Weight 
X 
X 
Study drug 
administration 
X 
X 
PK blood sampling 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PD blood sampling - 
IgA, IgM, IgG 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PD blood sampling - 
IgG subtypes 1-4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PD blood sampling – 
CIC 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Immunogenicity blood 
sampling - ADA 
X 
FcRn occupancy 
X 
X 
X 
X 
X 
X 
X 
X 
Biochemistrye,f 
X 
X 
X 
Hematologye 
X 
X 
X 
X 
Exploratory biomarker 
sample 
X 
Urinalysisg 
X 
X 
X 
X 
Vital signsh 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG (triplicate) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Infusion site evaluationi 
X 
Xg 
X 
X 
X 
X 
X 
Xj 
Concomitant 
medications 
←Monitor continuously (after ICF is signed at Screening)→ 
Adverse events 
←Monitor continuously (after ICF is signed at Screening)→ 


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a Participant will be discharged from the CRU after completing all Day 9, 16, 30, 37, 44, 51, 58, 65, 72, and 85 assessments. 
b Postdose evaluations at the 2-hour, 4-hour, 12-hour, and 24-hour timepoints are to be completed based on the start of infusion time. When multiple procedures 
are scheduled to occur at the same time, the following order of events should be strictly adhered to whenever possible: ECG, vital signs, blood sampling, and 
study intervention administration. 
c Serum pregnancy test at Screening and Day -1 and urine pregnancy test for all other timepoints in CRU. 
d Full PE at screening and symptom directed PE thereafter. 
e May be done on the day prior to dosing. 
f Fasting, due to lipid panel. Note: lipid panel is not performed at Screening. 
g Visit window (hours) is not applicable for urinalysis. 
h Including temperature, respiratory rate, and pulse oximetry. 
i In the event of an IRR, it is recommended to collect a blood sample for assessment of tryptase, histamine, CRP, cytokines, and complement as soon as the IRR 
is observed (prior to administering any IRR medication), and 2 hours, 24 hours, and 7 days (prior to the next dose of study drug) after onset of the IRR; a 
sample for PK/PD and ADAs may be collected if there is no predefined sample collection on the same day. 
j IRR evaluation will continue until the reaction is fully resolved. 
Abbreviations: ADA = antidrug antibodies; CIC = circulating immune complexes; CRP = C-reactive protein; CRU = Clinical Research Unit; 
ECG = electrocardiogram; EOI = end of infusion; FcRn = neonatal crystallizable fragment receptor; ICF = informed consent form; Ig = immunoglobulin; 
IRR = infusion related reaction; NA = not applicable; OP = outpatient; PD = pharmacodynamic(s); PE = physical examination; PK = pharmacokinetic(s); 
WOCBP = women of childbearing potential. 


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Table 6: 
SoA – Day 29 Through Day 44 for Multiple-Dose Cohort 3 
Study Day 
29 
30a 
35 
36 
37a 
42 
43 
44a 
Assessments 
Pre- 
dose 
EOI 
2 hb 
24 hb 
Admit 
Pre- 
dose 
EOI 
2 hb 
24 hb 
Admit 
Pre- 
dose 
EOI 
2 hb 
24 hb 
Window (hours) 
NA 
+0.25
±0.25 
±1 
NA 
+0.25
±0.25 
±1 
NA 
+0.25
±0.25 
±1 
Status (OP or CRU) 
CRU 
Pregnancy test (WOCBP)c 
X 
X 
Alcohol breath test 
X 
X 
Urine drug screen 
X 
X 
Physical examinationd 
X 
X 
X 
Weight 
X 
X 
X 
Study drug administration 
X 
X 
X 
PK blood sampling 
X 
X 
X 
PD blood sampling - IgA, IgM, 
IgG 
X 
X 
X 
PD blood sampling - IgG 
subtypes 1-4 
X 
X 
X 
PD blood sampling – CIC 
X 
X 
X 
Immunogenicity blood sampling 
- ADA 
X 
X 
FcRn occupancy 
X 
X 
X 
Biochemistrye,f 
X 
X 
Hematologye 
X 
X 
X 
Exploratory biomarker sample 
X 
Urinalysisg 
X 
X 
Vital signsh 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG (triplicate)
X 
X 
X 
Infusion site evaluationi 
X 
Xj 
X 
X 
Xj 
X 
X 
Xj 
X 
Concomitant medications 
←Monitor continuously (after ICF is signed at Screening)→ 
Adverse events 
←Monitor continuously (after ICF is signed at Screening)→ 
a Participant will be discharged from the CRU after completing all Day 9, 16, 30, 37, 44, 51, 58, 65, 72, and 85 assessments. 
b Postdose evaluations at the 2-hour and 24-hour timepoints are to be completed based on the start of infusion time. When multiple procedures are scheduled to 
occur at the same time, the following order of events should be strictly adhered to whenever possible: ECG, vital signs, blood sampling, and study intervention 
administration. 
c Serum pregnancy test at Screening and Day -1 and urine pregnancy test for all other timepoints in CRU. 
d Full PE at screening and symptom directed PE thereafter. 
e May be done on the day prior to dosing. 
f Fasting, due to lipid panel. Note: lipid panel is not performed at Screening. 


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25 Jun 2021 
ALXN1830-HV-108 
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g Visit window (hours) is not applicable for urinalysis. 
h Including temperature, respiratory rate, and pulse oximetry. 
i In the event of an IRR, it is recommended to collect a blood sample for assessment of tryptase, histamine, CRP, cytokines, and complement as soon as the IRR 
is observed (prior to administering any IRR medication), and 2 hours, 24 hours, and 7 days (prior to the next dose of study drug) after onset of the IRR; a 
sample for PK/PD and ADAs may be collected if there is no predefined sample collection on the same day. 
j IRR evaluation will continue until the reaction is fully resolved. 
Abbreviations: ADA = antidrug antibodies; CIC = circulating immune complexes; CRP = C-reactive protein; CRU = Clinical Research Unit; 
ECG = electrocardiogram; EOI = end of infusion; FcRn = neonatal crystallizable fragment receptor; ICF = informed consent form; Ig = immunoglobulin; 
IRR = infusion related reaction; NA = not applicable; OP = outpatient; PD = pharmacodynamic(s); PE = physical examination; PK = pharmacokinetic(s); 
WOCBP = women of childbearing potential. 


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Table 7: 
SoA – Day 49 Through Day 65 for Multiple-Dose Cohort 3 
 
Study Day 
49 
50 
51a 
56 
57 
58a 
63 
64 
65a 
Assessments 
Admit 
Pre-dose 
EOI 
2 hb 
24 hb 
Admit 
Pre-dose 
EOI 
2 hb 
24 hb 
Admit 
Pre-dose 
EOI 
2 hb 
24 hb 
Window (hours) 
NA 
+0.25 
±0.25 
±1 
NA 
+0.25 
±0.25 
±1 
NA 
+0.25 
±0.25 
±1 
Status (OP or CRU) 
CRU 
Pregnancy test (WOCBP)c 
X 
X 
X 
Alcohol breath test 
X 
X 
X 
Urine drug screen 
X 
X 
X 
Physical examinationd 
X 
X 
X 
Weight 
X 
X 
X 
Study drug administration 
X 
X 
X 
PK blood sampling 
X 
X 
X 
PD blood sampling - IgA, IgM, IgG 
X 
X 
X 
PD blood sampling - IgG subtypes 1-4 
X 
X 
X 
PD blood sampling – CIC 
X 
X 
X 
Immunogenicity blood sampling - ADA 
X 
X 
X 
FcRn occupancy 
X 
Biochemistrye,f 
X 
X 
X 
Hematologye 
X 
X 
X 
Exploratory biomarker sample 
X 
X 
X 
Urinalysisg 
X 
X 
X 
Vital signsh 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG (triplicate) 
X 
X 
X 
Infusion site evaluationi 
X 
Xj 
X 
X 
Xj 
X 
X 
Xj 
X 
Concomitant medications 
←Monitor continuously (after ICF is signed at Screening)→ 
Adverse events 
←Monitor continuously (after ICF is signed at Screening)→ 
a Participant will be discharged from the CRU after completing all Day 9, 16, 30, 37, 44, 51, 58, 65, 72, and 85 assessments. 
b Postdose evaluations at the 2-hour and 24-hour timepoints are to be completed based on the start of infusion time. When multiple procedures are scheduled to 
occur at the same time, the following order of events should be strictly adhered to whenever possible: ECG, vital signs, blood sampling, and study intervention 
administration. 
c Serum pregnancy test at Screening and Day -1 and urine pregnancy test for all other timepoints in CRU. 
d Full PE at screening and symptom directed PE thereafter. 
e May be done on the day prior to dosing. 
f Fasting, due to lipid panel. Note: lipid panel is not performed at Screening. 
g Visit window (hours) is not applicable for urinalysis. 
h Including temperature, respiratory rate, and pulse oximetry. 


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i In the event of an IRR, it is recommended to collect a blood sample for assessment of tryptase, histamine, CRP, cytokines, and complement as soon as the IRR 
is observed (prior to administering any IRR medication), and 2 hours, 24 hours, and 7 days (prior to the next dose of study drug) after onset of the IRR; a 
sample for PK/PD and ADAs may be collected if there is no predefined sample collection on the same day. 
j IRR evaluation will continue until the reaction is fully resolved. 
Abbreviations: ADA = antidrug antibodies; CIC = circulating immune complexes; CRP = C-reactive protein; CRU = Clinical Research Unit; 
ECG = electrocardiogram; EOI = end of infusion; FcRn = neonatal crystallizable fragment receptor; ICF = informed consent form; Ig = immunoglobulin; 
IRR = infusion related reaction; NA = not applicable; OP = outpatient; PD = pharmacodynamic(s); PE = physical examination; PK = pharmacokinetic(s); 
WOCBP = women of childbearing potential. 


Protocol Amendment 4 
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Table 8: 
SoA – Day 70 Through Day 79 for Multiple-Dose Cohort 3 
Study Day 
70 
71 
72a 
77 
78 
79 
Assessments 
Admit 
Pre- 
dose 
EOI 
2 hb 
24 hb 
Admit 
Pre- 
dose 
EOI 
2 hb 
4 hb 
12 hb 
24 hb 
Window (hours) 
NA 
+0.25
±0.25 
±1 
NA 
+0.25
±0.25 
±0.5 
±0.5 
±1 
Status (OP or CRU) 
CRU 
Pregnancy test (WOCBP)c 
X 
X 
Alcohol breath test 
X 
X 
Urine drug screen 
X 
X 
Physical examinationd 
X 
X 
Weight 
X 
X 
Study drug administration 
X 
X 
PK blood sampling 
X 
X 
X 
X 
X 
X 
PD blood sampling - IgA, IgM, IgG 
X 
X 
X 
X 
X 
X 
PD blood sampling - IgG subtypes 1-4 
X 
X 
X 
X 
X 
X 
PD blood sampling – CIC 
X 
X 
X 
X 
X 
X 
Immunogenicity blood sampling - ADA 
X 
FcRn occupancy 
X 
X 
X 
X 
X 
Biochemistrye 
X 
X 
Hematology 
X 
X 
X 
Urinalysisf 
X 
X 
X 
Vital signsg 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG (triplicate)
X 
X 
X 
X 
X 
X 
Infusion site evaluationh 
X 
X 
Xi 
X 
X 
X 
X 
Xi 
Concomitant medications 
←Monitor continuously (after ICF is signed at Screening)→ 
Adverse events 
←Monitor continuously (after ICF is signed at Screening)→ 
a Participant will be discharged from the CRU after completing all Day 9, 16, 30, 37, 44, 51, 58, 65, 72, and 85 assessments. 
b Postdose evaluations at the 2-hour, 4-hour, 12-hour, and 24-hour timepoints are to be completed based on the start of infusion time. When multiple procedures 
are scheduled to occur at the same time, the following order of events should be strictly adhered to whenever possible: ECG, vital signs, blood sampling, and 
study intervention administration. 
c Serum pregnancy test at Screening and Day -1 and urine pregnancy test for all other timepoints in CRU. 
d Full PE at screening and symptom directed PE thereafter. 
e Fasting, due to lipid panel. Note: lipid panel is not performed at Screening. 
f Visit window (hours) is not applicable for urinalysis. 
g Including temperature, respiratory rate, and pulse oximetry. 


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h In the event of an IRR, it is recommended to collect a blood sample for assessment of tryptase, histamine, CRP, cytokines, and complement as soon as the IRR 
is observed (prior to administering any IRR medication), and 2 hours, 24 hours, and 7 days (prior to the next dose of study drug) after onset of the IRR; a 
sample for PK/PD and ADAs may be collected if there is no predefined sample collection on the same day. 
i IRR evaluation will continue until the reaction is fully resolved. 
Abbreviations: ADA = antidrug antibodies; CIC = circulating immune complexes; CRP = C-reactive protein; CRU = Clinical Research Unit; 
ECG = electrocardiogram; EOI = end of infusion; FcRn = neonatal crystallizable fragment receptor; ICF = informed consent form; Ig = immunoglobulin; 
IRR = infusion related reaction; NA = not applicable; OP = outpatient; PD = pharmacodynamic(s); PE = physical examination; PK = pharmacokinetic(s); 
WOCBP = women of childbearing potential. 


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Table 9: 
SoA – Day 80 Through Day 141 for Multiple-Dose Cohort 3 
 
Study Day 
80 
81 
82 
83 
84 
85a 
99 
113 
120 
134 
141/ET 
Day 169 
Follow-up 
Phone Call 
Assessments 
48 h 
72 h 
96 h 
120 h 
144 h 
168 h 
NA 
NA 
NA 
NA 
NA 
NA 
Window (CRU = hours; OP = days) 
±1 h 
±1 h 
±1 h 
±1 h 
±1 h 
±1 h 
±1 day 
±1 day 
±1 day 
±1 day 
±1 day 
±3 days 
Status (OP or CRU) 
CRU 
OP 
Pregnancy test (WOCBP)b 
X 
X 
Xc 
Xd 
Physical examinatione 
X 
X 
Weight 
X 
X 
PK blood sampling 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PD blood sampling - IgA, IgM, IgG 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PD blood sampling - IgG subtypes 1-4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PD blood sampling – CIC 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Immunogenicity blood sampling - ADA 
X 
X 
X 
X 
FcRn occupancy 
X 
X 
X 
X 
X 
Biochemistryf 
X 
X 
X 
X 
Coagulation 
X 
X 
Hematology 
X 
X 
X 
X 
Exploratory biomarker sample 
X 
X 
X 
Urinalysisg 
X 
X 
Vital signsh 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG (triplicate) 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
←Monitor continuously (after ICF is signed at Screening)→ 
Adverse events 
←Monitor continuously (after ICF is signed at Screening)→ 
a Participant will be discharged from the CRU after completing all Day 9, 16, 30, 37, 44, 51, 58, 65, 72, and 85 assessments. 
b Serum pregnancy test at Screening and Day -1 and urine pregnancy test for all other timepoints in CRU and OP. 
c For the Day 141 Visit, dispense a urine pregnancy test kit for the Day 169 Follow-up Phone Call. For an ET Visit, dispense urine pregnancy test kits to allow 
monthly testing for 3 months after the last dose. 
d Participants will be requested to take a urine pregnancy test at home at approximately Day 169, or if ET, monthly for 3 months after the last dose; the site will 
solicit pregnancy test results, along with adverse events and concomitant medications, via phone call. 
e Full PE at screening and symptom directed PE thereafter. 
f Fasting, due to lipid panel. Note: lipid panel is not performed at Screening. 
g Visit window (hours) is not applicable for urinalysis. 
h Including temperature, respiratory rate, and pulse oximetry. 
Abbreviations: ADA = antidrug antibodies; CIC = circulating immune complexes; CRU = Clinical Research Unit; ECG = electrocardiogram; EOI = end of 
infusion; ET = early termination; FcRn = neonatal crystallizable fragment receptor; h = hours; ICF = informed consent form; Ig = immunoglobulin; NA = not 
applicable; OP = outpatient; PD = pharmacodynamic(s); PE = physical examination; PK = pharmacokinetic(s); WOCBP = women of childbearing potential. 


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Table 10: 
SoA – Screening Through Day 7 for Multiple-Dose Cohorts 4 to 6 
 
Study Day 
Screening 
-1 
1 
2 
3 
4 
5 
6 
7 
Assessments 
Day –60 to 
Day -2 
Admit 
Pre- 
dose 
EOI 
2 ha 
4 ha 
12 ha 
24 ha 
48 h 
72 h 
96 h 
120 h 
144 h 
Window (hours) 
NA 
+0.25 
±0.25 
±0.5 
±0.5 
±1 
±1 
±1 
±1 
±1 
±1 
Status (CRU or OP) 
OP 
CRU 
Informed consent 
X 
Inclusion/exclusion criteria 
X 
Xb 
Pregnancy test (WOCBP)c 
X 
X 
FSH test (postmenopausal women) 
X 
Alcohol breath test 
X 
X 
Urine drug screen 
X 
X 
Hepatitis B and C screen 
X 
Evidence of vaccinationd 
X 
Xb 
HIV (types 1 and 2) screen 
X 
Medical history and demographics 
X 
Xb 
Physical examinatione 
X 
X 
Height, weight, and BMIf 
X 
X 
Randomization 
X 
Study drug administration 
X 
PK blood sampling 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PD blood sampling - IgA, IgM, 
IgG 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PD blood sampling - IgG subtypes 
1-4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PD blood sampling – CIC 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Immunogenicity blood sampling - 
ADA 
X 
FcRn occupancy 
X 
X 
X 
X 
X 
X 
X 
Biochemistryg 
X 
X 
X 
Coagulation 
X 
X 
X 
Hematology 
X 
X 
X 
X 
Exploratory biomarker sample 
X 
X 
Urinalysish 
X 
X 
X 
X 
Vital signsi 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG (triplicate) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Infusion site evaluationj 
X 
X 
X 
X 
Xk 
Concomitant medications 
←Monitor continuously (after ICF is signed at Screening)→ 
Adverse events 
←Monitor continuously (after ICF is signed at Screening)→ 


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a Postdose evaluations at the 2-hour, 4-hour, 12-hour, and 24-hour timepoints are to be completed based on the start of infusion time. When multiple procedures 
are scheduled to occur at the same time, the following order of events should be strictly adhered to whenever possible: ECG, vital signs, blood sampling, and 
study intervention administration. 
b Activities will be performed on Day -1 only. 
c Serum pregnancy test at Screening and Day -1 and urine pregnancy test for all other timepoints in CRU. 
d All participants must be vaccinated as described in Section 6.5.3. 
e Full PE at screening and symptom directed PE thereafter. 
f Height and BMI at Screening only. 
g Fasting, due to lipid panel. Note: lipid panel is not performed at Screening. 
h Visit window (hours) is not applicable for urinalysis. 
i Including temperature, respiratory rate, and pulse oximetry. 
j In the event of an IRR, it is recommended to collect a blood sample for assessment of tryptase, histamine, CRP, cytokines, and complement as soon as the IRR 
is observed (prior to administering any IRR medication), and 2 hours, 24 hours and 7 days (prior to the next dose of study drug) after onset of the IRR; a blood 
sample for PK/PD and ADAs may be collected if there is no predefined sample collection on the same day. 
k IRR evaluation will continue until the reaction is fully resolved. 
Abbreviations: ADA = antidrug antibodies; BMI = body mass index; CIC = circulating immune complexes; CRP = C-reactive protein; CRU = Clinical Research 
Unit; ECG = electrocardiogram; EOI = end of infusion; FcRn = neonatal crystallizable fragment receptor; FSH = follicle stimulating hormone; h = hours; 
HIV = human immunodeficiency virus; ICF = informed consent form; Ig = immunoglobulin; IRR = infusion related reaction; NA = not applicable; 
OP = outpatient; PD = pharmacodynamic(s); PE = physical examination; PK = pharmacokinetic(s); WOCBP = women of childbearing potential. 


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Table 11: 
SoA – Day 8 Through Day 23 for Multiple-Dose Cohorts 4 to 6 
 
Study Day 
8 
9a 
14 
15 
16a 
21 
22 
23 
Assessments 
Pre- 
dose 
EOI 
2 hb 
24 hb 
Admit 
Pre- 
dose 
EOI 
2 hb 
24 hb 
Admit 
Pre- 
dose 
EOI 
2 hb 
4 hb 
12 hb 
24 hb 
Window (hours) 
NA 
+0.25 
±0.25 
±1 
NA 
+0.25 
±0.25 
±1 
NA 
+0.25 
±0.25 
±0.5 
±0.5 
±1 
Status (OP or CRU) 
CRU 
Pregnancy test (WOCBP)c 
X 
X 
Alcohol breath test 
X 
X 
Urine drug screen 
X 
X 
Physical examinationd 
X 
X 
X 
Weight 
X 
X 
X 
Study drug administration 
X 
X 
X 
PK blood sampling 
X 
X 
X 
X 
X 
X 
X 
X 
PD blood sampling - IgA, 
IgM, IgG 
X 
X 
X 
X 
X 
X 
X 
X 
PD blood sampling - IgG 
subtypes 1-4 
X 
X 
X 
X 
X 
X 
X 
X 
PD blood sampling – CIC 
X 
X 
X 
X 
X 
X 
X 
X 
Immunogenicity blood 
sampling - ADA 
X 
FcRn occupancy 
X 
X 
X 
X 
X 
X 
X 
Biochemistrye 
X 
X 
Hematology 
X 
X 
X 
X 
X 
Urinalysisf 
X 
X 
Vital signsg 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG (triplicate) 
X 
X 
X 
X 
X 
X 
X 
X 
Infusion site evaluationh 
X 
Xi 
X 
X 
Xi 
X 
X 
X 
X 
X 
Xi 
Concomitant medications 
←Monitor continuously (after ICF is signed at Screening)→ 
Adverse events 
←Monitor continuously (after ICF is signed at Screening)→ 
a Participant will be discharged from the CRU after completing all Day 9, 16, and 29 assessments. 
b Postdose evaluations at the 2-hour, 4-hour, 12-hour, and 24-hour timepoints are to be completed based on the start of infusion time. When multiple procedures 
are scheduled to occur at the same time, the following order of events should be strictly adhered to whenever possible: ECG, vital signs, blood sampling, and 
study intervention administration. 
c Serum pregnancy test at Screening and Day -1 and urine pregnancy test for all other timepoints in CRU. 
d Full PE at screening and symptom directed PE thereafter. 
e Fasting, due to lipid panel. Note: lipid panel is not performed at Screening. 
f Visit window (hours) is not applicable for urinalysis. 
g Including temperature, respiratory rate, and pulse oximetry. 


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h In the event of an IRR, it is recommended to collect a blood sample for assessment of tryptase, histamine, CRP, cytokines, and complement as soon as the IRR 
is observed (prior to administering any IRR medication), and 2 hours, 24 hours and 7 days (prior to the next dose of study drug) after onset of the IRR; a blood 
sample for PK/PD and ADAs may be collected if there is no predefined sample collection on the same day. 
i IRR evaluation will continue until the reaction is fully resolved. 
Abbreviations: ADA = antidrug antibodies; BMI = body mass index; CIC = circulating immune complexes; CRP = C-reactive protein; CRU = Clinical Research 
Unit; ECG = electrocardiogram; EOI = end of infusion; FcRn = neonatal crystallizable fragment receptor; h = hours; ICF = informed consent form; 
Ig = immunoglobulin; IRR = infusion related reaction; NA = not applicable; OP = outpatient; PD = pharmacodynamic(s); PE = physical examination; 
PK = pharmacokinetic(s); WOCBP = women of childbearing potential. 


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Table 12: 
SoA – Day 24 Through Day 85 for Multiple-Dose Cohorts 4 to 6 
 
Study Day 
24 
25 
26 
27 
28 
29a 
36 
50 
64 
78 
85/ET 
Day 113 
Follow-up 
Phone Call 
Assessments 
48 h 
72 h 
96 h 
120 h 
144 h 
168 h 
NA 
NA 
NA 
NA 
NA 
NA 
Window (CRU = hours; OP = days) 
±1 h 
±1 h 
±1 h 
±1 h 
±1 h 
±1 h 
±1 day 
±1 day 
±1 day 
±1 day 
±1 day 
±3 days 
Status (OP or CRU) 
CRU 
OP 
Pregnancy test (WOCBP)b 
X 
Xc 
Xd 
Physical examinatione 
X 
X 
X 
Weight 
X 
X 
X 
PK blood sampling 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PD blood sampling - IgA, IgM, IgG 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PD blood sampling - IgG subtypes 1-4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PD blood sampling – CIC 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Immunogenicity blood sampling - ADA 
X 
X 
X 
X 
FcRn occupancy 
X 
X 
X 
X 
X 
Biochemistryf 
X 
X 
X 
Coagulation 
X 
X 
Hematology 
X 
X 
X 
X 
Exploratory biomarker sample 
X 
X 
Urinalysis 
Xg 
X 
X 
Vital signsh 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG (triplicate) 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
←Monitor continuously (after ICF is signed at Screening)→ 
Adverse events 
←Monitor continuously (after ICF is signed at Screening)→ 
a Participant will be discharged from the CRU after completing all Day 9, 16, and 29 assessments. 
b Serum pregnancy test at Screening and Day -1 and urine pregnancy test for all other timepoints in CRU and OP. 
c For the Day 85 Visit, dispense a urine pregnancy test kit for the Day 113 Follow-up Phone Call. For an ET Visit, dispense urine pregnancy test kits to allow 
monthly testing for 3 months after the last dose. 
d Participants will be requested to take a urine pregnancy test at home at approximately Day 113, or, if ET, monthly for 3 months after the last dose; the site will 
solicit results, along with adverse events and concomitant medications, via phone call. 
e Full PE at screening and symptom directed PE thereafter. 
f Fasting, due to lipid panel. Note: lipid panel is not performed at Screening. 
g Visit window (hours) is not applicable for urinalysis. 
h Including temperature, respiratory rate, and pulse oximetry. 


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Abbreviations: ADA = antidrug antibodies; BMI = body mass index; CIC = circulating immune complexes; CRU = Clinical Research Unit; 
ECG = electrocardiogram; ET = early termination; FcRn = neonatal crystallizable fragment receptor; h = hours; ICF = informed consent form; 
Ig = immunoglobulin; NA = not applicable; OP = outpatient; PD = pharmacodynamic(s); PE = physical examination; PK = pharmacokinetic(s); 
WOCBP = women of childbearing potential. 


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2. 
INTRODUCTION 
ALXN1830 is a humanized, affinity-matured IgG4 kappa mAb that binds to the FcRn and blocks 
FcRn-mediated recycling of IgG and IgG immune complexes (ICs), thereby lowering total IgG 
(including pathogenic autoantibodies) and ICs in circulation. As FcRn is also involved in 
albumin recycling, ALXN1830 was designed to specifically block the IgG-binding site but not 
the albumin-binding site on FcRn. Studies in both nonhuman primates and humans have 
demonstrated that ALXN1830 treatment leads to decreases in endogenous IgG levels without 
affecting serum albumin levels (Mezo, 2008; Nixon, 2015). 
Immunoglobulin G can indirectly cause disease activity through the formation of ICs, which 
induce the production of inflammatory cytokines or promote antigen presentation and the 
pathogenic activity of T cells, which also provide help to B cells resulting in the production of 
additional pathogenic IgG antibodies (Blumberg and Lencer, 2005). The FcRn contributes to 
such immunopathology by both maintaining the levels of pathogenic IgG antibodies and 
orchestrating the inflammatory activities of IgG-ICs (Baker, 2009; Pyzik, 2015; 
Roopenian and Akilesh 2007). 
There has been increasing recognition that FcRn blockade is a novel, reversible, and potentially 
effective means to treat a large number of autoimmune diseases in humans. The potential 
efficacy of FcRn blockade was originally supported by preclinical studies in experimental 
autoimmune myasthenia gravis (MG) in rats, wherein such FcRn blockade can impede both 
passive MG induced by administration of an anti-acetylcholine receptor antibody, or in active 
MG in rats that were immunized against the acetylcholine receptor (Liu, 2007). More recently, 
clinical studies in patients with MG and other IgG-mediated autoimmune diseases have 
demonstrated improvement in disease endpoints following treatment with anti-FcRn 
therapeutics. 
While current treatments for certain autoimmune disorders, including chronic steroids, 
immunosuppressants, intravenous immunoglobulin (IVIG), plasmapheresis, and anti-CD20 
mAbs (such as rituximab), can be effective, they are associated with significant adverse effects, 
and delayed or non-durable responses particularly in an elderly population. There remains a clear 
unmet medical need for the treatment of IgG-mediated diseases. Administration of ALXN1830, 
leading to a significant decrease in total IgG, pathogenic IgG autoantibodies, and the circulating 
immune complexes (CICs) of which these IgG are constituents, should lead to a decrease in the 
clinical manifestations of diseases of this type. Moreover, the ability of ALXN1830 to reduce 
CICs and the innate and adaptive immune responses triggered by CICs may result in sustained 
disease modification. 
The purpose of this Phase 1 study in healthy adult participants is to evaluate the safety, 
tolerability, PK, PD, and immunogenicity of single ascending and once weekly (qw) multiple 
ascending SC doses of ALXN1830. 
Data from this study are anticipated to help design future studies in patients with IgG-mediated 
diseases. 


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2.1. 
Study Rationale 
ALXN1830 has been studied in 4 completed clinical studies using the IV route of administration. 
It was initially tested in an IV SAD study in healthy participants, Study SYNT001-101. The 
highest IV dose tested in the SAD study, 30 mg/kg, was well tolerated. ALXN1830 was then 
studied in 2 Phase 1b/2a studies in autoimmune patients: Study SYNT001-102 in warm 
autoimmune hemolytic anemia (WAIHA) patients, and Study SYNT001-103 in pemphigus 
vulgaris (PV) patients. In both studies, the participants received 5 qw doses of 10 mg/kg, a dose 
and regimen which was well tolerated. 
Subsequently, a MAD study in healthy participants, Study SYNT001-104, was initiated to 
investigate the safety, tolerability, PK, PD, and immunogenicity of ALXN1830 IV. The dose 
level of the first cohort in the MAD study was 20 mg/kg IV, with 3 doses given qw (3 × qw) 
followed by 3 doses given every 2 weeks (3 × q2w). A second cohort was initiated using a dose 
level of 30 mg/kg, but the study was paused after 4 participants in Cohort 2 each received only a 
single dose due to the observation of acute infusion related reactions (IRRs) in the 20 mg/kg 
cohort. 
SYNT001-102 and SYNT001-103 were also paused at that time for a Good Manufacturing 
Practice (GMP) investigation of the study drug batches. Although there was no conclusive 
clinical or safety link between the findings of the GMP investigation and the IRRs, and the drug 
product lots used had met all of the approved release specifications, the investigation did identify 
potential impurities in the drug product that could have possibly confounded the safety profile. 
Alexion has implemented changes to the manufacturing process for future batches to enhance the 
control and detection of impurities. 
Another Phase 1 study in healthy participants using the SC route of administration, Study 
ALXN1830-HV-105, was initiated at a single site in the United Kingdom to investigate the 
safety, tolerability, PK, PD, and immunogenicity of single and multiple SC doses of ALXN1830. 
A total of 12 participants received a single SC dose of 750 mg (n = 6) or 1,250 mg (n = 3) or 
placebo (PBO; n = 3) before the study was terminated due to the coronavirus disease 2019 
(COVID-19) pandemic. The highest SC single dose tested in this study, 1250 mg, was well 
tolerated. 
The purpose of this Phase 1 study in healthy adult participants is to evaluate the safety, 
tolerability, PK, PD, and immunogenicity of single ascending and multiple ascending doses of 
ALXN1830 administered SC and to compare safety, tolerability, PK, PD, and immunogenicity of 
ALXN1830 in Japanese participants with non-Japanese participants. Data from this study are 
anticipated to help design future studies in patients with IgG-mediated diseases. 
Healthy participants are the appropriate population for this study because they will enable PK 
and PD assessments without the potential confounding effects due to other disease activities, 
comorbidities, or medications. This study has been designed to minimize risks to participants 
with strict inclusion/exclusion criteria, as well as a robust safety monitoring and risk mitigation 
plan. 


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2.2. 
Background 
A detailed description of the chemistry, pharmacology, efficacy, safety, and toxicology data 
available for ALXN1830 is provided in the Investigator’s Brochure (IB). 
Nonclinical studies have assessed both the potential toxicity and primary PD effects associated 
with ALXN1830 antagonism of IgG binding to FcRn and IgG recycling mediated by FcRn. The 
administration of ALXN1830 to cynomolgus monkeys by qw IV infusion at doses from 5 to 
100 mg/kg for 2 to 27 weeks was well tolerated, with the exception of immunogenicity related 
effects of this humanized mAb in monkeys, and produced dose-dependent, specific, and 
reversible reductions in circulating IgG levels. No effects on IgA, IgM, or albumin levels were 
observed. 
ALXN1830 has been evaluated in 4 completed clinical studies: SYNT001-101 (healthy 
participants, single dose study), SYNT001-102 (WAIHA patients, 5 × 10 mg/kg qw), 
SYNT001-103 (PV patients, 5 × 10 mg/kg qw), and SYNT001-104 (healthy participants, 3 × 20 
mg/kg qw, then 3 × 20 mg/kg q2w), and 1 clinical study ALXN1830-HV-105, in healthy 
participants, was paused2 after completing the first cohort and part of the second cohort (single 
SC doses of 750 mg and 1,250 mg). In all the clinical studies, ALXN1830 was shown to increase 
the catabolism of IgG, as manifested by decreased total IgG in serum in a dose-dependent 
manner up to 64% decrease from baseline, with no effects on IgA, IgM, or albumin. ALXN1830 
also decreased the level of circulating IgG IC. This predicts that ALXN1830 will also accelerate 
degradation of endogenous circulating IgG autoantibodies and IgG IC specifically involved in 
the pathogenesis of autoimmunity. 
 
2.3. 
Benefit/Risk Assessment 
This is a healthy participant study, and there is no direct benefit to study participants. However, 
the PK/PD data together with safety profiles without being confounded by underlying disease or 
concomitant medications, may benefit future human studies in general. Detailed risk assessment 
is listed in Table 13, as well as in the IB. In addition, a discussion of theoretical risks associated 
with the reduction of IgG is provided in Section 10.7.1. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2 A temporary halt was implemented to allow assessment of the extent of SARS-CoV2 exposure in the UK. 


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2.3.1. 
Risk Assessment 
Table 13: 
Risk Assessment for ALXN1830 
Identified and Potential Risk 
of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation 
Strategy 
Study Drug (s) ALXN1830 
Infusion-Related Reaction 
A total of 6 IRRs in clinical studies have been 
observed. The safety data may have been 
confounded by Chemistry and Manufacturing 
Control findings. 
See Section 10.4 for 
IRR management. 
Immunogenicity 
Treatment with any therapeutic protein may induce 
an immune response. Occasionally, this immune 
response is clinically meaningful. The 
consequences of an immune reaction to a 
therapeutic protein range from transient 
appearance of antibodies, without any clinical 
consequence, to severe, life-threatening 
conditions. Potential clinical consequences also 
may include severe hypersensitivity-type 
reactions, decrease in efficacy, and induction of 
autoimmunity. 
See SoA (Section 1.3 
and Section 10.4 for 
IRR (including ADA 
associated IRR) 
management. 
Abbreviations: ADA = antidrug antibody; IRR = infusion-related reaction. 
2.3.2. 
Benefit Assessment 
As this is a study in healthy participants, only societal benefit is expected. Initial testing in 
healthy participants is warranted, as studies in patients, especially those with rare autoimmune 
diseases, may take years to accrue and complete. Healthy participant studies however may be 
completed more rapidly and without the multiple confounding variables of the underlying 
disease and concomitant medications. Also, for studies in healthy participants, the study duration 
is limited to the protocol-defined dosing regimen. Therefore, the total exposure is considerably 
less than what is likely to be required for patients who may require chronic dosing. Most adverse 
events (AEs) reported in previous studies with ALXN1830 were nonserious and resolved with 
discontinuation of study drug. While the potential of serious AEs or unexpected AEs exists, this 
healthy participant study will provide meaningful scientific information which will continue to 
play an important role in future development of this drug. 
2.3.3. 
Overall Benefit: Risk Conclusion 
ALXN1830 was well tolerated after single doses up to 30 mg/kg IV and 1250 mg SC (the 
highest single doses tested in SAD studies) in healthy adults. Also, ALXN1830 was well 
tolerated after multiple IV doses at 10 mg/kg × 5 doses in autoimmune patients. However, at 
multiple IV doses of 20 mg/kg in healthy participants, the development of potentially immune 
mediated IRRs that resulted in immediate and permanent discontinuation of study drug, together 
with 100% incidence rate of headache, suggested that close safety monitoring and 
implementation of risk mitigation measures are warranted for future studies in the clinical 
development program (Section 10.6). Of note, these IRRs were mild and moderate in severity 
and all resolved after cessation of the study drug, without treatment. Similarly, all AEs of 
headache were mild to moderate and were resolved. 


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As described in Section 2.1, potential impurities in the drug product could possibly have 
confounded the safety profile. Alexion has implemented changes to the manufacturing process 
for the current and future batches to enhance the control and detection of impurities. 
The proposed safety measures in this study include documentation of pneumococcal and current 
seasonal flu vaccination; staggered dosing; stopping rules; close participant monitoring through 
60 days after the last dose; close safety and PD monitoring with an unblinded medical monitor; 
avoidance of participants with a high risk of infections; antibiotics to manage infection as 
needed; rescue measures such as IVIG replacement in an extremely unlikely event of profoundly 
low IgG; as well as use of an SRC for safety monitoring and dose selections. 
Considering the measures taken to minimize risk to participants in this study, the risks associated 
with ALXN1830 are justified by the anticipated benefits that may be afforded to patients with 
autoimmune disease. 


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3. 
OBJECTIVES AND ENDPOINTS 
Objectives and Endpoints: 
 
Objectives 
Endpoints 
Primary 
• 
To assess the safety and tolerability of 
single and multiple doses of 
ALXN1830 SC 
• 
Safety assessed by the incidence and relatedness of 
TEAEs, SAEs, AESIs, physical examination, vital 
sign measurements, clinical laboratory, and ECG 
results 
Secondary 
• 
To assess the PK of single and 
multiple doses of ALXN1830 SC 
• 
To explore the PD effects of single 
and multiple doses of ALXN1830 SC 
• 
To assess the immunogenicity of 
ALXN1830 SC 
• 
To compare safety and tolerability, 
PK, PD, and immunogenicity of 
ALXN1830 SC between Japanese and 
non-Japanese healthy participants 
• 
Serum ALXN1830 concentration profiles and single- 
and multiple-dose PK parameters 
• 
Change in serum IgG levels over time; FcRn 
saturation as measured by receptor occupancy 
• 
Incidence of antidrug antibodies and neutralizing 
antibodies to ALXN1830 
• 
Quantitative assessment of safety, PK parameters, PD 
parameters, and immunogenicity between Japanese 
and non-Japanese healthy participants 
Abbreviations: AESI = adverse events of special interest; ECG = electrocardiogram; FcRn = neonatal crystallizable 
fragment receptor; IgG = immunoglobulin G; PD = pharmacodynamics; PK = pharmacokinetics; SAE = serious 
adverse event; SC = subcutaneous; TEAE = treatment-emergent adverse event. 


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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a Phase 1 study in up to a maximum of 48 healthy adult participants (36 on active 
treatment, 12 on PBO). The study will consist of 2 SAD (Cohorts 1 and 2) and 4 MAD cohorts 
(Cohorts 3 to 6). Cohort 6 will enroll Japanese1 participants. Eight participants will be randomly 
assigned in a 6:2 ratio in each of the 6 cohorts to receive either single or multiple SC doses of 
ALXN1830 (n = 6 per cohort) or single or multiple doses of PBO (n = 2 per cohort). The 
planned study duration is approximately 124 days for Cohorts 1 and 2: up to 60 days for 
screening and approximately 64 days for dosing and follow-up; 201 days for Cohort 3: up to 
60 days for screening and approximately 141 days for dosing and follow-up; and 148 days for 
Cohorts 4 to 6: 60 days for screening and approximately 88 days for dosing and follow-up. 
Participants will be admitted to an inpatient facility during the dosing and follow-up period as 
shown in Section 1.3. 
Initially, the first 4 participants randomized to each cohort will be dosed with 3 participants on 
active treatment and 1 participant on PBO. The dosing will be staggered, with an interval of at 
least 3 days for the SAD cohorts and at least 7 days for the MAD cohorts, before dosing the rest 
of the participants in the cohort. The shorter interval of staggered dosing for the SAD cohorts 
compared to the MAD cohorts is considered appropriate as the expected PK exposure of the 
ALXN1830 SC doses will be a fraction of that of the IV dose demonstrated to be safe and well 
tolerated in previous IV studies. The reduction of IgG after a single SC dose will be similar to 
the observed IgG reduction in previous IV studies; and in general, there will be low risk of 
immunogenicity and IRRs after a single dose. See Section 4.3 for details regarding expected PK 
exposures and IgG reduction. All participants will be observed during the drug administration 
and for 2 hours after dosing for safety and participants will be encouraged to report any 
discomfort immediately, especially within 24 hours post dosing. At no time will more than 4 
participants per cohort be dosed on a given day. 
An SRC, consisting of the Investigator, and Alexion Safety Physician, Medical Monitor, Study 
Statistician, and Clinical Pharmacologist, will evaluate the study data at prespecified time points 
for participant safety and make recommendations on dose escalation, dose modification, or 
termination of the study (see SRC charter for description of membership, schedule of meetings, 
data required for each safety review, and requirements for documenting meeting discussions and 
outcome). Relevant safety data from any other studies ongoing with ALXN1830 will be made 
available to the SRC. At Alexion’s discretion, and after consultation with the SRC, additional 
participants may be enrolled as replacement participants only if a participant discontinues within 
3 weeks of the last dose for reasons other than drug-related AEs. 
The timing and dependencies of the dosing cohorts are described in Table 14 and Table 15. 


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Table 14: 
Planned Dose and Dose Regimens of ALXN1830 in Healthy Participants 
Cohort No. 
Regimen/Route of Administration 
Study Drug (N) 
1 
Single dose SC 
Placebo (n = 2) or 
ALXN1830 1500 mg (n = 6) 
2 
Single dose SC 
Placebo (n = 2) or 
ALXN1830 2250 mg (n = 6) 
3 
Multiple dose (12 doses qw) SC 
Placebo (n = 2) or 
ALXN1830 750 mg (n = 6) 
4 
Multiple dose (4 doses qw) SC 
Placebo (n = 2) or 
ALXN1830 1500 mg (n = 6) 
5 
Multiple dose (4 doses qw) SC 
Placebo (n = 2) or 
ALXN1830 2250 mg (n = 6) 
6a 
Multiple dose (4 doses qw) SC 
Japanese healthy participants 
Placebo (n = 2) or 
ALXN1830 HTD (n = 6) 
a Healthy, Japanese participants enrolled in Cohort 6 will be dosed according to the HTD established in the 
non-Japanese cohorts. 
Abbreviations: qw = weekly; SC = subcutaneous; HTD = highest tolerated dose. 


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Table 15: 
Minimum Data Requirements for Dose Escalation 
 
Decision- 
making 
Time 
Point: 
Dosing 
Regimen 
Person 
or Body 
Making 
the 
Decision: 
Minimum Data to be 
Looked at (in Accordance 
With the CSP): 
Method of Documentation 
of Decision and/or 
Communication to 
Alexion (if Applicable): 
Continuation 
from any 
sub-cohort to 
the next sub- 
cohort, 
within any 
cohort 
As per relevant 
cohort 
PI 
A minimum of 3 days (SAD) / 
7 days (MAD) post-dose safety 
and tolerability data from the 
first sub-cohort. 
The Investigator will document 
the decision in an email to 
Alexion. The email does not 
require Alexion’s response, 
unless there is disagreement 
with the Investigator’s 
decision. 
Cohort 1 
1500 mg, 
single dose SC 
N/A 
N/A 
N/A 
Cohort 2 
2250 mg, 
single dose SC 
SRC 
Review all available safety 
data and IgA, IgG, and IgM 
data through Day 15 from 
Cohort 1, from a minimum of 
6 participants. 
The SRC will document the 
decision on the 
escalation/progression 
approval form. 
Cohort 3 
750 mg, 
12 doses SC, 
once weekly 
SRC 
N/A 
This cohort may start in 
parallel to Cohort 1. 
N/A 
Cohort 4 
1500 mg, 
4 doses SC, 
once weekly 
SRC 
Review all available safety 
data and IgA, IgG, and IgM 
data through Day 22 from 
Cohort 3, from a minimum of 
6 participants. 
The SRC will document the 
decision on the 
escalation/progression 
approval form. 
Cohort 5 
2250 mg, 
4 doses SC, 
once weekly 
SRC 
Review all available safety 
data and IgA, IgG, and IgM 
data through Day 22 from 
Cohort 4, from a minimum of 
6 participants. 
The SRC will document the 
decision on the 
escalation/progression 
approval form. 
Cohort 6a 
HTD, 
4 doses SC, 
once weekly 
SRC 
Review all available safety 
data and IgA, IgG, and IgM 
data through Day 22 from 
Cohort 5. 
The SRC will document the 
decision on the 
escalation/progression 
approval form. 
a Healthy, Japanese participants enrolled in Cohort 6 will be dosed according to the HTD established in the non- 
Japanese cohorts. 
Abbreviations: CSP = Clinical Study Protocol; HTD = highest tolerated dose; Ig = immunoglobulin; 
MAD = multiple ascending dose; N/A = not applicable; PI = Principal Investigator; PK = pharmacokinetics; 
SAD = single ascending dose; SC = subcutaneous; SRC = Safety Review Committee. 


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4.2. 
Scientific Rationale for Study Design 
ALXN1830 has been studied in 5 clinical studies, 4 studies using the IV route of administration 
and one SC administration. Refer to Section 2.2 for background on clinical studies conducted 
with ALXN1830 to date. 
This randomized, double-blind, PBO-controlled, SAD/MAD design was chosen for assessment 
of the safety, tolerability, PK/PD, and immunogenicity of single- and multiple ascending doses 
of ALXN1830 administered SC. 
Healthy participants are the appropriate population for this study, enabling the effects of 
ALXN1830 to be evaluated without the potential confounding effects of other disease activities, 
comorbidities, or medications. 
A staggered dosing paradigm is being used for participant protection. A PBO control is 
implemented in each cohort. Due to the difficulty of providing a matching PBO, participants 
randomized to PBO will receive an equivalent volume of saline at the same SC infusion rate as 
the active treatment. 
ALXN1830 is an anti-FcRn mAb that blocks recycling of IgG antibodies, reducing the total IgG 
in circulation, including potentially pathogenic IgG autoantibodies associated with multiple 
autoimmune diseases. Thus, reduction in IgG level is used to measure the anti-FcRn PD activity 
of ALXN1830. 
This study uses a comprehensive approach to minimize the potential risk of infection in the 
healthy participants due to the theoretical concerns associated with reducing total IgG (discussed 
in greater detail in Section 10.6). The following criteria will be observed as part of the 
enrollment criteria (Section 5.1), monitoring, and specified response to certain signs, symptoms, 
or laboratory results: 
• Inclusion criteria of heathy participants with: 
− Immunoglobulin G levels of ≥ 1,000 mg/dL 
− No history of acute and chronic infections, ie, enrolled healthy participants will be 
immunocompetent 
− Absence of any immunologic deficiencies, as per the Investigator’s discretion 
− Pneumococcus and seasonal influenza vaccination 
• To ensure a timely and adequate intervention if needed, IgG levels will be 
continuously and closely monitored during this study. 
• Stopping rules (Section 7.2) for individuals and cohorts will be based on reduction of 
IgG level to ≤ 300 mg/dL (justification for IgG level to ≤ 300 mg/dL is provided in 
Section 10.6). 
− Dosing will be permanently stopped in any individual if the IgG level is reduced 
to ≤ 300 mg/dL. 
− If 2 or more participants in a cohort exhibit an IgG reduction to ≤ 300 mg/dL, 
dosing in that cohort will stop and no further dose escalation will occur. 


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• Although unlikely to occur, in the unexpected instance of an IgG reduction falling 
into the severe category (ie, less than 100 mg/dL) or if there is any suggestion, signs, 
or symptoms of infection, antibiotics and/or IVIG will be considered. 
4.3. 
Justification for Dose 
Single and multiple IV doses of ALXN1830 have been administered in healthy participants, and 
in patients with WAIHA and PV. In healthy participants, single IV doses were given at 1, 3, 10 
and 30 mg/kg (Study SYNT001-101), and multiple IV doses were given at 20 mg/kg qw for 
3 doses and then q2w for 3 doses (Study SYNT001-104). In WAIHA (Study SYNT001-102) and 
PV (Study SYNT001-103) patients, IV doses of 10 mg/kg qw for 5 doses were given. Also, 
single SC doses of 750 mg and 1250 mg ALXN1830 have been administered in a limited number 
of healthy participants (Study ALXN1830-HV-105). 
A physiologically based PK/PD model for IV dosing was established and was fitted to the IV 
PK/PD data from healthy participants. Due to the lack of robust SC data in humans, an SC 
PK/PD model is not yet available. However, the following has been observed: 
1. The bioavailability (F) of ALXN1830 after SC administration is likely low: 
a. Based on the preliminary results from the 5-week SC monkey toxicity study 
(Study 2455024), F after a single dose of 30 mg/kg SC in monkeys is around 21.5%. 
2. The maximum reduction of IgG for ALXN1830 is likely similar between IV and SC at 
the same mg/kg dose: 
a. At 100 mg/kg IV or SC in the 5-week Good Laboratory Practice (GLP) toxicology 
studies (Studies 2455-002 and 2455-024), the maximum IgG reduction was 68% after 
IV and 69% after SC. 
b. At 750 mg SC or 10 mg/kg IV, similar IgG reduction was observed in a clinical study 
in healthy participants (Studies ALXN1830-HV-105, SYNT001-01). 
3. ALXN1830 bioavailability after SC administration is 20%. 
Based on these observations, ALXN1830 exposure, safety margin, and IgG reduction after SC 
administration was predicted (see Table 16). The following assumptions have been used: 
ALXN1830 clearance (CL) and body weight have the following relationship: 
CL = (Median CL) × (body weight/median body weight)0.75 


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Table 16: 
Predicted ALXN1830 Exposure, Safety Margin, and Immunoglobulin G 
Reduction after Subcutaneous Administration 
 
Cohort 
Dose 
(mg) 
Body 
Weight 
(kg) a 
Weekly 
Dose in 
mg/kg a,b 
F 
AUC of SC 
Dosing 
(h*μg/mL) a,c 
Margin 
Based on 
NOAEL of 
Monkey 
Toxicology 
Studies a,d 
Margin 
Based on 
5-week 
Monkey 
SC 
Toxicology 
Studya,e 
Margin 
Based on 
27-week 
Monkey IV 
Toxicology 
Study a,f 
Expected 
Maximum 
IgG 
Reduction 
(%) g 
1 
1500, 
75 
20 
0.2 
1451 
5 
4 
24 
-45 
single 
(50 - 90) 
(16.7 - 30) 
(1265 - 2664) 
(3.3 - 6) 
(2 - 5) 
(13 - 28) 
dose 
2 
2250, 
75 
30 
0.2 
2948 
3.3 
2.2 
12 
-48 
single 
(50 - 90) 
(25 - 45) 
(2571 - 3996) 
(2.2 - 4) 
(1.6 - 2.5) 
(9 - 14) 
dose 
3 
750 qw × 
75 
10 
0.2 
675 
10 
10 
52 
-68 
12 
(50 - 90) 
(8.3 - 15) 
(589 - 983) 
(7 - 12) 
(7 - 11) 
(35 - 59) 
4 
1500 qw 
75 
20 
0.2 
1451 
5 
4 
24 
-69 
× 4 
(50 - 90) 
(16.7 - 30) 
(1265 - 2664) 
(3 - 6) 
(2 - 5) 
(13 - 28) 
5 
2250 qw 
75 
30 
0.2 
2948 
3 
2.2 
12 
-72 
× 4 
(50 - 90) 
(25 - 45) 
(2571 - 3996) 
(2 - 4) 
(1.6 - 2.5) 
(9 - 14) 
a Values are median (min - max). 
b Weekly dose in mg/kg = (dose in mg) / (body weight in kg). 
c AUCSC = (Dose/CLIV) * F, where CLIV is scaled as CLIV = (Median CLIV) × (body weight/median body weight)0 75. Median 
CLIV at 10 mg/kg = 239 mL/h with a median body weight of 82.7 kg (SYNT001-101); Median CLIV at 20mg/kg = 215 mL/h 
with a median body weight of 79 kg (SYNT001-104); Median CLIV at 30 mg/kg = 154 mL/h with a median body weight of 
75.8 kg (SYNT001-101). Where median CLIV is not available at certain dose levels (eg 15 mg/kg), doses (mg/kg) are round up 
to obtain a conservative estimate. Median CLIV for 45 mg/kg is set to equal to median AUCIV at 30 mg/kg (2.03 mL/h/kg). The 
AUC represents AUC0-inf and AUCss for single and multiple doses respectively. 
d Safety margin = (Monkey NOAEL in mg/kg) / (Human dose in mg/kg). Monkey NOAEL for weekly dosing is 100 mg/kg 
(Studies 2455-024 and 2455-016). 
e Safety margin = (Monkey AUC0-120h at NOAEL) / (Predicted human AUCSC). Day 29 AUC0-120h = 6420 h*μg/mL at 100 mg/kg 
weekly SC (Study 2455-024). 
f Safety margin = (Monkey AUC0-Tlast at NOAEL) / (Predicted human AUCSC). Day 92 AUC0-Tlast = 34800 h*μg/mL at 
100 mg/kg weekly IV (Study 2455-016). 
g IgG reduction is based on predicted IgG reduction at equivalent IV dose in mg/kg. IgG reduction at median body weight is 
presented. 
Abbreviations: AUC = area under the concentration-time curve; AUC0-120h = area under the concentration-time curve from time 0 
(dosing) to 120 hours post-dose; AUC0-inf = area under the concentration-time curve from time 0 to infinity; AUC0-Tlast = area 
under the concentration-time curve from time 0 to the last quantifiable concentration; AUCss = area under the concentration-time 
curve from time 0 to steady state; CL = total body clearance of drug from the plasma; F = absolute bioavailability; 
IgG = immunoglobulin G; IV = intravenous; min = minimum; max = maximum; NOAEL = no observed adverse effect level; qw 
= weekly; SC = subcutaneous. 
Study ALXN1830-HV-108 will include 2 SAD cohorts and up to 4 MAD cohorts in healthy 
adult participants (Figure 1). The starting dose of the SAD portion of the SC study will be 
1500 mg, equivalent to 20 mg/kg in a 75-kg participant, or 25 mg/kg in a 60-kg participant. 
Previously, 30 mg/kg has been shown to be well tolerated when administered as a single dose by 
IV infusion in healthy participants (Study SYNT001-101). Compared to the no observed adverse 
effect level (NOAEL) in the GLP IV (100 mg/kg/week IV, Study 2455-002 and Study 2455-016) 
or SC (100 mg/kg/week SC, Study 2455-024) toxicology studies in monkeys, the SC starting 
dose of 1500 mg will have a safety margin of approximately 2-fold (for a 50-kg participant) or 4- 
fold (for a 75-kg participant) on a mg/kg dose basis. Assuming a human bioavailability of 20% 
the expected area under the concentration-time curve (AUC) at 1500 mg SC will have a safety 
margin of 2-fold (for a 50-kg participant) or 4-fold (for a 75-kg participant) based on the 
NOAEL exposure from the 5-week SC monkey toxicity study, and 13-fold (for a 50-kg 


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participant) or 24-fold (for a 75-kg participant) based on the NOAEL exposure from the 27-week 
IV monkey toxicity study. More importantly, a 30 mg/kg IV single dose has been tested in 
healthy participants and this starting dose of 1500 mg SC is expected to be roughly one-fifth to 
one-eighth of the exposure at 30 mg/kg IV, based on the low bioavailability observed in 
monkeys for ALXN1830 and in healthy participants from other anti-FcRn compounds. Based on 
these observations, the expected maximum IgG reduction at 1500 mg SC would be around -45% 
from baseline. 
In the SAD portion, the SC dose will be escalated 1.5-fold from 1500 mg (Cohort 1) to 2250 mg 
(Cohort 2). An SRC review of safety, tolerability, and IgG data will be conducted before each 
dose escalation. Staggered dosing and pre-specified stopping rules based on safety and IgG 
reduction will be implemented in all cohorts. 
As shown in Table 16 the first MAD cohort will be administered 750 mg SC qw for 12 weeks 
(Cohort 3). On a mg/kg basis, the 750 mg SC qw dose represents at least a 7 to 35-fold safety 
margin when compared to the NOAEL exposures of the 5-week SC and 27-week IV monkey 
GLP studies. The first MAD cohort (750 mg, qw, Cohort 3) may start at the same time as the 
single-dose Cohort 1 (1500 mg) while the rest of the MAD cohorts will start after SRC review of 
the previous MAD cohorts. While all the MAD cohorts have a treatment duration of 4 weeks, 
Cohort 3 (750 mg SC qw for 12 weeks) is of an extended duration to enable the evaluation of 
immunogenicity and safety after long term administration of ALXN1830. 
The SC multiple doses will be escalated 2-fold from 750 mg qw to 1500 mg qw (Cohort 4), and 
then 1.5-fold to 2250 mg qw (Cohort 5) after SRC review. At these dose levels, the expected 
maximum IgG reduction after 4 qw doses is expected to be around 69% and 72%, respectively, 
which is similar to that observed with 20 mg/kg IV in Study SYNT001-104 (after the 3 qw 
loading doses). 
As shown in Table 15, Cohort 6 will assess the safety, tolerability, PK, PD, safety, and 
immunogenicity of ALXN1830 in Japanese participants at the highest tolerable dose established 
in the non-Japanese participants (ie, either up to 1500 mg or up to 2250 mg SC qw for 4 doses). 
The exact dose and time of dosing will be determined after SRC review of all safety data through 
Day 36 from Cohort 5 as well as from all prior cohorts. Japanese participants are expected to 
have a lower mean body weight than non-Japanese participants. This and other differences (eg, 
genetics) may impact PK/PD in Japanese participants. Although Japanese participants may 
potentially have slightly higher exposure based on the lower mean body weight, the overall 
exposure in Japanese participants is predicted not to exceed established safety margins. 
 
4.4. 
End of Study Definition 
A participant is considered to have completed the study if he/she has completed the last 
scheduled visit shown in the SoA (Section 1.3). 
The end of the study is defined as the date of the last participant follow-up visit in the study, as 
specified in the SoA. 


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5. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
 
5.1. 
Inclusion Criteria 
Male and female participants are eligible to be included in the study only if all of the following 
criteria apply: 
Age 
1. Participants must be between the ages of 18 and 55 years, inclusive, at the time of signing 
the informed consent. 
Type of Participant 
2. Participants who are healthy as determined by medical evaluation including medical 
history, physical examination, laboratory tests, and cardiac monitoring. 
3. Participant agrees to not donate blood for 4 months after completion of their last study 
visit. 
4. Baseline IgG concentrations ≥ 1,000 mg/dL at Screening. 
5. Baseline IgA and IgM3 above the lower limit of normal at Screening. 
6. Participants must have had vaccination against pneumococcus (Pneumovax 23 
[PPSV23]) at least 28 days, and maximally 4 years prior to Day 1. 
7. Participants must have had seasonal influenza vaccination for the current season at least 
28 days prior to Day 1. 
8. Participants of Japanese descent (Cohort 6) are defined as: 
a. First generation (born to 2 Japanese parents and 4 Japanese grandparents). 
b. Participant must have been born in Japan, and not have lived outside Japan for greater 
than 10 years. 
c. Lifestyle, including diet, must not have significantly changed since leaving Japan. 
Weight 
9. Body weight within 60 to 90 kg, inclusive, and body mass index (BMI) within the range 
of 18 to 30 kg/m2, inclusive. 
 
 
 
 
 
 
 
 
 
3IgM levels are expected to be above the upper level of normal per local laboratory reference range if the participant 
has recently received Pneumovax 23 vaccination. Therefore, participants are eligible if they have been recently 
vaccinated with Pneumovax 23 per vaccination criteria described in Section 6.5.3 and the IgM level corresponds 
with the post-vaccination normal limits, per the Investigator’s discretion. 


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Contraception 
10. Female participants of childbearing potential and male participants with female partners
of childbearing potential must be willing to follow protocol-specified contraception
guidance during the study and for 3 months after last dose of study drug (see Section 10.5
for more contraceptive guidance).
Informed Consent 
11. Capable of giving signed informed consent which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and the protocol.
5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
Medical Conditions 
1. History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal,
endocrinological, hematological, or neurological disorders capable of significantly
altering the absorption, metabolism, or elimination of drugs; constituting a risk when
taking the study drug; or interfering with the interpretation of data.
2. Abnormal blood pressure (BP) as determined by the Investigator (resting BP should be
between 140/80 mmHg and 90/60 mmHg) at Screening.
3. Participants who have any clinically significant history of allergy or hypersensitivity.
4. History of unexplained, recurrent infection, or infection requiring treatment with systemic
antibiotics within 90 days prior to dosing on Day 1.
5. Participants with a history of frequent and/or chronic headaches, including migraine
disorder, cluster headache disorder, and tension headache disorder.
6. Previous history of cancer, except for adequately treated basal cell or squamous cell
carcinoma of the skin.
7. Clinically significant abnormalities and laboratory test results.
8. Current or chronic history of liver disease or known hepatic or biliary abnormalities (with
the exception of Gilbert's syndrome or asymptomatic gallstones).
9. Corrected QT (QTc) > 450 msec for male participants or > 470 msec for female
participants.
NOTE: The QTc is the QT interval corrected for heart rate according to Fridericia’s
formula (QTcF). It is either machine-read or manually over-read.
10. Female participants who are pregnant or breastfeeding.
Prior/Concomitant Therapy 
11. Past or intended use of over-the-counter or prescription medication including herbal
medications within 14 days (or longer in case of a specific herbal medication) prior to
dosing.


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12. Known exposure to investigational or marketed therapeutic proteins, such as mAbs, 
fusion proteins, bispecific molecules, or antibody drug conjugates, within 60 days or 5 
half-lives (whichever is longer) prior to dosing. 
13. Participants who have prior exposure to ALXN1830. 
14. Any vaccination within 2 weeks of screening other than those required for this study. 
15. Any live virus vaccination within 6 months of screening. 
Prior/Concurrent Clinical Study Experience 
16. Exposure to more than 4 new (small molecule) investigational compounds within 
12 months prior to dosing. 
17. Current enrollment or past participation within the last 90 days before signing of consent 
in this or any other interventional clinical study. 
Diagnostic Assessments 
18. Presence of hepatitis B surface antigen (HBsAg) at Screening. 
19. Positive hepatitis C antibody test result at Screening. 
20. Positive pre-study drug/alcohol screen at Screening. 
21. Positive human immunodeficiency virus (HIV) antibody test at Screening. 
Other Exclusions 
22. History of illicit drug abuse and/or history of significant alcohol abuse within 1 year prior 
to the Screening Visit or clinical evidence of substance and/or alcohol dependence within 
the 2 years before screening. 
23. Use of tobacco in any form (eg, smoking or chewing) or other nicotine-containing 
products in any form (eg, gum, patch, electronic cigarettes) within 24 hours prior to the 
planned first day of dosing. 
24. Has a tattoo or body piercing which might interfere with infusion site examination 
throughout the duration of the study. 
25. Individuals who are either immunocompromised or have one of the following underlying 
medical conditions: anatomic or functional asplenia (including sickle cell disease); 
primary antibody deficiencies; or HIV. 
26. Professional healthcare workers exposed to environments of greater risk for infectious 
disease. 
27. Research, industrial, and clinical laboratory personnel routinely exposed to infectious 
agents (bacterial or viral). 
28. Students living on a college or university campus. 
29. Daycare center workers 
30. Individuals who are in prolonged contact (defined as providing personal care for or living 
under the same roof) with: 
a. Children who attend daycare 


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b. Students living on a college or university campus 
 
5.3. 
Lifestyle Considerations 
5.3.1. 
Meals and Dietary Restrictions 
• Participants are required to abstain from ingesting food containing poppy seeds 
within 24 hours prior to admission. 
• No outside food or drink is permitted at the inpatient facility. All meals and snacks 
will be provided. Participants will receive standard meals and snacks at scheduled 
times during confinement. 
5.3.2. 
Caffeine, Alcohol, and Tobacco 
Participants will be required to abstain from: 
• Ingesting caffeine- or xanthine-containing products (eg, coffee, tea, cola drinks, and 
chocolate) 24 hours before admission through discharge from the inpatient facility, 
and 24 hours before each study follow-up visit. 
• Ingesting alcohol 24 hours before admission through discharge from the inpatient 
facility, and 24 hours before each study follow-up visit. 
• Smoking tobacco products from 24 hours before admission through discharge from 
the inpatient facility, and 24 hours before each study follow-up visit. 
 
5.3.3. 
Activity 
Participants will be required to abstain from strenuous physical activity within 48 hours prior to 
blood draws for clinical safety laboratory testing. 
 
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently randomly assigned to study drug. A minimal set of screen failure information is 
required to ensure transparent reporting of screen failure participants to meet the Consolidated 
Standards of Reporting Trials (CONSORT) publishing requirements (Schulz, 2010) and to 
respond to queries from regulatory authorities. Minimal information includes demography, 
screen failure details (eg, failed eligibility criteria), and any serious adverse event (SAE) 
occurring during the screening period. 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened. Rescreened participants should be assigned the same participant number as for the 
initial screening. 
Any study-related testing performed at Screening may be repeated within the screening visit 
window per the Investigator’s discretion for the purpose of further determining eligibility. 


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6. 
STUDY INTERVENTION 
Study intervention is defined as any investigational intervention(s), marketed product(s), PBO, or 
medical device(s) intended to be administered to a study participant according to the study 
protocol. 
6.1. 
Study Interventions Administered 
The doses and formulations to be administered in this study are presented in Table 17. The SAD 
and MAD cohorts may use study drug that has been manufactured with different compositions 
which can be considered comparable based on analytical and characterization data. Refer to the 
IB for the compositions of ALXN1830. Placebo will be commercially available normal saline. 
Table 17: 
Study Drug 
 
Drug name 
ALXN1830 
Placebo 
Type 
Biologic 
Diluent 
Dose 
formulation 
Sterile liquid 
Sterile liquid 
Unit dose 
strength(s) 
ALXN1830 is formulated at 150 mg/mL, 
and supplied as a 1500 mg/10 mL vial 
Placebo 
Dosage level(s) 
Refer to Table 14 
Not applicable 
Route of 
administration 
SC infusion 
SC infusion 
Use 
Investigational Product 
Placebo 
IMP and NIMP 
IMP 
IMP 
Sourcing 
Provided by Alexion 
Provided by study site 
Packaging and 
labeling 
Study drug will be provided in a 10 mL 
vial. Each vial will be labeled as required 
per country requirement 
Placebo (normal saline) will be provided in 
country-specific commercially available form 
Abbreviations: IMP = investigational medicinal product; NIMP = non-IMP; SC = subcutaneous. 
 
6.2. 
Preparation/Handling/Storage/Accountability 
Details regarding preparation, handling, storage, accountability, and administration of the study 
drug are discussed below. Additional guidance is provided in the pharmacy manual. 
1. The Investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study drug received and any discrepancies are reported 
and resolved before use of the study drug. 
2. Only participants enrolled in the study may receive study drug and only authorized site 
staff may supply or administer study drug. All study drug must be stored in a secure, 
environmentally controlled, and monitored (manual or automated) area in accordance 
with the labeled storage conditions with access limited to the Investigator and authorized 
site staff. 


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3. The site’s pharmacy staff is responsible for study drug accountability, reconciliation, and
record maintenance (ie, receipt, reconciliation, and final disposition records).
a.
This responsibility includes the reporting of any product complaints to
 within 1 business day. A product complaint is
defined as any written, electronic, or oral communication that alleges deficiencies
related to the identity, quality, durability, reliability, usability, safety, effectiveness, or
performance of a product or clinical trial material and/or its packaging components
after it is has been released for distribution to an end customer that affects the
performance of such product.
4. Further guidance regarding preparation, handling, storage, and accountability and
information for the final disposition of unused study drug is provided in the Pharmacy
Manual.
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
This is a double-blind study. Eligible participants who meet all inclusion and no exclusion 
criteria will be assigned unique numbers for enrollment and randomization. 
On Day 1 participants will be assigned a unique number (randomization number) in ascending 
numerical order. The randomization number encodes the participant’s assignment to one of the 
6 cohorts of the study, according to the randomization schedule generated prior to the study by 
the Statistics Department at Syneos Health. 
Participants will be randomly assigned in a 6:2 ratio to receive either single or multiple doses of 
ALXN1830 or PBO (Table 14). The Investigator will remain blinded to each participant’s 
assigned study drug throughout the course of the study. In order to maintain this blind, site's 
pharmacy staff will be responsible for the reconstitution and dispensation of all study drug. 
In the event of a Quality Assurance audit, the auditor(s) will be allowed access to unblinded 
study drug records at the site(s) to verify that randomization/dispensing has been done 
accurately. 
In the event of an emergency, an envelope for each participant containing his/her study drug 
assignment will be available in the pharmacy at the clinical study site. Unblinding should only be 
considered for the safety of the participant. If unblinding is deemed necessary by the 
Investigator, the Investigator can unblind the participant’s treatment allocation using the 
envelope available from the pharmacy staff. The Investigator must note the date, time, and 
reason for unblinding. The Investigator should inform the Medical Monitor that the participant 
was unblinded; however, the Investigator should not reveal to the Medical Monitor the 
participant’s treatment allocation. The blind will be maintained for persons responsible for the 
ongoing conduct of the study (such as the management, monitors, Investigator) and those 
responsible for data analysis and interpretation of results at the conclusion of the study, such as 
biometrics personnel. Unblinded information will only be accessible to those who need to be 
involved in the safety reporting to health authorities, independent ethics committees (IECs), or 
persons performing ongoing safety evaluations during the study. The Investigator will receive 
only blinded information unless unblinded information is judged necessary for safety reasons. 


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6.4. 
Study Intervention Compliance 
Participants will receive study drug directly from the Investigator, under medical supervision. 
The date and time of each dose administered in the clinic will be recorded in the source 
documents and recorded in the CRF. The dose of study drug and study participant identification 
will be confirmed at the time of dosing by a member of the study site staff other than the person 
administering the study drug. 


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6.5. 
Concomitant Therapy 
Any medication or vaccine (including over-the-counter or prescription medicines, vitamins, 
and/or herbal supplements, or other specific categories of interest) that the participant is 
receiving at the time of enrollment or receives during the study must be recorded along with: 
• Reason for use 
• Dates of administration including start and end dates 
• Dosage information including dose and frequency 
Concomitant treatment that is medically indicated for any AEs the participant experiences during 
the study is permitted. 
If concomitant medication is needed during the study, this medication must be recorded on the 
eCRF, stating its generic name, time of administration, dose, route and duration, as well as the 
reason for administration. 
The Medical Monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. 
 
6.5.1. 
Hydration 
 
It is recommended that study participants drink approximately 2 L (women)/2.5 L (men) of 
water every day during the 3 days preceding and following an infusion treatment (further 
information on hydration prior to dosing is provided in Section 10.7.2). 
 
6.5.2. 
Supportive/Symptomatic Care 
The use of supportive therapy/symptomatic treatment is allowable at any time during the study to 
treat AEs. The date and time of administration of supportive therapy/symptomatic treatment as 
well as the name and dosage regimen of any medication must be recorded. Details are provided 
in the study manual. 
Supportive/symptomatic care such as histamine H1 and H2 receptor blockers, eg, 
diphenhydramine and famotidine are recommended for any manifesting allergic reactions and 
associated gastrointestinal symptoms; ondansetron for persistent nausea; bronchodilators for 
potential dyspnea, eg, salbutamol or pirbuterol; analgesics/antipyretics for headache, pyrexia and 
myalgia, eg, acetaminophen; and fluids or normal saline in case of hypotension. 
Adhere to infectious disease preventive measures per World Health Organization (WHO) and 
local guidance. If a participant develops any signs or symptoms suggestive of infection (any), 
they should be treated as per the relevant local guidelines. 
 
6.5.3. 
Vaccinations 
To mitigate the potential of sinopulmonary infections associated with anti-FcRN targeted IgG 
reduction therapy, all participants in this study must have been adequately vaccinated against the 
following: 
1. Pneumococcus 
2. Seasonal influenza 


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6.5.4. 
Antibiotics Use 
Antibiotics may be administered as needed to manage infection. 
6.5.5. 
Disallowed Medication 
During the study, participants are not allowed to use any kind of prescribed medication, 
including mAbs other than the study drug, any investigational drug or device, and vaccinations 
within 2 weeks of screening (other than those to be administered as part of this study; refer to 
Section 6.5.3) and for the duration of the study. 
The use of over-the-counter medication is not allowed from 14 days prior to the first 
administration of study drug until the end of study (EOS) except the medications described 
above. 
6.6. 
Dose Modification 
Decisions to continue or modify dosing will be made by the Investigator and/or SRC after review 
of the blinded data. The SRC may also make recommendations regarding safety issues, study 
conduct, or study suspension. 
6.7. 
Intervention After the End of the Study 
This is a healthy participant study and no follow-up study drug administration is planned. 


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7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of Study Intervention 
In rare instances, it may be necessary for a participant to permanently discontinue (definitive 
discontinuation) study drug. Unless a participant fully withdraws their consent, they will 
continue their enrollment without study drug administration but will be required to complete a 
follow up visit for safety purposes. See the SoA (Section 1.3) for data to be collected at the time 
of discontinuation of study drug and follow-up and for any further evaluations that need to be 
completed. 
 
7.2. 
Stopping Criteria 
7.2.1. 
Immunoglobulin Stopping Rules 
It is proposed that the lower limit of IgG will be set at ≤ 300 mg/dL as an individual stopping 
rule for the healthy participant study. More specifically, if any predose measurements show a 
reduction of IgG level to ≤ 300 mg/dL, the individual stopping rule will be met. Repeat testing to 
confirm the consistency of the result is permitted. Healthy participants can rebound to their 
baseline IgG level when the drug is discontinued because they are not immunocompromised, as 
evidenced by existing anti-FcRn studies. Additionally, risk mitigation strategies such as 
antibiotics or IVIG replacement therapy may be implemented if participants have laboratory 
evidence of infection and/or are clinically symptomatic. 
If 2 or more participants in a cohort exhibit IgG reduction to ≤ 300 mg/dL, dosing in that 
cohort/dose level will stop and no further dose escalation will occur. 
In addition, any participant for whom IgA or IgM falls below the normal limits (according to the 
reference ranges of the laboratory) and is associated with clinical signs and symptoms will be 
discontinued from further dosing. 


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7.2.2. 
Safety Stopping Rules (Individual, Cohort and Study Level Stopping Rules) 
Individual Level: 
• Study drug will be discontinued immediately (if applicable) and permanently if any of 
the following occurs: 
− Development of a ‘serious’ adverse reaction (AR), or ‘severe’ (≥ Grade 3) AR. 
− Development of a ‘serious’ adverse reaction (AR), or ‘severe’ (≥ Grade 3) IRR. 
• If a moderate Grade 2 AR is observed, study drug administration may be continued, 
delayed, or discontinued in accordance with Investigator’s clinical judgment and in 
consultation with Alexion. 
Cohort and Study Level: 
• A cohort and other cohort with a dose at an equal or higher level will be stopped or 
not initiated if any of the following occurs: 
− ≥ 2 participants on study drug in the cohort experience a moderate (Grade 2) AR 
that does not improve by 14 days after treatment 
− ≥ 2 participants on study drug in the cohort experience an IRR as described earlier 
(see individual level) 
• Study will be discontinued (all dosing [lower, equal, or higher doses]) and 
continuation of the cohort or study will require a substantial amendment, if any of the 
following occurs: 
− Two participants on study drug in any cohort experience a severe (Grade 3) AR 
− One participant on study drug in any cohort experiences a serious AR 


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7.3. 
Participant Discontinuation/Withdrawal from the Study 
•
All efforts should be made to ensure participants are willing to comply with study
participation prior to conducting the screening procedures. The study staff should
notify Alexion and their site monitor of all study withdrawals as soon as possible. The
reason for participant discontinuation must be recorded in the source documents and
CRF.
•
A participant may withdraw from the study at any time at his/her own request or may
be withdrawn at any time at the discretion of the Investigator for safety, behavioral,
compliance, or administrative reasons. This is expected to be uncommon.
•
At the time of discontinuing from the study, if possible, an early termination visit
should be conducted, as shown in the SoA (Section 1.3). See SoA for data to be
collected at the time of study discontinuation and follow-up and for any further
evaluations that need to be completed.
•
The participant will be permanently discontinued both from the study drug and from
the study at that time.
•
If the participant withdraws consent for disclosure of future information, Alexion may
retain and continue to use any data collected before such a withdrawal of consent.
•
If a participant withdraws from the study, he/she may request destruction of any
samples taken and not tested, and the Investigator must document this in the site
study records.
Not all participants who withdraw will be replaced. At Alexion’s discretion, and after 
consultation with the SRC, additional participants may be enrolled as replacement participants 
only if a participant discontinues within 3 weeks of the last dose for reasons other than drug- 
related AEs. 
7.4. 
Lost to Follow-up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
•
The site must attempt to contact the participant and reschedule the missed visit as
soon as possible and counsel the participant on the importance of maintaining the
assigned visit schedule and ascertain whether the participant wishes to and/or should
continue in the study.
•
Before a participant is deemed lost to follow-up, the Investigator must make every
effort to regain contact with the participant (where possible, 3 telephone calls and, if
necessary, a certified letter to the participant’s last known mailing address or local
equivalent methods). These contact attempts should be documented in the
participant’s medical record.


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• Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
Discontinuation of specific sites or of the study is handled as part of Section 10.1.9 Study and 
Site Start and Closure. 
The Investigator, competent authority, or Sponsor may terminate the study for reasonable cause. 
Conditions that warrant termination of the study include, but are not limited to, the following: 
• Discovery of an unexpected, serious, or unacceptable risk to participants enrolled in 
the study. 
• Decision on the part of Alexion to suspend or discontinue testing, evaluation, or 
development of the study drug. 
• Failure of the Investigator to comply with the approved protocol, pertinent guidelines, 
and/or regulations. 
• Submission of knowingly false information from the Investigator to Alexion and/or 
regulatory authorities. 


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8. 
STUDY ASSESSMENTS AND PROCEDURES 
• Study procedures and their timing are summarized in the SoA (Section 1.3). Protocol 
waivers or exemptions are not allowed. 
• Immediate safety concerns should be discussed with Alexion immediately upon 
occurrence or awareness to determine if the participant should continue or 
discontinue study drug. 
• Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct. 
• All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The Investigator will maintain a screening log 
to record details of all participants screened and to confirm eligibility or record 
reasons for screening failure, as applicable. 
• Procedures conducted as part of the participant’s routine clinical management (eg, 
blood count) and obtained before signing of the ICF may be utilized for screening or 
baseline purposes provided the procedures met the protocol-specified criteria and 
were performed within the time frame defined in the SoA. 
 
8.1. 
Efficacy Assessments 
No efficacy assessments will be obtained during the study. 
 
8.2. 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA (Section 1.3). 
 
8.2.1. 
Physical Examinations 
A full physical examination will be performed at Screening. A symptom-driven physical 
examination will be performed predose and at the EOS visit and may be performed at other 
times, at the Investigator’s discretion. 
Each examination will include the following assessments: general appearance; skin; head, ears, 
eyes, nose, and throat; neck; lymph nodes; chest; heart; abdominal cavity; limbs; central nervous 
system; and musculoskeletal system. 
Height and BMI will be recorded at Screening. Weight will also be recorded predose. 
 
8.2.2. 
Vital Signs 
• Vital signs will be taken after the participant has been resting in the supine or semi 
recumbent position for at least 5 minutes and will include temperature (°C); tympanic 
or oral), respiratory rate, and pulse oxymetry. The timing of vital sign measurements 
is described in the SoA (Section 1.3). Out of range BP or pulse measurements will be 
repeated at the Investigator’s discretion. Confirmed, clinically significant vital sign 
measurements will be recorded as AEs. 


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•
Blood pressure and pulse measurements will be assessed in a semi-supine position
with a completely automated device. Manual techniques will be used only if an
automated device is not available.
•
Blood pressure and pulse measurements should be preceded by at least 5 minutes of
rest for the participant in a quiet setting without distractions (eg, television, cell
phones). Ideally, the same arm for each participant should be used for measurements.
8.2.3. 
Electrocardiograms
12-lead electrocardiogram (ECG) will be conducted as outlined in the SoA (see Section 1.3) to
obtain heart rate, PR, QRS, QT, and QTc intervals after participant has been in the supine
position for at least 5 minutes.
The subjects will avoid postural changes, and clinical staff will ensure that subjects are awake 
during the ECG recording. 
At each time point, the ECG will be recorded in triplicate, to reduce variance and improve the 
precision of measurement. The triplicates will be performed at approximately 1-minute intervals. 
Each ECG recording (trace) will last 10 seconds. Repeat ECGs will be performed until at least 
three 10-second ECG records per scheduled time point meet the quality criteria. 
8.2.4. 
Clinical Safety Laboratory Assessments 
•
See Section 10.2 for the list of clinical laboratory tests to be performed and to the
SoA (Section 1.3) for the timing and frequency.
•
The Investigator must review the laboratory report, document this review, and record
any clinically relevant changes occurring during the study in the AE section of the
case report form (CRF). The laboratory reports must be filed with the source
documents.
•
All laboratory tests with values considered clinically significantly abnormal during
participation in the study or within 5 half-lives after the last dose of study drug should
be repeated until the values return to normal or baseline or are no longer considered
clinically significant by the Investigator or Medical Monitor.
−If such values do not return to normal/baseline within a period of time judged
reasonable by the Investigator, the etiology should be identified, and Alexion
notified.
−
All protocol required- laboratory assessments, as defined in Section 10.2, must be
conducted in accordance with the laboratory manual and the SoA.
−
If laboratory values from non-protocol specified laboratory assessments
performed at the institution’s local laboratory require a change in participant
management or are considered clinically significant by the Investigator (eg, SAE
or AE or dose modification), then the results must be recorded in the CRF.


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8.2.5. 
Virus Serology 
Blood samples collected at Screening will be analyzed for HIV-1, HIV-2, HBsAg, hepatitis B 
core antibody, and hepatitis C virus antibody titers. 
 
8.2.6. 
Vaccination 
Participants will be adequately vaccinated as described in Section 6.5.3 and Section 5.1. 
 
8.2.7. 
Drug and Alcohol Screen 
A urine sample for drug screen will be analyzed for the substances listed in Section 10.2. Timing 
of urine drug and alcohol breath tests is specified in the SoA (Section 1.3). 
 
8.2.8. 
Pregnancy 
• Pregnancy data from female participants and female spouses/partners of male 
participants will be collected from the first dose of study drug until 3 months after the 
last dose of study drug. Any female participant who becomes pregnant while 
participating in the study will be discontinued from the study drug. If a pregnancy is 
reported, the Investigator must immediately inform Alexion within 24 hours of 
awareness of the pregnancy and follow the procedures outlined in Section 10.5. 
• For all Alexion products, both in development or postapproval, exposure during 
pregnancy must be recorded and the pregnancy followed, until the outcome of the 
pregnancy is known (ie, spontaneous miscarriage, elective termination, normal birth, 
or congenital abnormality), even if the participant discontinues the study drug or 
withdraws from the study. The corresponding infant must be followed-up for 3 
months postpartum. 
• Pregnancy is not considered as an AE (Section 10.5.3) unless there is a suspicion that 
the study drug may have interfered with the effectiveness of a contraceptive 
medication. However, complications of pregnancy and abnormal outcomes of 
pregnancy are AEs and may meet the criteria for an SAE (eg, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital 
anomaly) (Section 8.3). Elective abortions without complications should not be 
reported as AEs. 
 
8.2.9. 
Infusion Site Evaluation 
Infusion site evaluations will be performed at the time points specified in the SoA (Section 1.3). 
Infusion site reactions (eg, induration ≤ 1 cm in size) will not be listed as an AE unless they 
persist for more than 24 hours. 
8.3. 
Adverse Events and Serious Adverse Events 
The definitions of AEs and SAEs and specific reporting requirements can be found in 
Section 10.3. 
All AEs will be reported to the Investigator or qualified designee by the participant (or, when 
appropriate, by a caregiver, surrogate, or the participant’s legally authorized representative). 


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The Investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for following 
up AEs that are serious, considered related to the study drug or study procedures, or that caused 
the participant to discontinue the study drug (see Section 7). 
Procedures for recording, evaluating, follow-up, and reporting AEs and SAEs are outlined in 
Section 10.3 (Appendix 3). 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE Information 
All AEs and SAEs will be collected from the signing of the ICF until the follow-up visit at the 
time points specified in the SoA (Section 1.3). 
All SAEs will be recorded and reported to Alexion or the designee immediately and under no 
circumstance should this exceed 24 hours, as indicated in Section 10.3. The Investigator will 
submit any updated SAE data to Alexion within 24 hours of it being available. 
Investigators are not obligated to actively seek AEs or SAE data after conclusion of the study 
participation. However, if the Investigator learns of any SAE, including a death, at any time after 
a participant has been discharged from the study, and he/she considers the event to be reasonably 
related to the study drug or study participation, the Investigator must promptly notify Alexion. 
8.3.2. 
Method of Detecting AEs and SAEs 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Section 10.3. 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about AE 
occurrences. 
8.3.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow-up on each 
participant at subsequent visits/contacts. All SAEs will be followed up until resolution, 
stabilization, the event is otherwise explained, or the participant is lost to follow-up (as defined 
in Section 7.4) Further information on follow-up procedures is provided in Section 10.3. 
8.3.4. 
Regulatory Reporting Requirements for SAEs 
•
Prompt notification of an SAE by the Investigator to Alexion is essential so that legal
obligations and ethical responsibilities towards the safety of participants and the
safety of a study drug under clinical investigation are met.
•
Alexion has a legal responsibility to notify both the local regulatory authority and
other regulatory agencies about the safety of a study drug under clinical investigation.
Alexion will comply with country-specific regulatory requirements relating to safety
reporting to the regulatory authority, IRBs/IECs, and Investigators.
•
Suspected unexpected serious adverse reactions (SUSARs) must be reported
according to local regulatory requirements and Alexion policy and forwarded to
Investigators as necessary.


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• An Investigator who receives an Investigator safety report describing an SAE or other 
specific safety information (eg, summary or listing of SAEs) from Alexion will 
review and then file it along with the IB and will notify the IRB/IEC, if appropriate 
according to local requirements. 
 
8.3.5. 
Adverse Events of Special Interest 
Any nonserious AE of special interest (AESI) is required to be reported by the Investigator to 
Alexion immediately (≤ 24 hours after learning of the AESI). The AESI will be documented in 
the safety database and a narrative will be required for each event. 
The AESIs for ALXN1830 include the following: 
• Any IRR equal to or higher than Grade 3; or any IRR that may jeopardize the 
participant and requires immediate intervention to prevent it from leading to severe 
outcomes. 
• Potential cases of any delayed hypersensitivity reactions, equal to or higher than 
Grade 2. 
 
8.3.5.1. 
Infusion-Related Reaction 
Infusion-related reactions to mAbs include both immune mediated and non-immune mediated 
reactions. Symptoms of IRRs may include flushing, alterations in heart rate and BP, dyspnea, 
bronchospasm, back pain, fever, urticaria, edema, nausea, and all types of rashes. Anaphylaxis is 
recognized as a severe, life-threatening, generalized, or systemic reaction. IRRs usually develop 
during drug infusion, or within hours of infusion, although may be delayed for up to 24 hours. 
Most IRRs are mild to moderate in severity. 
Refer to Section See Section 10.4 for guidance on management of IRRs. 
 
8.3.5.2. 
Non-acute Hypersensitivity Reaction 
Non-acute hypersensitivity (ie, serum sickness) and immune responses secondary to IC 
formation typically have a subacute presentation (FDA, 2014). Clinical signs may include 
delayed onset of fever, rash, arthralgia, myalgia, hematuria, proteinuria, and serositis, in the face 
of an ongoing antibody response to the study drug (Hunley, 2004). Assessment of AE causality 
will likely require evaluation of CICs and complement activation. 


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8.4. 
Treatment of Overdose 
An overdose is defined as a significant variation above the recommended/scheduled dosage for a 
product. The dosing for this study will be conducted in a controlled clinical setting and an 
overdose is not anticipated. However, in the event of an accident, for this study, an overdose of 
ALXN1830 is considered any dose of ALXN1830 greater than 2250 mg. 
Overdoses are medication errors that are not considered AEs unless there is an untoward medical 
occurrence resulting from the overdose. 
In the event of an overdose, the Investigator should: 
•
Contact the Medical Monitor immediately.
•
Closely monitor the participant for any AE/SAE and laboratory abnormalities until
IgG levels have returned to normal.
•
Follow-up until ALXN1830 can no longer be detected systemically or IgG levels
have returned to Baseline.
•
Document the quantity of the excess dose as well as the duration of the overdose in
the CRF.
Decisions regarding dose interruptions or modifications will be made by the Investigator in 
consultation with the Medical Monitor based on the clinical evaluation of the participant. 
8.5. 
Pharmacokinetics 
Whole blood samples will be collected for measurement of serum concentrations of ALXN1830 
as specified in the SoA. All efforts should be made to obtain the PK samples at the exact nominal 
time relative to dosing within the specified window. Additional samples may be collected during 
the study if warranted and agreed upon between the Investigator and Alexion. The total blood 
volume will not exceed the blood volume limit for healthy participants (Section 8.2.4). 
Instructions for the collection and handling of biological samples will be provided by Alexion. 
The actual date and time (24-hour clock time) of each sample will be recorded. 
Samples will be analyzed using a validated analytical method in compliance with Alexion 
standard operating procedures. 
8.6. 
Pharmacodynamics 
Venous blood samples will be collected for measurement of IgA, IgM, IgG, and IgG subtypes 
(1 - 4), FcRn receptor occupancy, and CIC at timepoints described in the SoA (Section 1.3). 
Blood will be separated into 2 aliquots for Igs; 1 each for Ig and subclass testing. A separate 
sample will be collected for CIC, and a separate sample will be collected for FcRn receptor 
occupancy on human monocytes. The actual date and time (24-hour clock time) of each sample 
will be recorded. 
As data become available during the study, the timing of PD sampling may be altered in order to 
ensure appropriate monitoring of participants. Detailed instructions on the procedure for 
collecting, processing, storing, and shipping serum samples for PD analysis will be provided in 
the laboratory manual. 


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8.7. 
Genetics 
Genetics are not evaluated in this study. 
 
8.8. 
Biomarkers 
Whole blood for assessment of exploratory biomarkers will be collected as per the SoA 
(Section 1.3). Residual PK/PD samples may also be used for exploratory analyses. 
In the event of an IRR, it is recommended to collect a blood sample for assessment of tryptase, 
histamine, C-reactive protein, complement, and cytokines as soon as the IRR is observed (prior 
to administering any IRR medication), and 2 hours, 24 hours and 7 days (prior to the next dose of 
study drug) after onset of the IRR. 
 
8.9. 
Immunogenicity Assessments 
Samples for immunogenicity should be collected at times specified in the SoA (Section 1.3). 
Assays for the determination of human antidrug (anti-ALXN1830) antibodies (ADA) will be 
performed. All samples that are positive in a screening assay will be confirmed for antibody 
specificity and further characterized for titer. All samples that are confirmed positive for ADA 
will be evaluated for the presence of neutralizing antibodies. Other analyses may be performed to 
verify the stability of antibodies to ALXN1830 and/or further characterize the immunogenicity 
of ALXN1830. 
In the event of an IRR, a sample for PK/PD and ADAs may be collected if there is no predefined 
sample collection on the same day. 
The detection and characterization of antibodies to ALXN1830 will be performed using a 
validated assay method by or under the supervision of Alexion. 
Participants found to have anti-ALXN1830 antibodies still present at the end of the study will be 
requested to return to the clinic for up to 1 year (from the first drug administration) or until ADA 
titers return to baseline levels (whichever occurs first). The follow-up visits are to be scheduled 
at 90-day intervals for blood collection to assess ADA. 
Detailed instructions on the procedure for collecting, processing, storing, and shipping serum 
samples for immunogenicity analysis will be provided in the laboratory manual. 
8.10. 
Medical Resource Utilization 
Medical resource utilization and health economics data, associated with medical encounters, will 
not be collected as a part of this study. 


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9.
STATISTICAL CONSIDERATIONS
9.1. 
Statistical Hypotheses 
No statistical hypotheses will be tested for this study. 
9.2. 
Sample Size Determination 
Up to 48 participants will be enrolled. Participants will be randomly assigned in a 6:2 ratio to up 
to 6 planned cohorts to receive either single or multiple doses of ALXN1830 SC (n = 6 per 
cohort) or single or multiple doses of PBO (n = 2 per cohort). Progression to the next dosing 
cohort will be gated by review of initial dosing data by an SRC. 
Formal sample size calculation has not been performed. The number of participants has been 
chosen based on feasibility and is considered adequate to meet the study objectives. 
9.3. 
Populations for Analyses 
For purposes of analysis, the following populations are defined: 
Table 18: 
Populations for Analyses 
Population 
Description 
Enrolled set 
All participants who sign the ICF and pass inclusion/exclusion criteria. 
Safety set 
All participants who receive at least 1 dose of study drug. Participants will be 
analyzed according to the study drug they actually received. 
PK analysis set 
All participants in the Enrolled set who have sufficient serum ALXN1830 
concentration data to evaluate PK parameters. Participants will be analyzed 
according to the study drug they actually received. 
PD analysis set 
All participants in the Enrolled set who have sufficient serum IgG data to 
evaluate PD effects. Participants will be analyzed according to the study drug 
they actually received. 
Abbreviations: ICF = informed consent form; IgG = immunoglobulin G; PD = pharmacodynamics; 
PK = pharmacokinetics. 
9.4. 
Statistical Analyses 
The Statistical Analysis Plan (SAP) will be developed and approved before database lock and 
will describe the participant populations to be included in the analyses, and procedures for 
accounting for missing data. This section is a summary of the planned statistical analyses of the 
primary and secondary endpoints. 
All data and all outcomes derived from the data will be presented in detailed data listings or 
summary tabulations. Graphical displays may also be provided when appropriate. All analyses 
will be performed using SAS® release, version 9.4 or higher (SAS Institute Inc., Cary, NC, 
USA) or other validated statistical software. Continuous variables will be summarized using 
descriptive statistics, including number of observations and mean, standard deviation, median, 
minimum, and maximum values. Categorical variables will be summarized by frequency counts 
and percentage of participants. 


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All cohorts will be summarized separately along with the overall summaries for SAD and MAD. 
Within the MAD cohorts, the non-Japanese Cohorts 3, 4, and 5 and the Japanese Cohort 6 will be 
quantitatively evaluated. 
One of the secondary objectives of this study is to compare safety, PK, PD, and immunogenicity 
of ALXN1830 SC between Japanese and non-Japanese healthy participants. For this, descriptive 
statistics for safety, PK parameters (maximum observed serum concentration [Cmax], AUC), PD 
parameters (percent change in IgG), and immunogenicity (ADA levels) will be summarized in 
each group separately. 
Details will be provided in the SAP. 
 
9.4.1. 
Safety Analyses 
All safety analyses will be performed on the Safety set. 
Safety analyses will include an analysis of all treatment-emergent adverse events (TEAEs), 
SAEs, AESIs, ECGs, clinical laboratory data, physical examinations, and vital sign 
measurements using descriptive statistics. No inferential statistical analyses are planned on the 
safety parameters of this study. Clinical AEs will be coded according to MedDRA Version 21.1 
or higher; AEs will be graded using the National Cancer Institute Common Terminology Criteria 
for Adverse Events (CTCAE), Version 5.0 or higher. AEs will be classified as pretreatment or 
treatment-emergent as follows: 
Pretreatment AEs are defined as AEs that were reported or worsened after signing the ICF up 
to the start of study drug dosing. 
Treatment-emergent AEs are defined as AEs that were reported or worsened on or after the 
start of study drug dosing through the Safety Follow-up Visit. 
Only TEAEs will be summarized. The number and percentage of participants experiencing a 
TEAE will be summarized, by System Organ Class and Preferred Term for each cohort, by 
relationship to study drug, and by severity of the AE. Serious AEs and TEAEs resulting in study 
drug discontinuation will be listed. Some rules that will apply to the summarization of AEs are 
(1) a participant with multiple occurrences of the same AE or a continuing AE will only be 
counted once; (2) only the maximum severity level will be presented in the severity summary; 
and (3) only the worst relationship level will be presented in the relationship summary. 
All statistical analyses of laboratory values will be performed using SI units. Changes from 
baseline in vital sign measurements and laboratory assessments (eg, chemistry, hematology, and 
urinalysis) at each scheduled time point will be summarized by cohort. Laboratory parameter 
values will be graded according to the CTCAE. Shift tables by cohort will be produced for these 
laboratory parameters. These tables will summarize the number of participants with each 
baseline grade relative to the reference ranges and changes to the worst highest grade assessed 
post-dose during the study. 
The ECG parameters will be measured at the specified time points, including heart rate, PR, RR 
QRS, QT, and QTcF intervals. The average of the triplicate ECG readings at the time points 
collected will be calculated, and changes from pretreatment baseline values will be assessed by 
each cohort. 


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An outlier analysis will be performed that will summarize the frequency and percentage of 
participants who meet any of the following outlier criteria at each visit by cohort: 
•
QT, QTcF interval > 450 msec
•
QT, QTcF interval > 480 msec
•
QT, QTcF interval > 500 msec
•
QT, QTcF interval increases from baseline > 30 msec
•
QT, QTcF interval increases from baseline > 60 msec
All concomitant medications will be coded using the current version of the WHO Drug 
Dictionary, and the frequency and percentage of concomitant medications will be summarized. 
9.4.2. 
Other Analyses 
9.4.2.1. 
Pharmacokinetic Analyses 
All PK analyses will be performed on the PK analysis set and will be reported by cohort and 
study drug within each cohort (ie, ALXN1830 or PBO). 
The individual serum concentration data from participants who receive ALXN1830 SC with 
actual sampling dates and times will be used to derive the PK parameters by noncompartmental 
analysis methods using Phoenix WinNonlin 6.3 or higher. Pharmacokinetic parameter data will 
be presented in tabular form and descriptively summarized for all participants by cohort. 
The following PK parameters will be derived as appropriate and data permitting: 
Parameters 
Dose 
Regimen 
Definitions 
Cmax 
SD, MD 
Maximum observed serum concentration 
tmax
SD, MD 
Time to maximum observed serum concentration 
AUCt 
SD, MD 
Area under the concentration-time curve from time 0 to the last quantifiable 
concentration 
AUCtau 
MD 
Area under the concentration-time curve during the dosing interval 
AUC0-∞ 
SD 
Area under the concentration-time curve from time 0 (dosing) to time 
infinity 
t½ 
SD, MD 
Terminal elimination half-life 
λz 
SD, MD 
Terminal-phase elimination rate constant 
CL/F 
SD 
Total body clearance or apparent clearance 
Vd/F 
SD 
Volume of distribution or apparent volume of distribution 
Rac 
MD 
Accumulation ratio 
Abbreviations: MD = multiple-dose; SD = single-dose. 
Additional details will be provided in the SAP. 
9.4.2.2. 
Pharmacodynamic Analyses 
All PD analyses will be performed on the PD analysis set and will be reported by cohort and 
study drug within each cohort (ie, ALXN1830 or PBO). 


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The PD effects of single and multiple SC doses of ALXN1830 will be evaluated by assessing 
changes in serum IgA, IgM, IgG, and IgG subtypes (1 to 4) over time. In addition, changes in 
CIC and FcRn receptor occupancy on human monocytes will be evaluated. 
Biomarker assays may be conducted as an exploratory analysis on collected samples. 
Pharmacokinetic, PD, immunogenicity (secondary analyses), and biomarker exploratory analyses 
will be described in the SAP (or the PK analysis plan, as applicable), and finalized before 
database lock. 
9.5. 
Interim Analyses 
No interim analyses are planned. 
 
9.6. 
Safety Review Committee (SRC) 
An SRC, consisting of the Investigator, and Alexion Safety Physician, Medical Monitor, Study 
Statistician, and Clinical Pharmacologist, will evaluate the study data at prespecified time points 
for participant safety and make recommendations on dose escalation, dose modification, or 
termination of the study (see SRC charter for description of membership, schedule of meetings, 
data required for each safety review, and requirements for documenting meeting discussions and 
outcome). Relevant safety data from any other studies ongoing with ALXN1830 will be made 
available to the SRC. 


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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
• This study will be conducted in accordance with the protocol and with the following: 
− Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines 
− Applicable International Council of Harmonisation (ICH) Good Clinical Practice 
(GCP) Guidelines 
−  Applicable laws and regulations 
• The protocol, protocol amendments, ICF, IB, and other relevant documents (eg, 
advertisements) must be submitted to an IRB/IEC by the Investigator and reviewed 
and approved by the IRB/IEC before the study is initiated. 
• Any amendments to the protocol will require IRB/IEC approval before 
implementation of changes made to the study design, except for changes necessary to 
eliminate an immediate hazard to study participants. 
• The Investigator will be responsible for the following: 
− Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC. 
− Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures. 
− Notifying the IRB/IEC of deviations from the study protocol or GCP as defined as 
a serious breach or as required by IRB/IEC procedures. 
− Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 Code of Federal Regulation (CFR), ICH guidelines, the 
IRB/IEC, European regulation 536/2014 for clinical studies (if applicable), and all 
other applicable local regulations. 
 
10.1.2. 
Financial Disclosure 
Investigators and Sub-Investigators will provide Alexion with sufficient, accurate financial 
information as requested to allow Alexion to submit complete and accurate financial certification 
or disclosure statements to the appropriate regulatory authorities. Investigators are responsible 
for providing information on financial interests during the course of the study and for 1 year after 
completion of the study. 


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10.1.3. 
Informed Consent Process 
• It is the responsibility of the Investigator to obtain signed (written or electronic 
signature) informed consent from all study participants prior to any study-related 
procedures including screening assessments. 
• The Investigator or his/her representative will explain the nature of the study 
(including but not limited to the objectives, potential benefits and risks, 
inconveniences, and the participant’s rights and responsibilities) to the participant or 
his/her legally authorized representative, defined according to local and country 
regulations where the study is taking place, and answer all questions regarding the 
study. 
• Participants must be informed that their participation is voluntary. Participants or 
their legally authorized representative defined according to local and country 
regulations where the study is taking place will be required to sign a statement of 
informed consent that meets the requirements of 21 CFR 50, local regulations, ICH 
guidelines, Health Insurance Portability and Accountability Act (HIPAA) 
requirements, where applicable, and the IRB/IEC or study center. 
• The medical record must include a statement that signed (written or electronic) 
informed consent was obtained before the participant was screened in the study and 
the date the written consent was obtained. The authorized person obtaining the 
informed consent must also sign the ICF. 
• Participants must be reconsented to the most current version of the ICF(s) during their 
participation in the study. 
• A copy of the signed (written or electronic) ICF(s) documentation (ie, a complete set 
of participant information sheets and fully executed signature pages) must be 
provided to the participant or the participant’s legally authorized representative, as 
applicable. This document may require translation into the local language. Signed 
(written or electronic) consent forms must remain in each participant’s study file and 
must be available for verification at any time. 
• Participants who are rescreened are required to sign a new ICF (see Section 5.4). 
• The ICF will contain a separate section that addresses the use of remaining mandatory 
samples for optional exploratory research. The Investigator or authorized designee 
will explain to each participant or their legally authorized representative the 
objectives of the exploratory research. If sharing exploratory research results with the 
Investigator is not planned, the ICF should mention it. Participants or their legally 
authorized representative will be told that they are free to refuse to participate and 
may withdraw their consent at any time and for any reason during the storage period. 
A separate signature will be required to document a participant’s agreement to allow 
any remaining specimens to be used for exploratory research. Participants who 
decline to participate in this optional research will not provide this separate signature. 


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10.1.4. 
Data Protection 
• Participants will be assigned a unique identifier by Alexion. Any participant records 
or datasets that are transferred to Alexion will contain the identifier only; participant 
names or any information which would make the participant identifiable will not be 
transferred. 
• Participants must be informed that their personal study-related data will be used by 
Alexion in accordance with local data protection law. The level of disclosure must 
also be explained to the participants who will be required to give consent for their 
data to be used as described in the informed consent 
• Participants must be informed that their medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by Alexion, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
 
10.1.5. 
Committees Structure 
An SRC, consisting of the Investigator, Alexion safety monitor, medical monitor, study 
statistician, and clinical pharmacologist, will evaluate the study data at prespecified time points 
for participant safety and make recommendations on dose escalation, dose modification, or 
termination of the study (see SRC charter for description of membership, schedule of meetings, 
data required for each safety review, and requirements for documenting meeting discussions and 
outcome). Relevant safety data from any other studies ongoing with ALXN1830 will be made 
available to the SRC. At Alexion’s discretion, and after consultation with the SRC, additional 
participants may be enrolled as replacement participants only if a participant discontinues within 
3 weeks of the last dose for reasons other than drug-related AEs. 
 
10.1.6. 
Dissemination of Clinical Study Data 
Study-related information and study results may be posted on publicly accessible clinical study 
databases (eg, the US website www.clinicaltrials.gov or the EU website 
www.clinicaltrialsregister.eu), as appropriate, and in accordance with national, regional, and 
local regulations. 
 
10.1.7. 
Data Quality Assurance 
• All participant data relating to the study will be recorded on printed or eCRF unless 
transmitted to Alexion electronically (eg, laboratory data). The Investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF. 
• The Investigator must maintain accurate documentation (source data) that supports 
the information entered in the CRF. 
• The Investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents. 
• Alexion is responsible for the data management of this study including quality 
checking of the data. 


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•
Study monitors will perform ongoing source data verification to confirm that data
entered into the CRF by authorized site personnel are accurate, complete, and
verifiable from source documents; that the safety and rights of participants are being
protected; and that the study is being conducted in accordance with the currently
approved protocol and any other study agreements, ICH GCP, and all applicable
regulatory requirements.
•
Records and documents, including signed ICFs, pertaining to the conduct of this
study must be retained by the Investigator for 2 years after the last marketing
application approval, or if not approved, 2 years following the discontinuance of the
study drug, unless local regulations or institutional policies require a longer retention
period. No records may be destroyed during the retention period without the written
approval of Alexion. No records may be transferred to another location or party
without written notification to Alexion.
10.1.8. 
Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. The Investigator will prepare and maintain adequate and accurate 
source documents (eg, medical records, ECGs, AE and concomitant medication reporting, raw 
data collection forms) designed to record all observations and other pertinent data for each 
participant. 
Data reported on the CRF that are transcribed from source documents must be consistent with 
the source documents or the discrepancies must be explained. The Investigator may need to 
request previous medical records or transfer records, depending on the study. Also, current 
medical records must be available. Source documents are filed at the Investigator’s site. 
10.1.9. 
Study and Site Start and Closure 
The study start date is the date on which the first participant is consented. 
Alexion reserves the right to close the study site or terminate the study at any time for any reason 
at the sole discretion of Alexion. Study sites will be closed after the study is completed or 
following the decision to close or terminate the study. A study site is considered closed when all 
participants have completed the end of study or early termination visit, all data have been 
collected and entered into electronic data capture system, all required documents and study 
supplies have been collected, and a study-site closure visit has been performed. 
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 Alexion 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, Alexion’s procedures, or GCP guidelines
•
Inadequate recruitment of participants by the Investigator
•
Discontinuation of further study drug development


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The Sponsor or health authority may terminate the study for reasonable cause. Conditions that 
may warrant termination of the study include, but are not limited to, 
•
Discovery of an unexpected, serious, or unacceptable risk of the study drug to
patients enrolled or continuing in the study.
•
Sponsor decision to suspend or discontinue testing, evaluation, or development of the
study drug.
If the study is prematurely terminated or suspended, Alexion shall promptly inform the 
Investigators, the IECs/IRBs, the regulatory authorities, and any contract research 
organization(s) used in the study of the reason for termination or suspension, as specified by the 
applicable regulatory requirements. The Investigator shall promptly inform the participant and 
should assure appropriate participant therapy and/or follow-up. 
10.1.10. 
Publication Policy 
The full terms regarding publication of the results of this study are outlined in the applicable 
Clinical Study Agreement. 


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10.2. 
Appendix 2: Clinical Laboratory Tests 
The tests detailed in Table 19 will be performed by the central laboratory. 
•
Protocol-specific requirements for inclusion or exclusion of participants are detailed
in Section 5 of the protocol.
•
Additional tests may be performed at any time during the study as determined
necessary by the Investigator or required by local regulations.


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Table 19: 
Protocol-Required Safety Laboratory Assessments 
Laboratory 
Assessments 
Parameters 
Hematology 
Platelet count 
RBC count 
Hemoglobin 
Hematocrit 
RBC indices: 
Mean corpuscular volume 
Mean corpuscular 
hemoglobin 
% Reticulocytes 
WBC count with differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
Clinical 
chemistry 
BUN 
Chloride 
Potassium 
Bicarbonate 
Sodium 
Glucose 
AST 
ALT 
Alkaline phosphatase 
Gamma glutamyltransferase 
HbA1C (Screening only) 
Urea 
Total and direct bilirubin 
Total protein 
Albumin 
Cholesterol (total) 
LDL 
HDL 
Triglycerides 
Creatinine 
Creatine phosphokinase 
Coagulation 
International normalized ratio, partial thromboplastin time, prothrombin time 
Routine 
urinalysis 
Specific gravity, pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, 
leukocyte esterase 
Microscopic examination (if any leucocytes, more than a trace protein, nitrites, and blood [if 
not menstruating] are abnormal) 
Other screening 
tests 
•
Alcohol breath and urine drug screen (to include at minimum: amphetamines,
barbiturates, benzodiazepines, cocaine, opiates, phencyclidine, methamphetamine,
3,4-methylenedioxy-methamphetamine, methadone, and tetrahydrocannabinol
[cannabinoids])
•
IgG, IgA and IgM concentration
•
HIV-1 and HIV-2 antibodies, HBsAg, anti-HBC IgG + IgM (if IgG positive), and
anti-HCV with confirmation by HCV RNA
•
Serum hCG pregnancy test (as needed for women of childbearing potential)
•
FSH (postmenopausal females only)
IRR 
•
In the event of an IRR, it is recommended to collect a blood sample for assessment
of tryptase, histamine, CRP, cytokines, and complement as soon as the IRR is
observed (prior to administering any IRR medication), and 2 hours, 24 hours and
7 days (prior to the next dose of study drug) after onset of the IRR.
Signs of infection 
If a participant shows signs of infection, the following investigations should be included: 
•
Blood cultures (taken prior to start of antibiotics)
•
Routine profile
Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; BUN = blood urea nitrogen; 
CRP = C-reactive protein; FSH = follicle stimulating hormone; HbA1c = glycated hemoglobin; HBC = hepatitis B 
core antibody; HBsAg = hepatitis B surface antigen; hCG = human chorionic gonadotropin; HCV = hepatitis C 
virus; HDL = high-density lipoprotein; HIV = human immunodeficiency virus; Ig = immunoglobulin; IRR = 
infusion-related reaction; LDL = low-density lipoprotein; RBC = red blood cells; RNA = ribonucleic acid; 
WBC = white blood cells. 
Investigators must document their review of each laboratory safety report. Laboratory/analyte 
results that could unblind the study will be reviewed by dedicated unblinded staff at the 
investigative sites or other blinded personnel until the study has been unblinded. 


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10.3. 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
10.3.1. 
Definition of AE 
AE Definition 
•
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered
a pharmaceutical product and which does not necessarily have to have a causal relationship with this
treatment (ICH E2A).
•
Note: An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory
finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention,
whether or not considered related to the study intervention.
Events Meeting the AE Definition 
•
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other safety
assessments (eg, ECG, radiological scans, vital signs measurements).
•
Exacerbation of a chronic or intermittent pre-existing condition including either an increase in frequency
and/or intensity of the condition.
•
New conditions detected or diagnosed after study intervention administration even though it may have been
present before the start of the study.
•
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.
•
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study intervention or a
concomitant medication. Overdose per se will not be reported as an AE/SAE unless it is an intentional
overdose taken with possible suicidal/self-harming intent. Such overdoses should be reported regardless of
sequelae.
Events Not Meeting the AE Definition 
•
Medical or surgical procedure (eg, endoscopy, appendectomy): The condition that leads to the procedure is
the AE. Situations in which an untoward medical occurrence did not occur (eg, hospitalization for elective
surgery if planned before the signing the ICF, admissions for social reasons or for convenience).
•
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or detected at the start of
the study that do not worsen.
•
A medication error (including intentional misuse, abuse, and overdose of the product) or use other than what
is defined in the protocol is not considered an AE unless there is an untoward medical occurrence as a result
of a medication error.
•
Cases of pregnancy that occur during maternal or paternal exposure to study intervention are to be reported
within 24 hours of Investigator/site awareness. Data on fetal outcome and breastfeeding will be collected for
regulatory reporting and safety evaluation.
•
Situations in which an untoward medical occurrence did not occur (social and/or convenience admission to a
hospital).


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10.3.2. 
Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (eg, hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease). 
An SAE is defined as any untoward medical occurrence that, at any dose: 
1.
Results in death
2.
Is life-threatening
The term “life-threatening” in the definition of “serious” refers to an event in which the participant was at risk of 
death at the time of the event. It does not refer to an event, which hypothetically might have caused death, if it
was more severe.
3.
Requires inpatient hospitalization or prolongation of existing hospitalization
•
In general, hospitalization signifies that the participant has been detained (usually involving at least an
overnight stay) at the hospital or emergency ward for observation and/or treatment that would not have been
appropriate in the physician’s office or outpatient setting. Complications that occur during hospitalization
are AEs. If a complication prolongs hospitalization or fulfills any other serious criteria, the event is serious.
When in doubt as to whether “hospitalization” occurred or was necessary, the AE should be considered
serious.
•
Hospitalization for elective treatment of a pre-existing condition that did not worsen from baseline is not
considered an AE.
4.
Results in persistent disability/incapacity
•
The term disability means a substantial disruption of a person’s ability to conduct normal life functions.
•
This definition is not intended to include experiences of relatively minor medical significance such as
uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma (eg, sprained ankle)
which may interfere with or prevent everyday life functions but do not constitute a substantial disruption.
5.
Is a congenital anomaly/birth defect
6.
Other situations:
•
Medical or scientific judgment should be exercised in deciding whether SAE reporting is appropriate in
other situations such as important medical events that may not be immediately life-threatening or result in
death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to
prevent one of the other outcomes listed in the above definition. These events should usually be considered
serious.
•
Examples of such events include invasive or malignant cancers, intensive treatment in an emergency room
or at home for allergic bronchospasm, blood dyscrasias or convulsions that do not result in hospitalization,
or development of drug dependency or drug abuse.


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10.3.3. 
Recording and Follow-Up of AE and/or SAE 
Recording of AE and/or SAE 
• 
When an AE/SAE occurs, it is the responsibility of the Investigator to review all documentation (eg, hospital 
progress notes, laboratory reports, and diagnostics reports) related to the event. 
• 
The Investigator will then record all relevant AE/SAE information in the CRF. 
• 
It is not acceptable for the Investigator to send photocopies of the participant’s medical records to Alexion 
in lieu of completion of the AE/SAE CRF page. 
• 
There may be instances when copies of medical records for certain cases are requested by Alexion. In this 
case, all participant identifiers, with the exception of the participant number, will be redacted on the copies 
of the medical records before submission to Alexion. 
• 
The Investigator will attempt to establish a diagnosis of the event based on signs, symptoms, and/or other 
clinical information. Whenever possible, the diagnosis (not the individual signs/symptoms) will be 
documented as the AE/SAE. 
Assessment of Intensity 
The Investigator will make an assessment of intensity for each AE and SAE reported during the study and assign 
it to one of the following categories from National Cancer Institute CTCAE v5.0, published 27 Nov 2017: 
• 
Grade 1: Mild (awareness of sign or symptom, but easily tolerated) 
• 
Grade 2: Moderate (discomfort sufficient to cause interference with normal activities) 
• 
Grade 3: Severe (incapacitating, with inability to perform normal activities) 
• 
Grade 4: Life-threatening 
• 
Grade 5: Fatal 


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Recording of AE and/or SAE 
Assessment of Causality 
• 
The Investigator is obligated to assess the relationship between the study intervention and each occurrence 
of each AE or SAE. An Investigator causality assessment must be provided for all AEs (both nonserious and 
serious). This assessment must be recorded in the CRF and on any additional forms, as appropriate. The 
definitions for the causality assessments are as follows: 
− 
Not related: There is no reasonable possibility the study intervention caused the AE. 
▪ 
The AE has a more likely alternative etiology; it may be due to underlying or 
concurrent illness, complications, concurrent treatments, or effects of another 
concurrent drug. 
▪ 
The event does not follow a reasonable temporal relationship to administration of the 
study intervention. 
−  Related: There is a reasonable possibility the study intervention caused the AE. 
▪ 
The AE has a temporal relationship to the administration of the study intervention. 
▪ 
The event does not have a likely alternative etiology. 
▪ 
The event corresponds with the known pharmaceutical profile of the study 
intervention. 
▪ 
There is improvement on discontinuation and/or reappearance on rechallenge. 
• 
The Investigator will use clinical judgment to determine the relationship. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, as well as the 
temporal relationship of the event to study intervention administration will be considered and investigated. 
• 
The Investigator will also consult the IB and/or Product Information, for marketed products, in his/her 
assessment. 
• 
For each AE/SAE, the Investigator must document in the medical notes that he/she has reviewed the 
AE/SAE and has provided an assessment of causality. 
• 
There may be situations in which an SAE has occurred, and the Investigator has minimal information to 
include in the initial report to Alexion. However, it is very important that the Investigator always make an 
assessment of causality for every event before the initial transmission of the SAE data to Alexion. 
• 
The Investigator may change his/her opinion of causality in light of follow-up information and send an SAE 
follow-up report with the updated causality assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory reporting requirements. 
 
 
Follow-up of AEs and SAEs 
• 
The Investigator is obligated to perform or arrange for the conduct of supplemental measurements and/or 
evaluations as medically indicated or as requested by Alexion to elucidate the nature and/or causality of the 
AE or SAE as fully as possible. This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other health care professionals. 
• 
If a participant dies during participation in the study or during a recognized follow-up period, the 
Investigator will provide Alexion with a copy of any post-mortem findings including histopathology. 
• 
New or updated information will be recorded in the originally completed CRF. 
• 
The Investigator will submit any updated SAE data to Alexion within 24 hours of receipt of the 
information. 


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10.3.4. 
Reporting of SAEs 
SAE Reporting to Alexion via Paper Safety Reporting Form 
• 
All SAEs will be recorded and reported to Alexion or designee immediately and within 24 hours of 
awareness. 
• 
SAEs will be reported using the Safety Reporting Form and submitted to Alexion Global Drug Safety 
(GDS). The Investigator must complete, sign, and date the SAE pages, verify the accuracy of the 
information recorded on the SAE pages with the corresponding source documents, and send a copy via 
email or facsimile to the contact information provided below: 
− 
Email: 
 or Fax: 
 
• 
Additional follow-up information, if required or available, should be entered into the CRF and sent to 
Alexion GDS within 24 hours of the Investigator or study site staff becoming aware of this additional 
information via the reporting process outlined above. 
• 
For all SAEs, the Investigator must provide the following: 
− 
Appropriate and requested follow-up information in the time frame detailed above 
− 
Causality of the SAE(s) 
− 
Treatment of/intervention for the SAE(s) 
− 
Outcome of the SAE(s) 
− 
Medical records and laboratory/diagnostic information 
• 
All paper forms and follow-up information submitted to Alexion GDS must be accompanied by a cover 
page signed by the Investigator. 
• 
Paper source documents and/or reports should be kept in the appropriate section of the study file. 


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10.4. 
Appendix 4: Guidelines for Grading and Management of Allergic or 
Infusion-Related Reactions 
Infusion-associated reactions are a potential risk with the use of monoclonal antibodies; these 
reactions can be nonimmune or immune mediated (eg, hypersensitivity reactions). Signs and 
symptoms may include headache, fever, facial flushing, pruritus, myalgia, nausea, chest 
tightness, dyspnea, vomiting, erythema, abdominal discomfort, diaphoresis, shivers, 
hypertension, lightheadedness, hypotension, palpitations, and somnolence. Signs and symptoms 
of hypersensitivity or allergic reactions may include hives, swollen face, eyelids, lips, or tongue, 
or trouble with breathing. 
All infusion-associated reactions will be reported to the Investigator and qualified designee. The 
Investigator and qualified designee are responsible for detecting, documenting, and recording 
events that meet the definition of AE or SAE and remain responsible for following up events that 
are serious, considered related to the study drug, or study procedures; or that caused the 
participant to discontinue ALXN1830. 
Definitions and procedures for recording, evaluating, follow-up, and reporting AEs and SAEs are 
outlined in Section 10.3. 
Before any infusion is started, the treating physician and other appropriate personnel must make 
certain that medication (i.e., adrenaline, inhaled beta agonists, antihistamines, corticosteroids) 
and other equipment to treat anaphylaxis are readily available. The infusion must be stopped 
immediately if Grade ≥ 2 allergic/hypersensitivity reactions (including drug fever) or Grade ≥ 3 
cytokine release syndrome/acute infusion reaction occurs. The Sponsor must be notified within 
24 hours of any infusion reaction requiring interruption or discontinuation of study drug or meet 
the criteria of AESI. 
Patients /subject who experience a reaction during the administration of study drug should be 
treated according to institutional guidelines. For a Grade 1 or Grade 2 infusion reaction, the 
infusion should be temporarily stopped and treatment with an antihistamine (eg, 
diphenhydramine 25 to 50 mg orally or equivalent) and acetaminophen (650 mg orally or 
equivalent) may be considered. If the patient’s signs and symptoms have resolved (with or 
without administration of the above medication), the infusion may be restarted. However, the 
patients should be infused at a slower rate and be monitored closely for any signs and symptoms 
of infusion reactions during the remainder of the infusion. Patients experiencing an infusion 
reaction should be observed in the clinic until resolution of the reaction, or until the Investigator 
determines the patient is no longer at risk. Patients who experience a severe reaction during 
administration of study drug resulting in discontinuation of study drug should undergo all 
scheduled safety, PK, and PD evaluations required by the protocol. 
If anaphylaxis occurs according to the criteria listed below, then administration of subcutaneous 
epinephrine (1/1000, 0.3 mL to 0.5 mL, or equivalent) should be considered. In the case of 
bronchospasm, treatment with an inhaled beta agonist also should be considered. Patients 
administered an antihistamine for the treatment or prevention of an infusion reaction should be 
given appropriate warnings about drowsiness and impairment of driving ability before being 
discharged from the center. 


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In the event of an IRR considered to be a hypersensitivity reaction, it is recommended to collect 
a blood sample for assessment of tryptase, histamine, CRP, and complement as soon as the IRR 
is observed (prior to administering any IRR medication), 2 hours after onset of the IRR, and 7 
days later, prior to the next dose of study drug. 
Table 20: 
Grading and Management of Allergic or Infusion-Related Reactions 
 
Adverse 
Event 
Grade 
1 
2 
3 
4 
5 
Infusion-related 
Mild 
Therapy or infusion 
Prolonged (eg, not 
Life-threatening 
Death 
reaction 
transient 
interruption indicated 
rapidly responsive to 
consequences; 
reaction; 
but responds promptly 
symptomatic medication 
urgent 
infusion 
to symptomatic 
and/or brief interruption 
intervention 
interruption 
treatment (eg, 
of infusion); recurrence 
required 
not indicated; 
antihistamines, 
of symptoms following 
intervention 
non-steroidal 
initial improvement, 
not indicated 
anti-inflammatory 
hospitalization indicated 
drugs [NSAIDs], 
for clinical sequelae 
narcotics, IV fluids): 
prophylactic 
medications indicated 
for ≤ 24 hours 
Allergic 
Transient 
Therapy or infusion 
Prolonged (eg, not 
Life-threatening 
Death 
reaction 
flushing or 
interruption indicated 
rapidly responsive to 
consequences; 
rash, drug 
but responds promptly 
symptomatic medication 
urgent 
fever 
to symptomatic 
and/or brief interruption 
intervention 
< 38.0°C. 
treatment (eg, 
of infusion); recurrence 
required 
Intervention 
antihistamines, 
of symptoms following 
not indicated 
NSAIDs, narcotics, IV 
initial improvement, 
fluids): prophylactic 
hospitalization indicated 
medications indicated 
for clinical sequelae (eg, 
for ≤ 24 hours 
renal impairment, 
pulmonary infiltrates) 
Anaphylaxis 
– 
– 
Symptomatic 
Life-threatening 
Death 
bronchospasm, with or 
consequences; 
without urticarial; 
urgent 
parenteral intervention 
intervention 
indicated; allergy-related 
required 
edema/angioedema; 
hypotension 
Cytokine 
Mild 
Therapy or infusion 
Prolonged (eg, not 
Life-threatening 
Death 
release 
reaction; 
interruption indicated 
rapidly responsive to 
consequences; 
syndrome 
infusion 
but responds promptly 
symptomatic medication 
pressor or 
interruption 
to symptomatic 
and/or brief interruption 
ventilator 
not indicated; 
treatment (eg, 
of infusion); recurrence 
support 
intervention 
antihistamines, 
of symptoms following 
indicated 
not indicated 
NSAIDs, narcotics, IV 
initial improvement, 
fluids): prophylactic 
hospitalization indicated 
medications indicated 
for clinical sequelae (eg, 
for ≤ 24 hours 
renal impairment, 
pulmonary infiltrates) 
Abstracted from NCI CTCAE Version 5.0. 
Abbreviations: IV = intravenous; NSAIDs = nonsteroidal anti-inflammatory drugs 


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10.5. 
Appendix 5: Contraceptive Guidance and Collection of Pregnancy 
Information 
10.5.1. 
Definitions 
 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile (see below). 
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of study intervention, additional evaluation should be considered. 
 
Women in the following categories are not considered WOCBP 
1. Premenarchal 
2. Premenopausal female with one of the following: 
• Documented hysterectomy 
• Documented bilateral salpingectomy 
• Documented bilateral oophorectomy 
For individuals with permanent infertility due to an alternate medical cause other than the above, 
(eg, Mullerian agenesis, androgen insensitivity), Investigator discretion should be applied to 
determining study entry. 
Note: Documentation can come from the site personnel’s: review of the participant’s medical 
records, medical examination, or medical history interview. 
3. Postmenopausal female 
• A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause prior to the Day 1 Visit. 
− A high follicle stimulating hormone (FSH) level in the postmenopausal range may 
be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). However, in the absence 
of 12 months of amenorrhea, confirmation with more than 1 FSH measurement 
may be required. In the absence of 12 months of amenorrhea the reason for not 
obtaining FSH levels should be documented by the Investigator at the time of 
Screening. 
• Females on HRT and whose menopausal status is in doubt will be required to use one 
of the non-estrogen hormonal highly effective contraception methods if they wish to 
continue their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before study enrollment. 
4. Permanent sterilization at least 6 weeks prior to the Day 1 Visit. 


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10.5.2. 
Contraception Guidance 
Contraceptive use by male or female participants should be consistent with local regulations 
regarding the methods of contraception utilized for those participating in clinical studies. If 
teratogenic effects are suspected to be transferred to a fetus/embryo from a female spouse/partner 
of a male participant, pregnancy follow-up information will be obtained for the partner who 
becomes pregnant (refer to Section 10.5.3.1). In these cases, follow-up will be conducted on the 
pregnant partner in the same manner as a female participant who becomes pregnant during the 
study. 
 
10.5.2.1. Guidance for Female Participants 
Female participants of childbearing potential must have a negative pregnancy test ([urine or 
serum]) as required by local regulations within 3 months before the first dose of study 
intervention. Additional requirements for pregnancy testing during and after dosing with study 
intervention are indicated in the SoA (Section 1.3). 
The Investigator is responsible for the review of medical history, menstrual history, and recent 
sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. 
The Investigator should evaluate the potential for contraceptive method in relationship to the first 
dose of study intervention. 
Female participants of childbearing potential must use a highly effective method of 
contraception, including at least 1 of the following until at least 3 months after the final dose of 
study intervention. 
1. Intrauterine device in place for at least 6 weeks prior to first dose of study intervention. 
2. Progestogen-only hormonal contraception associated with inhibition of ovulation (either 
oral, injectable, or implantable) for at least 6 weeks prior to first dose of study 
intervention. 
3. Intrauterine progestogen releasing system for at least 6 weeks prior to first dose of study 
intervention. 
4. Bilateral tubal occlusion for at least 6 weeks prior to first dose of study intervention. 
5. Combined (estrogen- and progestogen-containing) hormonal contraception (either oral, 
intravaginal, or transdermal) for at least 6 weeks prior to first dose of study intervention. 
6. Surgical sterilization of the male partner (medical assessment of azoospermia is required 
if vasectomy was performed within 6 months prior to first dose of study intervention). 
Male partner is still required to use condom during sexual intercourse. 
7. Sexual abstinence for female participants: 
a. Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse. In this study, abstinence is only acceptable 
if consistent with the participant’s preferred and usual lifestyle. Abstinent female 
participants must refrain from heterosexual intercourse for at least 3 months after the 
final dose of study intervention. 


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10.5.2.2. Guidance for Male Participants 
Contraception is the responsibility of the heterosexually active male participants, regardless of 
his female partner’s method of contraception. 
Male participants who have had a vasectomy > 6 months prior to the first dose of study 
intervention must use a condom during heterosexual intercourse. Male participants who have had 
a vasectomy < 6 months prior to the first dose of study intervention must use a condom and 
spermicide during heterosexual intercourse for at least 3 months after their final dose of study 
intervention. 
 
10.5.2.2.1. Sexual Abstinence for Male Participants 
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse. In this study, abstinence is only acceptable if consistent with the 
participants’ s preferred and usual lifestyle. Abstinent male participants who become 
heterosexually active must use a condom and spermicide during intercourse. 
Periodic abstinence (eg, calendar, symptothermal, or post-ovulation methods for a female 
partner) is not considered a highly effective method of contraception for male participants. 
Male participants must not donate sperm from the Day 1 visit until at least 3 months after the last 
dose of study intervention. 
10.5.3. 
Collection of Pregnancy Information 
Pregnancy data will be collected during this study for all female participants and female 
spouses/partners of male participants. Exposure during pregnancy (also referred to as exposure in 
utero) can be the result of either maternal exposure or transmission of study intervention via 
semen following paternal exposure. If a female participant or a male participant’s female partner 
becomes pregnant from the first dose of study intervention up to 3 months after the last dose of 
study intervention, the Investigator must submit the “Pregnancy/Breastfeeding Reporting and 
Outcome Form” to Alexion GDS via facsimile or email (Email: 
 or Fax: 
). When the outcome of the pregnancy becomes known, the form should be 
updated and submitted to Alexion GDS. If additional follow-up is required, the Investigator will 
be requested to provide the information. 
Exposure of an infant to study intervention during breastfeeding must also be reported (via the 
“Pregnancy/Breastfeeding Reporting and Outcome Form”) and any AEs experienced by the 
infant must be reported to Alexion GDS or designee via email or facsimile. 
Pregnancy is not regarded as an AE unless there is a suspicion that the study intervention may 
have interfered with the effectiveness of a contraceptive medication. However, complications of 
pregnancy and abnormal outcomes of pregnancy are AEs and may meet the criteria for an SAE 
(eg, ectopic pregnancy, spontaneous abortion, intrauterine fetal demise, neonatal death, or 
congenital anomaly). Elective abortions without complications should not be reported as AEs. 
Any female participant who becomes pregnant while participating in the study will be 
discontinued from study intervention. 


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10.5.3.1. Male Participants With Partners Who Become Pregnant 
• The Investigator will attempt to collect pregnancy information on any male 
participant’s female partner who becomes pregnant while the male participant is in 
this study. This applies only to male participants who receive study intervention. 
• After obtaining the necessary signed informed consent from the pregnant female 
partner directly, the Investigator will record pregnancy information on the appropriate 
Pregnancy /Breastfeeding Reporting and Outcome Form and submit it to Alexion 
within 24 hours of learning of the partner’s pregnancy. The female partner will also 
be followed to determine the outcome of the pregnancy. Information on the status of 
the mother and child will be forwarded to Alexion. Generally, the follow-up will be 
no longer than 3 months following the estimated delivery date. Any termination of the 
pregnancy will be reported regardless of fetal status (presence or absence of 
anomalies) or indication for the procedure. 
 
10.5.3.2. Female Participants who become pregnant 
• The Investigator will collect pregnancy information on any female participant who 
becomes pregnant while participating in this study. The initial information will be 
recorded on the appropriate form and submitted to Alexion within 24 hours of 
learning of a participant’s pregnancy. 
• For all Alexion products, both in development or postapproval, exposure during 
pregnancy must be recorded and the pregnancy followed, until the outcome of the 
pregnancy is known (ie, spontaneous miscarriage, elective termination, normal birth, 
or congenital abnormality), even if the participant discontinues the study intervention 
or withdraws from the study. The Investigator will collect follow-up information on 
the participant and the neonate and the information will be forwarded to Alexion. 
Generally, follow-up will not be required for longer than 3 months beyond the 
estimated delivery date. Any termination of pregnancy will be reported, regardless of 
fetal status (presence or absence of anomalies) or indication for the procedure. 
• Pregnancy is not considered as an AE unless there is a suspicion that the study 
intervention may have interfered with the effectiveness of a contraceptive medication 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy for medical reasons will be 
reported as an AE or SAE. A spontaneous abortion (occurring at < 22 weeks 
gestational age) or still birth (occurring at > 22 weeks gestational age) is always 
considered to be an SAE and will be reported as such. Any post-study pregnancy 
related SAE considered reasonably related to the study intervention by the 
Investigator will be reported to Alexion as described in Section 8.3.4. While the 
Investigator is not obligated to actively seek this information in former study 
participants, he or she may learn of an SAE through spontaneous reporting. 
• Any female participant who becomes pregnant while participating in the study will be 
withdrawn from the study. 


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10.6. 
Appendix 6: Biomarkers 
• Blood samples will be collected for biomarker analyses and the data will be used for 
research (eg, exploratory) related to ALXN1830 and related diseases. The samples 
may also be used to develop tests/assays including diagnostic tests related to 
ALXN1830 and/or others of this study drug class. 
• The samples may be analyzed as part of a multistudy assessment of biomarkers in the 
response to ALXN1830 to understand study disease or related conditions. 
• The results of biomarker analyses may be reported in the CSR or in a separate study 
summary. 
• Alexion or designee will store the samples obtained for biomarker analyses in a 
secure storage space with adequate measures to protect confidentiality. 
• The samples will be retained while research on ALXN1830 continues but no longer 
than allowed per local requirements. 
 
10.7. 
Appendix 7: Justification for Protective Measures 
The proposed safety measures in this study include documentation of pneumococcal and current 
seasonal flu vaccination; staggered dosing; stopping rules; close participant monitoring through 
60 days after the last dose; close safety and PD monitoring with an unblinded medical monitor; 
avoidance of participants with a high risk of infections; antibiotics to manage infection as 
needed; rescue measures such as IVIG replacement in an extremely unlikely event of profoundly 
low IgG; as well as use of an SRC for safety monitoring and dose selections. 
 
10.7.1. 
IgG Lowering and the Potential Risk of Infection 
ALXN1830 is an anti-FcRn mAb that blocks recycling of IgG antibodies, reducing the total IgG 
in circulation, including potentially pathogenic IgG autoantibodies associated with multiple 
autoimmune diseases. Thus, reduction in IgG level is used to measure the anti-FcRn PD activity 
of ALXN1830. 
Chronic deficiency of Ig across multiple Ig classes can be associated with an increased risk of 
infections (eg, in patients with known hypogammaglobulinemia due to primary causes and for 
secondary reasons due to iatrogenic intervention in patients treated with broadly active therapies, 
such as rituximab or plasma exchange). For example, rituximab has been documented to widely 
deplete the B-cell population and affect other Ig classes, while plasma exchange removes all 
types of serum proteins (Marco, 2014). Likewise, hereditary hypogammaglobulinemia is 
generally characterized by persistent deficiency of both IgG and other Ig (IgA or IgM) due to 
inadequate production of gamma globulin. Other immune system disorders, such as common 
variable immunodeficiency are characterized by lower percentages of memory and isotype 
switched-memory B cells; increased infection susceptibility; chronic recurrent, persistent 
infections; and insufficient immune responses to most vaccines, which in turn is also underlined 
by low levels of IgG and at least 1 other subclass of Ig, such as IgA or IgM documented by 
laboratory investigations (Filion, 2019). 


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In contrast to the broadly active agents and immune system disorders discussed above, 
ALXN1830 is highly specific in reducing IgG in circulation. ALXN1830 has no effect on IgM or 
IgA levels, and it is also not expected to affect the catabolism of complement, cytokines, or other 
proteins involved in the immune response, or affect pre-existing cellular immunity 
(Rath, 2015). Thus, most of the immune system repertoire has been shown to be unaffected by 
ALXN1830 treatment, maintaining an immunocompetent host. This is supported by prior 
experience with anti-FcRn therapeutics in healthy participants, which has shown no increase in 
infection risk despite a significant reduction in tIgG. 
The lack of infection risk following anti-FcRn treatment is likely due to both the specificity and 
transient nature of the IgG reduction, which returns to baseline relatively rapidly after 
discontinuation of treatment. Specifically, in a single dose and 4-week multiple dose study of the 
anti-FcRn antibody M281 in healthy participants (n = 50), tIgG was reduced by 85% compared 
to baseline, and at least 50% of participants experienced a decrease of IgG to < 200 mg/dL over 
the 2 highest SAD and both MAD cohorts, with no SAEs and few moderate AEs. The incidence 
of infection-related AEs in this study was similar between the drug-treated groups and PBO, and 
IgG levels returned to within 20% to 25% of baseline levels within 56 days (Ling, 2019). 
Similarly, in a 4-week multiple dose study in healthy participants (n = 62) using the anti-FcRn, 
efgartigimod, tIgG was decreased on average by approximately 75%, with some individuals 
showing reductions of up to 85%. There was no increase in infections due to efgartigimod 
treatment, and IgG levels returned to baseline within 8 weeks after the last dose (Ulrichts, 2018). 
Also, in a SAD study in healthy participants (n = 48) of the anti-FcRn, rozanolixizumab, IgG 
levels were reduced by up to 47.6% and returned to baseline within 57 days post dose, with little 
or no TEAEs reported (Kiessling, 2017). Recently, in a SAD and 4-week MAD study of RVT- 
1401, total IgG was reduced by up to > 75%, with all AEs being mild to moderate in severity and 
no participants requiring premature discontinuation due to AEs (Collins, 2019). 
Finally, in the previous SAD and MAD studies of ALXN1830 in healthy participants, an IgG 
lowering of up to 64% was observed (in the 20 mg/kg MAD cohort) with no increased risk of 
infection, and the IgG levels returned to baseline levels 43 days after the last dose. In total, 
studies with 5 different anti-FcRn therapeutics (M281, efgartigimod, rozanolixizumab, 
RVT-1401, and ALXN1830) in well over 200 healthy participants have generally shown no 
increased risk of infection, and there have been no cases of severe or serious infections reported 
following anti-FcRn treatment. 
In summary, treatment with ALXN1830 is known to lead to a specific reduction of IgG, but not 
of IgA or IgM, and the IgG lowering is a transient effect with a robust, predictable, and 
consistent return to baseline in healthy participants. Prior experience with anti-FcRn therapies 
suggests a low risk of infection even with lowering of IgG to below 200 mg/dL. There have been 
no cases of severe or serious infections reported following anti-FcRn treatment in healthy 
participants. 
 
10.7.1.1. IgG Level Stopping Rule 
The stopping rule based on IgG level of ≤ 300 mg/dL was chosen based on generally used 
classifications of IgG lowering and the prior experience with anti-FcRn treatments discussed 
above. Classification of reduction in IgG levels has been specified as “mild to moderate” (300 to 
600 mg/dL), “significant” (100 to 299 g/dL), or “profoundly reduced” (< 100 mg/dL). 


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Participants with IgG levels of 200 to 400 mg/dL and total Ig level of 400 to 600 mg/dL are 
considered to have adequate antibody levels to convey humoral immunity, but this is less likely 
if total Ig levels are less than 400 mg/dL or serum IgG levels are less than 200 mg/dL 
(Agarwal and Cunningham-Rundles, 2007). Prior experience with anti-FcRn therapeutics in 
healthy participants showed no increased risk of evidence of infection despite reduction in IgG 
less than 200 mg/dL. Thus, isolated reduction of IgG to levels as low as 200 mg/dL in the 
presence of normal IgA and IgM levels and normal cellular elements of immunity (white blood 
cell [WBC]/differential) would most likely maintain an immunocompetent status. However, to 
avoid IgG reductions below the mild to moderate range, we will utilize a more conservative level 
of 300 mg/dL as the threshold for individual and cohort level stopping rules. 
To further ensure the IgG nadir would not drop below 300 mg/dL, the inclusion criterion for IgG 
was set to ≥ 1000 mg/dL, higher than the lower limit of normal. Since the proposed dosing 
regimens of ALXN1830 are not expected to lower IgG levels more than ~ 70% as predicted by 
PK/PD modeling, the IgG levels should remain above 300 mg/dL. Furthermore, the IgG nadir is 
a transient phenomenon, with IgG levels rising back towards baseline in a relatively rapid 
timeframe. 
Finally, IVIG replacement will be considered only if IgG is profoundly low, ie, below 
100 mg/dL, and this low nadir is sustained for more than 7 days despite discontinuation of 
ALXN1830, which again would be an extremely unlikely event as discussed above. 
10.7.1.2. Evidence of Immunity/Vaccination 
To mitigate the risk of sinopulmonary infections associated with anti-FcRn targeted IgG 
reduction therapy, healthy participants will have current vaccinations against pneumococcus and 
seasonal influenza. 
10.7.2. 
Hydration 
Adverse events of anti-FcRn agents and other Ig are commonly reported to be associated with 
headaches (Robak, 2010; Ling, 2019; Kiessling, 2017). Similarly, in ALXN1830 studies, both in 
patients and healthy participants, headaches (mild to moderate in grade) occurred in both SAD 
and MAD dose regimens with or without nonprescription analgesics. In the case of Ig, multiple 
mechanistic factors have been postulated, such as osmolality, volume load, total volume infused, 
rate of infusion, concentration, and total dose of the Ig infused, which were shown to affect 
infusion tolerability (Vo, 2006). Hydration was considered to be an important factor for 
improvement of infusion-induced headaches (Feldmeyer, 2010). To ensure adequate hydration, it 
is recommended that study participants drink approximately 2 L (women)/2.5 L (men) of 
water every day during the 3 days preceding and following an infusion treatment 
(National Academies of Sciences, Engineering, and Medicine, 2004). 


Protocol Amendment 4 
25 Jun 2021 
ALXN1830-HV-108 
Page 94 of 98 
Alexion Confidential 
 
 
10.8. 
Appendix 11: Abbreviations 
Abbreviation 
Explanation 
ADA 
antidrug antibody 
AE 
adverse event 
AESI 
adverse event of special interest 
ALT 
alanine transaminase 
AR 
adverse reaction 
AUC 
area under the concentration-time curve 
biw 
twice weekly 
BMI 
body mass index 
BP 
blood pressure 
CIC 
circulating immune complexes 
CL 
clearance 
CRF 
case report form 
CRP 
C-reactive protein 
CRU 
clinical research unit 
CTCAE 
Common Terminology Criteria for Adverse Events 
D 
day 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EOI 
end of infusion 
EOS 
end of study 
ET 
early termination 
F 
bioavailability 
FcRn 
neonatal crystallizable fragment receptor 
FSH 
follicle stimulating hormone 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
GMP 
Good Manufacturing Practices 
HBsAg 
hepatitis B surface antigen 
HIV 
human immunodeficiency virus 
HRT 
hormonal replacement therapy 
IB 
Investigator’s Brochure 
IC 
immune complex 
ICF 
informed consent form 
IEC 
independent ethics committee 
Ig 
immunoglobulin 
IgA 
immunoglobulin A 
IgG 
immunoglobulin G 
IgM 
immunoglobulin M 
IMP 
investigational medicinal product 
IRB 
institutional review board 
IRR 
infusion related reaction 
IV 
intravenous 
IVIG 
intravenous immunoglobulin 
mAb 
monoclonal antibody 
MAD 
multiple ascending dose 
MG 
myasthenia gravis 
NOAEL 
no observed adverse effect level 
OP 
outpatient 
PBO 
placebo 


Protocol Amendment 4 
25 Jun 2021 
ALXN1830-HV-108 
Page 95 of 98 
Alexion Confidential 
 
 
 
Abbreviation 
Explanation 
PD 
pharmacodynamics 
PK 
pharmacokinetics 
PV 
pemphigus vulgaris 
q2w 
every 2 weeks 
QTcF 
QT interval corrected for heart rate according to Fridericia’s formula 
qw 
weekly 
SAD 
single ascending dose 
SAE 
serious adverse event 
SC 
subcutaneous 
SoA 
schedule of activities 
SRC 
Safety Review Committee 
SUSAR 
suspected unexpected serious adverse reactions 
TEAE 
treatment-emergent adverse event 
ULN 
upper limit of normal 
WAIHA 
warm autoimmune hemolytic anemia 
WBC 
white blood cell 
WHO 
World Health Organization 


Protocol Amendment 4 
25 Jun 2021 
ALXN1830-HV-108 
Page 96 of 98 
Alexion Confidential 
 
 
10.9. 
Protocol Amendment History 
The protocol amendment summary of changes table for the current amendment is located 
directly before the Table of Contents. 
DOCUMENT HISTORY 
Document 
Type of 
Amendment 
(Global or 
Country-specific) 
Date 
Summary of Key Changes in the 
Amendment 
Amendment 4 
Not applicable 
(single site) 
25 JUN 2021 
Added pregnancy follow-up testing for female 
participants of childbearing potential 
approximately monthly for 3 months after the 
last dose of study drug to be consistent with the 
Investigator’s Brochure; added changes made 
in Administrative Letters 2, 3, and 4. 
Amendment 3 
Not applicable 
(single site) 
8 FEB 2021 
Extended Screening period from 42 to 60 days; 
reduced the overall blood volume required to 
be drawn from participants in the MAD cohorts 
during the study, added conditions that may 
warrant termination of the study, and included 
additional clarifying text and corrections in 
other sections of the document. 
Amendment 2 
Not applicable 
(single site) 
20 DEC 2020 
Revised lower limit of body weight eligibility 
from 50 to 60 kg and updated dose justification 
based on revised body weight criteria; added 
clarity on prior exposure to which therapeutic 
proteins excludes participation. 
Amendment 1 
Not applicable 
(single site) 
09 NOV 2020 
Added vital sign measurement (including 
temperature and pulse oximetry) time points 
after infusion on dosing day to the SoA 
(Section 1.3), removed limitations for the type 
of IUD and hormonal contraception to be 
considered highly effective methods of 
contraception (Section 10.5.2), and changed the 
period for contraception use after last dose of 
study drug, from “at least 2 months” to 
“3 months”. 
Original 
protocol (not 
submitted) 
Not applicable 
28 OCT 2020 
Not applicable. 
Abbreviations: IUD = intrauterine device; MAD = multiple ascending dose; SOA = schedule of activities. 


Protocol Amendment 4 
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ALXN1830-HV-108 
Page 97 of 98 
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11. 
REFERENCES 
Agarwal S, Cunningham-Rundles C. Assessment and clinical interpretation of reduced IgG 
values. Ann Allergy Asthma Immunol. 2007;99(3): 281 283. 
Baker K, Qiao SW, Kuo T, et al. Immune and non-immune functions of the (not so) neonatal Fc 
receptor, FcRn. Semin Immunopathol. 2009;31(2): 223 236. 
Blumberg RS, Lencer WI. Antibodies in the breakdown lane. Nat Biotechnol. 2005; 23(10): 
1232 1234. 
Collins J, Jones L, Michele Snyder, et al. RVT-1401, A novel anti-FcRn monoclonal antibody is 
well tolerated in healthy subjects and reduces plasma IgG following subcutaneous or intravenous 
administration (P5.2-079). Neurology. 2019;92 (Suppl 15). 
FDA. Guidance for Industry, Clinical/Medical, Guidance for Industry: Immunogenicity 
assessment for therapeutic protein product. 2014. 
Feldmeyer L, Benden C, Haile SR, et al. Not all intravenous immunoglobulin preparations are 
equally well tolerated. Acta Derm Venereol. 2010;90(5): 494 497. 
Filion CA, Taylor-Black S, Maglione PJ, Radigan L, Cunningham-Rundles C. Differentiation of 
common variable immunodeficiency from IgG deficiency. J Allergy Clin Immunol Pract. 
2019;7(4):1277-1284. 
Hunley TE, Corzo D, Dudek M, et al. Nephrotic syndrome complicating alpha-glucosidase 
replacement therapy for Pompe disease. Pediatrics. 2004;114(4): e532 535. 
Kiessling P, Lledo-Garcia, R, Watanabe S, et al. The FcRn inhibitor rozanolixizumab reduces 
human serum IgG concentration: A randomized phase 1 study. Sci Transl Med. 2017;9(414). 
Ling LE, Hillson JL, Tiessen RG, et al. M281, an anti-FcRn antibody: Pharmacodynamics, 
pharmacokinetics, and safety across the full range of IgG reduction in a first-in-human study. 
Clin Pharmacol Ther. 2019;105(4): 1031 1039. 
Liu L, Garcia AM, Santoro H, et al. Amelioration of experimental autoimmune myasthenia 
gravis in rats by neonatal FcR blockade. J Immunol. 2007;178(8): 5390 5398. 
Marco H, Smith RM, Jones RB, et al. The effect of rituximab therapy on immunoglobulin levels 
in patients with multisystem autoimmune disease. BMC Musculoskelet Disord. 2014;15: 178. 
Mezo AR, McDonnell KA, Hehir CA, et al. Reduction of IgG in nonhuman primates by a 
peptide antagonist of the neonatal Fc receptor FcRn. Proc Natl Acad Sci U S A. 2008;105(7): 
2337 2342. 
National Academies of Sciences, Engineering, and Medicine. 2004. Available at: 
http://www.nationalacademies.org/ Accessed on 23 Sep 2019. 
Nixon AE, Chen J, Sexton DJ, et al. Fully human monoclonal antibody inhibitors of the neonatal 
fc receptor reduce circulating IgG in non-human primates. Front Immunol. 2015;6: 176. 
Pyzik M, Rath T, Lencer WI, Baker K, Blumberg RS. FcRn: The architect behind the immune 
and nonimmune functions of IgG and albumin. J Immunol. 2015;194(10): 4595 4603. 


Protocol Amendment 4 
25 Jun 2021 
ALXN1830-HV-108 
Page 98 of 98 
Alexion Confidential 
 
 
Rath T, Baker K., Pyzik M, Blumberg RS. Regulation of immune responses by the neonatal Fc 
receptor and its therapeutic implications. Front Immunol. 2015;5: 664. 
Robak T, Mainau C, Pyringer B, et al. Efficacy and safety of a new intravenous immunoglobulin 
10% formulation (octagam® 10%) in patients with immune thrombocytopenia. Hematology. 
2010;15(5): 351 359. 
Roopenian DC, Akilesh S. FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol. 
2007;7(9): 715 725. 
Schulz KF, Altman DG, Moher D, for the CONSORT Group. CONSORT 2010 Statement: 
updated guidelines for reporting parallel group randomised trials. Ann Intern Med. 
2010;152(11): 726 732. 
Ulrichts P, Guglietta A, Dreier T, et al. Neonatal Fc receptor antagonist efgartigimod safely and 
sustainably reduces IgGs in humans. J Clin Invest. 2018;128(10):4372-4386. 
Vo AA, Cam V, Toyoda M, et al. Safety and adverse events profiles of intravenous 
gammaglobulin products used for immunomodulation: a single-center experience. Clin J Am Soc 
Nephrol. 2006;1(4): 844 852. 

SAP_001.pdf: 
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Statistical Analysis Plan for Interventional Studies 
SAP Version Number: 2.0 
SAP Date: 24-Feb-2022 
Sponsor Name: Alexion Pharmaceuticals, Inc. 
Protocol Number: ALXN1830-HV-108 
Protocol Title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple 
Ascending Dose Study of Subcutaneous ALXN1830 in Healthy Participants 
Protocol Version and Date: Protocol Amendment 4, 25-Jun-2021 
Syneos Health Project Code:  7019592  
Authors: 
 
 
Notice of Confidential and Proprietary Information: 
The information contained in this document is confidential belonging to Alexion Pharmaceuticals, Inc.. 
Acceptance of this document constitutes agreement by the recipient that no information contained herein 
will be published or disclosed without prior written authorization from an official of Alexion 
Pharmaceuticals, Inc. However, this document may be disclosed to appropriate Institutional Review 
Board and Ethics Committees or duly authorized representatives of a national regulatory authority under 
the condition that they are requested to keep it confidential. In the event of an actual or suspected breach 
of this obligation, Syneos Health should be notified promptly. 
NCT #: NCT04730804


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I confirm that I have reviewed this document and agree with the content.
Approvals
Syneos Health Approval
 
Signature
Date (DD-Mmm-
YYYY)
Signature
Date (DD-Mmm-
YYYY)
Signature
Date (DD-Mmm-
YYYY)
Alexion Pharmaceuticals, Inc. Approval
 
Alexion Pharmaceuticals
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Alexion Pharmaceuticals
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Table of Contents
Approvals ..................................................................................................................................2
Glossary of Abbreviations...................................................................................................6
Purpose..............................................................................................................................9
Study Objectives and Endpoints.......................................................................................10
Study Details/Design........................................................................................................11
Endpoints .........................................................................................................................15
Analysis Sets....................................................................................................................16
General Aspects for Statistical Analysis ...........................................................................17


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Participant Disposition, Demographic, Other Baseline Characteristics and Medication ....19
Pharmacokinetics.............................................................................................................21
Pharmacodynamics..........................................................................................................25
Immunogenicity................................................................................................................26
Safety...............................................................................................................................27


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Interim Analyses...............................................................................................................33
Changes from Analysis Planned in Protocol.....................................................................34
Reference List..................................................................................................................35
Quality Control .................................................................................................................36


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Glossary of Abbreviations
Abbreviation
Description
AUCextrap
AUC extrapolated from time t to infinity as a percentage of total AUC
z
Apparent terminal phase elimination rate constant
ADA
Anti-drug antibodies
AE
Adverse Event
AESI
Adverse event of special interest
ALT
Alanine aminotransferase
ANOVA
Analysis of Variance
AST
Aspartate aminotransferase
AUC
Area under the serum concentration versus time curve
AUCt
Area under the serum concentration versus time curve from time 0 to the last 
quantifiable concentration
AUCtau
Area under the concentration-time curve during the dosing interval
AUC
Area under the serum concentration versus time curve from zero to infinity
BLQ
Below Lower Limit of Quantitation
BMI
Body Mass index
BUN
Blood urea nitrogen
CI
Confidence Interval
CIC
Circulating immune complexes
CL/F
Apparent oral clearance
Cmax
Maximum observed concentration 
Ctrough
Concentration at predose times on Day 8, 15 and 22. Observed directly from Data
CTCAE
Common Terminology Criteria for Adverse Events
CTMS
Clinical Trial Management System
CV
Coefficient of Variation
ECG
Electrocardiogram
eDISH
Evaluation of drug-induced serious hepatotoxicity
EMA
European Medicines Agency
EOS
End of Study 


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FcRn 
Neonatal crystallizable fragment receptor 
FDA 
Food and Drug Administration 
FSH 
Follicle-stimulating hormone 
GMR 
Geometric mean ratio 
HbA1c 
Glycated Hemoglobin 
HBC 
Hepatitis B core antibody 
HBsAg 
Hepatitis B surface antigen 
hCG 
Human chorionic gonadotropin 
HCV 
Hepatitis C virus 
HDL 
High-density lipoprotein 
HIV 
Human Immunodeficiency Virus 
HTD 
Highest tolerated dose 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
Ig 
immunoglobulin 
IGS 
Immunogenicity Set 
IMP 
Investigational medicinal product 
IQR 
Interquartile range 
IRR 
Infusion related reaction 
IV 
Intravenous 
LDL 
Low-density lipoprotein 
MAD 
Multiple ascending dose 
Max 
Maximum 
MD 
Multiple dose 
MedDRA 
Medical Dictionary for Regulatory Activities 
Min 
Minimum 
NAb 
Neutralizing Antibodies 
NIMP 
non-IMP 
PBO 
Placebo 
PD 
Pharmacodynamic(s) 


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PDS 
PD Analysis Set 
PK 
Pharmacokinetic(s) 
PKS 
PK Analysis Set 
PT 
Preferred Term 
Q1 
First quartile, 25th percentile of the data 
Q3 
Third quartile, 75th percentile of the data 
QTcF 
qw 
Weekly 
Rac 
Accumulation ratio 
RBC 
Red blood cells 
RNA 
Ribonucleic acid 
SAD 
Singlel ascending dose 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SC 
Subcutaneous 
SD 
Standard Deviation / Single dose 
SI 
Standard International System of Units 
SoA 
Schedule of Activities 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
SS 
Safety Set 
t½ 
Terminal elimination half-life 
TEAE 
Treatment-Emergent Adverse Event 
TESAE 
Treatment-Emergent Serious Adverse Event 
Tmax 
Time to maximum concentration 
ULN 
Upper limit of normal 
Vd/F 
Apparent volume of distribution 
WHO 
World Health Organization 


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Purpose
The purpose of this statistical analysis plan (SAP) is to ensure that the data listings, summary tables and 
figures which will be produced, and the statistical methodologies which will be used, are complete and 
appropriate to allow valid conclusions regarding the study objectives.
Responsibilities
Syneos Health will perform the statistical analyses and is responsible for the production and quality 
control of all tables, figures and listings
Timings of Analyses
The primary analysis of safety, pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity is 
planned after all participants complete the final study visit or terminate early from the study.


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Study Objectives and Endpoints
Objectives
Endpoints
Primary
To assess the safety and tolerability 
of single and multiple doses of 
ALXN1830 SC
Safety assessed by the incidence and relatedness of 
TEAEs, SAEs, AESIs, physical examination, vital sign 
measurements, clinical laboratory, and ECG results
Secondary
To assess the PK of single and 
multiple doses of ALXN1830 SC
To explore the PD effects of single 
and multiple doses of ALXN1830 SC
To assess the immunogenicity of 
ALXN1830 SC
To compare safety and tolerability, 
PK, PD, and immunogenicity of 
ALXN1830 SC between Japanese 
and non-Japanese healthy 
participants*
Serum ALXN1830 concentration profiles and single- and 
multiple-dose PK parameters
Change in serum IgG levels over time; FcRn saturation as 
measured by receptor occupancy
Incidence of anti-drug antibodies and neutralizing antibodies 
to ALXN1830
Quantitative assessment of safety, PK parameters, PD 
parameters, and immunogenicity between Japanese and 
non-Japanese healthy participants*
Abbreviations: AESI = adverse events of special interest; ECG = electrocardiogram; FcRn = neonatal crystallizable fragment 
receptor; IgG = immunoglobulin G; PD = pharmacodynamics; PK = pharmacokinetics; SAE = serious adverse event; SC = 
subcutaneous; TEAE = treatment-emergent adverse event.
*: These objectives/endpoints were not achieved due to early termination of the study.


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Study Details/Design
Brief Description
This is a Phase 1 study in up to 48 healthy adult participants (36 on active treatment, 12 on placebo 
[PBO]). The study will consist of 2 SAD (Cohorts 1 and 2) and 4 MAD cohorts  (Cohorts 3 to 6). Cohort 6 
will enroll only Japanese participants). Eight participants will be randomly assigned in a 6:2 ratio to each 
of the 6 cohorts to receive either single or multiple doses of ALXN1830 SC (n = 6 per cohort) or single or 
multiple doses of PBO (n = 2 per cohort). The study was terminated early, therefore cohort 2 has only 2 
participants and cohort 6 has none. 
Initially, the first 4 participants randomized to each cohort will be dosed, 3 participants with ALXN1830 
and 1 participant with PBO. The dosing will be staggered, with an interval of at least 3 days for the SAD 
cohorts and at least 7 days for the MAD cohorts, before dosing the rest of the participants in the cohort. 
The shorter interval of staggered dosing for the SAD cohorts compared to the MAD cohorts is 
considered appropriate as the expected PK exposure of the ALXN1830 SC doses will be a fraction of 
that of the intravenous (IV) dose demonstrated to be safe and well tolerated in previous IV studies. The 
reduction of IgG after a single SC dose will be similar to the observed IgG reduction in previous IV 
studies; and in general, there will be low risk of immunogenicity and infusion related reactions after a 
single dose. All participants will be observed during the infusion and for 2 hours following the end of 
infusion for safety and participants will be encouraged to report any discomfort immediately, especially 
within 24 hours post dosing. At no time will more than 4 participants per cohort be dosed on a given day.
Progression to the next dosing cohort will be gated by review of initial dosing data by a Safety Review 
ditional participants 
may be enrolled as replacement participants only if a participant discontinues within 3 weeks of the 
last dose for reasons other than drug-related adverse events.
Participants will be randomly assigned in a 6:2 ratio to each of the 6 cohorts to receive either single or 
multiple doses of ALXN1830 SC (n = 6 per cohort) or single or multiple doses of PBO (n = 2 per cohort). 
The planned dose and dose regimens are shown in Table 1. The planned study duration is approximately 
124 days for Cohorts 1 and 2: up to 60 days for screening and approximately 64 days for dosing and 
follow-up; 201 days for Cohort 3: up to 60 days for screening and approximately 141 days for dosing and 
follow-up; and 148 days for Cohorts 4 to 6: 60 days for screening and approximately 88 days for dosing 
and follow-up. Participants will be admitted to an inpatient facility during the dosing and follow-up period 
as shown in the schedule of activities (SoA) in Protocol Section 1.3 . The study design is presented in
Figure 1.


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Table 1: Planned Dose and Dose Regimens in Healthy Participants
Cohort No.
Regimen/Route of Administration
Study Drug (N)
1
Single dose SC
Placebo (n = 2) or 
ALXN1830 1500 mg (n = 6)
2
Single dose SC
Placebo (n = 2) or 
ALXN1830 2250 mg (n = 6)
3
Multiple dose (12 doses qw) SC
Placebo (n = 2) or
ALXN1830 750 mg (n = 6)
4
Multiple dose (4 doses qw) SC
Placebo (n = 2) or 
ALXN1830 1500 mg (n = 6)
5
Multiple dose (4 doses qw) SC
Placebo (n = 2) or 
ALXN1830 2250 mg (n = 6)
6a
Multiple dose (4 doses qw) SC 
Japanese healthy participants
Placebo (n = 2) or 
ALXN1830 HTD (n = 6)
a Healthy, Japanese participants enrolled in Cohort 6 will be dosed according to the HTD established in the non-
Japanese cohorts. This cohort was not achieved due to early termination of the study. Abbreviations: qw = weekly; 
SC = subcutaneous; HTD = highest tolerated dose.
Figure 1:
Study Design Schematic
Abbreviations: D = day; HTD = highest tolerated dose; MAD = multiple ascending dose; PBO = placebo; qw = weekly; SAD = single
ascending dose; SC = subcutaneous; SRC = Safety Review Committee.
Progression to the next dosing cohort will be gated by review of initial dosing data by an SRC 
consisting of the Investigator, and Alexion Safety Physician, Medical Monitor, Study Statistician, 
and Clinical Pharmacologist.
Participant Selection
Inclusion- and exclusion criteria are described in detail in Protocol Sections 5.1 and 5.2.


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Lifestyle Considerations are described in Protocol Section 5.3.
Determination of Sample Size
Up to 48 participants will be enrolled. Participants will be randomly assigned in a 6:2 ratio to up to 6 
planned cohorts to receive either single or multiple doses of ALXN1830 SC (n = 6 per cohort) or single or 
multiple doses of PBO (n = 2 per cohort). Progression to the next dosing cohort will be gated by review of 
initial dosing data by an SRC.
Formal sample size calculation has not been performed. The number of participants has been chosen 
based on feasibility and is considered adequate to meet the study objectives.
Treatment Assignment and Blinding
This is a double-blind study. Eligible participants who meet all inclusion and no exclusion criteria will be 
assigned unique numbers for enrollment and randomization.
On Day 1 participants will be assigned a unique number (randomization number) in ascending numerical 
ent to one of the 6 cohorts of the 
study, according to the randomization schedule generated prior to the study by Syneos Health 
Biostatistics.
Participants will be randomly assigned in a 6:2 ratio to receive either single or multiple doses of 
ALXN1830 or PBO (Table 1
drug throughout the course of the study. In order to maintain this blind, site's pharmacy staff will be 
responsible for the reconstitution and dispensation of all study drug.
In the event of a Quality Assurance audit, the auditor(s) will be allowed access to unblinded study drug 
records at the site(s) to verify that randomization/dispensing has been done accurately.
In the event of an emergency, an envelope for each participant containing his/her study drug assignment 
will be available in the pharmacy at the clinical study site. Unblinding should only be considered for the 
safety of the participant. If unblinding is deemed necessary by the Investigator, the Investigator can 
Investigator must note the date, time, and reason for unblinding. The Investigator should inform the 
Medical Monitor that the participant was unblinded; however, the Investigator should not reveal to the 
responsible for the ongoing conduct of the study (such as the management, monitors, Investigator) and 
those responsible for data analysis and interpretation of results at the conclusion of the study, such as 
biometrics personnel. Unblinded information will only be accessible to those who need to be involved in 
the safety reporting to health authorities, independent ethics committees (IECs), or persons performing 
ongoing safety evaluations during the study. The Investigator will receive only blinded information unless 
unblinded information is judged necessary for safety reasons.
Administration of Study Medication
The doses to be administered in the study and study drug dose formulation are provided in Table 2.


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The SAD and MAD cohorts will use study drug that has been manufactured with different
composition. Analytical and characterization data provide assurance that the formulations can be 
considered comparable. Placebo will be commercially available normal saline.
Table 2:
Study Drug
Drug name
ALXN1830
Placebo
Type
Biologic
Diluent
Dose 
formulation
Sterile liquid
Sterile liquid
Unit dose 
strength(s)
ALXN1830 is formulated at 150 
mg/mL, and supplied as a 1500 
mg/10 mL vial
Placebo
Dosage level(s)
Refer to Table 1
Not applicable
Route of 
administration
SC infusion
SC infusion
Use
Investigational Product
Placebo
IMP and NIMP
IMP
IMP
Sourcing
Provided by Alexion
Provided by study site
Packaging and 
labeling
Study drug will be provided in a 10 
mL vial. Each vial will be labeled as 
required per country requirement
Placebo (normal saline) will be provided in 
country-specific commercially available form
Abbreviations: IMP = investigational medicinal product; NIMP = non-IMP; SC = subcutaneous.
Study Procedures and Flowchart
Schedules of activities are in Protocol Section 1.3. 


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Endpoints
Primary Endpoints
Safety assessed by the incidence and relatedness of TEAEs, SAEs, AESIs, physical examination, 
vital sign measurements, clinical laboratory, and ECG results
Secondary Endpoints
Serum ALXN1830 concentration profiles and single- and multiple-dose PK parameters
Change in serum IgG levels over time; FcRn saturation as measured by receptor occupancy
Incidence of anti-drug antibodies and neutralizing antibodies to ALXN1830
Quantitative assessment of safety, PK parameters, PD parameters, and immunogenicity between 
Japanese and non-Japanese healthy participants


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Analysis Sets
Enrolled Set
The Enrolled Set will include all participants who sign the informed consent form (ICF) and pass 
inclusion/exclusion criteria and are randomized. Unless specified otherwise, this set will be used for 
participant listings and summaries of participant disposition.
Safety Set 
The Safety Set (SS) will include all participants who receive at least 1 dose of study drug. Participants will 
be analyzed according to the study drug they actually received. The SS will be used for all analyses of 
safety endpoints. 
Pharmacokinetic Set 
The Pharmacokinetic Set (PKS) will include all participants who received at least 1 dose of study drug 
(only active) and have at least one post-dose serum ALXN1830 concentration measured. Participants will 
be analyzed according to the study drug they actually received. Serum concentrations will be summarized 
for all participants in the PKS. The exclusions from summary statistics for serum concentrations and/or 
PK parameters will be defined based on review of protocol deviations (if any) prior to database lock by PK 
scientist and study statistician at the discretion of the sponsor. Pharmacokinetic analyses will be 
performed using the PKS.
Pharmacodynamic Set 
The Pharmacodynamic Set (PDS) will include all participants who received at least 1 dose of study drug 
(active and placebo) who have evaluable serum Immunoglobulin data (IgG, IgG subtypes, Ig subtypes, 
and CIC) or FcRn data. Participants will be analyzed according to the study drug they actually received. 
Pharmacodynamic analyses will be performed using the PDS.
Immunogenicity Set
The Immunogenicity Set (IGS) will include all participants who have a predose (baseline) and at least 1 
postdose ADA sample collected. Immunogenicity analyses will be performed using the IGS.


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General Aspects for Statistical Analysis
General Methods
In general, descriptive statistics for continuous variables will include number of non-missing values, 
arithmetic mean, SD, median,interquartile range (IQR), Q1, Q3, minimum, and maximum. Categorical 
variables will be summarized using percentages and frequency counts. Descriptive statistics and 
percentages and frequency counts will be summarized by treatment, and period, where appropriate.
For the summary statistics of all continuous variables unless otherwise specified, minimum and 
maximum will be presented to the same number of decimal places as the raw data. Mean, median, 
Q1, Q3, and IQR will be presented to one more decimal places than the raw data, and SD will be 
presented to two more decimal places than the raw data.
All statistical analyses will be conducted using SAS® for Windows® Version 9.4 or higher.
All relevant participant data will be included in listings. All participants entered into the database will 
be included in participant data listings.
In general, tables will be split over multiple pages, with the following columns:
Cohort 1: SAD ALXN1830 1500 mg
Cohort 2: SAD ALXN1830 2250 mg
Cohort 3: MAD ALXN1830 750 mg QW x 12
Cohort 4: MAD ALXN1830 1500 mg QW x 4
Cohort 5: MAD ALXN1830 2250 mg QW x 4
All Cohorts Placebo
All Cohorts Total
Key Definitions
End of Study (EOS) 
The EOS for each participant is defined as the date the last participant completes the last visit as shown 
in the Schedule of Activities in Section 1.3 of the Protocol.
Trial day
= event date 
date of first dose of IP + 1.
If the event date < date of first dose of IP, trial day = event date 
date of first dose of IP.
Nominal Time
Nominal time is the scheduled measurement time relative to time 0. Time 0 is the time of start of study 
drug dosing on Day 1. 
Baseline Value
Baseline value will be defined as the last non-missing value recorded prior to first intake of study 
treatment.
Change from Baseline (CFB)


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CFB = Post-baseline value 
Value at baseline
Missing Data
For participants who are withdrawn from the study prior to the end of the study, all data collected up to the 
point of discontinuation will be used for analysis. There will be no imputation for missing data, unless 
otherwise specified. 
Visit Windows
If there are multiple planned assessments for any study procedure at a given time point the latest non-
missing value will be used for summarization. Unscheduled assessments will be listed and will be used to 
flag baseline visit if this is the last non-missing assessment before the first dose of study drug, but 
unscheduled assessments will not be included in the summarization.
Pooling of Centers
Not Applicable.
Subgroups
Not Applicable.


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Participant Disposition, Demographic, Other Baseline 
Characteristics and Medication
Participant Disposition and Withdrawals
assignment to treatment, will be presented.
The following frequencies (number and percent) will be displayed for all participants in the Enrolled Set: 
participants enrolled, participants randomized, screen failures, and reasons for screen failure. 
The analysis sets will be summarized with counts and percentages by treatment. This table will include
the following: number of participants in Enrolled Set, participants in Safety Set, reasons for exclusion from 
the Safety Set, participants in PK set, reasons for exclusion from the PK set, number of participants in PD 
Set, reasons for exclusion from the PD Set.
The following frequencies (number and percent) will be displayed for all participants in the Enrolled Set: 
randomized participants, participants in the Safety Set, participants in the PK Set and participants in the 
PD Set, participants who completed the study (including follow-up), participants who discontinued early, 
participants who completed study treatment, participants who discontinued study treatment early also 
presented by reason for early discontinuation and study duration in days. The denominators will be the 
number of enrolled participants. 
Completion/discontinuation status, inclusion/exclusion criteria definitions and Inclusion/exclusion criteria 
violations will be listed by participant. 
A listing of participants excluded from the analysis populations will also be generated.
Protocol Deviations
Protocol deviation management at Syneos Health is detailed in Protocol Deviation and Non-compliance 
Management). For details on the process for defining analysis datasets refer to (Blind) Data Review and 
Definition of Analysis Sets SOP.
All protocol deviations recorded in Clinical Trial Management System (CTMS) will be listed. The Protocol 
deviation criteria are graded as not important or important. Protocol deviations will be summarized by the 
number and percentage of participants for the Safety Set.
Demographic and Baseline Characteristics
Demographic and baseline characteristics, including age, sex, race, ethnicity, child-bearing potential, 
evidence of vaccination, height, body weight, and BMI will be summarized using standard descriptive 
statistics. No formal statistical comparisons between populations will be performed. Demographics will be 
listed for all participants in the Enrolled Set.


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Medical and Surgical History 
Medical and surgical history will be coded using MedDRA 23.1 and summarized for the Safety Set 
presenting the number and percentages of participants within each preferred term (PT) grouped by the 
system organ class (SOC). A participant  with multiple occurrences of an event in a PT is counted only 
once. Medical and surgical history will be listed by participant. 
Medication
The WHO Drug, September 2020, B3 will be used to classify prior and concomitant medications by 
therapeutic class and drug name. 
Prior medication is defined as any medication taken before the date of the first dose of study treatment. 
Concomitant medication is defined as any medication taken on or after the date of the first dose of study 
treatment. 
The use of prior and concomitant medications will be summarized by the number and percentage of 
participants for the Safety Set. If a participant takes a specific medication multiple times or takes multiple 
medications within a specific therapeutic class, that participant would be counted only once for the coded 
drug name or therapeutic class.
Non-Medication Therapies or Procedures
The WHO Drug, September 2020, B3 will be used to classify non-medication therapies by therapeutic 
class. Prior non-medication therapy is defined as any non-medication therapy taken before the date of the 
first dose of study treatment. Concomitant non-medication therapy is defined as any non-medication
therapy taken on or after the date of the first dose of study treatment.
Non-medication procedure data will be listed but not summarized. 
Extent of Exposure
Exposure data will be summarized by total dose administered (mg), total volume administerd (mL) and 
the number of interruptions (SC Infusion). Study drug administration data will be listed.
Treatment Compliance 
Not Applicable.


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Pharmacokinetics
Pharmacokinetic analyses will be performed using the PKS. Note that placebo are not required.
PK parameters will be calculated for ALXN1830 using noncompartmental methods with Phoenix®
WinNonlin® (Certara USA Inc., Princeton, New Jersey) Version 8.0 or higher. Calculations of individual 
PK parameters will be based on ALXN1830 concentrations and the actual sampling times elapsed from 
the actual reference dosing time data recorded during the study.
PK Sampling Schedule 
Whole blood samples will be collected for measurement of serum concentrations of ALXN1830 as 
specified in the SoA (Protocol Section 1.3). All efforts should be made to obtain the PK samples at the 
exact nominal time relative to dosing within the specified window. Additional samples may be collected 
during the study.
Serum PK Endpoint
Following PK parameters will be derived from the serum ALXN1830 concentrations when feasible and 
supported by the available data.
For the single dose cohorts 1-2, PK parameters will be derived on Day 1.
For the multiple dose cohort 3, PK parameters will be derived on Days 1, 22, and 78.
For the multiple dose cohort 4 to 5, PK parameters will be derived on Days 1, and 22.
Parameters
Dosing
Definition
Cmax 
SD, MD
Maximum observed serum concentration
Tmax 
SD, MD
Time to maximum observed serum concentration
AUCt
SD, MD
Area under the serum concentration versus time curve from time 0 to the 
last quantifiable concentration
AUCtau
MD
Area under the concentration-time curve during the dosing interval
AUC0-
SD, MD
Area under the concentration-time curve from time 0 (dosing) to time 
infinity
Ctrough
MD
Concentration at predose times on Day 8, 15 and 22. Observed directly 
from Data
t½
SD, MD
Terminal elimination half-life
z
SD, MD
Terminal-phase elimination rate constant
CL or CL/F
SD, MD
Total body clearance or apparent clearance
Vd or Vd/F
SD, MD
Volume of distribution or apparent volume of distribution
Rac 
MD
Accumulation ratio
Abbreviations: MD = Multiple-dose; SD = Single dose
Note: tau is the dosing interval for steady-state data, i.e., the time between doses (tau = 1 week).
The primary PK parameters will be summarized by overall treatment and the sub treatment category ADA 
status (at least one positive/negative). Boxplots will present PK parameters by ADA status and by healthy 
non-Japanese participants. Some PK parameters may not be calculated for all or some subjects, at the 


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discretion of the pharmacokineticist, if the concentration data are not deemed to be amenable to 
evaluation. Explanations for PK parameters that could not be estimated will be provided in the report.
Additional serum PK parameters may be calculated if deemed appropriate.
Presentation of Concentration Data
Handling of Missing Data
Missing concentration data for all participants who are administered scheduled study treatments will be 
considered as non-informative missing and will not be imputed. No concentration estimates will be provided 
for missing sample values.
For the derivation of AUC and for the individual serum concentration versus time curves, the following rules 
will apply:
-dose Day 1
samples will be treated as zero;
The sampling time of pre-dose samples relative to dosing will also be treated as zero;
;
The first BLQ after the last measurable sample will be set to zero
set to zero;
For serum concentration summary the following rules will apply:
All BLQ values will be set to zero;
No further imputation will be applied to any missing values.
Listing and Presentation of Individual PK Data
The actual and nominal sampling times of PK blood sample collection will be listed for each participant and 
will include the deviation in time from the protocol scheduled time (i.e., nominal time), if applicable.
All measured concentrations will be presented in original precisions (i.e., significant figures) and units as 
reported by Bioanalytical lab 
eg ng/mL.
Serum concentrations and time deviation data will be presented in a data listing by participant.
Summary of PK Concentrations by Matrix 
Serum concentration data will be summarized separately by time point for each cohort/actual treatment 
using the following descriptive statistics: number of participants, arithmetic mean, SD, CV, geometric 
mean, geometric CV, median, minimum, and maximum. 
Mean serum concentration versus scheduled time profiles will be presented in figures on both linear and 
semilogarithmic scales. Individual serum concentration versus nominal time profiles will be presented 
similarly. 
Derivation of Pharmacokinetic Parameters
The apparent Cmax and the corresponding Tmax will be read directly from the concentration-time 
plot (observed data).


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AUCt will be calculated using the log-linear trapezoidal interpolation rule for extravascular model.
z) will be determined by log linear regression obtained on
at least the 3 last quantifiable concentrations and will not include Cmax; t1/2 is calculated by the 
z;
AUC will be calculated by the program as: AUC = AUCt + AUCextrap where last is the sampling 
time point of the last measurable concentration (tlast). AUCextrap will be calculated by the program 
as: Clast
z, where Clast is the observed concentration at time tlast
z is the elimination rate 
constant during the apparent terminal elimination phase. AUC
will only be presented for 
z;
CL/F will be calculated by program as dose amount/AUC ;
Vz/F will be calculated by the program as (dose amount/AUC
z;
The following PK acceptance criteria will be applied to assess the reliability of elimination parameters:
z is greater than or equal to 3 excluding Cmax point;
The adjusted square of the correlation coefficient or coefficient of determination (R square adjusted) 
f
80;
AUCextrap
Unreliable PK parameters will be listed but flagged and excluded from summary.
PK Parameters Summarization
Pharmacokinetic parameters derived from serum concentrations will be presented in data listings and 
summarized separately using the following descriptive statistics: number of participants, arithmetic mean, 
SD, arithmetic CV, geometric mean, geometric CV, median, minimum, and maximum.
Planned Statistical Models for PK Parameters and Concentrations
The primary analysis will be based on the PKS.


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Dose proportionality of Multiple-Dose (Cohort 3 to 5)
The power model will be used and will include the PK parameter as the response variable and dose (mg) 
as the explanatory variable. For this model, the variable dose will be treated as a continuous variable.
The form of the model is as follows:
PK Parameter = e × Dose × e
e represents the associated error. 
following a natural-log transformation, to which a linear regression will be fit by ordinary least squares 
(OLS): 
, where Dose > 0, 
and 
represents the associated error. 
model), and this will be used to quantify dose proportionality. According to Hummel et al. (2009), the 
following criterion may be used for exploratory dose proportionality evaluations: If the (two-sided) 90% CI 
ty is 
(presented to three decimal places).
ln(PK Parameter) = mu + 
*ln(Dose)
*where 
= 1 indicates perfect dose proportionality. Estimation of beta, along with its 90% CI, will be 
provided.
Assessment of Steady State (MAD)
For the MAD study portion, a visual assessment of Ctrough concentrations will be undertaken. The 
geometric mean of Ctrough values obtained from Days 8 through 22 will be plotted (y-axis) agains visit 
number (x-axis). The data points will be connected, and a box plot of individual values (for that visit) will 
juxtaposed to each geometric mean.
Deviation from Analyses Planned in Protocol
The study was terminated early, therefore cohort 2 has only 2 participants and cohort 6 has none. 
Therefore the secondary objective, to compare safety and tolerability, PK, PD, and immunogenicity of 
ALXN1830 SC between Japanese and non-Japanese healthy participants cannot be met and the 
secondary endpoint the quantitative assessment of safety, PK parameters, PD parameters, and 
immunogenicity between Japanese and non-Japanese healthy participants cannot be analyzed.
.


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Pharmacodynamics
Venous blood samples will be collected for measurement of IgA, IgM, IgG, and IgG subtypes (1 - 4), FcRn 
receptor occupancy, and CIC at timepoints described in the SoA (Protocol Section 1.3). 
As data become available during the study, the timing of PD sampling may be altered in order to ensure 
appropriate monitoring of participants. 
Whole blood for assessment of exploratory biomarkers will be collected as per the SoA (Protocol Section 
1.3). Residual PK/PD samples may also be used for exploratory analyses.
Endpoints and Analysis
Endpoints
Change in serum levels of IgA, IgM, IgG, and IgG subtypes (1 to 4)) over time 
FcRn saturation as measured by receptor occupancy
Quantitative assessment of PD parameters between Japanese and non-Japanese healthy 
participants
Analysis of the Endpoints
Pharmacodynamic analyses will be performed using the PD Set. 
The endpoint regarding the quantitative assessment of PD parameters between Japanese and non-
Japanese healthy participants cannot be analyzed due to early termination of the study.
Missing concentration data for all participants who are administered scheduled study treatments will be 
considered as non-informative missing and will not be imputed. No concentration estimates will be provided 
for missing sample values.
For the PD/biomarker levels, actual values, changes from baseline and percentage change from baseline 
will be summarized by time point for each treatment using the following descriptive statistics: number of 
participants, arithmetic mean, SD, CV, geometric mean, geometric CV, median, minimum, and maximum.
Mean PD/biomarker levels (change from baseline and percentage change from baseline) versus scheduled 
time profiles will be presented in figures.
Individual PD/biomarker levels (change from baseline and percentage change from baseline) versus 
scheduled time profiles will be presented similarly.
PD/biomarker levels, change from baseline and percentage change from baseline will be presented in a 
data listing by participant.


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Immunogenicity
The population used for immunogencity analyses will be the Immunogenicity Set (IGS).
Samples for immunogenicity should be collected at times specified in the SoA (Protocol Section 1.3). 
The immunogenicity analyses will include an analysis of anti-drug antibodies (ADA) using descriptive 
statistics. 
The actual date and time (24-hour clock time) of each sample will be recorded. 
All samples that are positive in a screening assay will be confirmed for antibody specificity and further 
characterized for titer. All samples that are confirmed positive for ADA will be evaluated for the presence 
of neutralizing antibodies. 
Participants found to have anti-ALXN1830 antibodies still present at the end of the study will be requested 
to return to the clinic for up to 1 year (from the first drug administration) or until ADA titers return to 
baseline levels (whichever occurs first). The follow-up visits are to be scheduled at 90-day intervals for 
blood collection to assess ADA.
Immunogenicity Endpoints
Incidence of anti-drug antibodies and neutralizing antibodies (NAb) to ALXN1830
Quantitative assessment of immunogenicity between Japanese and non-Japanese healthy 
participants
Analysis of the Endpoints
The endpoint regarding the quantitative assessment of immunogenicity between Japanese and non-
Japanese healthy participants cannot be analyzed due to early termination of the study.
ADA and NAb data reporting 
Incidence, titer, duration, time to detection, pre-existing ADA
PK concentration or parameter by immunogenicity response
PD response by immunogenicity response  
Individual PK data listing or spaghetti plots with ADA category overlaid.
For ADA categories and participants, summary of individual plots of PK, PD, ADA titer, and 
NAb time course to better understand the clinical impact of immunogenicity at a subject level. 


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Safety
The population used for safety analyses will be the Safety Set. 
Safety analyses will include an analysis of all treatment-emergent adverse events (TEAEs), SAEs, AESIs, 
ECGs, clinical laboratory data, physical examinations, and vital sign measurements using descriptive 
statistics. 
No inferential statistical analyses are planned on the safety parameters of this study. 
Adverse Events / Adverse Drug Reactions
AEs for all participants in the Safety Set will be included in the AE summaries. 
Adverse events will be summarized by system organ class (SOC) and preferred term (PT) for each 
treatment and overall, based on the MedDRA dictionary version 23.1. 
If the relationship to study drug is missing for TEAEs, then the relationship will be counted as related to 
study product for the summary tables. Missing severity for TEAEs will be counted as Grade 3. 
Pretreatment AEs are defined as AEs that were reported or worsened after signing the ICF up to the start 
of study drug dosing. Treatment-emergent AEs are defined as AEs that were reported or worsened on or 
after the start of study drug dosing through the safety follow-up visit.
If the start date of an AE is partially or completely missing, the date will be compared as far as possible 
with the date of the start of administration of study drug. The AE will be assumed to be treatment-
emergent if it cannot be definitively shown that the AE did not occur or increase in severity during the 
treatment period (worst case approach). The following general rules will be used:
If the start day is missing but the start month and year are complete, an AE will not be considered 
as being treatment-emergent only if the start month/year is before the month/year of the first 
study drug administration.
If the start day and month are missing but the start year is complete, an AE will not be considered 
as being treatment-emergent only if the start year is before the year of the first study drug 
administration.
If the start date is completely missing, an AE will be considered treatment-emergent unless the 
stop date is before the first study drug administration.
Duration will be calculated for AEs that resolve as the difference between the resolution date and onset 
date plus 1 and expressed in days. Should an AE have a short duration (i.e. < 24 hours), the duration will 
be calculated as the difference between the resolution time and the onset time.
Adverse events of special interest are defined as any IRR equal to or higher than Grade 3; or any IRR 
that may jeopardize the participant and requires immediate intervention to prevent it from leading to 
severe outcomes. Potential cases of any delayed hypersensitivity reactions, equal to or higher than 
Grade 2.
The summary tables will include the number of participants and the number of events. Percentages will 
be based on the number of participants and on the number of events. For summaries by SOC and PT, a 
participant will be counted once at the SOC level and once at each PT within the SOC level. 


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For summaries by SOC, PT, and maximum severity, a participant will be counted once at the highest 
severity level for which the event occurred at the SOC level and the highest severity level for each unique 
PT within that SOC level. Therefore, participants may only contribute once to each PT and once to each 
SOC level.  
The summaries presenting frequency of AEs by SOC and PT will be ordered by overall descending 
frequency of SOC and then, within a SOC, by overall descending frequency of PT.  
The following tables will be provided: 
An overall summary of the number and percentage of participants reporting TEAEs, serious 
TEAEs (TESAEs), TEAEs resulting in death, TEAEs of special interest, TEAEs leading to study 
drug discontinuation, TESAEs leading study drug discontinuation, TEAEs by relationship and 
TEAEs by toxicity grade;  
TEAEs overall by system organ class and preferred term;  
TEAEs by maximum toxicity grade, overall and by system organ class and preferred term;  
TEAEs by toxicity grade, overall and by system organ class and preferred term; 
TEAEs by maximum relationship to study medication, overall and by system organ class and 
preferred term;  
TEAEs by relationship to study medication, overall and by system organ class and preferred term; 
TEAEs by system organ class sorted by decreasing frequency;TEAEs by preferred term sorted 
by decreasing frequency; 
Related TEAEs by preferred term sorted by decreasing frequency; 
TESAEs, overall and by system organ class and preferred term; 
TESAEs by maximum relationship to study medication, overall and by system organ class and 
preferred term;  
TESAEs by relationship to study medication, overall and by system organ class and preferred 
term;  
Non-serious TEAEs overall and by system organ class and preferred term;   
TEAEs leading to study drug discontinuation, overall and by system organ class and preferred 
term;  
TEAEs leading to death, overall and by system organ class and preferred term; 
TEAEs of special interest, overall and by system organ class and preferred term; 
Only TEAEs will be included in the summary tables, however separate listings for treatment-emergent 
and non-treatment-emergent  AEs will be generated. Additional listings will be provided for deaths, AESIs, 
serious AEs and Adverse Events Leading to Study Drug Discontinuation. 


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Laboratory Evaluations
Safety laboratory samples for chemistry, hematology, urinalysis and coagulation will be collected at various 
different timepoints for different cohorts. 
Refer to Section 1.3 of the Protocol for the schedule of activities indicating when the respective samples 
are taken for each cohort.
The following parameters will be included:
Clinical chemistry: BUN, chloride, potassium, bicarbonate, sodium, glucose, AST, ALT, alkaline 
phosphatase, gamma glutamyltransferase, HbA1C (Screening only), urea, total and direct bilirubin, total 
protein, albumin, cholesterol (total), LDL, HDL, triglycerides, creatinine, creatine phosphokinase.
Hematology: Platelet count, RBC count, hemoglobin, hematocrit, mean corpuscular volume, mean 
corpuscular hemoglobin, % reticulocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils.
Urinalysis: Specific gravity, pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte 
esterase. Microscopic examination (if any leucocytes, more than a trace protein, nitrites, and blood [if not 
menstruating] are abnormal).
Coagulation: International normalized ratio, partial thromboplastin time, prothrombin time.
Serology: HIV-1 and HIV-2 antibodies, HBsAg, anti-HBC IgG + IgM (if IgG positive), and anti-HCV with 
confirmation by HCV RNA.
Serum hCG pregnancy test (as needed for women of childbearing potential), FSH (postmenopausal 
females only)
Alcohol breath and urine drug screen: Amphetamines, barbiturates, benzodiazepines, cocaine, 
opiates, phencyclidine, methamphetamine, 3,4-methylenedioxy-methamphetamine, methadone, and 
tetrahydrocannabinol [cannabinoids]) at minimum.
IRR: In the event of an IRR, it is recommended to collect a blood sample for assessment of tryptase, 
histamine, C-reactive protein, complement C3, complement C5a, complement C5,  Interleukin 1 Beta, 
Interleukin 2, Interleukin 4, Interleukin 5, Interleukin 6, Interleukin 8, Interferon Gamma, Interleukin 10, 
Interleukin 12 and Tumor Necrosis Factor as soon as the IRR is observed (prior to administering any IRR 
medication), and 2 hours, 24 hours and 7 days (prior to the next dose of study drug) after onset of the 
IRR.
Signs of infection: If a participant shows signs of infection, the following investigations should be 
included:
Blood cultures (taken prior to start of antibiotics)
Routine profile
Laboratory parameter values will be graded according to the National Cancer Institute Common 
Terminology Criteria for Adverse Events (CTCAE).
All summaries will be based on results in SI (standard international system of units) units and will be 


Statistical Analysis Plan for Interventional Studies
Sponsor: Alexion Pharmaceuticals, Inc.; Protocol No.: ALXN1830-HV-108 
SAP Version: 2.0 24-Feb-2022 
This document is confidential. 
Controlled Document ID: 3903A.02, Effective Date 31-Aug-2020 
Filing requirements: TMF 
Page 30 of 36
output in the order listed above. 
Toxicity grading following the NCI CTCAE grades version 5.0 will also be derived for laboratory variables 
where applicable (see list below). Note, where gradings require investigator/clinical input, this will not be 
considered and only the numeric criteria will be used for the assignments. If this results in the criteria for 
more than one grade being met, the highest (worst) CTCAE grade will be assigned. For creatinine only, 
the criteria based on the upper limit of normal (ULN) will be used (changes compared to the baseline 
value will not be used), eg, CTCAE defines Grade 1 as > ULN - 1.5 x ULN or > 1 - 1.5 x baseline. Only 
the ULN  1.5 x ULN criterion will be used (and not the baseline criterion). 
The following parameters are CTCAE gradable: 
: Alanine aminotransferase  albumin, alkaline phosphatase, aspartate 
aminotransferase, total bilirubin, creatinine, gamma-glutamyl transferase , glucose  (only do the grading 
the hypoglycemia, no grading for hyperglycemia), creatine kinase. 
: Absolute neutrophil count (neutrophil) , total leukocytes (Leukocytes) , hemoglobin  (only 
do the grading for anemia, no grading for hemoglobin increased), platelet count , lymphocyte. 
:International normalized ratio. 
Actual values and changes from baseline in clinical chemistry, hematology and coagulation,  will be 
summarized by treatment. 
Shift tables for clinical chemistry, hematology, and coagulation from baseline CTCAE toxicity for each visit 
and to the maximum grade on treatment for each parameter will be provided. Participants with both a 
non-missing baseline and at least one non-missing post-baseline grade will be included in the shift tables. 
Unscheduled data will be included in the worst case across all scheduled and unscheduled visits after the 
first dose of study treatment. This means that if there are CTCAE grades derived from both unscheduled 
and scheduled visits data per test per participant then the highest grade will be summarized.  
For non-CTCAE gradable tests, a shift table will be provided showing shifts relative to the normal ranges. 
This summary of normal range category changes illustrates the number and percentage of participants 
who fall into specified categories (Decrease to Low, Change to Normal or No Change, Increase to High) 
by comparing the baseline normal range category to the overall worst-case normal range category. The 
worst-case post-baseline row w
-case normal range
category change. The determination of the worst-case takes into account both planned and unscheduled 
assessments. Only laboratory tests which cannot be graded per CTCAE v. 5.0 specified criteria will be 
included.  
Participants with missing baseline value are to be assumed to have normal baseline value. Worst-case 
can be either High or Low. If a participant has a Decrease to Low and an Increase to High during the 
same time interval, t
categories. If a participant was high at baseline and decreases to Low during the time interval, then the 
, if a participant was Low at baseline 


Statistical Analysis Plan for Interventional Studies
Sponsor: Alexion Pharmaceuticals, Inc.; Protocol No.: ALXN1830-HV-108
SAP Version: 2.0 24-Feb-2022
This document is confidential.
Controlled Document ID: 3903A.02, Effective Date 31-Aug-2020
Filing requirements: TMF
Page 31 of 36
Normal at baseline and have no normal range High and no normal range Low values during the 
time interval
High at baseline and do not change to Low during the time interval
Low at baseline and do not change to High during the time interval 
Shift tables by treatment will be produced for these laboratory parameters. These tables will summarize 
the number of participants with each baseline grade relative to the reference ranges and changes to the 
worst highest grade assessed post-dose during the study.
All events of AL
er function results will be presented in a 
summary table and eDISH (evaluation of drug-induced serious hepatotoxicity) plots.
All laboratory results, as well as CTCAE grades will be included in data listings. Abnormal results for 
clinical chemistry, hematology,  urinalysis and coagulation will be listed separately. Laboratory results for 
serology, pregnancy tests, FSH, urine drug screen, alcohol breath test, IRR lab data and signs of 
infection lab data will be listed only.
Vital Signs 
Systolic blood pressure (mmHg), diastolic blood pressure (mmHg), heart rate (bpm), respiratory rate 
(breaths per minute), pulse oximetry (%) and temperature (degree Celsius) will be measured at different 
timepoints as per the SoA in Protocol Section 1.3.
Actual values and changes from baseline in vital sign measurements will be summarized by treatment.
All vital signs will be provided in data listings.
ECG
The ECG parameters include heart rate, PR, RR, QRS, QT, and corrected QTcF intervals. 
12-lead ECGs in triplicate will be taken at at different timepoints as per the SoA in Protocol Section 1.3.
12-lead ECGs should be measured after a minimum of 5 minutes in supine position. The average of the
triplicate ECG readings at the time points collected will be calculated and used in the analyses.
An outlier analysis will be performed that will summarize the absolute count, frequency and percentage of 
participants who meet any of the following outlier criteria at each visit by treatment:
QT, QTcF interval > 450 msec
QT, QTcF interval > 480 msec
QT, QTcF interval > 500 msec
QT, QTcF interval increases from baseline > 30 msec
QT, QTcF interval increases from baseline > 60 msec
Actual values and change from baseline of these average ECGs will be summarized by treatment. 


Statistical Analysis Plan for Interventional Studies
Sponsor: Alexion Pharmaceuticals, Inc.; Protocol No.: ALXN1830-HV-108
SAP Version: 2.0 24-Feb-2022
This document is confidential.
Controlled Document ID: 3903A.02, Effective Date 31-Aug-2020
Filing requirements: TMF
Page 32 of 36
All ECG parameters, including all single ECG measurements, but also the mean value and overall ECG 
evaluation will be provided in data listings.
Physical Examination
A full physical examination will be performed at different timepoints as per the SoA (Section 1.3) in the 
Protocol. A symptom-driven physical examination of relevant body systems may be performed at other 
Physical examination data will be listed.


Statistical Analysis Plan for Interventional Studies
Sponsor: Alexion Pharmaceuticals, Inc.; Protocol No.: ALXN1830-HV-108
SAP Version: 2.0 24-Feb-2022
This document is confidential.
Controlled Document ID: 3903A.02, Effective Date 31-Aug-2020
Filing requirements: TMF
Page 33 of 36
Interim Analyses
No interim analyses are planned.


Statistical Analysis Plan for Interventional Studies
Sponsor: Alexion Pharmaceuticals, Inc.; Protocol No.: ALXN1830-HV-108
SAP Version: 2.0 24-Feb-2022
This document is confidential.
Controlled Document ID: 3903A.02, Effective Date 31-Aug-2020
Filing requirements: TMF
Page 34 of 36
Changes from Analysis Planned in Protocol
The study was terminated early, therefore cohort 2 has only 2 participants and cohort 6 has none. 
Therefore the secondary objective, to compare safety and tolerability, PK, PD, and immunogenicity of 
ALXN1830 SC between Japanese and non-Japanese healthy participants cannot be met and the 
secondary endpoint the quantitative assessment of safety, PK parameters, PD parameters, and 
immunogenicity between Japanese and non-Japanese healthy participants cannot be analyzed.
Analysis sets definitions as specified in Protocol Section 9.3 were updated as follows:
For the Enrolled Set participants also need to be randomized.
For the Pharmacokinetic Set participants need to receive at least 1 dose of study drug (only active) and 
have at least one post-dose serum ALXN1830 concentration measured. Participants will be analyzed 
according to the study drug they actually received. Serum concentrations will be summarized for all 
participants in the PKS. The exclusions from summary statistics for serum concentrations and/or PK 
parameters will be defined based on review of protocol deviations (if any) prior to database lock by PK 
scientist and study statistician at the discretion of the sponsor. 
For the Pharmacodynamic Set participants need to receive at least 1 dose of study drug (active and 
placebo) and have evaluable serum Immunoglobulin data (IgG, IgG subtypes, Ig subtypes, CIC) or FcRn. 
Immunogenicity Set was not define in the protocol, but added to the SAP as follows: The Immunogenicity 
Set (IGS) will include all participants who have a predose and at least 1 postdose ADA sample collected. 
Immunogenicity analyses will be performed using the IGS.


Statistical Analysis Plan for Interventional Studies
Sponsor: Alexion Pharmaceuticals, Inc.; Protocol No.: ALXN1830-HV-108
SAP Version: 2.0 24-Feb-2022
This document is confidential.
Controlled Document ID: 3903A.02, Effective Date 31-Aug-2020
Filing requirements: TMF
Page 35 of 36
Reference List
FDA. Guidance for Industry, Clinical/Medical, Guidance for Industry: Immunogenicity assessment for 
therapeutic protein product. 2014.
Hunley TE, Corzo D, Dudek M, et al. Nephrotic syndrome complicating alpha-glucosidase 
replacement therapy for Pompe disease. Pediatrics. 2004;114(4): e532 535.
Smith BP, Vandenhende FR, DeSante KA, et al. Confidence interval criteria for assessment of 
dose proportionality. Pharm Res. 2000;17(10):1278-1283.


Statistical Analysis Plan for Interventional Studies
Sponsor: Alexion Pharmaceuticals, Inc.; Protocol No.: ALXN1830-HV-108
SAP Version: 2.0 24-Feb-2022
This document is confidential.
Controlled Document ID: 3903A.02, Effective Date 31-Aug-2020
Filing requirements: TMF
Page 36 of 36
Quality Control
SAS programs are developed to produce output such as analysis data sets, summary tables, data 
listings, figures or statistical analyses. An overview of the development of programs is detailed in Syneos 
Health Developing Statistical Programs SOP (3907) .
Syneos Health Developing Statistical Programs SOP (3907), Conducting the Transfer of Biostatistical 
Deliverables SOP (3908) and the SAS Programming and Vaidation Plan describes the quality control 
procedures that are performed for all SAS programs and output. Quality control is defined here as the 
operational techniques and activities undertaken to verify that the SAS programs produce the output by 
checking for their logic, efficiency and commenting and by review of the produced output. 
Syneos Health SOP Pharmacokinetic and Related Data Analysis (3913) describes the process for the 
interaction between the Biostatistics and Pharmacokinetics departments for the analysis of 
pharmacokinetic and pharmacodynamic data. 


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