Clinical trial NCT04835441
Conditions: Systemic Lupus Erythematosus
Keywords: CD28 ICOS Autoimmune disease Immune system disease Immunosuppressive agent
Sponsor: Alpine Immune Sciences Inc, A Subsidiary of Vertex
Start date: 2021-06-22; Completion date: 2024-07-09
Enrollment: 76 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is Phase 2, multinational, randomized, blinded study to evaluate the safety, tolerability, efficacy, immunogenicity, pharmacokinetics and pharmacodynamics of ALPN-101 (acazicolcept) in adults with moderate to severe active systemic lupus erythematosus (SLE)

Detailed description:

Arms: arm 1: Participants received a weight-based dose of 3 milligrams/kilogram (mg/kg) ALPN-101 once every 2 weeks (Q2W) up to 24 weeks. arm 2: Participants received placebo matched to ALPN-101 up to 24 weeks.
Interventions: intervention 1: ALPN-101 intervention 2: Placebo
Intervention descriptions: intervention 1: Intravenous infusion via an infusion pump. intervention 2: Intravenous infusion via an infusion pump.

Protocol documents:
Prot_000.pdf: 
 
 
A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED 
STUDY OF ALPN-101 IN SYSTEMIC LUPUS ERYTHEMATOSUS 
 
Sponsor Protocol Number: 
AIS-A03 
Investigational Product: 
ALPN-101 (acazicolcept) 
Investigational Phase: 
2 
Protocol Version: 
4.0 
07 NOV 2022 
Previous Version(s) 
3.0 
29 SEP 2021 
2.1 (Germany-specific) 
19 JUL 2021 
2.0 
01 APR 2021 
1.0 
05 OCT 2020 
EudraCT Number: 
2020-004047-86 
IND Number: 
 
Sponsor: 
Funded By: 
Alpine Immune Sciences, Inc. 
Compliance: 
The study will be conducted in accordance with the International 
Council for Harmonisation Guidelines for Good Clinical Practice and 
applicable local and federal regulations. 
 
Sponsor Approval: 
 
 
 
 
CONFIDENTIAL 
This document contains proprietary and confidential information of Alpine Immune Sciences, Inc. 
Acceptance of this document constitutes agreement by the recipient that no previously unpublished 
information contained herein will be published or disclosed without the prior written approval of 
Alpine Immune Sciences, Inc., excepting disclosure to study personnel and appropriate Institutional 
Review Boards (IRBs)/Independent Ethics Committees (IECs), under the condition that such personnel 
have agreed to keep this information confidential. The foregoing shall not apply to disclosure required 
by governmental regulations or laws; however, Alpine Immune Sciences, Inc. shall be promptly 
notified of any such disclosure. 


CONFIDENTIAL 
 
 
 
Protocol No. AIS-A03 
PRINCIPAL INVESTIGATOR 
PROTOCOL AGREEMENT 
A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF ALPN-101 IN 
SYSTEMIC LUPUS ERYTHEMATOSUS 
Version: 4.0 [07 NOV 2022] 
I attest that I have read this protocol. I agree to conduct the trial in accordance with the provisions 
herein, the International Council for Harmonisation (ICH) Guidelines for Good Clinical Practice, and 
local and federal regulations. 
All documentation for this study that is supplied to me and that has not been previously published will 
be kept in the strictest confidence. This documentation includes this study protocol, Investigator's 
Brochure(s), and other scientific data. 
 
 
 
 
 
 
 
Principal Investigator name 
 
 
 
 
 
Principal Investigator signature 
Date 


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TABLE OF CONTENTS 
1. 
STUDY SUMMARY ........................................................................................................ 6 
2. 
BACKGROUND ............................................................................................................ 10 
2.1. Systemic Lupus Erythematosus ............................................................................... 10 
2.2. CD28 and ICOS Inflammatory Pathways in Murine and Human Lupus .................. 11 
2.3. Investigational Agent .............................................................................................. 11 
2.4. Nonclinical Data ..................................................................................................... 12 
2.5. Clinical Studies....................................................................................................... 12 
2.6. Trial Rationale ........................................................................................................ 13 
2.7. Benefit-Risk Statement ........................................................................................... 13 
3. 
STUDY OBJECTIVES .................................................................................................. 14 
3.1. Primary Objective ................................................................................................... 14 
3.2. Secondary Objectives.............................................................................................. 14 
4. 
TRIAL DESIGN ............................................................................................................ 15 
4.1. Overview of Study Design ...................................................................................... 15 
4.2. Estimated Duration of Participation......................................................................... 15 
4.3. Stopping and Discontinuation Criteria .................................................................... 15 
4.4. Rationale for Study Design, Dose Regimen, and Population.................................... 17 
5. 
SELECTION OF SUBJECTS ....................................................................................... 20 
5.1. Inclusion Criteria .................................................................................................... 20 
5.2. Exclusion Criteria ................................................................................................... 22 
6. 
CLINICAL TRIAL PROCESSES AND PROCEDURES ............................................ 26 
6.1. Screening (Day -42 to -1)........................................................................................ 26 
6.2. Day 1: Baseline, Randomization and Initiation of Treatment ................................... 27 
6.3. Days 2, 4, and 8 (Dense PK Subset Only) ............................................................... 28 
6.4. Treatment Period .................................................................................................... 28 
6.5. Day 197 (End of Study) .......................................................................................... 34 
6.6. Unscheduled Visits ................................................................................................. 34 
6.7. Description of Study Procedures ............................................................................. 35 
7. 
STUDY DRUG ............................................................................................................... 39 
7.1. Packaging, Labeling and Storage ............................................................................ 39 
7.2. Preparation and Dosing ........................................................................................... 39 
7.3. Accountability ........................................................................................................ 40 
8. 
CLINICAL MANAGEMENT GUIDELINES AND REQUIREMENTS .................... 41 
8.1. Clinical Management of Adverse Events of Interest ................................................ 41 
8.2. Allowed Medications or Treatments........................................................................ 43 
8.3. Prohibited Medications or Treatments ..................................................................... 45 


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9. 
ADVERSE EVENT REPORTING................................................................................ 46 
9.1. Adverse Event Definition ........................................................................................ 46 
9.2. Adverse Event Reporting and Follow-up................................................................. 46 
9.3. Serious Adverse Event Definition ........................................................................... 47 
9.4. Emergency Unblinding ........................................................................................... 48 
9.5. Serious Adverse Event Reporting and Follow Up .................................................... 48 
9.6. Suspected Adverse Reaction Definition .................................................................. 48 
9.7. Adverse Event Expectedness ................................................................................... 49 
9.8. Adverse Events of Interest ...................................................................................... 49 
9.9. Pregnancy ............................................................................................................... 53 
10. 
STATISTICAL AND DATA ANALYSIS METHODS ................................................ 54 
10.1. Overview of Statistical Methods ............................................................................. 54 
10.2. Sample Size ............................................................................................................ 54 
10.3. Method of Assignment to Treatment ....................................................................... 54 
10.4. Analysis Populations ............................................................................................... 54 
10.5. Planned Analyses .................................................................................................... 55 
10.6. Interim Analysis ..................................................................................................... 56 
11. 
REGULATORY AND ADMINISTRATIVE REQUIREMENTS ................................ 57 
11.1. Trial Conduct.......................................................................................................... 57 
11.2. Informed Consent ................................................................................................... 57 
11.3. Institutional Review Board/Independent Ethics Committee Approval ..................... 57 
11.4. Subject Privacy ....................................................................................................... 57 
11.5. Investigator Responsibilities and Requirements ....................................................... 58 
11.6. Data Identification, Handling, and Record Keeping ................................................ 58 
11.7. Source Documentation ............................................................................................ 58 
11.8. Quality Control and Quality Assurance ................................................................... 59 
11.9. Publication Plan ...................................................................................................... 59 
12. 
REFERENCES .............................................................................................................. 60 
 
LIST OF TABLES 
Table 1 
Schedule of Procedures and Assessments ..................................................... 37 
Table 2 
Investigational Product Description .............................................................. 39 
Table 3 
Guidelines for Management of IRRs............................................................. 42 
Table 4 
NIAID/FAAN Clinical Criteria for Diagnosis of Anaphylaxis ...................... 50 
Table 5 
AE Terms and Grades for Reporting IRRs .................................................... 50 
Table 6 
AE Terms and Grades for Reporting Oral Mucocutaneous Lesions ............... 52 


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LIST OF APPENDICES 
APPENDIX 1 
GUIDANCE ON CHILDBEARING POTENTIAL AND HIGHLY EFFECTIVE 
METHODS OF CONTRACEPTION ........................................................... 67 
APPENDIX 2 
CLINICAL LABORATORY ASSESSMENTS ............................................ 69 
APPENDIX 3 
LIST OF ABBREVIATIONS ....................................................................... 71 


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1. 
STUDY SUMMARY 
 
Protocol Title 
A randomized, double-blind, placebo-controlled study of ALPN-101 in 
systemic lupus erythematosus 
Protocol Number 
AIS-A03 
Investigational Phase 
2 
Investigational Product ALPN-101 Injection 
Study Sites 
Approximately 75 international sites 
Sample Size 
At least 130 subjects 
Study Duration 
Each subject will participate for up to 34 weeks, including a Screening 
period of up to 6 weeks, a 24-week Treatment period, and a 4-week 
Follow-up period. 
Study Population 
Adults 18 to 70 years of age, inclusive, with active systemic lupus 
erythematosus (SLE) 
Study Design 
This is a Phase 2, multinational, multicenter, randomized, double-blind, 
placebo-controlled, parallel group study to evaluate the safety, tolerability, 
efficacy, immunogenicity, pharmacokinetics (PK), 
 of ALPN-101 in adults with moderate to severe active SLE. 
After signing the Informed Consent Form (ICF), subjects will be evaluated 
during a Screening period of up to 42 days. Screening laboratory evaluations 
will be performed; assessment of disease activity will be performed by the 
Investigator and reviewed by the Sponsor or designee to confirm eligibility. 
Subjects will return to the clinic on Day 1 and undergo Baseline procedures, 
including assessment and confirmation of disease activity by the 
Investigator. Subjects who continue to meet eligibility criteria will be 
randomized 1:1 to receive blinded study drug once every 2 weeks (Q2W) for 
a total of 12 doses of: 
(1) 
3 mg/kg ALPN-101 or 
(2) 
Placebo 
Baseline medications that are used for the treatment of SLE (i.e., 
hydroxychloroquine/hydroxychloroquine-like drugs, corticosteroids, 
immunosuppressants) must be maintained at stable doses through the 
Day 169 assessments, except for incidences of toxicity, for a 
protocol-permitted short-term increase (burst and taper) of corticosteroid 
dose in response to increased disease activity, or discretionary reduction in 
corticosteroids (taper) after Day 85 in the context of improvement in disease 
activity. 
Assessments of safety, efficacy, PK, anti-drug antibodies (ADA), and 
 will be performed throughout the study. Refer to the 
Schedule of Procedures and Assessments (Table 1). 
Cumulative safety data will be reviewed at intervals by the Data Monitoring 
Committee (DMC), which will provide recommendations regarding study 
conduct, if indicated. 


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Primary Objectives 
 To evaluate the safety and tolerability of ALPN-101 compared to placebo 
in subjects with chronic, moderate to severe active SLE 
Secondary Objectives 
 To evaluate the efficacy of ALPN-101 in subjects with active SLE 
 To assess the PK of ALPN-101 in subjects with active SLE 
 To assess the incidence of ADA against ALPN-101 in subjects with 
active SLE 
Summary of Key 
Inclusion Criteria 
 Males and females, age 18 through 70 years, inclusive, at Screening 
 Diagnosis of SLE for ≥ 6 months prior to Screening, as defined in §5.1 
 Positive anti-nuclear antibodies (ANA) (≥ 1:80) and/or elevated 
anti-double-stranded DNA (dsDNA) and/or elevated anti-Smith antibody 
test 
 Active SLE as defined in §5.1 at Screening as confirmed by Sponsor or 
designee, and at Baseline (i.e., prior to randomization on Day 1) as 
confirmed by Investigator 
 Stable, appropriate standard of care for SLE, as described in §5.1 
Summary of Key 
Exclusion Criteria 
 Life-threatening or organ system-threatening SLE activity, that is 
sufficiently active that it is expected to require increase in treatment 
during the study 
 Proteinuria consistent with nephrotic syndrome: ≥ 3.5 g proteinuria/day, 
estimated based on urine protein-creatinine ratio (UPCR) 
≥ 350 mg/mmol at Screening 
 Active lupus-related neuropsychiatric disease (with the exceptions of 
mild stable lupus headache, fatigue, mild stable organic brain syndrome) 
 Drug-induced lupus 
 Evidence of active infection or risk or history of serious infection with 
tuberculosis; hepatitis B, hepatitis C; HIV 
 
Evidence of active infection with SARS-CoV-2 
Study Drug 
Administration 
ALPN-101 or matching placebo will be administered by intravenous (IV) 
infusion via an infusion pump over approximately 30 minutes; study drug 
will be given Q2W for 12 total doses. 
Primary Endpoints and 
Assessments 
Safety and tolerability will be assessed by evaluating the type, frequency, 
severity, and seriousness of adverse events, including clinically significant 
changes in symptoms, physical exam findings, vital signs, laboratory tests 
(hematology, serum chemistries and coagulation, urinalysis), and 
electrocardiograms. Additional laboratory assessments and/or documentation 
may be collected as needed for characterization of adverse events of interest 
(AEIs). 
Efficacy Endpoints and 
Assessments 
Efficacy endpoints will be assessed by evaluating disease activity relative to 
baseline and across treatment groups using the tools and assessments listed 
below, and derivatives calculated from them (e.g., SLE Responder Index 
[SRI] -4, -5, -6 response; time to and proportion with flare of SLE; others). 


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Global Disease Activity Assessment Tools: 
 British Isles Lupus Assessment Group index (BILAG) 2004 
 Systemic Lupus Erythematosus Disease Activity Index 2000 
(SLEDAI-2K); SLEDAI-2K 30-Day (SLEDAI-2K 30) 
 Physician’s Global Assessment of SLE Disease Activity (PhGA) 
Patient Reported Outcomes and Quality of Life Assessment tools: 
 Patient’s Global Assessment of Disease Activity (PtGA) 
 Short Form-36 (SF-36) health survey 
 Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) 
(13-item) 
Clinical Biomarkers of SLE Activity: 
 High-sensitivity C-reactive protein (hsCRP) 
 Complement levels: C3, C4, CH50 
 Anti-dsDNA antibodies 
Corticosteroids: 
 Dose of oral and parenteral corticosteroids 
Pharmacokinetic 
Endpoints and 
Assessments 
Serum concentrations of ALPN-101 will be measured. Pharmacokinetic 
endpoints include estimates of maximum concentration (Cmax), area under 
the concentration-time curve (AUC), and trough concentration (Ctrough) at the 
end of dosing intervals. A population PK approach may be used to 
characterize the PK of ALPN-101 in SLE subjects. 
Immunogenicity 
Endpoints and 
Assessments 
The presence and titer of ADA against ALPN-101 will be assessed at 
Baseline (prior to study drug administration on Day 1) and at intervals 
throughout the study. Samples confirmed positive for ADA may be explored 
for neutralizing capacity. The relationship between ADA and PK will be 
analyzed; relationship between ADA and clinical outcomes may be explored. 
Statistical 
Considerations 
Randomization: Subjects will be randomized 1:1; randomization will be 
stratified by background immunosuppressive therapy and geographic region. 
Subjects who are randomized but do not receive study drug may be replaced. 


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Sample Size: A sample size of approximately 130 (~65 subjects/arm) will 
provide approximately 83–88% power (chi square two-sided test, alpha 0.05) 
to detect an absolute increase of 25% compared to placebo in the proportion 
of responders (e.g., as assessed by SRI-4 at Day 169) in the active treatment 
group, assuming a placebo response rate of 20–40%. 
Statistical Methods: 
All safety data will be summarized descriptively by treatment group and 
analyzed based on the safety population. Categorical safety endpoints will be 
summarized using incidence rates. The mean change from baseline, standard 
deviation, minimum, and maximum will be used to summarize continuous 
safety endpoints. No statistical inference is planned for the analysis of safety 
endpoints. 
All efficacy endpoints will be summarized and analyzed for the modified 
Intent-to-Treat population. For categorical endpoints, the number and 
proportion of subjects in each category will be presented by treatment group. 
Proportions of subjects achieving response will be compared using a 
Cochran-Mantel-Haenszel test adjusted for randomization stratification 
factors. An estimate of the difference in proportions and corresponding 95% 
confidence interval. P-value will be presented for efficacy endpoints of 
primary interest. For continuous endpoints, the mean, standard deviation, 
median, minimum, and maximum will be presented by treatment group. For 
continuous endpoints with multiple post-Baseline visits, the treatment effect 
will be assessed through Mixed-effect Model Repeated Measures (MMRM) 
based on observed data. Difference in least-squares means will be derived 
using an analysis of covariance model controlling for stratification factors 
and baseline scores. For each treatment comparison, an estimate of the 
difference in least-squares means, and corresponding 95% confidence 
interval will be presented. 


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2. 
BACKGROUND 
2.1. 
Systemic Lupus Erythematosus 
Systemic lupus erythematosus (SLE) is an autoimmune disease that affects 0.01% to 0.2% of people 
worldwide, and is characterized by failures of immune self-tolerance, with the generation of pathogenic 
subsets of lymphocytes and autoantibodies that disrupt the function of cells and homeostatic systems and 
mediate tissue injury in multiple organs. Etiology remains incompletely defined; there is evidence that 
genetic, epigenetic, environmental, immunologic, and hormonal factors may contribute to disease 
susceptibility and severity (1-5). 
Clinically, lupus is characterized by periods of remission and relapse of constitutional and organ-specific 
signs and symptoms that are highly variable across populations and can change over time in individual 
patients. The most common clinical features include fever, debilitating fatigue, joint inflammation, skin 
and mucosal lesions, serositis, hematologic disorders including anemia, leukopenia or 
thrombocytopenia, and lupus nephritis. The latter is the most common life- and organ-threatening 
manifestation of SLE, estimated to impact 40% to 70% of patients, with progression to renal failure in 
10% to 20% (6, 7). Less common but serious SLE manifestations include neuropsychiatric, 
demyelinating and neurovascular disease, and antiphospholipid antibody syndrome with venous 
thrombosis, arterial occlusion and/or fetal loss. Most other organ systems can also be involved (8-17). 
Therapeutic management is tailored to the severity of disease and organ systems involved. Practice 
guidelines and consensus statements have been developed for treatment of SLE, lupus nephritis, and 
other organ-specific manifestations, and are revised at regular intervals to incorporate emerging data 
(18-20). Current standard of care (SOC) includes antimalarial agents for treatment of skin disease to 
reduce risk of flare in all patients, nonsteroidal anti-inflammatory drugs (NSAIDs) for management of 
headache and musculoskeletal pain, and corticosteroids for rapid reduction of inflammation and 
management of fatigue. Oral immunosuppressive agents (e.g., methotrexate, azathioprine, 
mycophenolate and others) are used to reduce dependence on corticosteroids and to address more 
persistent manifestations. Belimumab, an inhibitor of B cell growth factors, has been approved for use in 
refractory SLE and B cell depletion with rituximab is indicated for immune thrombocytopenia, including 
that arising in SLE, with benefit reported in other manifestations. High dose corticosteroids and 
cytotoxic agents (e.g., cyclophosphamide) are used for serious manifestations refractory to other agents. 
Initial treatment for clinically significant lupus nephritis comprises corticosteroids together with 
cyclophosphamide, azathioprine or mycophenolate. For lupus nephritis refractory to initial therapy, 
selective inhibition of the T cell-mediated immune response through the addition of calcineurin 
inhibitors has demonstrated benefit (21). 
Despite earlier diagnosis and improved treatment regimens, more than 60% of patients with access to 
current best standards of medical care develop clinically-detectable organ damage within 2 to 7 years 
(22). A recent meta-analysis involving over 27,000 patients with SLE reported a 3-fold increase in the 
risk of death compared with the general population, primarily due to cardiovascular disease (23). 
Toxicity associated with corticosteroids and immunosuppression contributes substantially to the burden 
of disease: corticosteroid use is associated with loss of bone integrity and development of metabolic 
syndrome, contributing to cardiovascular disease; broad spectrum immunosuppressants increase the risk 
of serious infection and neoplasm, and use of calcineurin inhibitors is limited by nephrotoxicity. There is 
a continuing need to develop pharmacologic interventions that more specifically target pathogenic 
pathways, with the goal of improving efficacy while limiting toxicity. 


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2.2. 
CD28 and ICOS Inflammatory Pathways in Murine and Human Lupus 
Both the cluster of differentiation (CD) 28-B7 and inducible T cell co-stimulator (ICOS) ligand 
(ICOS-L) co-stimulatory pathways have been implicated in the pathogenesis of both murine and human 
lupus. Numerous studies demonstrated that therapeutic inhibition of CD28, CD80, and/or CD86 reduces 
disease activity in animal models of lupus (24-37). In humans, polymorphisms in CD28 may confer 
susceptibility to at least some subsets of SLE (38); circulating levels of CD28, CD80, and/or CD86 are 
associated with disease activity and/or severity (39-41); and in SLE, T cells may exhibit an exaggerated 
response to CD28 signaling (38). However, therapeutic intervention on the CD28-B7 pathway with 
abatacept (Cytotoxic T-Lymphocyte-Associated Antigen 4-immunoglobulin [Ig]) or antibodies against 
CD28 have shown promising, but not statistically significant, efficacy in human SLE or lupus nephritis 
(42-44), suggesting that additional pathogenic pathways compensate during CD28-B7 inhibition. 
Indeed, CD28-low or -negative T cells, which presumably function independently of CD28 
co-stimulation, are observed in SLE, often correlating with disease activity and/or severity (45-50). 
The ICOS/ICOS-L costimulatory system is a candidate for a pathway that may account for bypass of, or 
resistance to, CD28-B7 inhibition. ICOS is highly homologous to CD28, but in contrast to CD28 the 
expression of ICOS is rapidly increased during T cell activation. It may therefore provide 
complementary and/or compensatory costimulatory signals in activated and/or effector T cells, which 
may otherwise be less dependent on CD28 signaling (51). Similar to CD28-B7, numerous preclinical 
studies have demonstrated that therapeutic inhibition of and/or deficiency in ICOS or ICOS-L reduces 
disease activity in animal models of lupus (28, 49, 52-59). Polymorphisms in ICOS may also confer 
susceptibility to at least some subsets of SLE (60); and there is similarly a correlation between 
expression of ICOS or ICOS-L and disease activity and/or severity, especially in association with 
follicular helper T cells which characteristically express ICOS (30, 44, 61-68), and in association with a 
subset of T peripheral helper cells that is expanded in active lupus nephritis and expresses ICOS and 
PD-1 (69). However, also similar to CD28 pathway inhibition, blockade of the ICOS/ICOS-L pathway 
alone appears also to be insufficient for the treatment of SLE, at least as suggested by early studies with 
prezalumab (AMG-557), an anti-ICOS-L monoclonal antibody (61, 70). 
Combined inhibition of both CD28 and ICOS pathways may therefore be required to achieve clinically 
meaningful outcomes in SLE. In preclinical studies, combined blockade is associated with superior 
inhibition of T and B cell activation, as well as reduced disease in multiple animal models of systemic 
autoimmunity including models with features of lupus, arthritis, and Sjögren’s syndrome (71, 72) 
(Alpine Immune Sciences, data on file). Novel therapeutics that concomitantly antagonize both the 
CD28 and ICOS pathways may prove beneficial in SLE by addressing two dominant, non-overlapping 
T cell costimulatory pathways, and may be superior to existing therapeutics. 
2.3. 
Investigational Agent 
ALPN-101 (acazicolcept; ICOS-L vIgD-Fc) is an Fc fusion protein of a human ICOS-L variant Ig 
domain (vIgD™) designed to inhibit simultaneously the CD28 and ICOS inflammation pathways. It is 
currently being evaluated for the treatment of alloimmune, autoimmune and/or inflammatory conditions 
that may be dependent on CD28 and/or ICOS pathways. 
This is the first study to evaluate ALPN-101 in subjects with active SLE. A previous first-in-human 
(FIH) study evaluated the safety, tolerability, pharmacokinetics (PK), 
 of 
single and repeat doses ALPN-101 in healthy volunteers (76). In this FIH study, ALPN-101 was 
generally well-tolerated with no evidence of cytokine release, clinically significant immunogenicity, or 
severe adverse events (AEs) following subcutaneous (SC) doses up to 3 mg/kg or single intravenous 
(IV) doses up to 10 mg/kg or up to 4 weekly IV doses of up to 1 mg/kg. An open label study of 


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ALPN-101 in subjects with steroid-resistant or steroid-refractory acute graft-versus-host disease 
(GVHD) (AIS-A02, NCT04227938) enrolled a single subject prior to discontinuation of the study due to 
a change in corporate strategy. As reported in a case study, the patient received ALPN-101 for 
treatment of severe (Grade 3) disease of the lower gastrointestinal tract. An IV infusion at 0.3 mg/kg 
was well-tolerated and sustained high level target saturation of circulating T cells for at least 7 days (77). 
Stool volume declined within 2 days, permitting steroid taper, and by study Day 8 acute GVHD had 
resolved to Grade 0. The course suggested that GVHD responded quickly to a single low dose of 
ALPN-101. 
2.4. 
Nonclinical Data 
ALPN-101 demonstrates high affinity binding to human and cynomolgus monkey CD28 and ICOS, with 
lower affinity binding to rodent orthologs. Nonclinical studies demonstrate potent inhibition of T cell 
activation and suppression of disease activity in mouse models of GVHD, inflammatory 
arthritis, sialadenitis (Sjögren’s syndrome), SLE, and other models of autoimmune and inflammatory 
diseases. 
Rats and cynomolgus monkeys were utilized for nonclinical safety assessment of ALPN-101. The 
program includes a 1-month SC and IV repeat dose toxicology study in rats and cynomolgus monkey, a 
3-month SC and IV repeat dose study in cynomolgus monkey, and a 6-month IV repeat dose study in 
cynomolgus monkeys. ALPN-101 was well tolerated; the no-observed-adverse-effect level (NOAEL) in 
the 1-month toxicology studies for both rat and cynomolgus monkey was the highest dose evaluated in 
each species via SC and IV administration: 200 mg/kg/week in rats and 150 mg/kg/week in cynomolgus 
monkeys. The NOAEL for ALPN-101 in both the 3-month and 6-month toxicology studies in 
cynomolgus monkey was the highest dose evaluated via SC and/or IV administration: 150 mg/kg/week. 
2.5. 
Clinical Studies 
Results of clinical studies are summarized below; please refer to the Investigator’s Brochure (IB) for 
detailed and updated information. 
AIS-A01: An FIH study (Study AIS-A01, NCT03748836) was conducted to assess the safety, 
tolerability, PK, and PD of single and repeated doses of ALPN-101 (N=66) or placebo (N=30) in adult 
healthy volunteers. Overall, ALPN-101 was safe and well tolerated at single ascending IV (0.001– 
10.0-mg/kg) or SC (1.0 mg/kg or 3.0 mg/kg) doses, as well as at multiple IV doses either once weekly 
(0.3 mg/kg or 1 mg/kg weekly) or once every 2 weeks (Q2W) (1.0 mg/kg fortnightly) for 4 weeks. 
There were no severe (Common Terminology Criteria for Adverse Events [CTCAE] Grade 3 or greater) 
AEs, no treatment-related serious adverse events (SAEs), and no treatment-related trends in laboratory 
safety parameters. The proportions of subjects reporting AEs of infection, headache, and aphthous ulcers 
were higher among subjects randomized to ALPN-101 compared to placebo; most were mild (Grade 1), 
and all resolved without sequelae. There were no infusion-related reactions (IRRs), no treatment-related 
hypersensitivity reactions, and no significant changes from baseline in circulating cytokines. 
Refer to the IB for details regarding PK 
 results from the study which are also reported by Yang 
et al (76). 
AIS-A02: Study AIS-A02 (NCT 04227938) was intended to be a single ascending dose study to assess 
the safety, tolerability, and efficacy of ALPN-101 in adults with steroid-resistant or -refractory acute 
GVHD. Due to a change in sponsor strategy, the study was terminated after enrollment of the first 
subject (0.3 mg/kg dose cohort). The enrolled subject had 6th-line steroid-refractory gastrointestinal 
tract acute GVHD. ALPN-101 was administered on study Day 1. No serious or Grade ≥ 3 AEs 


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attributable to ALPN-101 were recorded after dosing. Disease activity in the gastrointestinal tract resolved 
from Grade 3 to Grade 0 (no clinical activity) by Study Day 8. The subject experienced critical 
thrombocytopenia, intracranial hemorrhage, aspiration pneumonia, and sepsis on Study Day 11 with fatal 
outcome, attributed to pre-existing thrombotic microangiopathy attributed to tacrolimus (77). There were 
no serious or Grade ≥ 3 AEs attributable to ALPN-101; AEs did not prompt early termination of the 
trial. 
2.6. 
Trial Rationale 
As outlined in §2.2 and §2.3, the results of preclinical and nonclinical data are consistent with the 
hypothesis that by inhibiting immune activation through CD28 and ICOS, ALPN-101 may attenuate the 
signs, symptoms, and clinical sequelae associated with autoimmune and inflammatory diseases such as 
active SLE. As summarized in §2.4 and §2.5, ALPN-101 has thus far shown a favorable safety profile at 
doses that achieve and maintain high level target saturation. The data to date support evaluation of 
ALPN-101 in patients with SLE. 
2.7. 
Benefit-Risk Statement 
There has been no prior clinical experience with ALPN-101 in SLE, so its risk (safety) and efficacy 
profile in SLE have not been determined. Participants in this study may gain benefit if ALPN-101 
results in improved clinical outcomes (e.g., improvements in disease activity, quality of life). 
In healthy volunteers, the most common AEs in subjects who received ALPN-101 included headache, 
upper respiratory tract infections, and aphthous ulcers. Subjects reporting these AEs should be 
monitored and treated when indicated in accordance with local practice. 
ALPN-101 did not cause cytokine release, and no infusion reactions were observed in healthy 
volunteers. Nonetheless, as with any biologic therapeutic administered by IV infusion, all subjects 
should be monitored during and immediately after dosing and treated if indicated according to local 
standard practices and guidance provided in §8.1.1. 
Based on its mechanism of action, ALPN-101 should be considered potentially immunosuppressive and 
therefore may potentially reduce immunosurveillance and increase infection risk; all subjects should be 
monitored for infections and treated as indicated. With respect to the coronavirus (COVID-19) 
pandemic, there has been no experience with ALPN-101 in patients or healthy volunteers who are 
known to have been exposed to SARS-CoV-2 or to have contracted COVID-19; therefore, it is not 
known whether subjects receiving ALPN-101 may be at an increased risk for COVID-19 infection or to 
experience serious illness if infected. Management of these AEs will be made on a case-by-case basis 
with consideration of benefit/risk. 
ALPN-101 may attenuate immune responses to—and production of potentially protective antibodies 
following—immunizations, including vaccines for SARS-CoV-2. Therefore, prior to study participation, 
subjects should be up to date on all age-appropriate vaccinations, including COVID-19, per local and 
professional guidelines for immunocompromised individuals (e.g., Centers for Disease Control [CDC], 
local professional society guidelines). Live vaccines should not be administered while receiving 
ALPN-101. Refer also to §8.3. 
Given the significant continued morbidity and mortality seen in patients with SLE despite treatment with 
current SOC therapies, evaluation of ALPN-101 in this population is appropriate. 


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3. 
STUDY OBJECTIVES 
3.1. 
Primary Objective 
The primary objective of this study is to evaluate the safety and tolerability of ALPN-101 compared to 
placebo in subjects with chronic, moderate to severe active SLE. 
3.2. 
Secondary Objectives 
The secondary objectives of this study are: 
 To evaluate the efficacy of ALPN-101 in subjects with active SLE 
 To assess the PK of ALPN-101 in subjects with active SLE 
 To assess the incidence of anti-drug antibodies (ADA) against ALPN-101 in subjects with 
active SLE 


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4. 
TRIAL DESIGN 
4.1. 
Overview of Study Design 
This is a randomized, double-blind, placebo-controlled, parallel-arm study to evaluate the safety, 
tolerability, efficacy, immunogenicity, PK, 
 of ALPN-101 in adult subjects with chronic, 
moderate to severe active SLE. Approximately 75 international sites will participate in this study. A 
total of approximately 130 subjects will be randomized 1:1 to receive a weight-based dose of ALPN-101 
or placebo Q2W for a total of 12 doses: 
 ALPN-101 at 3 mg/kg (n≈65) 
 Placebo (n≈65) 
Randomization will be stratified based on SLE treatment at Baseline and geographic region (see §10.2). 
Subjects will be followed for 4 weeks from the End of Treatment (EoT) visit (i.e., 6 weeks after the last 
dose of study drug), from the end of Day 155 through Day 197. Assessments of AEs and disease 
activity, and collection of blood and urine for safety laboratory values, biomarkers of disease activity, 
PK, ADA, 
, will be performed throughout the study. Refer to the Schedule of 
Procedures and Assessments (Table 1). 
Dense PK samples will be collected in subjects that agree to participate; subjects in this subset will stay 
in the clinic for 4 hours following administration of the first dose of study drug, and will return to the 
clinic 1, 3, and 7 days following the first study drug administration for collection of additional samples. 
Medications that are used for treatment of SLE at baseline (i.e., hydroxychloroquine/ 
hydroxychloroquine-like drugs, corticosteroids, immunosuppressants) should be maintained at stable 
doses through the Day 169 assessments, except for incidences of toxicity or for a protocol-defined 
short-term increase (burst and taper) of corticosteroid dose in response to increased disease activity or 
reduction in corticosteroids (taper) to reduce toxicity in the context of improvement in disease activity 
are detailed in §8.2. 
Randomization will be stratified by geographic region and will be stratified based on SLE treatment at 
Baseline (see §10.2). 
4.2. 
Estimated Duration of Participation 
Each subject will participate for up to 34 weeks, including a Screening period of up to 6 weeks, a 
24-week Treatment period, and a 4-week Follow-up period. 
4.3. 
Stopping and Discontinuation Criteria 
4.3.1. 
Study Stopping Criteria 
The Sponsor may choose to discontinue the study at any time for any reason. 
If any event(s) occur that, in the opinion of the Medical Monitor(s) or the Data Monitoring Committee 
(DMC), may contraindicate further administration of ALPN-101, enrollment of additional subjects, as 
well as administration of study drug, may be suspended. Such events may include, but are not limited to: 
 SAEs assessed as related to study drug 
 Grade 3 or 4 AEs assessed as related to study drug 
The DMC and Sponsor will conduct a prompt review of cumulative safety data and the circumstances of 
the event(s) in question to determine whether randomization and dosing should be resumed, whether the 


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dose should be modified, whether the protocol should be modified, or whether the study should be 
discontinued permanently. Where applicable, the regulatory authorities and Institutional Review Boards 
(IRBs)/Independent Ethics Committees (IECs) will be notified of any actions taken with the study. 
In the event of unanticipated suspension of dosing, subjects will continue regularly scheduled visits until 
a decision is reached by the Sponsor. If the study is stopped, subjects who have received study drug will 
continue to be followed for assessment of safety and other outcomes for at least 8 weeks following the 
last dose of study drug. 
4.3.2. 
Individual Subject Stopping Criteria 
Discontinuation of Study Drug 
Individual subjects must pause or discontinue treatment with study drug in the following settings: 
 Development or worsening of lupus manifestations requiring introduction of certain 
prohibited medications or prohibited dosages of background drugs, when continuation of the 
study drug would place the subject at risk, as determined by the Investigator or Medical 
Monitor; see §8.2.2. 
 Clinically significant abnormal laboratory results or AEs which rule out continuation of the 
study drug, as determined by the Investigator or the Medical Monitor. 
 Infection with SARS-CoV-2 during the Treatment Period; the Medical Monitor must approve 
the resumption of study drug dosing for any subject with confirmed (viral test positive) or 
suspected COVID-19 infection. 
 Grade ≥ 3 infection (e.g., pneumonia, sepsis) which cannot be sufficiently controlled within 
an adequate timeframe by anti-infective treatment or would put the subject at risk for 
continued participation in the trial, as determined by the Investigator or the Medical Monitor. 
 Inclusion or exclusion criteria violation that was noted after the subject started study drug, 
AND the Investigator and/or Medical Monitor determine that continuation of the study drug 
would place the subject at risk. 
 Development of an electrocardiogram (ECG) change considered clinically significant and 
with reasonable possibility of relationship to study drug; or a confirmed absolute QT interval 
corrected for heart rate using Fridericia’s correction formula (QTcF) value > 500 msec or 
confirmed increase of ≥ 60 msec from Baseline (i.e., if a subject’s QTcF increases from 
Baseline ≥ 60 msec, the Investigator will evaluate, confirm the value, and treatment should 
be stopped). 
 Development of active or latent tuberculosis (TB) at any time during the study; a subject with 
active or latent TB must pause dosing with blinded study drug; dosing can only be resumed 
following initiation of appropriate treatment and with the approval of the Medical Monitor. 
 Pregnancy while on study drug. 
 Malignancy, except for localized non-melanoma skin cancer or carcinoma in situ of the 
cervix; if localized cancer is surgically excised with clear margins, dosing may resume 
following consultation with the Medical Monitor. 
 Significant non-compliance with study procedures to a degree that would put the subject at 
risk for continued participation in the trial as determined by the Investigator or the Medical 
Monitor. 


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 Development of active neuropsychiatric SLE (excluding lupus headache) sufficiently severe 
to interfere with ability of the subject to provide ongoing informed consent. 
 Investigator decision: Investigator believes it is in the best interest of the subject to 
discontinue treatment with study drug. 
Subjects who prematurely discontinue treatment with study drug should have all procedures outlined in 
the EoT visit, as well as an unscheduled ECG, performed as soon as possible, and not later than the next 
scheduled visit. 
To minimize missing data for efficacy and safety assessments, subjects who prematurely discontinue 
treatment, and who do not withdraw consent, should otherwise continue with their regular study visit 
schedule without receiving study drug. In subjects who are unable to continue their regularly scheduled 
visits, a follow-up phone call should occur approximately 8 weeks (corresponding to 5X half-life) after 
the last dose of study drug to determine the status of any ongoing AEs/SAEs or the occurrence of any 
new AEs/SAEs. 
Discontinuation from the Study (Early Termination) 
In addition to the criteria for discontinuing study drug summarized above, individual subjects may be 
discontinued from the study prematurely (i.e., prior to Day 197) for any of the following reasons: 
 Subject decision / withdrawal of consent; subjects can request to be discontinued from 
participation in the study at any time for any reason 
 Investigator decision: Investigator believes it is in the best interest of the subject to be 
withdrawn from the study 
For subjects who withdraw from the study prematurely (i.e., prior to Day 197), the End of Study (EoS) 
evaluations should be completed if possible, preferably within 2 weeks of study drug discontinuation. In 
addition, a follow-up phone call should occur approximately 8 weeks (corresponding to 5X half-life) 
after the last dose of study drug to determine the status of any ongoing AEs/SAEs or the occurrence of 
any new AEs/SAEs. 
4.4. 
Rationale for Study Design, Dose Regimen, and Population 
4.4.1. 
Choice of Study Population 
The study population will comprise adults with at least 6 months history of SLE, who have moderate to 
severe active disease on stable SOC, but who do not require immediate aggressive therapy to prevent 
organ system damage. Subjects are required to have activity in the musculoskeletal system, and/or 
mucocutaneous system, and/or renal system and/or have pleuritis or pericarditis at Screening and 
Baseline. This population will allow assessment of the safety of ALPN-101 in the context of active 
inflammatory disease, and on a background of treatments commonly used for SLE. Assessment in 
subjects with this level of activity and involvement of relatively assessable organ systems at baseline 
may allow changes to be detected through use of general and/or organ-specific assessment tools. 
A central verification system will be used to confirm that the level of disease activity at Screening is 
consistent with inclusion/exclusion criteria, thereby reducing the impact of variability in Investigator 
assessment of disease activity and use of assessment tools. 
4.4.2. 
Justification of Study Design 
The study will be randomized, placebo-controlled, and blinded to minimize bias in reporting of safety 
events, partially-subjective disease activity measures, and patient-reported outcomes. 


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Randomization will be stratified by use of concomitant oral immunosuppressive therapy; stratification 
will reduce the risk that the safety assessment of ALPN-101 may be confounded by imbalance in SOC 
agents that carry their own risks of AEs. 
Randomization also will be stratified by geographic region. 
4.4.3. 
Justification of Dose 
The dosing regimen for this study is 3 mg/kg IV administration Q2W for 12 total doses. This regimen 
was selected to provide sufficient drug exposure to achieve and sustain high target saturation (≥ 90%) on 
peripheral T cells and to be within appropriate safety margins of the NOAEL in Good Laboratory 
Practice (GLP) toxicology studies in cynomolgus monkeys. 
Specifically, the geometric mean and lower limit of 95% confidence interval of the serum concentration 
of ALPN-101 at 3 mg/kg Q2W are predicted to maintain target saturation greater than 90% for at least 
24 weeks. The projected steady state exposures at 3 mg/kg are 47-fold (maximum concentration [Cmax]) 
and 31-fold (area under the concentration-time curve [AUC]) lower relative to exposures at NOAEL 
(150 mg/kg/week) in the 13-week and 6-month GLP toxicology studies in cynomolgus monkeys. 
4.4.4. 
Justification of Endpoints 
This is the first clinical investigation to evaluate ALPN-101 in patients with active SLE, and the first 
clinical investigation of dosing over a duration of greater than 4 weeks. Therefore, the primary objective 
is safety and tolerability which will be assessed by the type, frequency, severity, and seriousness of AEs, 
including clinically significant changes in symptoms, physical exam findings, vital signs, laboratory 
tests (hematology, serum chemistries, coagulation and urinalysis), and ECGs, and will be evaluated by 
comparison to placebo. Additional assessments and/or documentation will be collected for SAEs and 
may be collected for adverse events of interest (AEIs) related to mechanism of action (i.e., infections), 
mode of administration (e.g., infusion reactions), or observations in completed and ongoing trials (e.g., 
aphthous ulcers). 
A secondary objective is to evaluate the efficacy of ALPN-101 based on change in disease activity 
compared to placebo. The measurement of disease activity in SLE involves an assessment of 
characteristic signs and symptoms across multiple organ systems, along with the results of laboratory 
parameters. Multiple tools for assessment of global disease activity have been developed. The present 
study employs the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and 
SLEDAI-2K 30-Day (SLEDAI-2K 30), British Isles Lupus Assessment Group index (BILAG) 2004, the 
Patient’s Global Assessment of Disease Activity (PtGA), and a Physician’s Global Assessment of SLE 
Disease Activity (PhGA). The data from these tools can be used alone or combined as responder indices 
to measure efficacy. 
To gain a broad understanding of the potential impact of the novel mechanisms of ALPN-101 on SLE 
activity, change from baseline over time and comparison to placebo in results of several other 
assessments will be explored. These include assessments that may be more sensitive to change in 
selected organ systems (Cutaneous Lupus Erythematosus Disease Area and Severity Index [CLASI] for 
mucocutaneous disease; 
); proteinuria and renal function for nephritis); combined responder indices (e.g., 
SLE Responder Index [SRI]-4, -5, -6, -7, BILAG-based responder indices, others); prevention of 
increases in disease activity (e.g., proportion with, and time to new BILAG A or new or worsening 
BILAG B score; requirement for increased or new treatment); changes in laboratory parameters 
associated with SLE activity (e.g., C3, C4, CH50, high-sensitivity C-reactive protein (hsCRP), level of 
antibodies to double-stranded DNA [dsDNA]); and/or changes in 
 potentially 


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associated with SLE disease activity. Detailed description of assessment tools is provided in the 
Procedures Manual. 
Corticosteroids are associated with significant morbidity but are often highly effective and are often 
used to quickly control disease flares or when other therapeutic measures are inadequate. Within defined 
limits, the present study permits short term use (burst and taper) for increased activity during the study 
and provides guidelines for taper from baseline dose if disease activity improves (see §8.2.2). Dose and 
indication for change in dose of corticosteroids will be captured as concomitant medications. Change 
from baseline, number of bursts, and total corticosteroid use will be explored as a potential indication of 
efficacy. 
Patient-reported outcomes provide information that expand upon, and may differ from, information 
derived from disease activity assessments, in that they incorporate important subjective experience, 
including fatigue and quality of life, and integrate potential negative impact of therapeutic interventions. 
Therefore, the PtGA, Short Form-36 (SF-36) health survey version 2, and the Functional Assessment of 
Chronic Illness Therapy–Fatigue (FACIT-F) (13-item) will be assessed at intervals, 
 
of change from baseline and across treatment groups will be performed. 
Pharmacokinetic parameters, the impact of ADA, and the relationships between exposure and target 
saturation that were defined in healthy volunteers may not be fully applicable in SLE patients, due to 
potential effects of SLE-related immune dysregulation, ongoing inflammation, proteinuria, and 
background medication. Serum levels of ALPN-101, target saturation by ALPN-101 on circulating 
T cells, and ADA will be assessed throughout the study. The impact of exposure, target saturation, and 
ADA on clinical outcomes may be explored. 


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5. 
SELECTION OF SUBJECTS 
Prospective approval of protocol deviations to recruitment and enrollment criteria is not permitted. 
5.1. 
Inclusion Criteria 
Subjects who provide informed consent are eligible to be included in the study only if all the following 
criteria apply: 
1. 
Males and females, age 18 through 70 years, inclusive, at Screening. 
2. 
SLE onset ≥ 6 months prior to Screening based on Investigator judgement with approval by 
Sponsor. 
Subject must have met the 2019 European League Against Rheumatism (EULAR) / American 
College of Rheumatology (ACR) Classification Criteria for SLE (73), including at least one 
clinical criterion and an additive criterion score of ≥ 10 at any time in the past up to and 
including the day of Screening. 
3. 
Subjects must have a positive anti-nuclear antibodies (ANA) (titer ≥ 1:80) and/or elevated 
anti-dsDNA and/or elevated anti-Smith antibody test (if the screening test(s) are negative [based 
on central or local testing], then an historic positive serology for ANA, elevated anti-dsDNA, 
and/or elevated anti-Smith antibody test, with unequivocal documentation, may be accepted). 
4. 
Subjects must demonstrate active SLE at Screening, as indicated by a SLEDAI-2K 30 score of 
≥ 6 (excluding lupus headache and/or organic brain syndrome), and must have a clinical score at 
Baseline (i.e., Day 1 prior to randomization) of ≥ 4 (excluding lupus headache and/or organic 
brain syndrome). 
5. 
Subjects must have SLEDAI-2K 30 clinical points in at least one of the following at Screening 
and Baseline: arthritis; myositis; urinary casts; hematuria; proteinuria; pyuria; rash; alopecia; 
mucosal ulcers; pleurisy; pericarditis. In addition: 
a. 
If all 4 of the required entry points are for arthritis, there must be a minimum of 3 joints 
that are painful and show signs of inflammation (i.e., tenderness, swelling, or effusion). 
b. 
If entry is based on renal parameters, at least one of the following must be true: 
 Active urinary sediment, assessed after excluding infection or contamination. 
OR 
 Urine protein-creatinine ratio (UPCR) at Screening of least 50 mg/mmol (or 24-hour 
urine protein at least 0.5 g) that has not improved by at least 25% over the prior month; 
if records are not available, this assessment should be made by the Investigator based 
on history and best judgement. 
OR 
 Histologic evidence of active nephritis within the last 3 months. 
6. 
The Investigator’s preliminary determination of organ system activity at Screening must be 
verified by the Sponsor or their designee to confirm eligibility. The Investigator will determine 
and confirm eligibility at Baseline (i.e., Day 1 prior to randomization). 
7. 
Subjects must be on appropriate SOC (i.e., at least one anti-malarial or an immunosuppressant) 
for SLE, based on the Investigator’s judgement. If taking the following medications, the subject 
must be on a stable dose prior to Baseline (i.e., Day 1 prior to randomization) for the period of 


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time specified below, and must intend to continue at stable doses throughout the 24-week 
Treatment Period, unless otherwise specified by this protocol: 
 Corticosteroids: stable between Screening and Baseline (NOTE: dose must not be 
greater than 20 mg/day prednisone or equivalent). 
 Hydroxychloroquine/hydroxychloroquine-like drugs: stable between Screening and 
Baseline (NOTE: dose must not be greater than 400 mg daily hydroxychloroquine or 
equivalent). 
 NSAIDs or cyclooxygenase-2 (COX-2) inhibitors that are used continuously (at or 
below the maximum approved dose, and with approval by the Sponsor or designee): 
stable for 14 days prior to Baseline; the requirement for stable and continuous use does 
not apply to NSAIDS that are used intermittently for management of pain. 
Subjects who are using NSAIDs infrequently or “as needed” should make every 
attempt to withhold dosing on study visit days until SLE assessments have been 
completed. 
For the following drugs, subjects must be on stable doses for 4 weeks prior to Screening until 
Baseline and for the remainder of the study: 
 Methotrexate (7.5–25 mg weekly) 
 Azathioprine (50–150 mg daily) 
 Leflunomide (10–20 mg daily) 
 6-Mercaptopurine (50–200 mg daily) 
 Mycophenolate mofetil (500–2000 mg daily) 
 Mycophenolic acid (360–1440 mg daily) 
 Permitted dose and stability period for agents not listed here, but not specifically 
excluded by this protocol, require discussion with, and agreement by, the Medical 
Monitor 
8. 
Willing to provide consent for serial photographic documentation of any cutaneous 
manifestations of SLE, and/or oral mucocutaneous lesions (including aphthous ulcers) not 
attributed to SLE, from Screening through the EoS. 
9. 
Women of child-bearing potential (WOCBP; defined in APPENDIX 1) or male patients with a 
WOBCP partner must agree to use highly effective methods of contraception as defined in 
APPENDIX 1 during study treatment and for 3 months following the last dose of study drug. 
10. 
Able to provide written, informed consent. 
11. 
Should be up-to-date on all age-appropriate vaccinations, including COVID-19, per local and 
professional guidelines for immunocompromised individuals (e.g., CDC, local professional 
society guidelines). 
12. 
Peripheral venous access anticipated to be adequate to tolerate planned dosing regimen of IV 
infusions and blood draws Q2W per Table 1. 


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5.2. 
Exclusion Criteria 
Subjects are excluded from the study if any of the following criteria apply: 
1. 
Life-threatening or organ system-threatening SLE activity that is sufficiently active that it is 
expected to require increase in treatment during the study. 
2. 
Proteinuria consistent with nephrotic syndrome (i.e., ≥ 3.5 grams proteinuria/day, estimated 
based on UPCR ≥ 350 mg/mmol) at Screening. 
3. 
Active lupus-related neuropsychiatric disease at Screening or Baseline (i.e., Day 1 prior to 
randomization), as defined by the central nervous system portion of SLEDAI-2K 30 or BILAG 
2004 (with the exceptions of mild stable lupus headache, fatigue, mild stable organic brain 
syndrome). 
4. 
Drug-induced lupus. 
5. 
Any serious health condition, which, in the opinion of the Investigator or Sponsor, would place 
the subject at undue risk from the study or would confound interpretation of safety or efficacy 
outcomes, including, but not limited to: 
a. Uncompensated congestive heart failure as defined by New York Heart Association Class III 
or IV. 
b. Clinically significant active cardiac disease (e.g., unstable angina or acute myocardial 
infarction ≤ 3 months prior to first dose of study drug). 
c. Clinically relevant or significant ECG abnormalities at Screening, including ECG with 
QTcF; in subjects with ventricular conduction delay (QRS > 120 msec), cardiologist 
consultation and discussion with, and agreement of, Medical Monitor is required for 
participation. 
d. Active cerebrovascular disease (e.g., stroke or transient ischemic attack) ≤ 3 months prior to 
first dose of study drug, unless attributed to SLE disease and stable on treatment. 
e. Uncontrolled hypertension, defined by a persistent systolic blood pressure > 160 mmHg or 
diastolic blood pressure > 100 mmHg. 
f. Uncontrolled diabetes. 
g. Known clinically significant immunodeficiency. 
h. Current or recent (within the past 12 months) history of alcoholism or significant drug abuse 
(recreational use of cannabis is not an exclusion criterion). 
i. Elective major surgery anticipated to take place during the study period. 
6. 
Recent serious or ongoing infection; risk or history of serious infection, including: 
a. Active or latent TB (refer to §6.7 for specific requirements for TB screening). 
Subjects with a history of latent TB are allowed with documentation of completed treatment 
with a regimen recommended by an appropriate local or national health authority (e.g., 
CDC). 
b. Hepatitis B virus: serologic evidence of hepatitis B infection based on the results of testing 
for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), and hepatitis B 
surface antibody (HBsAb) as follows: 
i. Subjects positive for HBsAg are excluded. 


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ii. Subjects negative for HBsAg but positive for HBcAb, regardless of HBsAb status will be 
excluded. 
c. Hepatitis C virus (HCV): HCV RNA detectable in any subject with positive HCV antibody. 
d. Seropositivity for HIV at Screening. 
e. Positive reverse transcription polymerase chain reaction (RT-PCR) test for SARS-CoV-2 at 
Screening. 
Patients who test positive for SARS-CoV-2 may only rescreen after they meet the following 
SARS-CoV-2 infection viral clearance criteria: 
 Symptomatic patients: At least 2 negative RT-PCR viral tests in a row, ≥ 24 hours apart, 
after at least 10 days have passed since recovery, defined as resolution of fever without 
use of antipyretics and improvement in respiratory symptoms (e.g., cough, shortness of 
breath). 
 Asymptomatic patients: At least 2 negative RT-PCR viral tests in a row, ≥ 24 hours apart, 
after at least 10 days have passed since prior positive result. 
f. History of progressive multifocal leukoencephalopathy. 
g. Receipt of oral or parenteral anti-infectives (antibacterials, antivirals, antifungals, or 
antiparasitic agents) for infection, ≤ 2 weeks prior to Day 1 (NOTE: chronic oral antibiotics 
used for prophylaxis may be permitted, dependent on discussion with, and agreement of, the 
Medical Monitor). 
7. 
Receipt of live vaccination ≤ 8 weeks prior to Baseline (i.e., Day 1 prior to randomization), or 
expected to require live vaccines during the study (see also §8.3). 
8. 
Screening laboratory abnormalities of any of the following: 
a. Hemoglobin < 8.0 g/dL. 
b. Absolute neutrophil count < 1000/μL (< 1.0 ×109/L). 
c. Platelet count < 50,000/μL. 
d. B cell count < 50 cells/μL. 
e. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 x upper limit of 
normal (ULN) unless associated with elevated creatine phosphokinase (CPK) in the context 
of active myositis. 
f. Serum total bilirubin > 1.5 x ULN, or > 3x ULN for patients with Gilbert’s syndrome. 
g. Estimated glomerular filtration rate (eGFR) < 40 mL/min/1.73m2 as assessed by the Chronic 
Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-equation. 
9. 
History of new, ongoing, or recurrent malignancy ≤ 5 years prior to first dose of study drug 
except basal cell carcinoma of the skin, squamous cell skin cancer, or in situ carcinoma that has 
been adequately treated with no evidence of recurrent disease for ≥ 12 months. 
10. 
Pregnant or breastfeeding at the time of screening, or plans to become pregnant ≤ 3 months 
following the last dose of study drug. 
11. 
Fulfills diagnostic criteria for another rheumatic disease that overlaps with SLE (e.g., mixed 
connective tissue disease, overlap connective tissue disease) that may confound clinical 


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assessments in the study. However secondary sicca or Sjögren’s syndrome or antiphospholipid 
antibody syndrome that is stable on appropriate therapy is allowed. 
12. 
Prior diagnosis of, or fulfills diagnostic criteria for, another autoimmune or inflammatory disease 
that may confound clinical assessments or increase subject risk in the study, including Behçet’s 
disease, periodic fever syndrome, spondyloarthritis (including psoriatic arthritis, ankylosing 
spondylitis, reactive arthritis, enteropathic arthritis), inflammatory bowel disease including celiac 
sprue, or multiple sclerosis. Autoimmune thyroid disease and history of type 1 diabetes are 
allowed. Other disorders not specifically named are subject to discuss with, and agreement by, 
the Sponsor or designee. 
13. 
Diagnosis of fibromyalgia or fulfills ACR Diagnostic Criteria for Fibromyalgia (e.g., 2010 
Preliminary Diagnostic Criteria). 
14. 
Functional class IV as defined by the ACR 1991 Revised Criteria for the Classification of Global 
Functional Status in Rheumatoid Arthritis. 
15. 
Medications not intended to be continued during the study period in compliance with Inclusion 
Criterion 7 must meet the following washout requirements prior to Baseline (i.e., Day 1 prior to 
randomization): 
a. Oral or parenteral glucocorticoids: 2 weeks if highest administered dose was 20 mg or less; 
4 weeks if highest administered dose was > 20 mg (NOTE: this applies only if corticosteroids 
are not planned to be continued. See Inclusion Criterion 7 if corticosteroids are planned to be 
used during the study). 
b. Cyclophosphamide: 12 weeks. 
c. Plasmapheresis: 24 weeks. 
d. Cyclosporine, tacrolimus, methotrexate, leflunomide, azathioprine, 6-mercaptopurine, 
mycophenolate, tofacitinib, or other Janus kinase inhibitors: 4 weeks. 
e. Biologic therapies, including but not limited to: atacicept, telitacicept, belimumab, abatacept, 
belatacept, anifrolumab, inhibitors of interleukin (IL) pathways IL-6, IL-12/23, IL-17, IL-1, 
tumor necrosis factor α, or interferon α: 12 weeks (exception: the use of prophylactic 
COVID-19 monoclonal antibodies in immunocompromised subjects is encouraged as per 
Principal Investigator’s discretion and local guidelines). 
f. Rituximab, ocrelizumab, obinutuzumab or other B cell-modulating therapies: 48 weeks, or at 
least 24 weeks if B cells have returned to 50 cells/μL). 
g. Vaccinations targeting immune pathways (e.g., interferon kinoid vaccination) (Note: this 
does not apply to vaccinations against infectious organisms): 104 weeks. 
h. Other biologics, including investigational products: 12 weeks or 5 half-lives, whichever is 
longer. 
i. Other drugs, including investigational products: 4 weeks or 5 half-lives, whichever is longer. 
j. Combination therapy with ≥ 2 immunosuppressants for the treatment of SLE: A discussion 
with, and agreement by, the Medical Monitor and Sponsor will be required. 
16. 
Serious SLE disease activity, which, in the opinion of the Investigator, warrants immediate 
immunosuppressive therapy not appropriate for the study (e.g., severely active neuropsychiatric 
SLE, rapidly progressive glomerulonephritis or vasculitis warranting immediate pulse 
corticosteroids and/or immunosuppressants such as cyclophosphamide) or which makes the 
possibility of receiving placebo or investigational agent an inappropriate risk. 


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Note: Independent of the Investigator’s opinion regarding therapy, subjects with histologic 
evidence of diffuse proliferative glomerulonephritis within 12 weeks of the start of Screening are 
not eligible. 
17. 
Ongoing participation in another therapeutic clinical trial. 
18. 
Known hypersensitivity to ALPN-101, components thereof, or excipients contained in the drug 
formulation. 
19. 
Any condition or circumstances which in the opinion of the Investigator or Sponsor may make a 
subject unlikely or unable to complete the study or comply with study procedures and 
requirements. 


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6. 
CLINICAL TRIAL PROCESSES AND PROCEDURES 
The schedule of study visits, procedures, and assessments is provided in Table 1. All visit windows are 
noted and should be calculated from randomization (Day 1). Unscheduled evaluations may be performed 
at any time at the discretion of the Investigator as needed to assess subject’s clinical status; in the event 
of increased disease activity requiring a change in treatment, subjects should return to clinic as soon as 
possible to facilitate detailed documentation of disease flare. 
All per-protocol clinical laboratory disease-related and safety assessments should be performed by the 
central laboratory. Planned time-sensitive laboratory evaluations may be duplicated at the site. A 
Laboratory Manual will provide specifics regarding procedures for the collection, processing, storage, 
and shipment of samples. 
A Procedures Manual will provide details regarding processes for subject screening, data collection, skin 
photography, oral mucocutaneous lesion photography, ECG requirements, eligibility verification, 
randomization, follow-up, and other study-related activities. The Procedures Manual will also include 
information regarding training, conduct, and reporting for efficacy assessments and quality of life 
measures. 
6.1. 
Screening (Day -42 to -1) 
All screening procedures must be performed within 42 days of Baseline (Day 1 prior to randomization). 
The screening evaluations may be carried out over more than one visit; however, all assessments should 
be completed and documented as soon as possible—and no later than 14 days prior to planned 
randomization—to ensure that verification of disease activity can be completed within the screening 
window. Screening laboratory assessments that are out-of-range may be repeated once. 
Subjects must undergo the following screening assessments and evaluations: 
 Obtain written informed consent inclusive of appropriate privacy authorization prior to 
undergoing any study-specific interventions. 
 Obtain Medical History, including complete EULAR/ACR SLE disease history and 
diagnosis form (refer to Procedures Manual). 
 Obtain demographic information. 
 Complete Review of Systems. 
 Perform complete physical exam including height measurement; obtain vital signs and 
weight. 
 Perform Investigator disease activity assessments (refer to Procedures Manual): 
 BILAG 2004 
 SLEDAI-2K 30 
 PhGA 
 In subjects with cutaneous involvement considered to be attributable to SLE, skin 
photography should be performed 


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 Perform TB screening, including chest x-ray (if applicable), as described in §6.7. 
 Obtain ECG. 
 Using the provided kits, collect blood, urine, and saliva or nasal swab for safety laboratory 
evaluations, thyroid stimulating hormone, infectious disease screen, diagnosis and 
characterization of SLE, and clinical biomarkers of SLE disease activity (see APPENDIX 2). 
 Perform urine pregnancy test for WOCBP (see APPENDIX 1) using the provided kits. 
Results from all Screening evaluations must be promptly entered, and no later than 14 days prior to 
planned randomization. Subjects who appear to meet eligibility criteria must undergo central review and 
verification of SLE disease activity by the Sponsor and/or designee prior to randomization (see Inclusion 
Criterion 2 and 6). Refer to the study Procedures Manual for details. 
Note: At screening, a local laboratory can be used with permission from the Sponsor. 
6.2. 
Day 1: Baseline, Randomization and Initiation of Treatment 
Baseline (Pre-randomization, Pre-dose) 
Ensure that Screening eligibility has been reviewed and verified. 
Perform the baseline assessments noted below: 
 Update medical history with any changes from the Screening visit as indicated 
 Update concomitant medications as indicated 
 Perform complete physical examination; obtain vital signs and weight 
Note: the baseline weight should be used to calculate all doses of study drug 
 Obtain ECG 
 Using the provided kit, collect blood and urine samples for safety laboratory evaluations and 
clinical biomarkers of SLE 
Note: all lab samples should be submitted to the central lab; local (duplicate) results may be 
used to confirm Baseline eligibility 
 Perform urine pregnancy test for WOCBP using the provided kits 
 Complete the Systemic Lupus International Collaborating Clinics/American College of 
Rheumatology (SLICC/ACR) Damage Index (SDI) (73) 
NOTE: Documentation to support damage will be collected when available (e.g., 
radiographic evidence to support diagnosis of avascular necrosis); refer to Procedures 
Manual 
 Perform Investigator disease activity assessments: BILAG 2004, SLEDAI-2K 30, PhGA, 
CLASI, 
 
NOTE: Additional procedures may be required to support activity in some organ systems (e.g., 
radiographic confirmation of pleural or pericardial effusion); refer to Procedures Manual. 
 Obtain skin photography, if applicable 
 Obtain subject’s disease assessments: PtGA, SF-36, FACIT-F (13-item) 
 Confirm subject’s eligibility based on Baseline assessments (see Inclusion Criterion 4) 


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 Using the provided kit, collect blood samples for PK
 
 Using the provided kit, collect DNA sample for subjects who have provided appropriate 
informed consent 
Randomization, Dosing, and Follow-up 
 Randomize eligible subjects according to the study Procedures Manual 
 Prepare and administer study drug in accordance with instructions in the Pharmacy Binder 
 Subjects should be observed for at least 2 hours following their first infusion of study drug 
 At 10 minutes (± 10 min) after dosing, obtain the following in the order listed: 
 Blood for PK
 using the provided kit, vital signs, and ECG 
 Record AEs and concomitant medications 
 Dense PK Subset only: at 4 hours (± 30 min) after dosing, obtain blood for PK using the 
provided kit 
6.3. 
Days 2, 4, and 8 (Dense PK Subset Only) 
The following assessments and procedures will be performed for subjects in the Dense PK subset only: 
 Record AEs and concomitant medications 
 Using the provided kit, collect blood sample for PK 
6.4. 
Treatment Period 
6.4.1. 
Day 15 
Predose 
 Record AEs and concomitant medications
 Photography of any oral mucocutaneous lesions reported as AEIs, if applicable 
 Perform physical examination and obtain vital signs
 Using the provided kit, collect blood and urine samples for safety laboratory evaluations and 
clinical biomarkers of SLE
 Using the provided kit, collect blood samples for PK

 Perform urine pregnancy test for WOCBP using the provided kits
 Perform limited Investigator disease activity assessments
 SLEDAI-2K: For this date, SLEDAI is assessed based on presentation without reference 
to the previous 30 days 
 PhGA 
 Skin photography, if applicable
Dosing and Follow-up 
 Prepare and administer study drug in accordance with instructions in the Pharmacy Binder
 At 10 minutes (± 10 min) after dosing, obtain vital signs


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 Subjects should be observed for 30 minutes following infusion of study drug
6.4.2. 
Day 29 
Predose 
 Record AEs and concomitant medications
 Photography of any oral mucocutaneous lesions reported as AEIs, if applicable 
 Perform physical examination; obtain vital signs and weight
 Using the provided kit, collect blood and urine samples for safety laboratory evaluations and 
clinical biomarkers of SLE
 Using the provided kit, collected blood samples for PK
 Perform urine pregnancy test for WOCBP using the provided kits
 Perform Investigator disease activity assessments: BILAG 2004, SLEDAI-2K 30, PhGA, 
CLASI, 

 Skin photography, if applicable
 Obtain subject’s disease assessments: PtGA, SF-36, FACIT-F (13-item)
Dosing and Follow-up 
 Prepare and administer study drug in accordance with instructions in the Pharmacy Binder
 At 10 minutes (± 10 min) after dosing, obtain vital signs
 Subjects should be observed for 30 minutes following infusion of study drug
6.4.3. 
Day 43 
Predose 
 Record AEs and concomitant medications
 Photography of any oral mucocutaneous lesions reported as AEIs, if applicable 
 Perform problem-oriented physical examination and obtain vital signs
 Perform urine pregnancy test for WOCBP using the provided kits
Dosing and Follow-up 
 Prepare and administer study drug in accordance with instructions in the Pharmacy Binder
 At 10 minutes (± 10 min) after dosing, obtain vital signs
 Subjects should be observed for 30 minutes following infusion of study drug
6.4.4. 
Day 57 
Predose 
 Record AEs and concomitant medications
 Photography of any oral mucocutaneous lesions reported as AEIs, if applicable 


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 Perform physical examination; obtain vital signs and weight
 Using the provided kit, collect blood and urine samples for safety laboratory evaluations and 
clinical biomarkers of SLE
 Using the provided kit, collect blood samples for PK

 Perform urine pregnancy test for WOCBP using the provided kits
 Perform Investigator disease activity assessments: BILAG 2004, SLEDAI-2K 30, PhGA, 
CLASI, 

 
 Skin photography, if applicable
 Obtain subject’s disease assessments: PtGA, SF-36, FACIT-F (13-item)
Dosing and Follow-up 
 Prepare and administer study drug in accordance with instructions in the Pharmacy Binder
 At 10 minutes (± 10 min) after dosing, obtain vital signs
 Subjects should be observed for 30 minutes following infusion of study drug
6.4.5. 
Day 71 
Predose 
 Record AEs and concomitant medications
 Photography of any oral mucocutaneous lesions reported as AEIs, if applicable 
 Perform problem-oriented physical examination and obtain vital signs
 Perform urine pregnancy test for WOCBP using the provided kits
Dosing and Follow-up 
 Prepare and administer study drug in accordance with instructions in the Pharmacy Binder
 At 10 minutes (± 10 min) after dosing, obtain vital signs
 Subjects should be observed for 30 minutes following infusion of study drug
6.4.6. 
Day 85 
Predose 
 Record AEs and concomitant medications
 Photography of any oral mucocutaneous lesions reported as AEIs, if applicable 
 Perform physical examination; obtain vital signs and weight
 Obtain ECG
 Using the provided kit, collect blood and urine samples for safety laboratory evaluations and 
clinical biomarkers of SLE
 Using the provided kit, collect blood samples for PK



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 Perform urine pregnancy test for WOCBP using the provided kits
 Perform Investigator disease activity assessments: BILAG 2004, SLEDAI-2K 30, PhGA, 
CLASI, 

 Skin photography, if applicable
 Obtain subject’s disease assessments: PtGA, SF-36, FACIT-F (13-item)
Dosing and Follow-up 
 Prepare and administer study drug in accordance with instructions in the Pharmacy Binder
 At 10 minutes (± 10 min) after dosing, obtain the following in the order listed: blood for 
PK/PD using the provided kit, vital signs, and ECG
 Subjects should be observed for 30 minutes following infusion of study drug
6.4.7. 
Day 99 
Predose 
 Record AEs and concomitant medications
 Photography of any oral mucocutaneous lesions reported as AEIs, if applicable 
 Perform problem-oriented physical examination and obtain vital signs
 Perform urine pregnancy test for WOCBP using the provided kits
Dosing and Follow-up 
 Prepare and administer study drug in accordance with instructions in the Pharmacy Binder
 At 10 minutes (± 10 min) after dosing, obtain vital signs
 Subjects should be observed for 30 minutes following infusion of study drug
6.4.8. 
Day 113 
Predose 
 Record AEs and concomitant medications
 Photography of any oral mucocutaneous lesions reported as AEIs, if applicable 
 Perform problem-oriented physical examination; obtain vital signs and weight
 Using the provided kit, collect blood and urine samples for safety laboratory evaluations and 
clinical biomarkers of SLE
 Using the provided kit, collect blood samples for PK

 Perform urine pregnancy test for WOCBP using the provided kits
 Perform Investigator disease activity assessments: BILAG 2004, SLEDAI-2K 30, PhGA, 
CLASI, 



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 Skin photography, if applicable
 Obtain subject’s disease assessments: PtGA, SF-36, FACIT-F (13-item)
Dosing and Follow-up 
 Prepare and administer study drug in accordance with instructions in the Pharmacy Binder
 At 10 minutes (± 10 min) after dosing, obtain vital signs
 Subjects should be observed for 30 minutes following infusion of study drug
6.4.9. 
Day 127 
Predose 
 Record AEs and concomitant medications
 Photography of any oral mucocutaneous lesions reported as AEIs, if applicable 
 Perform problem-oriented physical examination and obtain vital signs
 Perform urine pregnancy test for WOCBP using the provided kits
Dosing and Follow-up 
 Prepare and administer study drug in accordance with instructions in the Pharmacy Binder
 At 10 minutes (± 10 min) after dosing, obtain vital signs
 Subjects should be observed for 30 minutes following infusion of study drug
6.4.10. 
Day 141 
Predose 
 Record AEs and concomitant medications
 Photography of any oral mucocutaneous lesions reported as AEIs, if applicable 
 Perform physical examination; obtain vital signs and weight
 Using the provided kit, collect blood and urine samples for safety laboratory evaluations and 
clinical biomarkers of SLE
 Using the provided kit, collect blood samples for PK

 Perform urine pregnancy test for WOCBP using the provided kits
 Perform Investigator disease activity assessments: BILAG 2004, SLEDAI-2K 30, PhGA, 
CLASI, 

 Skin photography, if applicable
 Obtain subject’s disease assessments: PtGA, SF-36, FACIT-F (13-item)
Dosing and Follow-up 
 Prepare and administer study drug in accordance with instructions in the Pharmacy Binder
 At 10 minutes (± 10 min) after dosing, obtain vital signs


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 Subjects should be observed for 30 minutes following infusion of study drug
6.4.11. 
Day 155 
Predose 
 Record AEs and concomitant medications
 Photography of any oral mucocutaneous lesions reported as AEIs, if applicable 
 Perform problem-oriented physical examination and obtain vital signs
 Obtain ECG
 Using the provided kit, collected blood samples for PK
 Perform urine pregnancy test for WOCBP using the provided kits
Dosing and Follow-up 
 Prepare and administer study drug in accordance with instructions in the Pharmacy Binder
 At 10 minutes (± 10 min) after dosing, obtain the following in the order listed: blood for PK 
using the provided kit, vital signs, and ECG
 Subjects should be observed for 30 minutes following infusion of study drug
6.4.12. 
Day 169 (End of Treatment) 
 Record AEs and concomitant medications
 Photography of any oral mucocutaneous lesions reported as AEIs, if applicable 
 Perform problem-oriented physical examination; obtain vital signs and weight
 Using the provided kit, collect blood and urine samples for safety laboratory evaluations and 
clinical biomarkers of SLE
 Using the provided kit, collect blood samples for PK

 Perform urine pregnancy test for WOCBP using the provided kits
 Complete the SDI
NOTE: Additional procedures and/or documentation to support diagnosis of new damage, 
compared to Baseline, may be required (e.g., radiographic evidence to support diagnosis of 
avascular necrosis; photography to support new diagnosis of skin damage; other); refer to 
Procedures Manual. 
 Perform Investigator disease activity assessments: BILAG 2004, SLEDAI-2K 30, PhGA, 
CLASI, 

 Skin photography, if applicable
 Obtain Subject’s disease assessments: PtGA, SF-36, FACIT-F (13-item)


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6.5. 
Day 197 (End of Study) 
The EoS visit should be scheduled 4 weeks after the EoT visit (Day 169) and should include the 
following: 
 Record AEs and concomitant medications 
 Photography of any oral mucocutaneous lesions reported as AEIs, if applicable 
 Perform complete physical examination; obtain vital signs and weight 
 Obtain ECG 
 Using the provided kit, collect blood and urine samples for safety laboratory evaluations and 
clinical biomarkers of SLE 
 Using the provided kit, collect blood samples for PK
/ADA 
 Perform urine pregnancy test for WOCBP using the provided kits 
 Complete the SDI 
NOTE: Additional procedures and/or documentation to support diagnosis of new damage, 
compared to Baseline, may be required (e.g., radiographic evidence to support diagnosis of 
avascular necrosis; photography to support new diagnosis of skin damage; other); refer to 
Procedures Manual 
 Perform Investigator disease activity assessments: BILAG 2004, SLEDAI-2K 30, PhGA, 
CLASI,
. 
NOTE: Additional procedures are required to support activity in some organ systems (e.g., 
confirmation of pleural or pericardial effusion). Refer to Procedures Manual 
 Obtain Subject’s disease assessments: PtGA, SF-36, FACIT-F (13-item) 
 Skin photography, if applicable 
6.6. 
Unscheduled Visits 
6.6.1. 
Early Termination 
If a subject withdraws consent for study participation prior to Day 197, the EoS evaluations should be 
completed if possible, preferably within 2 weeks of study drug discontinuation. In addition, a follow-up 
phone call should occur 8 weeks after the last dose of study drug to determine the status of any ongoing 
AEs/SAEs or the occurrence of any new AEs/SAEs. 
As noted in §4.3, subjects who prematurely discontinue treatment with study drug (i.e., due to subject 
choice, Investigator decision, an AE or other contraindication for ongoing receipt of study drug, etc.), 
and who do not withdraw consent, should have all procedures outlined in the EoT visit as well as an 
unscheduled ECG, as soon as possible, preferably within 2 weeks. Afterwards, subjects should resume 
following the regular visit schedule as outlined in Table 1, and adhere to all study procedures except for 
study drug dosing. As the subject has discontinued study drug, all concomitant medication restrictions as 
outlined in §8.2.2 no longer apply. If at any point subsequently a subject no longer wants to provide 
assessments (withdrawal of consent) following discontinuation of study drug and completion of the EoT 
assessments, an EoS visit is not required. 


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6.6.2. 
Unscheduled Visits for Increased SLE Activity 
Subjects requiring an unscheduled visit due to an increase in their SLE activity should have all safety 
assessments completed, SLEDAI-2K (assessed based on presentation without reference to the previous 
30 days), the PhGA, and the clinical biomarkers of SLE. BILAG will not be performed at an 
unscheduled visit for increased SLE activity; increased activity should be captured at the next scheduled 
BILAG assessment, if applicable. See Procedures Manual. 
6.6.3. 
Other Unscheduled Visits 
At any other unscheduled visits, the full set of safety assessments should be completed. 
6.7. 
Description of Study Procedures 
Medical and Disease History, Demographics 
Includes medical, surgical, and disease histories. Disease history includes date of diagnosis, prior 
treatment and responses, and remarkable toxicities. Demographic information includes sex, age, and 
self-reported race/ethnicity. Ongoing medical conditions will be documented, together with medications 
and therapeutic procedures that are expected to continue during the study. At Screening, a detailed 
history of prior SLE activity will be obtained. 
Physical Examination 
Complete physical examination will be performed at intervals designated in the schedule of assessments, 
and will include examination of head, eyes, ears, nose and throat, lungs, heart, abdomen, joints, muscle 
and soft tissues, neurologic system, skin and lymph nodes. 
Physical examination that is adequate to assess SLE disease activity by BILAG and SLEDAI-2K 30 will 
be performed at each visit at which those assessment tools are employed, as designated in the schedule 
of assessments and detailed in the Procedures Manual. 
Physical examination directed based on the review of system and/or AEs will be performed at planned 
and unplanned visits as indicated. 
Vital Signs 
Vital signs (temperature, blood pressure, pulse rate, and respiratory rate) will be obtained with the 
subject at the times indicated in the summary of assessments. Unless otherwise specified, all vital signs 
should be measured after the subject has been resting, preferably for at least 5 minutes, and prior to 
invasive procedures such as drawing blood. 
Weight 
Body weight (kilograms) will be obtained with the patient’s shoes and jacket or coat removed. Total 
dose of blinded study drug administered will be based on the weight at Baseline (Day 1) unless weight 
has changed from baseline by more than 10%. In that case, total dose of blinded study drug administered 
will be based on the most current weight. 
Electrocardiogram 
All ECGs should be obtained in accordance with the central ECG instructions in the Procedures Manual. 
Subjects are to be resting, preferably in the supine position for approximately 5 minutes before each 
ECG. 


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TB Screening 
The imaging and diagnostic tests for TB screening should be interpreted in the context of the subject's 
epidemiology, history, exam findings, etc., and it is the responsibility of the Investigator to determine if 
a subject has previous, active, or latent TB. 
At Screening, a chest x-ray will be performed for all subjects to rule out the presence of TB; however, 
the chest x-ray will not be required if a subject had a previously normal imaging result (chest x-ray or 
computed tomography) within 3 months of screening, provided all source documentation is available at 
the site and provided nothing has changed in the subject’s medical history to warrant a repeat test. 
All subjects will be tested for TB infection by QuantiFERON-TB Gold test at Screening. However, if a 
subject had a negative QuantiFERON-TB Gold (or interferon-gamma release assay equivalent test, such 
as T-SPOT TB test) or negative purified protein derivative (PPD) test within 3 months of screening, and 
source documentation is available, the test does not need to be repeated, provided nothing has changed 
in the subject’s medical history to warrant a repeat test. 
Note: If the QuantiFERON-TB Gold test is indeterminate, the site should repeat the test. If the second 
QuantiFERON-TB Gold test is indeterminate, then a PPD test should be administered and interpreted 
per local guidance. If either the second QuantiFERON-TB Gold test or PPD test is negative, then the 
subject is considered negative for TB. 
Laboratory Evaluations 
Laboratory evaluations will include infectious disease, hematology, clinical chemistry, coagulation, 
urinalysis, and pregnancy tests. Tests to evaluate and characterize disease activity of SLE will also be 
performed, as will PK and PD. All per-protocol laboratory samples should be collected and sent to the 
central lab using the kits provided, as described in the Laboratory Manual. At Screening, a local 
laboratory can be used with permission from the Sponsor. Variables to be tested and reported are 
summarized in APPENDIX 2. If time-sensitive laboratory results are needed (e.g., in the context of an 
AE or increase in SLE activity), every attempt should be made to send duplicate samples for analysis at 
the central laboratory. 
Physicians Characterization of SLE and Assessment of Disease Activity 
Detailed descriptions of the assessment tools, including information on how they should be administered 
and recorded, are provided in the Procedures Manual. These include SDI, BILAG-2004, SLEDAI-2K 
(SLEDAI-2K and SLEDAI-2K 30 versions), PhGA, CLASI, 
 and photography of skin 
lesions (photography when lesions are present and imaging is appropriate). 
Prior to initiation of the study, all assessors must be trained and certified on the assessment tools 
(e.g., SLEDAI-2K 30, BILAG-2004, SDI, CLASI, and others as per the Procedures Manual) unless 
certification within the past 2 years is documented. Whenever possible, all SLE activity assessments 
should be performed by the same assessor. 
Photography of Oral Mucocutaneous Lesions Reported as AEIs 
Oral mucocutaneous lesions reported as AEIs should be documented photographically at presentation 
and in the event of significant change (see §9.8.2 and the Procedures Manual for more information). 
Patient Reported Outcomes 
Detailed description of the patient reported outcomes’ tools, including information on how they should 
be administered and recorded, are provided in the Procedures Manual. These include SF-36, PtGA, and 
FACIT-F (13-item). Patient’s assessments should be completed before the physician’s assessments. 


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Table 1 
Schedule of Procedures and Assessments 
 
Study Period: 
Screen 
Treatment1 
EoT 
EoS2 
Visit: 
1 
1b3 
1c3 
1d3 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
Day: 
-42 to -1 
1 
2 
4 
8 
15 
29 
43 
57 
71 
85 
99 
113 
127 
141 
155 
169 
197 
Visit Window: 
NA 
NA 
NA 
± 1 
± 1 
± 1 
± 2 
± 2 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
Demographics 
X 
Medical History 
X 
X5 
Eligibility Review 
X4 
X5 
Chest X-ray 
X6 
Physical Exam7 
X 
X5 
X8 
X8 
X8 
X8 
X8 
X8 
X8 
X8 
X8 
X8 
X8 
X8 
X 
Electrocardiogram 
X 
2X9 
2X9 
2X9 
X 
Weight 
X 
X5 
X 
X 
X 
X 
X 
X 
X 
Vital Signs 
X 
2X9 
2X9 
2X9 
2X9 
2X9 
2X9 
2X9 
2X9 
2X9 
2X9 
2X9 
2X9 
X 
X 
SLE Damage Assessment (SDI) 
X5 
X 
X 
Physician SLE Assessment10 
X11 
X5 
X12 
X 
X 
X 
X 
X 
X 
X 
Skin Photography13 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Patient SLE Assessment14 
X5 
X 
X 
X 
X 
X 
X 
X 
Safety Lab Evaluations15 
X16 
X5 
X 
X 
X 
X 
X 
X 
X 
X 
Infectious Disease Screen17 
X 
Urine Pregnancy Test18 
X 
X5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical Biomarkers of SLE19 
X 
X5 
X 
X 
X 
X 
X 
X 
X 
X 
PK/ADA/
2X9 
X 
X 
X 
2X9 
X 
X 
2X9 
X 
X 
(Dense PK Subject Subset)21 
(3X22) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(2X9) 
(X) 
(X) 
(2X9) 
(X) 
(X) 
(DNA)21 
X 
Randomization 
X 
Study Drug Administration23 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant Medications 
X 
(X) 
(X) 
(X) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events24 
X 
(X) 
(X) 
(X) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ADA, Anti-drug antibodies; AEI, Adverse event of interest: BILAG, British Isles Lupus Assessment Group index; CLASI, Cutaneous Lupus Erythematosus Disease Area and Severity 
Index; EoS, End of study; EoT, End of treatment; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; 
 PhGA, Physician’s Global Assessment of 
SLE Disease Activity; PK, Pharmacokinetics; PtGA, Patient’s Global Assessment of Disease Activity; SDI, Systemic Lupus International Collaborating Clinics/American College of 
Rheumatology (SLICC/ACR) Damage Index; 
; SF-36, Short Form-36; SLE, Systemic lupus erythematosus; SLEDAI, Systemic Lupus Erythematosus 
Disease Activity Index; 
; TSH, Thyroid stimulating hormone. 


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Notes: 
1 
On the days of study drug administration, all assessments and procedures must be performed prior to dosing except where otherwise specified. 
2 
Assessments should also be performed in the event of early discontinuation. 
3 
Visit held only for subjects in the Dense PK
subset. 
4 
Investigator’s screening eligibility assessment must be reviewed and confirmed by Sponsor or designee. Refer to Inclusion Criterion 4. 
5 
Perform prior to randomization and study-drug dosing. 
6 
This requirement may be met with documentation of a previous chest x-ray performed within 3 months of Screening. 
7 
Complete physical examination required at Screening, Baseline, and EoS or early discontinuation. 
8 
A problem-oriented exam may be performed at the physician’s discretion; however, at applicable visits, physical examination required for SLEDAI and 
BILAG assessment must be performed. 
9 
Obtain pre-dose, and then at 10 minutes (± 10 min) following completion of infusion. 
10 BILAG, SLEDAI-2K 30 (or SLEDAI-2K on Day 15 per footnote 12), PhGA, CLASI,
NOTE: only a subset of these will be conducted at 
Screening (see footnote 11) and Day 15 (see footnote 12). 
11 SLEDAI-2K 30, BILAG, 
 and PhGA; lupus history should be recorded at Screening. 
12 SLEDAI-2K, PhGA. 
13 Skin photography should be performed as indicated if any abnormalities are recorded on CLASI. 
14 PtGA, SF-36, FACIT-F (13-item). Note: Patient’s assessments should be completed before physician’s assessment. 
15 Collect blood and urine samples using kit provided by the central laboratory; refer to APPENDIX 2. 
16 In addition to standard safety lab evaluations, includes TSH. 
17 Collect samples using kit provided by the central laboratory; refer to APPENDIX 2. 
18 Perform at the clinical site using provided kit; negative results must be confirmed prior to study drug dosing. 
19 Collect blood samples using kit provided by the central laboratory; refer to APPENDIX 2. 
20 Pharmacokinetics, anti-drug antibodies, 
 biomarkers. Please reference Procedures Manual for more detailed timepoints and 
instructions. 
21 In subjects who provide supplemental consent. 
22 Obtain pre-dose, and then at 10 minutes (± 10 min) and 4 hours (± 30 min) following completion of infusion. 
23 Subjects should be observed for at least 2 hours following their first infusion of study drug and for 30 minutes following each subsequent infusion. 
24 For oral mucocutaneous lesions reported as AEIs (see §9.8.2), photographic documentation should be collected at presentation and in the event of significant 
change (as detailed in the Procedures Manual). 


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7. 
STUDY DRUG 
7.1. 
Packaging, Labeling and Storage 
Blinded study drug is a sterile, clear to slightly opalescent, colorless to yellow preservative-free liquid 
solution contained in clear glass, single-dose vials. Each 3 mL vial has 2 mL extractable volume 
containing either: 
 ALPN-101 Injection 
or 
 Placebo 
Blinded study drug should be stored at 2℃ to 8℃, protected from light. 
The Pharmacy Binder contains additional information regarding the receipt, storage, and preparation of 
study drug. 
Table 2 
Investigational Product Description 
 
ALPN-101 
Placebo 
Components 
ALPN-101 (active ingredient), 20 
mM L-histidine, 250 mM sucrose, 
pH 6.7 
20 mM L-histidine, 250 mM 
sucrose, pH 6.7 
Dosage Form: 
Liquid solution for IV infusion 
Liquid solution for IV infusion 
Unit Dose 
Each 3 mL vial contains an 
extractable volume of 2 mL 
Route of Administration 
IV 
IV 
Physical Description 
Clear to slightly opalescent, 
colorless to yellow liquid solution 
Clear to slightly opalescent, 
colorless to yellow liquid solution 
IV, Intravenous. 
 
7.2. 
Preparation and Dosing 
Subject eligibility must be independently confirmed prior to randomization and administration of study 
drug. 
The planned dosing regimen for this study is 3 mg/kg ALPN-101 or placebo IV administered Q2W for 
12 total doses. If a dose of study drug is missed, consult with the Medical Monitor. Dose or dose 
intensity may be decreased based on DMC recommendation and Sponsor decision; refer to§4.3. 
Doses of study drug are calculated and prepared based on each subject’s body weight at Baseline, 
rounded to the nearest kilogram, unless weight changes by more than 10%; in that case doses of study 
drug will be calculated and prepared based on the subject’s most current body weight. Study drug will 
be prepared in accordance with instructions in the Pharmacy Binder and will be infused over 
approximately 30 minutes (±15 minutes) using a volumetric pump with a 0.2 micron in-line filter. Study 
drug is NOT to be administered as an IV push or bolus injection. 
Subjects should be observed for at least 2 hours following their first infusion of study drug and for 
30 minutes following each subsequent infusion. 


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The Investigator is responsible for the education of study staff in the correct administration of study 
drug. 
7.3. 
Accountability 
A record will be maintained by the investigational site which will account for all dispensing, destruction, 
or return of any used and unused study drug. 


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8. 
CLINICAL MANAGEMENT GUIDELINES AND REQUIREMENTS 
8.1. 
Clinical Management of Adverse Events of Interest 
8.1.1. 
Infusion-Related Reactions 
Guidelines for assessing, grading, and reporting IRRs are provided in §9.8 and §9.8.1. 
No infusion reactions were observed following single or repeated IV infusions of ALPN-101 in a 
previous study in healthy volunteers. The incidence and nature of ALPN-101-related IRRs, if any, 
remain uncharacterized. Based on experience with other immunomodulatory compounds, including 
approved CD28 pathway inhibitors, IRRs may include hypersensitivity reactions (e.g., anaphylaxis) 
and/or cytokine release syndromes. IRRs typically present with dizziness, headache, circulatory 
(hypo- or hypertension), respiratory (cough, wheezing, dyspnea), mucocutaneous (flushing, urticaria, 
pruritis, rash), and abdominal (nausea, vomiting, cramps, diarrhea) symptoms. Symptoms typically 
begin during or within 24 hours of drug administration. 
If any subject experiences an infusion reaction, including anaphylaxis or cytokine release syndrome: 
 Monitoring frequency and duration will be increased, and will continue until episode is 
resolved.
 Supportive care will be initiated per institutional guidelines. This may include, but is not 
limited to, slowing and/or interruption of the current infusion; administration of 
antihistamines such as diphenhydramine or loratadine; administration of antipyretics such as 
acetaminophen or paracetamol; administration of corticosteroids; IV fluid support such as 
normal saline; vasopressors; anti-rigor medication such as meperidine.
 Using the kits provided by the central laboratory, blood will be collected for assessment of 
serum levels of mast cell tryptase and quantitative IgE; blood should be collected as soon as 
possible after initiation of the event, and repeated at 60 minutes and following resolution or 
discharge from care for the event. In addition, a serum sample for exploratory analysis of 
chemokines and cytokines should be collected.
In the event that an IRR occurs when the subject is not in the clinic, all subjects should undergo an 
unscheduled visit as soon as possible (< 24 hr). 


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Table 3 
Guidelines for Management of IRRs 
 
AE Grade 
ALPN-101 Dose Modification 
Toxicity Management 
Any 
Manage per institutional standards at the discretion of 
Investigator. 
Monitor subjects for signs and symptoms of IRR (e.g., fever 
and/or shaking chills, flushing and/or itching, alterations in 
heart rate and blood pressure, dyspnea or chest discomfort, or 
skin rashes) and anaphylaxis (e.g., acute onset of generalized 
urticaria, angioedema, wheezing, hypotension, or tachycardia). 
1 
The infusion rate may be decreased by 
50% or temporarily interrupted until 
resolution of the event. 
Acetaminophen, antihistamines, meperidine, etc. may be 
administered per institutional standards 
Consider premedication, such as with antihistamines, 
acetaminophen, NSAIDs, or meperidine per institutional 
standard prior to subsequent doses 
Steroids should not be used for routine premedication of 
Grade ≤ 2 infusion reactions 
2 
The infusion rate may be decreased 
50% or temporarily interrupted until 
resolution of the event. 
Subsequent infusions, if applicable, 
may be given at 50% of the initial 
infusion rate 
3 
Consult with Medical Monitor or 
Sponsor 
Stop infusion. 
Manage per institutional standards (e.g., oral or parenteral 
corticosteroids, antihistamines, antipyretics, meperidine) 
Premedication per institutional standard prior to subsequent 
doses 
Consider hospitalization. 
4 
Permanently discontinue 
Stop infusion. Hospitalize. 
Manage severe infusion-related reactions per institutional 
standards (e.g., IM epinephrine, followed by IV 
diphenhydramine and ranitidine, and IV glucocorticoid). 
AE, Adverse event; IM, Intramuscular; IRR, Infusion-related reaction; IV, Intravenous; NSAIDs, Nonsteroidal anti- 
inflammatory drugs. 
 
8.1.2. 
Oral Mucocutaneous Lesions 
Aphthous ulcers were observed in 5 of 66 (7.5%) of healthy volunteers randomized to ALPN-101 in the 
previous study in healthy volunteers. All events were mild or moderate and were self-limited or resolved 
with topical therapy (i.e., lidocaine; corticosteroids). 
Oral mucocutaneous lesions (including aphthous ulcers) not attributed to SLE are considered AEIs for 
assessment in the present study; any oral mucocutaneous lesions attributed to underlying SLE should be 
reported in the appropriate disease index and not as AEs. Guidelines for reporting oral mucocutaneous 
lesions are provided in §9.8 and §9.8.2. 
The differential diagnosis of new or worsening oral mucocutaneous lesions that may occur during this 
study includes, but is not limited to: new or worsening SLE activity; infections (e.g., coxsackie A, 
herpes simplex, herpes zoster, cytomegalovirus, Epstein-Barr, HIV, TB; other bacterial or fungal 
infections); trauma (e.g., dental appliances); drug reactions (e.g., methotrexate-related mucositis, 
others); other autoimmune or inflammatory diseases (e.g., inflammatory bowel disease; Behcet’s; 
others). If new oral mucocutaneous lesions are observed during this study, efforts should be made to 
definitively determine cause, to the extent possible. 
Evaluation should include: 
 Culture to assess for infection, if indicated


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 Consider specialist evaluation by ear, nose and throat or oral medicine if diagnosis is not 
clear; biopsy may be indicated in severe or refractory cases
 For lesions reported as AEIs: photographic documentation of lesions at presentation and in 
the event of significant change
Therapy should be guided by diagnosis, severity, and response to initial therapy. Options may include: 
 Oral and/or topical analgesics, if indicated for discomfort
 Topical corticosteroids, if indicated for control of inflammation
 Treatment of underlying condition
8.1.3. 
Infections Grade ≥ 3 
In general, study drug administration should be withheld in the event of any infection that the 
Investigator judges to be clinically significant. If the infection resolves, study drug may be restarted at 
the next scheduled dose, with approval of the Medical Monitor. For this study, infections of Grade ≥ 3 
are considered AEIs (see §9.8.3). Reporting requirements for AEIs are described in §9.8. 
8.2. 
Allowed Medications or Treatments 
8.2.1. 
Non-SLE Concomitant Medications 
Use of non-SLE concomitant medications (including prescription and over-the-counter medications, 
herbal supplements/teas and vitamins, analgesics, non-prescription NSAIDs and other agents for 
treatment of AEs or supportive care that are not specifically prohibited) is permitted when deemed 
necessary by the Investigator or subject’s care provider; subjects who are using NSAIDs infrequently or 
“as needed” should make every attempt to withhold dosing on study visit days until SLE assessments 
have been completed. 
For all non-SLE concomitant medications used at baseline, or that are used intermittently and expected 
to be used during the study (e.g., NSAIDs for menstrual discomfort; rescue inhalers for asthma), name 
and indication should be recorded in the medical history. 
For all non-SLE medications initiated during the study, date of initiation, dose, date of change in dose or 
discontinuation, and indication should be recorded. The associated AE should be documented. 
8.2.2. 
Concomitant Medications for SLE 
From the signing of informed consent through completion of all assessments though the EoS visit, 
subject should receive stable doses of medications used as SOC for SLE (including oral corticosteroids, 
hydroxychloroquine/hydroxychloroquine-like drugs and permitted immunosuppressants, as listed in 
Inclusion Criterion 7), except in circumstances summarized below: 
 Reduction in dose or discontinuation due to toxicity (§8.2.2.1)
 Changes to control increased disease activity or flare/ significant worsening of disease 
(§8.2.2.3)
8.2.2.1. 
Reduction in SLE Medication Dose Due to Toxicity 
Standard of care medications for SLE may be reduced or temporarily discontinued if indicated for 
management of immediate safety concerns; the event leading to reduction or discontinuation should be 
documented as an AE, and the relationship to SOC should be recorded (e.g., mucosal ulcers secondary 
to methotrexate; poor diabetic control secondary to corticosteroids; nausea and vomiting secondary to 
mycophenolate; others). 


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8.2.2.2. 
Discretionary Reduction in Corticosteroid Dose Due Decreased SLE Disease Activity 
After Day 85 
Corticosteroids may not be reduced due to decreased disease activity until after all assessments have 
been completed through Study Day 85 (End of Week 12). Thereafter, corticosteroids may be tapered if 
all of the following are true (note that taper is permitted, but is NOT required): 
 In the Investigator’s judgement, it is in the subject’s best interest to taper corticosteroids. 
 If there has been an increase in disease activity during the Treatment Period that required a 
burst and taper of corticosteroids to control increased SLE disease activity (§8.2.2.3), the 
corticosteroids have been tapered back to the dose at Baseline or the dose prior to initiation 
of the burst, and must have remained stable for at least 4 weeks. 
 The SLEDAI-2K 30 score must have improved (be reduced) by at least 4 points from the 
score recorded at the Baseline Visit. 
 The taper must be anticipated to be completed by Day 141 (end of Week 20); corticosteroid 
dose should be planned to remain stable from Day 141 (end of Week 20) through Day 169 
(EoT). 
General guidelines for tapering corticosteroids: 
 If the current dose is ≥ 15 mg/day prednisone equivalent, taper by not more than 5 mg over 
the following 28 days. 
 If the current dose is 7. 5 to < 15 mg/day prednisone equivalent, taper by no more than 
2.5 mg prednisone equivalent over the following 28 days. 
 If the current dose is > 0 to < 7.5 mg/day, taper by not more than1 mg over the following 
28 days. 
8.2.2.3. 
Treating Increases in SLE Activity 
The decision to treat increased SLE disease activity is based on the judgement of the Investigator. 
Increased disease activity should not be recorded as an AE; however, information regarding the organ 
system involved and the severity of disease activity leading to treatment should be captured in the 
disease assessments tools (e.g., BILAG 2004, SLEDAI-2K 30, PhGA) and also recorded as the 
indication for treatment with the concomitant medication. Increase in corticosteroids is treated 
separately from increase in, or addition of, other agents, as detailed below. 
Burst and Taper of Corticosteroids 
Prior to initiation of a burst of corticosteroids, all assessments should be completed that pertain to the 
visit at which the increased disease was recognized, if possible. If the increased disease was recognized 
between scheduled visits, then the subject should return to the clinic and all assessments listed for an 
unscheduled visit due to increased SLE activity (see §6.6.2) should be performed. 
From Day 1 through Day 141, subjects with increased disease activity that require a temporary increase 
from the baseline oral corticosteroid dose may initiate either of the following: 
 Oral corticosteroids administered up to a maximum dose of 40 mg prednisone/day (or 
equivalent) and tapered to the Day 1 dose by the end of the 14th day after initiation at the 
latest, or 
 Intramuscular methylprednisolone up to a maximum of 160 mg administered at a single 
timepoint 


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The following additional guidelines apply: 
 A course of oral or intramuscular corticosteroids cannot be initiated more frequently than 
every 28 days 
If a subject requires initiation of a burst of corticosteroids after Day 141, or at a higher dose, or more 
frequently, or for longer than permitted, the subject should remain in the study for evaluation of safety 
and outcomes. Blinded study drug may be continued if not contraindicated in the judgement of the 
Investigator following discussion with, and agreement by, the Medical Monitor. 
Increase or Addition of Hydroxychloroquine/Hydroxychloroquine-like Drugs and/or 
Immunosuppressants for Increased SLE Activity 
If during the Treatment period (Day 1 to 169) the SOC medications used at Baseline, together with the 
permitted bursts and taper of corticosteroids, are considered to not be adequate for the treatment of 
increased disease activity, a subject may receive medications deemed necessary by the Investigator or 
treating physician. In that case, all of the following should be done: 
 Blinded study drug will be discontinued 
 The subject should remain in the study for assessment of outcomes, including safety 
 The Investigator should consult the Medical Monitor AND the updated IB to discuss any 
additional safety assessments to be performed in addition to those included in the protocol 
8.3. 
Prohibited Medications or Treatments 
The inclusion criteria list medications that are permitted for SOC treatment of SLE in the present study. 
For each permitted medication, the dose and duration over which it must be stable prior to Screening or 
Baseline is provided. 
No new medication for treatment of SLE can be started during the study, and no SOC treatment can be 
increased or decreased, excepted as detailed in §8.2. 
Subjects should not receive live vaccines during the study; all vaccinations (live, killed, or conjugated) 
must be approved by the Medical Monitor prior to administration. 
Medications that are specifically excluded are listed in the exclusion criteria (§5.2). These agents must 
have been discontinued prior to Screening or Baseline. The length of time that must have passed 
following the last dose of each agent is provided in (§5.2). 
Other medications not listed, but with significant immunosuppressive or immunomodulatory activity, 
should be reviewed and approved by the Medical Monitor prior to initiation. 


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9. 
ADVERSE EVENT REPORTING 
The following sections describe the minimum requirements for assessing and reporting AEs, including 
SAEs and serious, unexpected, suspected adverse reactions for subjects participating in trial AIS-A03. 
9.1. 
Adverse Event Definition 
An AE is any untoward medical occurrence associated with the use of a drug in a patient or clinical trial 
participant, whether or not considered drug-related. An AE can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding, for example), symptom, or disease 
temporally associated with the use of a drug, whether or not considered related to the drug (i.e., does not 
imply any judgment about causality). 
In the context of a clinical trial, AEs include exacerbation of a pre-existing illness or symptom, an 
increase in frequency or intensity of a pre-existing episodic event or condition, or a condition detected or 
diagnosed after investigational product administration even though it may have been present prior to the 
start of the study. 
Events that do not meet the definition of an AE include: 
 Medical or surgical procedures (e.g., endoscopy, appendectomy); the condition that leads to 
the procedure should be reported as an AE if applicable; 
 Situations where an untoward medical occurrence did not occur (e.g., social and/or 
observational and/or convenience admission to a hospital); 
 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. 
Abnormal laboratory values or test results constitute AEs if they are clinically significant and/or induce 
clinical signs or symptoms, or if they require intervention or therapy. Wherever possible, the clinical 
rather than laboratory term should be reported (e.g., “anemia” rather than “low hemoglobin”). 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study drug or a concomitant 
medication should also be reported as AEs (overdose per se will not be reported as an AE/SAE). 
For this study, signs and symptoms of SLE activity are not to be reported as AEs, but should be 
captured in activity assessment tools. However, if SLE symptoms meet SAE criteria (see §9.3), 
expedited reporting requirements apply as per §9.4. 
9.2. 
Adverse Event Reporting and Follow-up 
Any medical condition with an onset or diagnosis before the first administration of study drug, but after 
signing the informed consent form (ICF), will be noted as part of the subject’s baseline medical 
conditions. Signs and symptoms of SLE activity should not be reported as AEs, but should be 
documented in the relevant activity assessments. 
Information regarding all AEs will be collected from the time of first dose of study drug until the EoS 
visit, or for at least 8 weeks following the last infusion of study drug if the subject discontinues early. 
Adverse events that are thought to be related to the study drug and continue beyond this collection 
period will be followed until resolution or until stabilized. Adverse events that begin after the defined 
collection period, but that the Investigator considers to be related to study drug, may be reported at any 
time. 
Adverse event severity will be graded using CTCAE, version 5.0. When CTCAE criteria cannot be used, 
the AE should be graded as follows: 


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 Grade 1 (Mild): Mild transient (< 48 hr) or mild discomfort not requiring medical 
intervention or therapy. 
 Grade 2 (Moderate): Mild to moderate limitation in activity; some assistance may be needed; 
no or minimal medical intervention or therapy required. 
 Grade 3 (Severe): Marked limitation in activity; some assistance usually required; medical 
intervention or therapy required; hospitalizations possible. 
 Grade 4 (Life-threatening): Extreme limitation in activity; significant assistance required; 
significant medical intervention or therapy required; hospitalization or hospice care probable. 
 Grade 5 (Fatal): Results in death 
In general, the use of a unifying diagnosis as the AE term is preferred to the listing of individual 
symptoms. Grouping of symptoms into a diagnosis should only be done if each component sign and/or 
symptom is a medically confirmed component of a diagnosis as evidenced by standard medical practice. 
If any aspect of a sign or symptom does not fit into a classic pattern of the diagnosis, the individual 
symptom should be reported as a separate AE. 
9.3. 
Serious Adverse Event Definition 
An SAE is any AE that, in the view of either the Investigator or the Sponsor, results in any of the 
following outcomes: 
 Death 
 A life-threatening AE 
 Inpatient hospitalization or prolongation of an existing hospitalization 
 A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions, or 
 A congenital anomaly/birth defect 
Important medical events that may not result in death, be life-threatening, or require hospitalization may 
be considered serious when, based upon appropriate medical judgment, they may jeopardize the subject 
and may require medical or surgical intervention to prevent one of the outcomes listed above. Examples 
of such medical events include allergic bronchospasm requiring intensive treatment in an emergency 
room or at home, blood dyscrasias or convulsions. 
The term "life-threatening” refers to an event in which the subject 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 were more severe. 
CTCAE Grade 4 events are not automatically defined as life threatening for SAE determination. For 
example, a Grade 4 increase in ALT may or may not be deemed as life threatening by the Investigator 
and/or Sponsor. 
For hospitalizations and surgical procedures, the illness leading to the surgical or diagnostic procedure 
should be recorded as the SAE, not the procedure itself. The procedure should be captured in the 
narrative as part of the therapeutic action taken in response to the illness. 
Additionally, hospitalization itself is not an AE but is an outcome of the event. Thus, hospitalization in 
the absence of an AE is not regarded as an SAE. The following are examples of hospitalization that may 
not be considered SAEs: 
 A visit to the emergency room or other hospital department < 24 hours, that does not result in 
admission 


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 Protocol-specified admission (e.g., for procedure required by study protocol) 
 Diagnostic admission (e.g., for a work-up of an existing condition such as persistent 
pretreatment lab abnormality) 
 Administrative admission (e.g., for annual physical) 
 Social admission (e.g., placement for lack of place to sleep) 
 Elective admission (e.g., for elective surgery) 
 Admission to a palliative unit or hospice facility 
9.4. 
Emergency Unblinding 
This study is blinded; neither subjects nor investigators or site staff will be aware of subjects’ treatment 
assignments. However, in the event of a medical emergency when knowledge of the treatment received 
is needed for medical management of an SAE, the investigator may unblind an individual subject’s 
treatment allocation. When possible, prior to unblinding, the investigator should attempt discuss the 
reason for wanting to unblind with the Medical Monitor. Instructions for emergency unblinding are 
contained in the Procedures Manual (IRT/Suvoda, Site Safety Reporting Instructions). 
9.5. 
Serious Adverse Event Reporting and Follow Up 
SAEs will be collected from the time of the first dose of study drug until the EoS visit, or for at least 
8 weeks following the infusion of study drug if the subject discontinues early. SAEs that are related to 
the investigational product and continue beyond the normal collection period will be followed until 
resolution or until stabilized. SAEs that begin after the defined collection period, but that the 
Investigator considers to be related to study drug, may be reported at any time. 
All SAEs must be reported to the Sponsor or designee within 24 hours of clinical site personnel 
becoming aware of the event. Refer to the study Procedures Manual for SAE reporting requirements and 
details. 
9.6. 
Suspected Adverse Reaction Definition 
A suspected adverse reaction is any AE for which there is a reasonable possibility that the 
investigational product caused the AE. "Reasonable possibility" means there is evidence to suggest a 
causal relationship between the drug and the AE. The following criteria may be used as a guide for 
assessing causality: 
 Yes/Related 
There is evidence exists to suggest a causal relationship between the drug and the AE, such 
as: 
 An event that is uncommon and known to be strongly associated with drug exposure 
(e.g., angioedema, hepatic injury, Stevens-Johnson Syndrome) 
 An event that is not commonly associated with drug exposure, but is otherwise 
uncommon in the population exposed to the drug (e.g., tendon rupture) 
 No/Unrelated 
Another cause of the AE is more plausible (e.g., due to underlying disease or occurs 
commonly in the study population), or a temporal sequence cannot be established with the 
onset of the AE and administration of the study treatment, or a causal relationship is 
considered biologically implausible. 


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9.7. 
Adverse Event Expectedness 
An AE or suspected adverse reaction is considered “unexpected” if it is not listed in the ALPN-101 IB. 
The Sponsor or Medical Monitor is responsible for determining the expectedness of all reported SAEs, 
including serious suspected adverse reactions. 
9.8. 
Adverse Events of Interest 
The occurrence of an AEI whether serious or nonserious, must be immediately reported to AIS within 
≤ 24 hours of site awareness by entering the information into the electronic data capture (EDC) system, 
then completing an AEI narrative form and sending it to the following email address: 
 safety@alpineimmunesciences.com 
The AEI reporting period will begin at the time of first dose of study drug and continues until the final 
study day (i.e., EoS visit, or end of follow-up for subjects prematurely withdrawn). 
Recommendations regarding the medical management of AEIs can be found in §8.1. 
AEIs are listed below: 
 IRRs (see §9.8.1) 
 Oral mucocutaneous lesions (including aphthous ulcers) not attributed to SLE (see §9.8.2) 
 Infections Grade ≥3 (see §9.8.3) 
9.8.1. 
Infusion-related Reactions 
Terminology and Grading of IRRs 
The term “IRR” should generally be used and the severity assessed per CTCAE v5.0. More specific 
terms should only be used when the mechanism and/or diagnosis can be definitively determined. For 
instance, “anaphylaxis” should only be used for events fitting the criteria in Table 4, while “cytokine 
release syndrome” should be used for fitting the description in Table 5 and determined to be in 
association with the release of cytokines. 
An allergic reaction which occurs in relationship to study drug administration should be reported as an 
IRR. Each sign or symptom of the reaction should be recorded as an individual AE. If multiple signs or 
symptoms occur with a given infusion-related event, each sign or symptom should be recorded 
separately with its level of severity. 


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Table 4 
NIAID/FAAN Clinical Criteria for Diagnosis of Anaphylaxis 
 
Anaphylaxis is highly likely when any one of the three following criteria are fulfilled: 
1. 
Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (e.g., 
generalized hives, pruritus or flushing, swollen lips-tongue-uvula) and at least one of the following: 
 Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia) 
 Reduced BP or associated symptoms of end-organ dysfunction (e.g., hypotonia [collapse], syncope, incontinence) 
2. 
Two or more of the following that occur rapidly after exposure to a likely allergen for that patient (minutes to several 
hours): 
 Involvement of the skin-mucosal tissue (e.g., generalized hives, itch-flush, swollen lips-tongue-uvula) 
 Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia) 
 Reduced BP or associated symptoms (e.g., hypotonia [collapse], syncope, incontinence) 
 Persistent gastrointestinal symptoms (e.g., crampy abdominal pain, vomiting) 
3. 
Reduced BP after exposure to known allergen for that patient (minutes to several hours): 
 Infants and children: low systolic BP (age specific) or greater than 30% decrease in systolic BP* 
 Adults: systolic BP of less than 90 mm Hg or greater than 30% decrease from that person’s baseline 
BP, Blood pressure; NIAID/FAAN, National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis 
Network; PEF, Peak expiratory flow. 
*Low systolic BP for children is defined as < 70 mm Hg from 1 month to 1 year, < (70 mm Hg + [2 x age]) from 1 to 10 
years, and < 90 mm Hg from 11 to 17 years. 
From (75) 
Table 5 
AE Terms and Grades for Reporting IRRs 
 
AE Term 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
Infusion 
Mild transient 
Therapy or infusion 
Prolonged (e.g., not 
Life-threatening 
Fatal 
Related 
reaction; 
interruption 
rapidly responsive to 
consequences; 
Reaction 
infusion 
indicated but 
symptomatic 
urgent intervention 
interruption not 
responds promptly 
medication and/or 
indicated 
indicated; 
to symptomatic 
brief interruption of 
intervention not 
treatment (e.g., 
infusion); recurrence 
indicated 
antihistamines, 
of symptoms 
NSAIDs, narcotics, 
following initial 
IV fluids); 
improvement; 
prophylactic 
hospitalisation 
medications 
indicated for clinical 
indicated for 
sequelae 
≤ 24 hrs 
Definition: A disorder characterized by adverse reaction to the infusion of pharmacological or biological substances. 


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Table 5 
AE Terms and Grades for Reporting IRRs (Continued) 
 
AE Term 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
Anaphylaxis 
Symptomatic 
Life-threatening 
Fatal 
bronchospasm, with 
consequences; 
or without urticaria; 
urgent intervention 
parenteral 
indicated 
intervention 
indicated; allergy- 
related 
edema/angioedema; 
hypotension 
Definition: A disorder characterized by an acute inflammatory reaction resulting from the release of histamine and 
histamine-like substances from mast cells, causing a hypersensitivity immune response. Clinically, it presents with 
breathing difficulty, dizziness, hypotension, cyanosis and loss of consciousness and may lead to death. 
Cytokine 
Fever with or 
Hypotension 
Hypotension 
Life-threatening 
Fatal 
release 
without 
responding to fluids; 
managed with one 
consequences; 
syndrome 
constitutional 
hypoxia responding 
pressor; hypoxia 
urgent intervention 
symptoms 
to <40% O2 
requiring ≥ 40% O2 
indicated 
Definition: A disorder characterized by fever, tachypnea, headache, tachycardia, hypotension, rash, and/or hypoxia caused 
by the release of cytokines. 
IRRs, Infusion-related reactions; NSAIDs, Nonsteroidal anti-inflammatory drugs; IV, Intravenous; O2, Oxygen. 
From NCI-CTCAE v5.0. 
9.8.2. 
Oral Mucocutaneous Lesions 
Efforts should be made to determine the cause of oral mucocutaneous lesions (including aphthous 
ulcers) observed during the study (see §8.1.2). 
Any oral mucocutaneous lesions attributed to underlying SLE (including new or worsening 
lesions) should not be reported as AEs, but should be recorded in SLEDAI-2K 30 (mucosal ulcers) 
and/or BILAG 2004 (mucosal ulceration–mild, or mucosal ulceration–severe, as appropriate consistent 
with glossary definitions) and/or CLASI (mucosal lesions). Treatment should be recorded as 
concomitant medications, listing SLE activity as the indication for treatment. 
Any oral mucocutaneous lesions not attributed to SLE should be reported as AEIs and graded 
according to CTCAE (see §9.2). Whenever possible, the specific cause or type (e.g., thrush) should be 
reported. Aphthous ulceration, if not assessed as related to SLE, may be reported as “aphthous ulcer,” 
“aphthous stomatitis” or other similar verbatim term as considered appropriate by the Investigator. 
However, in such cases when no specific term exists in CTCAE, the AE should be graded according to 
“mucositis oral” or “pharyngeal mucositis,” as appropriate to the anatomical location of the lesion(s). 
Table 6 provides terms and for grading for some oral mucocutaneous lesions per CTCAE. 
Note: For lesions reported as AEIs, photographic documentation should be collected at 
presentation and in the event of significant change (as detailed in the Procedures Manual). 


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Table 6 
AE Terms and Grades for Reporting Oral Mucocutaneous Lesions 
 
AE Term 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
Mucositis, 
oral 
Asymptomatic 
or mild 
symptoms; 
intervention 
not indicated 
Moderate pain or 
ulcer that does not 
interfere with oral 
intake; modified 
diet indicated 
Severe pain; 
interfering with oral 
intake 
Life-threatening 
consequences; 
urgent 
intervention 
indicated 
Fatal 
Definition: A disorder characterized by ulceration or inflammation of the oral mucosa. 
Pharyngeal 
mucositis 
Endoscopic 
findings only; 
minimal 
symptoms with 
normal oral 
intake; mild 
pain but 
analgesics not 
indicated 
Moderate pain, 
analgesics 
indicated; altered 
oral intake; 
limiting 
instrumental ADL 
Severe pain; unable 
to adequately 
aliment or hydrate 
orally; limiting self 
care ADL 
Life-threatening 
consequences; 
urgent 
intervention 
indicated 
Fatal 
Definition: A disorder characterized by ulceration or inflammation involving the mucous membrane of the 
pharynx. 
Mucosal 
infection 
Localized, 
local 
intervention 
indicated 
Oral intervention 
indicated (e.g., 
antibiotic, 
antifungal, or 
antiviral) 
IV antibiotic, 
antifungal, or 
antiviral 
intervention 
indicated; invasive 
intervention 
indicated 
Life-threatening 
consequences; 
urgent 
intervention 
indicated 
Definition: A disorder characterized by an infectious process involving a mucosal surface. 
Pharyngitis 
Oral intervention 
indicated (e.g., 
antibiotic, 
antifungal, or 
antiviral) 
IV antibiotic, 
antifungal, or 
antiviral 
intervention 
indicated; invasive 
intervention 
indicated 
Life-threatening 
consequences; 
urgent 
intervention 
indicated 
Fatal 
Definition: A disorder characterized by inflammation of the throat. 
Thrush 
Asymptomatic; 
local 
symptomatic 
management 
Oral intervention 
indicated (e.g., 
antifungal) 
IV antifungal 
intervention 
indicated 
Definition: A disorder characterized by a suspected candidal infection involving an oral mucosal surface. 
ADL, Activities of daily living; AE, Adverse event; IV, Intravenous. 
From NCI-CTCAE v5.0. 
9.8.3. 
Infections Grade ≥ 3 
For this clinical study, severe (Grade ≥ 3) infections have been defined as AEIs (see §9.2 for details 
regarding severity grading). 


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9.9. 
Pregnancy 
Pregnancies that occur from the time of first study drug dose until the EoS visit, including any 
pregnancies that occur in the female partner of a male study subject, must be reported to the Sponsor or 
designee within 48 hours of the Investigator becoming aware of the pregnancy. Pregnancy outcomes of 
elective or spontaneous abortion, stillbirth, or congenital anomaly, as well as any pregnancy-related 
events that meet the criteria for an SAE (see §9.3) must be reported as per §9.5. 
All pregnancies will be monitored for the full duration; all perinatal and neonatal outcomes should be 
reported. Refer to the Procedures Manual for complete instructions. 


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10. 
STATISTICAL AND DATA ANALYSIS METHODS 
10.1. 
Overview of Statistical Methods 
Detailed methodology and statistical analyses of the data collected in this study will be documented in a 
statistical analysis plan (SAP), which will be finalized prior to unblinding the study database. A general 
overview of the planned methodology is provided below. Any deviation from the planned analysis will 
be detailed in the SAP. In all cases, analyses defined in the SAP take precedence over descriptions in the 
Protocol. All post-hoc analyses will be detailed in the final clinical study report. 
10.2. 
Sample Size 
The primary purpose of this phase 2 study is to access the safety of ALPN-101 in subjects with moderate 
to severe SLE. As such, the anticipated sample size of approximately 130 subjects randomized 1:1 to 
receive ALPN-101 or placebo was not derived to support formal hypothesis testing of efficacy 
endpoints. 
To estimate the power to detect potential differences in efficacy endpoints of primary interest, placebo 
response rates of 40% for SRI-4 and 20% for BILAG were assumed. A sample size of 65 subjects per 
treatment arm will provide 82% and 87% power to detect a difference of at least 25% between the 
ALPN-101 arm and the placebo arm at Day 169 in SRI-4 and BILAG response, respectively, based on a 
chi-square test with a two-sided significance level of 0.05 and no adjustments for multiple testing. 
10.3. 
Method of Assignment to Treatment 
Randomization will be stratified by geographical region and by use of concomitant oral 
immunosuppressive therapy at enrollment in two groups: 
 Concomitant use of at least one of the permitted immunosuppressants (e.g., methotrexate, 
leflunomide, azathioprine, 6-mercaptopurine, mycophenolate mofetil, mycophenolic acid), and/or 
corticosteroids at doses > 5 mg prednisone or equivalent daily with or without hydroxychloroquine/ 
hydroxychloroquine-like drugs ; vs 
 No use of permitted immunosuppressant and/or corticosteroids at doses > 5 mg prednisone or 
equivalent daily; with or without use of lower doses of corticosteroids and/or hydroxychloroquine/ 
hydroxychloroquine-like drugs 
10.4. 
Analysis Populations 
 Modified Intent-To-Treat (mITT) Population: all randomized subjects who received any amount 
of study drug and completed at least one post-baseline disease assessment. mITT subjects will be 
analyzed according to the treatment arm into which they were randomized regardless of the actual 
treatment received. The mITT is the analysis population for the primary efficacy analysis. 
 Safety Population: all randomized subjects, classified according to the actual treatment received, 
who received any amount of study drug and have at least one post-baseline safety evaluation. This is 
the primary analysis population for the safety analysis. 
 PK Population: all subjects who received ≥ 1 dose of ALPN-101 and have ≥ 1 post-dose PK 
concentration reported. 
Other analysis populations may be defined in the SAP. 


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10.5. 
Planned Analyses 
10.5.1. 
Disposition of the Study Subjects 
The disposition of the randomized subjects will be described by treatment group of the number of 
subjects randomized, the number of subjects treated, the number of subjects in each analysis set, and the 
number of subjects permanently discontinued (from the study along with the primary reasons for 
discontinuation). 
10.5.2. 
Demographic and Baseline Characteristics 
Demographic and baseline disease characteristics will be summarized and compared by treatment group. 
Medical history will be summarized by the Medical Dictionary for Regulatory Activities (MedDRA) 
System Organ Class and Preferred Term, according to treatment group. Prior medications will be 
categorized using the Anatomical Therapeutic Chemical (ATC) codes in the World Health Organization 
Drug (WHODRUG) dictionary and summarized according to treatment group. 
10.5.3. 
Investigational Product and Concomitant Therapies 
Exposure to investigational product will be calculated for each subject and summarized. The total 
amount of investigational product given will be calculated for each subject and will be compared to the 
amount expected to be given for each subject. Treatment compliance will be calculated for each subject 
and summarized using descriptive statistics. 
Concomitant therapies will be classified according to the ATC codes in the WHODRUG dictionary. 
Corticosteroid usage will be standardized to equivalent prednisone doses. The incidence rate of each 
coded concomitant medication will be tabulated by treatment group. The table will be sorted by the 
incidence use of the entire sample. 
10.5.4. 
Efficacy Analyses 
In all cases, analyses defined in the SAP take precedence over descriptions in the Protocol. 
To address the secondary study objective of assessing evidence of efficacy, the efficacy endpoints of 
primary interest include the proportion of subjects achieving SRI-4 response at Day 169 and the 
proportion of subjects achieving BILAG-based Composite Lupus Assessment (BICLA) response at Day 
169. 
All efficacy measures will be summarized and analyzed for the mITT population. 
For categorical endpoints, the number and proportion of subjects in each at each visit will be presented 
by treatment group. Proportions will be compared using a Cochran-Mantel-Haenszel test adjusted for 
randomization stratification factors. An estimate of the difference in proportions and corresponding 95% 
confidence interval will be presented. P-values may be presented for the efficacy endpoints of primary 
interest. 
For continuous endpoints, the mean, standard deviation, median, minimum, and maximum at each visit. 
For continuous endpoints with multiple post-Baseline visits, the treatment effect will be assessed 
through Mixed-effect Model Repeated Measures (MMRM) based on observed data. 
10.5.5. 
Safety Analyses 
All safety data will be summarized descriptively by treatment group and analyzed based on the safety 
population. The safety endpoints include the incidence of treatment-emergent AEs, SAEs, AEIs, and the 
incidence of clinically significant abnormalities in laboratory analytes, ECG parameters, and vital signs. 


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All AEs will be coded using MedDRA and will be assessed for severity, relationship to investigational 
product, and seriousness. Incidence will be presented by System Organ Class and Preferred Term. The 
mean change from baseline in the continuous safety measures including vital signs and laboratory values 
will be summarized by treatment arm and visits. 
Continuous endpoints will be summarized using descriptive statistics, including number of subjects, 
mean, median, standard deviation, minimum and maximum. Categorical endpoints will be summarized 
using frequency distributions and corresponding percentages. 
10.5.6. 
Pharmacokinetic 
Analyses 
In all cases, analyses defined in the SAP take precedence over descriptions in the Protocol. 
Data from the PK population will be used in the analysis of PK endpoints. The PK data obtained in 
dense PK subset subjects will be analyzed using non-compartmental analysis (NCA). The PK 
parameters including Cmax, AUC, and trough concentration (Ctrough) will be determined based on the 
available data. Descriptive statistics (n, arithmetic mean, standard deviation, minimum, median, and 
maximum) will be calculated for the PK parameters. The PK data may be analyzed using a population 
approach via nonlinear mixed effect modeling. Estimated PK parameters and population PK parameters, 
if available, may be examined for relationship with patient factors such as age, weight, sex, disease 
characteristics, safety, efficacy, 
 
The incidence, timing, and titer of ADA to study drug will be summarized using descriptive statistics by 
treatment groups. Samples confirmed positive for ADA may be explored for neutralizing capacity. The 
possible effects of ADA on PK, efficacy and safety may be explored. 
10.6. 
Interim Analysis 
An administrative interim analysis may be performed when approximately 50% of subjects have 
completed assessments through Week 24. Details regarding interim analysis will be included in the SAP. 


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11. 
REGULATORY AND ADMINISTRATIVE REQUIREMENTS 
11.1. 
Trial Conduct 
The study will be conducted in accordance with the International Council for Harmonisation (ICH) 
Guidelines for Good Clinical Practice (GCP), the Declaration of Helsinki, and applicable local and 
federal regulations. No deviation from the protocol will be implemented without the prior approval from 
the study’s Sponsor, as well as review and approval from the IRB/IEC except where it may be necessary 
to eliminate an immediate hazard to a research subject. In such case, the deviation will be reported to the 
IRB/IEC as soon as possible in accordance with IRB/IEC policies. 
11.2. 
Informed Consent 
Patients meeting the criteria set forth in the protocol may be offered the opportunity to participate in this 
study. Candidate subjects will receive an explanation of the study, including the investigational status of 
ALPN-101, a summary of known or observed adverse reactions, alternative therapies available, and 
other factors which are part of obtaining appropriately informed consent. Subjects will be given the 
opportunity to ask questions of qualified personnel who are knowledgeable about the study and provided 
adequate time to consider whether to participate. 
Informed consent will be documented with an ICF that has been approved by the IRB/IEC. The ICF is to 
be signed and dated by the subject, by the person who conducts the consent process, and any additional 
signatures required by the IRB/IEC. 
Any changes to the ICF must be reviewed and approved by the IRB/IEC. The revised ICF must be used 
to re-consent any subject currently enrolled in the study who is affected by the change. 
If a subject’s partner becomes pregnant during the subject’s participation in the study, their partner will 
be asked to sign the pregnant partner ICF to allow the collection of safety data regarding the pregnancy 
and its outcome. The pregnant partner ICF should be obtained at the time the Investigator becomes 
aware of the pregnancy. 
11.3. 
Institutional Review Board/Independent Ethics Committee Approval 
The protocol, ICF, and all relevant supporting materials must be reviewed and approved by the IRB/IEC 
or equivalent. A copy of the IRB’s/IEC’s written approval must be provided to the study’s Sponsor or its 
representatives prior to commencement of subject enrollment. The IRB/IEC should be informed by the 
Investigator of the study’s progress and provide written documentation of periodic review and ongoing 
approval according to IRB/IEC policies. 
Any changes in the study protocol, revisions to the ICF, and all unanticipated problems involving risks 
to human subjects must be submitted promptly to the IRB/IEC in accordance with their policies. Written 
approval from the IRB/IEC must be obtained prior to implementation of any change(s), if applicable. 
11.4. 
Subject Privacy 
The Investigator, Contract Research Organization (CRO), and Alpine Immune Sciences shall comply 
with applicable local and federal privacy laws. The medical records of participating subjects are 
considered confidential and disclosure to third parties other than those noted below is prohibited. 
The medical records of participating study subjects and all data generated as a result of participation in 
this study are to be available for review upon request by the Alpine Immune Sciences or its 
representatives or partners, the IRB/IEC, and applicable regulatory authorities. The IRB/IEC-approved 


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ICF must clearly indicate that the subject’s medical records will be inspected by said parties, and 
permission for such review and use of personal information is a requirement for study participation. 
11.5. 
Investigator Responsibilities and Requirements 
By agreeing to participate in this clinical trial, the Principal Investigator and all sub-Investigators agree 
to perform the study in accordance with all stipulations of the protocol, ICH Guidelines for GCP, and 
local and federal regulations. 
The Principal Investigator must provide the CRO or Alpine Immune Sciences with the following 
documentation prior to initiation of the study at his/her clinical site: 
 Signed clinical study agreement 
 Signed Investigator Protocol Agreement 
 Signed FDA form 1572 or Statement of Investigator 
 Curriculum vitae of all Investigators 
 Current medical licenses for all Investigators 
 Copy of IRB/IEC approval for the study and informed consent form 
 IRB/IEC Membership List or Assurance Number/Letter as applicable 
11.6. 
Data Identification, Handling, and Record Keeping 
11.7. 
Source Documentation 
Adequate and accurate case histories, including all data and observations relevant to the clinical 
investigation, should be maintained for each subject screened or enrolled in the study. Such case 
histories include all medical records or original documents regarding the subject’s participation in the 
study, including medical history, progress notes, laboratory reports, imaging studies, ECG tracings, 
hospital records, and details regarding administration of investigational drug. 
11.7.1. 
Case Report Forms and Electronic Data Capture 
The Investigator will be provided with access to a secure, web-based system for capturing and reporting 
all study-related data (EDC). Such data will be entered into the EDC system by the Investigator or site 
personnel in a timely and accurate manner. The Investigator must review all submitted data and attest to 
its accuracy and consistency with the protocol. 
11.7.2. 
Essential Documents 
The Principal Investigator and clinical site personnel are responsible for maintaining a file of all 
essential documents required to demonstrate compliance with applicable regulatory authority 
requirements. Such documents include, but are not limited to: 
 Protocol with all amendments, signed Investigator Protocol Agreements, and ICFs 
 IB, including all updates 
 Copy of the signed FDA form 1572 or Statement of Investigator 
 CVs and medical licenses for the Principal Investigator and sub-Investigators 


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 IRB/IEC approval of the protocol and amendment(s), ICF(s), and any other study-related 
materials 
 IRB/IEC membership list or Assurance Letter/Number as applicable 
 Subject Screening and Enrollment Log, denoting the subjects’ names and assigned study 
subject identifier 
 IRB/IEC submissions of relevant safety information as required by IRB/IEC policies 
 Laboratory certifications and reference ranges 
 Significant correspondence from the CRO or Sponsor 
These files must be available for inspection by the CRO or Alpine Immune Sciences, their 
representatives, the IRB/IEC, or applicable regulatory authorities at any time. 
11.7.3. 
Record Retention 
The Investigator will retain all study records for a period of 2 years after marketing approval is received 
for ALPN-101, or for 2 years after all clinical and product development of ALPN-101 is discontinued. 
The Investigator must notify Alpine Immune Sciences prior to the destruction of any records relating to 
this study. 
11.8. 
Quality Control and Quality Assurance 
11.8.1. 
Site Training and Monitoring Procedures 
Prior to the initiation of the study, personnel from the Sponsor or its representatives will meet with the 
Investigator and clinical staff to review and discuss the protocol, all procedural and administrative 
requirements, the investigational drug, GCP guidelines, and monitoring requirements. During the course 
of the study, representatives from the Sponsor will provide additional study-specific training to site staff 
upon request by the Investigator, in response to a change in key clinical site staff, or if issues with study 
conduct or GCP compliance are observed. 
A representative from Alpine Immune Sciences will monitor adherence to the protocol and review 
study-related data. The frequency of monitoring visits depends on the rate of enrollment at the site, and 
the Investigator will permit the Sponsor's representatives to monitor the study as frequently as the 
Sponsor deems necessary to determine that protocol adherence and data entry are acceptable. The 
monitor will be permitted full access to subjects’ complete medical records. Other study records, such as 
essential regulatory documents, subject screening log, and study drug disposition logs will also be 
inspected. 
11.8.2. 
Deviation Reporting 
Important protocol deviations will be presented in a listing. 
11.8.3. 
Auditing Procedures 
Alpine Immune Sciences maintains the right to conduct audits at the clinical site. 
11.9. 
Publication Plan 
The publication policy is addressed separately from this clinical study protocol. 


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12. 
REFERENCES 
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2. 
Mohan C and Putterman C. Genetics and pathogenesis of systemic lupus erythematosus and lupus 
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Mok CC and Lau CS. Pathogenesis of systemic lupus erythematosus. J Clin Pathol. 
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Rees F, Doherty M, Grainge MJ, et al. The worldwide incidence and prevalence of systemic lupus 
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Zucchi D, Elefante E, Calabresi E, et al. One year in review 2019: systemic lupus erythematosus. 
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Almaani S, Meara A and Rovin BH. Update on Lupus Nephritis. Clin J Am Soc Nephrol. 
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APPENDIX 1 
GUIDANCE ON CHILDBEARING POTENTIAL AND HIGHLY 
EFFECTIVE METHODS OF CONTRACEPTION 
Contraceptive Guidance 
Investigators shall counsel WOCBP and fertile male participants who are sexually active with WOCBP 
on the importance of pregnancy prevention and the implications of an unexpected pregnancy. 
Investigators shall advise these participants on the use of highly effective methods of contraception for 
WOCBP and will check for adherence during study visits. 
Guidance for WOCBP Participants 
WOCBP must use a highly effective method of contraception consistently and correctly during the study 
and for at least 3 months after the last dose of investigational product. 
Highly effective methods of contraception have a failure rate of < 1% per year when used consistently 
and correctly. 
The following methods of contraception are considered highly effective: 
 Combined hormonal (estrogen + progestin) contraception (oral, intravaginal, transdermal) 
associated with inhibition of ovulation. 
 Progestogen- or progestin-only hormonal contraception (oral, injectable, implantable) 
associated with inhibition of ovulation. 
 Intrauterine device. 
 Intrauterine hormone-releasing system. 
 Bilateral tubal occlusion. 
 Vasectomized partner. 
 Sexual abstinence: defined as refraining from heterosexual intercourse during the entire 
period of risk associated with the study treatments (i.e., during the study and for at least 3 
months after the last dose of investigational product). The reliability of sexual abstinence 
needs to be evaluated in relation to the duration of the clinical study and the preferred and 
usual lifestyle of the participant. 
Guidance for Male Participants with WOCBP Partners 
Male participants with a pregnant or non-pregnant WOCBP partner must use a condom during the study 
and for at least 3 months after the last dose of investigational product. In addition, non-pregnant 
WOCBP partners of fertile male participants must use a highly effective method of contraception as 
defined above for WOCBP participants. 
Woman of Childbearing Potential 
A woman is considered a WOCBP, i.e., fertile, following menarche and until becoming postmenopausal 
unless permanently sterile. 
 Permanent sterilization methods include the following: hysterectomy, bilateral 
salpingectomy, and bilateral oophorectomy. 
 Postmenopausal is defined as no menses for 12 months without an alternative medical cause. 
A high follicle stimulating hormone level in the postmenopausal range will be used to 
confirm a postmenopausal state in women not using hormonal contraception or hormone 


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replacement therapy. However, in the absences of 12 months of amenorrhea, a single follicle 
stimulating hormone (FSH) measurement is insufficient. 
Fertile Man 
A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy. 


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APPENDIX 2 
CLINICAL LABORATORY ASSESSMENTS 
All per-protocol laboratory assessments will be performed by the central lab as scheduled in Table 1. At 
Screening, a local laboratory can be used with permission from the Sponsor. Screening laboratory 
assessments that are out-of-range may be repeated once. Investigators must document their review of 
each laboratory safety report. NOTE: the Investigator is responsible for performing urine 
pregnancy testing using the provided kits as noted in Table 1. 
 
Assessment 
Parameters 
 
Safety: Hematology 
Platelet count 
Red blood cell (RBC) count and indices: mean corpuscular volume (MCV), 
mean corpuscular hemoglobin (MCH), percent reticulocytes 
 
White blood cell (WBC) count with differential: neutrophils, lymphocytes, 
monocytes, eosinophils, basophils 
Absolute neutrophil count and lymphocyte count; CD4 and CD8 lymphocytes 
Hemoglobin 
Hematocrit 
Safety: Clinical 
Chemistry 
Electrolytes: sodium, potassium, chloride, bicarbonate 
Other cations: calcium, magnesium, phosphorus 
Amylase 
Lipase 
Glucose 
Creatine phosphokinase (CPK) 
Lactate dehydrogenase (LDH) 
Renal Function: creatinine, estimated glomerular filtration rate (eGFR) 
 
Liver Function Tests: alanine aminotransferase (ALT), albumin, alkaline 
phosphatase, aspartate aminotransferase (AST), total and direct bilirubin, total 
protein 
 
Safety: Coagulation 
Prothrombin time (PT) (i.e., international normalized ratio [INR]), activated partial 
thromboplastin time (aPTT), 
Safety: Urinalysis 
Specific gravity, pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, 
nitrite, leukocyte esterase; microscopic examination if blood or protein is 
abnormal; urine protein-creatinine ratio (UPCR) 
 
Infectious Disease 
Hepatitis B and C viruses, Human Immunodeficiency Virus (HIV), tuberculosis 
(TB), and SARS-CoV-2 
 
Other Tests 
Thyroid stimulating hormone 
Follicle-stimulating hormone (FSH) and estradiol (female subjects only, if 
needed to confirm menopausal status [see Appendix 1]) 
Clinical Biomarkers 
of SLE 
Screening only: anti-nuclear antibodies (ANA), anti-Smith antibodies, anti- 
Sjögren’s syndrome type A (SSA) antibodies, anti-Sjögren’s syndrome type B 
(SSB) antibodies, anti-ribonucleoprotein (RNP) antibodies, Scl 70 
(topoisomerase 1) antibodies, anti-centromere antibodies, anti-cardiolipin 
antibodies (IgG and IgM), lupus anticoagulant (LAC), anti-beta-2-glycoprotein 
I antibodies 
 
 


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Assessment 
Parameters 
 
All applicable visits: high-sensitivity C-reactive protein (hsCRP); complement 
(C3, C4, CH50); quantitative IgM, IgG, IgA, IgE; anti-double-stranded DNA 
(dsDNA) antibodies 
 


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APPENDIX 3 
LIST OF ABBREVIATIONS 
 
Abbreviation or 
Term 
Definition/Explanation 
ACR 
American College of Rheumatology 
ADA 
Anti-drug antibodies 
AE 
Adverse event 
AEI 
Adverse event of interest 
ALT (SGPT) 
Alanine aminotransferase (serum glutamic pyruvic transaminase) 
ANA 
Anti-nuclear antibodies 
AST (SGOT) 
Aspartate aminotransferase (serum glutamic oxaloacetic transaminase) 
ATC 
Anatomical therapeutic chemical 
AUC 
Area under the concentration-time curve 
BILAG 
British Isles Lupus Assessment Group index 
C3 
Complement component 3 
C4 
Complement component 4 
CD 
Cluster of differentiation 
CDC 
Centers for Disease Control 
CH50 
Total complement 
CLASI 
Cutaneous Lupus Erythematosus Disease Area and Severity Index 
Cmax 
Maximum concentration 
COVID-19 
Coronavirus Disease of 2019 
CRO 
Contract Research Organization 
CTCAE 
 Common Terminology Criteria for Adverse Events 
DMC 
Data Monitoring Committee 
dsDNA 
Double-stranded DNA 
ECG 
Electrocardiogram 
EDC 
Electronic data capture 
EoS 
End of Study 
EoT 
End of Treatment 
EULAR 
European League Against Rheumatism 
FACIT-F 
Functional Assessment of Chronic Illness Therapy-Fatigue 
FDA 
Food and Drug Administration 
FIH 
First-in-human 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
GVHD 
Graft-versus-host disease 
HBcAb 
Hepatitis B core antibody 
HBsAb 
Hepatitis B surface antibody 
HBsAg 
Hepatitis B surface antigen 
HCV 
Hepatitis C virus 


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Abbreviation or 
Term 
Definition/Explanation 
HIV 
Human Immunodeficiency Virus 
IB 
Investigator's Brochure 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
ICOS 
Inducible T cell co-stimulator 
ICOS-L 
Inducible T cell co-stimulator ligand 
IEC 
Independent Ethics Committee 
Ig 
Immunoglobulin 
IL 
Interleukin 
IRB 
Institutional Review Board 
IRR 
Infusion-related reaction 
IV 
Intravenous 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
Modified Intent-to-Treat 
NCI CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse Events 
NOAEL 
No-observed-adverse-effect level 
NSAID 
Nonsteroidal anti-inflammatory drug 
pH 
Hydrogen ion concentration 
PK 
Pharmacokinetics 
PPD 
Purified protein derivative 
PhGA 
Physician’s Global Assessment of SLE Disease Activity 
PtGA 
Patient’s Global Assessment of Disease Activity 
Q2W 
Once every 2 weeks 
QTcF 
QT interval corrected for heart rate using Fridericia’s correction formula 
RNA 
Ribonucleic acid 
RT-PCR 
Reverse transcription polymerase chain reaction 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SARS-CoV-2 
Severe Acute Respiratory Syndrome Coronavirus 2 
SC 
Subcutaneous 
SDI 
SLICC/ACR Damage Index 
SF-36 
Short Form-36 
SLE 
Systemic lupus erythematosus 
SLEDAI-2K 
Systemic Lupus Erythematosus Disease Activity Index 2000 
SLEDAI-2K 30 
Systemic Lupus Erythematosus Disease Activity Index 2000 30-Day 
SLICC/ACR 
Systemic Lupus International Collaborating Clinics/American College of Rheumatology 
SOC 
Standard of care 


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Abbreviation or 
Term 
Definition/Explanation 
SRI 
SLE Responder Index 
TB 
Tuberculosis 
ULN 
Upper limit of normal 
UPCR 
Urine protein-creatinine ratio 
WHODRUG 
World Health Organization Drug 
WOCBP 
Woman of Childbearing Potential 

SAP_001.pdf: 
Confidential 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
Protocol Number 
AIS-A03 
Protocol Title: 
A Randomized, Double-Blind, Placebo-Controlled Study of 
ALPN-101 In Systemic Lupus Erythematosus 
Product: 
ALPN-101 (acazicolcept) 
Indication: 
Systemic Lupus Erythematosus 
Development Phase: 
2 
Version: 
2.0 (Final) 
Date: 
26 SEP 2024 


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Protocol No. AIS-A03 
Statistical Analysis Plan 
Version: 2.0 (26 SEP 2024) 
 
 


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TABLE OF CONTENTS 
1. 
INTRODUCTION AND BACKGROUND ............................................................... 9 
2. 
STUDY OBJECTIVES ........................................................................................... 10 
2.1. 
Primary Study Objective ......................................................................................... 10 
2.2. 
Secondary Study Objectives .................................................................................... 10 
 
 
3. 
STUDY ENDPOINTS ............................................................................................ 11 
3.1. 
Efficacy Endpoints .................................................................................................. 11 
3.1.1. 
Primary Efficacy Endpoints .................................................................................... 11 
3.1.2. 
Secondary Efficacy Endpoints ................................................................................. 11 
 
 
3.2. 
Safety Endpoints ..................................................................................................... 13 
3.3. 
Biomarker and 
................................................. 14 
3.4. 
Pharmacokinetic Endpoints ..................................................................................... 14 
3.5. 
Immunogenicity Endpoints ..................................................................................... 15 
4. 
STUDY DESIGN ................................................................................................... 16 
4.1. 
General Description ................................................................................................ 16 
4.2. 
Determination of Sample Size ................................................................................. 17 
4.3. 
Methods of Assigning Subjects to Treatment........................................................... 17 
5. 
ANALYSIS POPULATIONS AND SUBGROUPS ................................................ 19 
5.1. 
Analysis Populations ............................................................................................... 19 
5.2. 
Subgroups of Interest .............................................................................................. 19 
6. 
ANALYTIC DEFINITIONS ................................................................................... 21 
6.1. 
Baseline and Change from Baseline ........................................................................ 21 
6.2. 
Treatment Exposure Duration ................................................................................. 21 
6.3. 
Overall Treatment Compliance ................................................................................ 21 
6.4. 
Treatment-Emergent Adverse Events ...................................................................... 21 
6.5. 
Systemic Lupus Erythematosus Responder Index .................................................... 21 
6.6. 
British Isles Lupus Assessment Group-based Composite Lupus Assessment ........... 22 
6.7. 
Time-to-First Response ........................................................................................... 22 
6.8. 
Systemic Lupus Erythematosus Flare ...................................................................... 22 
6.9. 
Time-to-First Systemic Lupus Erythematosus Flare ................................................ 23 


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6.10. 
Annualized Flare Rate ............................................................................................. 23 
6.11. 
BILAG-2004 System Organ-Specific Response ...................................................... 23 
6.12. 
Initial Clinical Response ......................................................................................... 23 
6.13. 
SLEDAI-2K Low Disease Activity ......................................................................... 24 
6.14. 
Lupus Low Disease Activity State ........................................................................... 24 
6.15. 
SLEDAI-2K Total Score ......................................................................................... 24 
6.16. 
SLEDAI-2K System Organ-Specific Response ....................................................... 24 
6.17. 
Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity 
Score ...................................................................................................................... 24 
6.18. 
50% Improvement in CLASI Activity Score ........................................................... 25 
6.19. 
Cutaneous Lupus Erythematosus Disease Area and Severity Index Damage 
Score ...................................................................................................................... 25 
6.20. 
SLICC/ACR Damage Index Global Score ............................................................... 25 
6.21. 
Restricted/Rescue Medications ................................................................................ 25 
7. 
STATISTICAL METHODS AND ANALYSIS ...................................................... 27 
7.1. 
Subject Accountability and Disposition ................................................................... 27 
7.2. 
Demographics and Baseline Characteristics and Medications .................................. 27 
7.3. 
Treatment Exposure and Compliance ...................................................................... 28 
7.4. 
Analysis of Efficacy Endpoints ............................................................................... 29 
7.4.1. 
General Considerations ........................................................................................... 29 
7.4.2. 
Handling of Missing Data and Intercurrent Events (IE) ........................................... 29 
7.5. 
Analysis of Primary Efficacy Endpoints .................................................................. 29 
7.5.1. 
Main Analysis ......................................................................................................... 29 
7.5.2. 
Sensitivity Analyses ................................................................................................ 30 
7.5.2.1. 
Robustness of Missing Data Imputation Method ..................................................... 30 
7.6. 
Analysis of Secondary and 
...................................... 30 
7.6.1. 
Analysis of Categorical Endpoints........................................................................... 30 
7.6.2. 
Analysis of Continuous Endpoints........................................................................... 31 
7.6.3. 
Analysis of Time-to-Event Endpoints ...................................................................... 31 
7.7. 
Estimands for the Primary and Secondary Endpoints ............................................... 31 
7.8. 
Analysis of Safety Endpoints .................................................................................. 33 
7.8.1. 
Treatment-Emergent Adverse Events ...................................................................... 33 
7.8.2. 
Laboratory Tests ..................................................................................................... 34 


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7.8.3. 
Vital Signs .............................................................................................................. 35 
7.8.4. 
Electrocardiogram ................................................................................................... 36 
7.8.5. 
Physical Examinations ............................................................................................ 36 
7.9. 
Analysis of Biomarkers and 
............................ 36 
7.10. 
Analysis of Pharmacokinetic Endpoints .................................................................. 36 
7.11. 
Analysis of Immunogenicity Endpoints ................................................................... 37 
8. 
CHANGES IN ANALYSIS FROM PROTOCOL ................................................... 38 
9. 
INTERIM ANALYSIS ........................................................................................... 39 
10. 
DATA REVIEW COMMITTEE ............................................................................. 40 
11. 
MULTIPLICITY ADJUSTMENT .......................................................................... 41 
12. 
VISIT WINDOWS.................................................................................................. 42 
13. 
DATA HANDLING ............................................................................................... 44 
14. 
REFERENCES ....................................................................................................... 47 
15. 
APPENDICES ........................................................................................................ 48 
15.1. 
Study Overview ...................................................................................................... 48 
15.2. 
Schedule of Assessments......................................................................................... 49 
15.3. 
Disease Assessment Tools ....................................................................................... 51 
15.3.1. 
SLEDAI-2K ............................................................................................................ 51 
15.3.2. 
BILAG 2004 ........................................................................................................... 53 
15.3.3. 
CLASI .................................................................................................................... 59 
15.3.4. 
SLICC/ACR Damage Index .................................................................................... 60 
15.3.5. 
FACIT – Fatigue ..................................................................................................... 62 
15.3.7. 
SF-36 ...................................................................................................................... 64 
15.4. 
Randomization Algorithm ....................................................................................... 65 
15.5. 
Laboratory Assessments .......................................................................................... 66 
15.6. 
Prednisone-Equivalent Conversion Table ................................................................ 68 
LIST OF TABLES 
Table 1: Estimated Power Based on N=65 Subjects per Treatment ............................................ 17 
Table 2: 
Estimand Attributes Corresponding to the Primary and Secondary Efficacy 
Endpoints ................................................................................................................ 32 
Table 3: 
Visit Windows for Data Collected at All Visits ....................................................... 42 


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Table 4: 
Visit Windows for Efficacy Date Collected in a Subset of All Visits ....................... 43 
Table 5: 
Visit Windows for ECG Data .................................................................................. 43 
Table 6: 
Dummy Coding for Multiple Imputation Modeling ................................................. 44 
Table 7: 
Imputation of Partial and Missing Date Values ........................................................ 46 
Table 8: 
Schedule of Procedures and Assessments ................................................................ 49 
Table 9: 
SLEDAI Weighted Score by Item ........................................................................... 51 
Table 10: BILAG Organ System Grades ................................................................................... 53 
Table 11: BILAG Grading Algorithms...................................................................................... 54 
Table 12: SLICC/ACR Organ Systems and Items ..................................................................... 60 
Table 13: FACIT – Fatigue Item Scoring .................................................................................. 62 
Table 14: Clinical Laboratory Assessments............................................................................... 66 
Table 15: Prednisone-Equivalent Conversion ............................................................................ 68 
 
LIST OF FIGURES 
Figure 1: 
Study Overview ...................................................................................................... 48 


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LIST OF ABBREVIATIONS 
 
ADA 
Anti-drug antibodies 
AE 
Adverse event 
AEI 
Adverse event of interest 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
AUC 
Area under concentration-time curve 
BICLA 
British Isles Lupus Assessment Group-based Composite Lupus Assessment 
BILAG 
British Isles Lupus Assessment Group 
BLOQ 
Below limit of quantitation 
BMI 
Body Mass Index 
CI 
Confidence interval 
CL 
Clearance 
CLASI 
Cutaneous Lupus Erythematosus Disease Area and Severity Index 
Cmax 
Maximum concentration 
CMH 
Cochran-Mantel-Haenszel 
CTCAE 
Common Terminology Criteria for Adverse Events 
Ctrough 
Trough concentration 
CV 
Coefficient of variation 
DMC 
Data monitoring committee 
dsDNA 
Double stranded DNA 
ECG 
Electrocardiogram 
EOS 
End of study 
EOT 
End of treatment 
FACIT-F 
Functional Assessment of Chronic Illness Therapy-Fatigue 
FDA 
US Food and Drug Administration 
ICH 
International Counsel for Harmonisation of Technical Requirements for Pharmaceuticals 
for Human Use 
ICOS-L 
Inducible T cell co-stimulator ligand 
IE 
Intercurrent event 
Ig 
Immunoglobulin 
Lambda z 
Terminal elimination rate constant 
LDA 
Low Disease Activity by SLEDAI-2k 
LLDAS 
Lupus Low Disease Activity State 


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LOCF 
Last observation carried forward 
LS 
Least squares 
max 
Maximum 
MedDRA 
Medical Dictionary for Regulatory Activities 
min 
Minimum 
mITT 
Modified Intent-to-Treat 
MMRM 
Mixed effects models for repeated measures 
NAb 
Neutralizing antibody 
 
PhGA 
Physician’s global assessment of disease activity 
PK 
Pharmacokinetics 
PT 
Preferred term 
PtGA 
Patient’s global assessment of disease activity 
Q2W 
Every other week 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SD 
Standard deviation 
SDI 
SLICC/ACR Damage Index 
SF-36 
Short Form Health Survey-36 
SLE 
Systemic lupus erythematosus 
SLEDAI-2K 
SLE Disease Activity Index 2000 
SLICC/ACR 
Systemic Lupus International Collaborating Clinics/American College of Rheumatology 
SOC 
System organ class 
SRI 
SLE Responder Index 
t1/2 
Elimination half-life 
TEAE 
Treatment-emergent adverse event 
Tmax 
Time to maximum concentration 
ULN 
Upper limit of normal 
Vd 
Volume of distribution 


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1. 
INTRODUCTION AND BACKGROUND 
The purpose of this Statistical Analysis Plan (SAP) is to describe the procedures and the 
statistical methods that will be used to analyze and report efficacy and safety results for Protocol 
AIS-A03, version 4.0 dated 7 November 2022, a randomized, double-blind, placebo-controlled 
study of ALPN-101 (acazicolcept) in systemic lupus erythematosus (SLE). 
The structure and content of this plan provides sufficient detail to meet the requirements 
identified by the Food and Drug Administration (FDA) and International Conference on 
Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use 
(ICH): Guidance on Statistical Principles in Clinical Trials. 
This plan is a supplement to the study protocol, which contains additional details on study 
design, study conduct, and other operational aspects of the study. 


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2. 
STUDY OBJECTIVES 
2.1. 
Primary Study Objective 
The primary objective of the study is to evaluate the safety and tolerability of ALPN-101 
compared to placebo in subjects with chronic, moderate to severe active SLE. 
2.2. 
Secondary Study Objectives 
The secondary objectives of this study are: 
 Evaluate the efficacy of ALPN-101 in subjects with active SLE 
 Assess PK of ALPN-101 in subjects with active SLE 
 Assess the incidence of anti-drug antibodies (ADA) against ALPN-101 in subjects with 
active SLE 


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3. 
STUDY ENDPOINTS 
3.1. 
Efficacy Endpoints 
Definitions for efficacy endpoints are provided in Section 6. 
3.1.1. 
Primary Efficacy Endpoints 
There are two primary efficacy endpoints being investigated for this study: 
 Achievement of SLE responder index (SRI)-4 at Day 169, or
 Achievement of British Isles Lupus Assessment Group-based Composite Lupus 
Assessment (BICLA) response at Day 169
3.1.2. 
Secondary Efficacy Endpoints 
Secondary efficacy endpoints are provided below: 
 Annualized flare rate by British Isles Lupus Assessment Group (BILAG)-2004 flare 
index through Day 169 – all flares
 Time-to-first flare by BILAG-2004 flare index
 Achievement of Lupus Low Disease Activity State (LLDAS) at Day 169
 Change from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 
(SLEDAI-2K) total score at Day 169
 Cumulative prednisone-equivalent dose use (total area under the curve of daily 
prednisone-equivalent dose) through Day 169
 Achievement of ≥50% reduction in Cutaneous Lupus Erythematosus Disease Area 
and Severity Index (CLASI) activity score at Day 169 in the subgroup of subjects 
with baseline CLASI activity score ≥8


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3.2. 
Safety Endpoints 
The primary study objective of assessing safety and tolerability of ALPN-101 will be evaluated 
using the endpoints listed in below: 
 Treatment-emergent adverse events (TEAEs), treatment-emergent adverse events of 
interest (AEIs; infusion-related reactions, oral mucocutaneous lesions, infections 
grade ≥3), and serious adverse events (SAEs) 
 Abnormal laboratory test results and observed and change/shift from baseline in over 
time for: 
 Chemistry 
 Hematology 
 Coagulation 
 Urinalysis 
 Abnormal vital signs results and observed and change/shift from baseline over time 
for: 
 Systolic and diastolic blood pressures (mmHg) 
 Heart rate (bpm) 
 Respiratory rate (bpm) 
 Body temperature (°C) 
 Weight (kg) 
 Abnormal electrocardiogram (ECG) parameters and observed and change/shift from 
baseline over time for: 
 Heart rate (bpm) 
 QT interval (msec) 


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 PR interval (msec) 
 QRS duration (msec) 
 RR interval (msec) 
 QTcB interval (msec) 
 QTcF interval (msec) 
3.3. 
Biomarker 
Key biomarker endpoints are specified below. Biomarker variables will also be analyzed over 
time, as applicable: 
 Observed and change/percent change from baseline by visit for clinical biomarkers of 
SLE: 
 C-reactive protein 
 Complements - C3, C4, CH50 
 Immunoglobulins (Igs) – IgM, IgG, IgA, IgE 
 Anti-double stranded DNA (dsDNA) antibodies 
 Proportion of subjects who converted from abnormal laboratory test values at 
baseline to normal laboratory test results at Day 169 in: 
 C-reactive protein 
 Complements - C3, C4, CH50 
 Immunoglobulins – IgM, IgG, IgA, IgE 
 Anti-dsDNA antibodies 
3.4. 
Pharmacokinetic Endpoints 
To examine the pharmacokinetics (PK) of ALPN-101 in subjects with active SLE the following 
variables will be analyzed: 
 ALPN-101 concentrations for each timepoint 
 Main PK parameters: 
 Area under the concentration-time curve (AUC)
 Maximum concentration (Cmax)
 Trough concentration (Ctrough)


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 Elimination half-life (t1/2)
 Additional PK parameters: 
 Time to maximum concentration (Tmax)
 Clearance (CL)
 Volume of distribution (Vd)
 Terminal elimination rate constant (Lambda z)
 Accumulation ratios
3.5. 
Immunogenicity Endpoints 
The following variables will be used to assess the immunogenicity of ALPN-101 over time: 
 Incidence of ADA positive 
 Minimum and maximum titer values 
 Incidence of neutralizing antibodies (NAb) positive 


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4. 
STUDY DESIGN 
4.1. 
General Description 
This is a Phase 2, multicenter, multinational, randomized, double-blind, placebo-controlled, 
parallel-group study to evaluate the safety, tolerability, efficacy, immunogenicity, PK 
 of 
ALPN-101 compared to placebo in adult subjects with chronic, moderate to severe active SLE. 
At least 130 subjects will be randomized in a 1:1 ratio to receive a weight-based dose of 3 mg/kg 
ALPN-101 administered by intravenous infusion via an infusion pump or matching placebo every 
other week (Q2W) for a total of 12 doses. An overview of the study design is provided in 
Appendix 15.1. 
Randomization will be stratified based by SLE treatment at baseline and geographic region 
(Appendix 15.5). Subjects will be followed for 4 weeks after the End of Treatment (EOT) visit, 6 
weeks after the last dose of study drug. Assessments of adverse events (AEs) and disease 
activity, and collection of blood and urine for safety laboratory values, biomarkers of disease 
activity, PK, ADA, and 
, will be performed throughout the study. The Schedule 
of Assessments is provided in Appendix 15.2. 
Each subject will participate for up to 34 weeks, including: 
 Screening Period: Up to 42 days prior to first dose date. All subjects must complete 
all screening assessments and make them available to the team for verification of 
disease activity. Subjects who appear to meet eligibility criteria must undergo central 
review and verification of SLE disease activity prior to randomization. 
 Treatment Period: Up to 24 weeks from first dose date. Subjects will receive 12 doses 
of study treatments Q2W. Safety, biologic activity, PK, ADA, 
will be conducted according to the Schedule of Assessments (Appendix 15.2). 
 Follow-up Period: 4 weeks after EOT. 
Dense PK will be collected in subjects who agree to participate. Additional PK samples will be 
collected from these subjects 4 hours following administration of the first dose of study drug, and 
on days 1, 3 and 7 following the first study drug administration. 
Medications that are used for treatment of SLE at baseline should be maintained at stable doses 
through the Day 169 assessments, except for incidences of toxicity or for a protocol-defined 
short-term increase (burst and taper) of corticosteroid dose in response to increased disease 
activity or reduction in corticosteroids (taper) to reduce toxicity in the context of improvement in 
disease activity. 
Subjects who prematurely discontinue treatment with study drug should have all procedures 
outlined in the EOT visit and an unscheduled ECG performed as soon as possible, and not later 
than the next scheduled visit. To minimize missing data for efficacy and safety assessments, 
subjects who prematurely discontinue treatment, and who do not withdraw from the study, 
should otherwise continue their regular study visit schedule without receiving study drug. In 
subjects who are unable to continue their regularly scheduled visits, a follow-up phone call 
should occur approximately 8 weeks (corresponding to 5X half-life) after the last dose of study 
drug to determine the status of any ongoing AEs/ SAEs or the occurrence of any new AEs/SAEs. 


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Subjects who withdraw from the study prematurely (i.e., prior to Day 197), the End of Study 
(EOS) evaluations should be completed, if possible, preferably within 2 weeks of study drug 
discontinuation. In addition, a follow-up phone call should occur approximately 8 weeks 
(corresponding to 5x half-life) after the last dose of study drug to determine the status of any 
ongoing AEs/SAEs or the occurrence of any new AEs/SAEs. 
It should be noted that while N=130 subjects were expected to be randomized in this study, 
enrollment was stopped at N=76 subjects. 
4.2. 
Determination of Sample Size 
The primary purpose of this Phase 2 study is to assess the safety of ALPN-101 in subjects with 
moderate to severe SLE. As such, the anticipated sample size of 130 subjects randomized 1:1 to 
receive ALPN-101 or placebo was not derived to support formal hypothesis testing of efficacy 
endpoints. 
Table 1 provides the estimated power to detect a range of potential differences in proportions. 
For these calculations, a sample size of 65 subjects per treatment group, a two-sided chi-square 
test statistic and a significance level (alpha) of 0.05 were used. Placebo response rates of 40% for 
SRI-4 and 20% for BICLA and effect sizes ranging from 15% to 35% were assumed. 
No adjustments for multiplicity are planned for this early phase study. 
Table 1: Estimated Power Based on N=65 Subjects per Treatment 
 
SRI-4 
BICLA 
Response Rate 
Estimated 
Power* 
Response Rate 
Estimated 
Power* 
Placebo 
ALPN-101 
Placebo 
ALPN-101 
40% 
55% 
40% 
20% 
35% 
48% 
40% 
60% 
63% 
20% 
40% 
71% 
40% 
65% 
82% 
20% 
45% 
87% 
40% 
70% 
94% 
20% 
50% 
96% 
40% 
75% 
99% 
20% 
55% 
99% 
*Assuming a 2-sided significance level of 0.05 using SAS version 9.4 
 
 
4.3. 
Methods of Assigning Subjects to Treatment 
A centralized interactive web-based response system will be used to randomly assign subjects to 
receive either ALPN-101 or placebo in a 1:1 ratio. Randomization will be stratified by 
geographic region and by use of concomitant oral immunosuppressive therapy at enrollment. 
Levels of each stratification factor, which result in 6 unique strata, are defined as follows: 
1. Background immunosuppressive therapy use: 
 Present: Concomitant use of at least one of the permitted immunosuppressants (e.g., 
methotrexate, leflunomide, azathioprine, 6-mercaptopurine, mycophenolate mofetil, 
mycophenolic acid) and/or corticosteroids at doses >5 mg prednisone or equivalent 
daily with or without hydroxychloroquine/hydroxychloroquine-like drugs; 


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 Absent: No use of permitted immunosuppressants and/or corticosteroids at doses >5 
mg prednisone or equivalent daily, with or without use of lower doses of 
corticosteroids and/or hydroxychloroquine/hydroxychloroquine-like drugs. 
2. Geographic region: 
 Region 1: North America or Western Europe 
 Region 2: Eastern Europe 
 Region 3: Asia 
Subjects, investigators, site staff, and individuals with direct contact with site staff (e.g., clinical 
research associates, project management, medical monitors, and data management) will remain 
blinded to treatment assignment until after final database lock. Select study team members may 
be unblinded to treatment assignment. A list of all individuals unblinded to treatment assignment 
prior to final database lock will be maintained. 


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5. 
ANALYSIS POPULATIONS AND SUBGROUPS 
5.1. 
Analysis Populations 
The following analysis populations will be used for the analysis of study data. 
 All Randomized Population: The randomized population will include all subjects 
who are assigned to study treatment, regardless of whether study treatment is 
received. The randomized population will be analyzed according to the treatment 
group into which they were randomized, regardless of the actual treatment received. 
 Modified Intent-to-Treat Population: The modified intent-to-treat (mITT) 
population includes all randomized subjects who received any amount of study drug 
and completed at least one post-baseline disease assessment. mITT subjects will be 
analyzed according to the treatment group into which they were randomized, 
regardless of the actual treatment received. Unless otherwise specified, this 
population will be used for the analysis of efficacy endpoints. 
 Safety Population: The safety population includes all subjects who received any 
amount of study drug. The safety population will be analyzed by treatment actually 
received. Unless otherwise is specified, this population will be used for the analysis 
of safety endpoints. 
 Pharmacokinetics Population: The PK population includes all subjects who 
received at least one dose of ALPN-101 and have at least one post-dose PK 
concentration reported. Unless otherwise is specified, this population will be used for 
the analysis of PK endpoints. 
 Anti-Drug Antibodies Population: The ADA population includes all subjects who 
received at least one dose of study drug and have at least one post-baseline ADA 
value. 
5.2. 
Subgroups of Interest 
Analyses of subgroups of subjects may be used to better understand the biological activity of 
ALPN-101 in subjects with SLE. Subgroup analyses will be performed on a case-by-case basis 
as post-hoc analyses. Possible subgroups of interest, depending on available data, and may 
include, but are not limited to: 
 Geographic region 
 Age group: <50 years, ≥50 years 
 Race 
 Baseline SLEDAI-2K: <10, ≥10 
 Baseline corticosteroid use: >7.5 mg/day, ≤7.5 mg/day 
 Sex at birth: Male, Female 


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 Body Mass Index (BMI): <30 kg/m2, ≥30 kg/m2 


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6. 
ANALYTIC DEFINITIONS 
6.1. 
Baseline and Change from Baseline 
Baseline values are the last values recorded prior to the first administration of study drug, unless 
otherwise specified. 
Change from baseline values for a subject are derived as the subject’s post-baseline value minus 
the subject’s baseline value of the same variable. 
Percent change from baseline is calculated by dividing the change from baseline value by the 
baseline value as follows: 
Percent change from baseline = ((post-baseline value – baseline value) / baseline value) x 100 
6.2. 
Treatment Exposure Duration 
Duration of treatment exposure is calculated as the number of days between the date of a 
subject’s last dose of study drug and the date of the first dose of study drug. Intervals of dosing 
interruption between a subject’s first and last doses will not be deducted from the overall 
treatment duration. That is: 
Date of last dose of study drug – date of first dose of study drug + 1 
6.3. 
Overall Treatment Compliance 
Overall treatment compliance (%) with protocol-specified treatment for a subject will be 
calculated as: 
100 x (number of doses received)/(weeks of study participation prior to the end of treatment/2) 
6.4. 
Treatment-Emergent Adverse Events 
TEAEs are defined as AEs that start or worsen in severity on or after the administration of the 
first dose of study drug through the end of study participation or at least 8 weeks after last study 
drug administration for subjects who discontinue treatment early. 
6.5. 
Systemic Lupus Erythematosus Responder Index 
SRI is a binary composite score defined by meeting all the following criteria: 
 Reduction from baseline in SLEDAI-2K total score ≥x, where x=4 points for SRI-4, 5 
points for SRI-5, 6 points for SRI-6, 7 points for SRI-7 and 8 points for SRI-8 
 No new BILAG-2004 disease activity A scores (severe disease) and no more than 1 
new activity score B (moderate disease) 
 No worsening from baseline in subjects’ lupus disease activity. Worsening is defined 
by an increase ≥10% (i.e., increase of ≥0.30 on a 3-point scale) in PhGA 


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6.6. 
British Isles Lupus Assessment Group-based Composite Lupus 
Assessment 
BICLA response is a binary composite score defined by meeting all the following criteria: 
 Reduction in all baseline BILAG-2004 A to B, C or D and baseline BILAG-2004 B to 
C or D, and no BILAG-2004 worsening in other organ systems, as defined by ≥1 new 
BILAG-2004 A or ≥2 new BILAG-2004 B 
 No worsening from baseline in SLEDAI-2K. Worsening is defined as an increase 
from baseline of >0 points in SLEDAI-2K total score 
 No worsening from baseline in subjects’ lupus disease activity. Worsening is defined 
by an increase ≥10% in PhGA (i.e., increase of ≥0.30 on a 3-point scale) 
Subjects with no BILAG-2004 A or B scores at baseline and no worsening in any organ systems 
(defined by ≥1 new BILAG-2004 A or ≥2 new BILAG-2004 B), as well as subjects with a 
baseline PhGA score >2.7 on a 3-point scale will be considered as having met the criteria defined 
above for BILAG and PhGA, respectively. 
6.7. 
Time-to-First Response 
Time-to-first response of a specified efficacy endpoint, such as SRI-4 or BICLA, is defined as 
the number of days from the administration of the first dose of study drug to the date of the visit 
during which the first response of the specified endpoint is recorded. Time-to-first response is 
calculated as: 
Date of first response – Date of first dose of study drug + 1 
Subjects who do not achieve a response will be censored at their EOT date. 
6.8. 
Systemic Lupus Erythematosus Flare 
Three definitions will be used to examine the occurrence of SLE flares during the study. 
BILAG Flare Index: BILAG-2004 responses will be used to identify SLE flares according to the 
following severity levels [Gordon, 2003]. 
 Mild BILAG Flare: One new BILAG-2004 B grade in an organ system with grade C, 
D or E at the previous visit, or 3 or more new BILAG-2004 C grades in organ 
systems with grade D or E at the previous visit 
 Moderate BILAG Flare: Two or more new BILAG-2004 B item in organ systems 
with grades of C, D or E at the previous visit 
 Severe BILAG Flare: One or more new BILAG-2004 A item compared to the 
previous visit 


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6.9. 
Time-to-First Systemic Lupus Erythematosus Flare 
Time-to-first SLE flare is defined as the number of days from the administration of first dose to 
the first occurrence of flare. That is: 
Date of first occurrence of SLE flare – date of first dose of study drug + 1 
Subjects who do not experience any SLE flares will be censored at their EOT date. 
Time-to-first SLE flare will be summarized for each definition of SLE flare. 
6.10. 
Annualized Flare Rate 
The annualized flare rate for each subject is defined as the number of flares observed during the 
treatment period divided by the flare exposure time in days multiplied by 365.25. Flare exposure 
time of a subject is defined as the difference in days between the last BILAG-2004 assessment 
date and the date of first dose + 1. For subjects who do not experience any flares for each of the 
SLE flare definitions, then the number of flares for that subject will be set to zero for each 
definition. 
Annualized flare rate will be calculated for each definition of SLE flare. 
6.11. 
BILAG-2004 System Organ-Specific Response 
For each system organ with A or B scores at baseline, treatment response is achieved if all of the 
following criteria are satisfied: 
 Reduction from A at baseline to B, C or D or reduction from B at baseline to C or D 
 No early discontinuation of study drug 
 No use of restricted medications beyond the protocol-allowed threshold before 
assessment (see Section 6.21) 
Response will not be calculated for system organ with no baseline score of A or B. 


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6.14. 
Lupus Low Disease Activity State 
Lupus Low Disease Activity State [Franklyn, 2016] is binary state achieved if all the following 
criteria are satisfied: 
 SLEDAI-2K total score ≤4, with no activity in major organ systems (renal, central 
nervous system, cardiopulmonary, vasculitis, fever) and no hemolytic anemia or 
gastrointestinal activity 
 No new features of lupus disease activity compared with the previous assessment, 
 PhGA ≤1 on a 3-point scale 
 Current prednisolone-equivalent dosage ≤7.5 mg/day 
 Well-tolerated standard maintenance dosages of immunosuppressive drugs and 
approved biologics 
6.15. 
SLEDAI-2K Total Score 
Total score is defined as the sum of the weighted scores of each individual item within each 
organ system class. 
6.17. 
Cutaneous Lupus Erythematosus Disease Area and Severity Index 
Activity Score 
The CLASI activity score is calculated by adding the numeric values of the responses to items in 
the erythema, scale/hypertrophy categories, the mucous membrane involvement question, 
questions about acute hair loss and non-scarring alopecia. The scores for affected body parts are 
weighted equally regardless of surface area and number of lesions present. More severe 
manifestation within an area is scored higher then less severe manifestation. 


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6.18. 
50% Improvement in CLASI Activity Score 
A 50% reduction in CLASI activity score compared to baseline defined by meeting all of the 
following criteria: 
 Achieve ≥50% reduction from baseline in CLASI activity score at Day 169 
6.21. 
Restricted/Rescue Medications 
During the Treatment Period, subjects treated with new concomitant medications or increased 
dose of the existing treatment will be considered non-responders (treatment failures) for 
assessments of SRI-X, BICLA, SLEDAI-2K Improvement, and 50% Improvement in CLASI 
activity score efficacy endpoints for visits after taking the restricted medication. Criteria for 
restricted/rescue medications include the following: 
 Oral corticosteroids (prednisone, methylprednisolone, prednisolone, fludrocortisone 
acetate) can be taken during the study per the protocol criteria however the following 
would qualify the subject as a treatment failure: 
 Increase in dose from baseline of oral corticosteroids (burst) from Day 1 through 
Day 141 lasting more than 14 days (i.e., subject must taper back down to baseline 
dose level by Day 14 of the increase; for subjects not previously taking oral 
corticosteroids, taper must be down to 0 mg/day within 14 days); such a course 
also cannot be initiated more frequently than every 28 days 
 Dose greater than 40 mg prednisone/day (or equivalent) 
 Initiation of new oral corticosteroids or an increase in dose after Day 141 
 Intramuscular corticosteroids can be taken during the study however, the following 
would qualify the subject as a treatment failure: 
 Intramuscular methylprednisolone dose greater than 160 mg administered at a 
single timepoint from Day 1 through Day 169 
 Intramuscular corticosteroids given at a frequency greater than 28 days 
 Initiation of new intramuscular corticosteroids or an increase in dose after Day 
141 


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 Topical corticosteroids can be taken during the study however, the following would 
qualify the subject as a treatment failure 
 Increase in dose from baseline of topical corticosteroids (burst) from Day 1 
through Day 141 lasting more than 14 days (i.e., subject must taper back down to 
baseline dose level by Day 14 of the increase; for subjects not previously taking 
topical corticosteroids, taper must be down to 0 mg/day within 14 days); such a 
course also cannot be initiated more frequently than every 28 days 
 Initiation of new topical corticosteroids or an increase in dose after Day 141 
 Intravenous corticosteroids 
 Increase in dose or addition of hydroxychloroquine or hydroxychloroquine-like drugs 
(hydroxychloroquine, hydroxychloroquine sulfate, chloroquine phosphate) 
 Any new medication started during the study for SLE. The following exceptions are 
allowable: 
 Corticosteroid burst as specified above 
 Medication may be reduced or temporarily discontinued for safety reasons and 
then started again. This would not be considered a new medication 
 Other restricted medications taken any time during the study: 
 Biologics (e.g., abatacept, anifrolumab, atacicept, belatacept, belimumab, 
obinutuzumab, ocrelizumab, rituximab, telitacicept) 
 Investigational agents 


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7. 
STATISTICAL METHODS AND ANALYSIS 
Summaries of study data will be presented by treatment group (ALPN-101 or placebo) and for 
all subjects combined, as applicable. 
Summaries of continuous data will present the number of non-missing observations (n), mean, 
standard deviation (SD), median, minimum (min), and maximum (max). Min and max values 
will be reported using the same number of decimal places as the raw data values; mean and 
medians will be reported to one more decimal place than the raw data values; and SD will be 
reported to two more decimal places than the respective raw data. If the raw data have three 
decimal places or more, three decimal places will be presented for all statistics. 
For categorical data, the frequency in each category and the percentage of the relevant 
population will be presented. In general, percentages will be presented to one decimal place. 
Percentages equal to 100 will be presented as 100% and percentages equal to 0 will be presented 
as 0%. 
Analyses will be conducted using SAS®, version 9.4 or higher. 
7.1. 
Subject Accountability and Disposition 
Subject disposition will be summarized by treatment group and for all subjects combined. The 
summary of subject disposition will include the numbers of subjects screened and randomized, 
the number of randomized subjects in each randomization stratification category, the number of 
subjects treated, and the numbers of subjects in each analysis population. The number and 
percentage of subjects in the randomized population who completed study treatment and who 
discontinued study treatment prematurely will be summarized with the primary reasons for 
treatment discontinuation. Similarly, the number percentage of subjects in the randomized 
population who completed the study and who permanently discontinued from study participation 
prematurely will be summarized with the primary reasons for study discontinuation. 
A summary of the number and percentage of subjects screened, randomized, and completing 
study participation will be presented by geographic region and country within geographic region. 
A listing of disposition for all randomized subjects including date of the subject’s completion or 
discontinuation and reasons for treatment or study discontinuation will be presented. A separate 
listing of analysis populations and randomization stratification will also be provided. 
Protocol deviations will be tracked throughout the study. Deviations may be related to 
inclusion/exclusion criteria, trial conduct, subject management or subject assessment. Prior to 
database lock all deviations will be reviewed and designated as important or not important. A 
summary of the number and percentage of subjects in the randomized population with important 
protocol deviations reported will be presented by treatment group and type of deviation. A by- 
subject listing of important protocol deviations will be provided. 
7.2. 
Demographics and Baseline Characteristics and Medications 
Descriptive summaries of demographics and baseline characteristics will be presented by 
treatment group for all randomized subjects. No formal statistical comparisons between the 
treatment arms will be performed. A by-subject listing of demographic and key baseline data will 
be provided. 


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History of significant non-SLE conditions and current medical conditions reported at screening 
and/or baseline will be summarized by Medical Dictionary for Regulatory Activities (MedDRA) 
system organ class (SOC) and preferred term (PT). The number and percentage of subjects in 
each treatment group of the safety population who reported each SOC and PT will be reported. 
The number and percentage of unique subjects in the safety population who report use of prior 
and concomitant medications will be summarized separately by treatment group and for all 
subjects combined. Prior medications are medications with start and end dates prior to the date of 
the first dose of study drug. A medication that was started prior to the first dose of study drug 
and continued after first dose of study or that has a first dose date after the first dose of study 
drug will be summarized as a concomitant medication. An additional table summarizing all 
concomitant medications which are initiated on or after the date of the first administration of 
study drug will be provided. Concomitant medications for treatment of SLE, including 
concomitant corticosteroids, will be summarized separately. A single subject will be counted 
once, regardless of the number of times a specific medication was used. 
Oral corticosteroid use during the study will be summarized for the mITT population using the 
following variables: 
 Incidence of subjects oral corticosteroid use 
 Incidence of subjects with changes in oral corticosteroid use 
 Total exposure to oral corticosteroid use (area under the oral corticosteroid exposure 
curve while on study treatment) using prednisone-equivalent doses as described in 
Appendix 15.6 
 Duration (days) of oral corticosteroid use while on study treatment 
Rescue medications will be summarized for the mITT population for each treatment group and 
for all subjects combined. 
A listing of all reported medications will be presented that includes the verbatim medication 
name reported, the Anatomical Therapeutic Chemical (ATC) coded terms, dosage, and 
frequency. Additionally, a listing of restricted medications taken during the study will be 
presented. 
7.3. 
Treatment Exposure and Compliance 
The extent of exposure to study drug will be summarized for the safety population by treatment 
group. Exposure duration in days will be calculated as defined in Section 6.2. Descriptive 
summaries of exposure days and the number and percentage of subjects in each exposure 
duration category, defined as ≥4 weeks, ≥12 weeks and ≥24 weeks will be presented. 
To assess compliance with protocol-specified administration of study treatment, subjects in the 
safety population who missed a study drug infusion at any scheduled dosing visit prior to 
treatment completion or discontinuation or who do not receive the targeted amount of study drug 
are considered non-compliant. The number and percentage of non-compliant subjects will be 
summarized by treatment group and visit. 
Overall compliance will be summarized descriptively. A by-subject listing of study drug 
administration will be provided. 


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7.4. 
Analysis of Efficacy Endpoints 
7.4.1. 
General Considerations 
Unless otherwise stated, all efficacy analyses will be conducted on the mITT population 
according to the randomized treatment. For efficacy endpoints, point estimates of treatment 
differences and 95% confidence intervals (CI) will be provided. Two-sided p-values will also be 
provided for efficacy endpoints, as applicable. Where possible, study outcomes will be presented 
graphically also. Due to small sample sizes of subjects randomized to the Asia geographic 
region, this region will be pooled with the Eastern Europe region in the statistical analysis 
models. 
7.4.2. 
Handling of Missing Data and Intercurrent Events (IE) 
Intercurrent events in this study include the following: 
 IE1: Premature discontinuation of study treatment
 IE2: Restricted/rescue medication use (criteria for restricted/rescue medication use is 
provided in Section 6.21)
The strategies to be used in the handling of intercurrent events and missing data for efficacy 
endpoints, when applicable, are provided below: 
 Binary endpoints (primary and secondary efficacy endpoints):
 IE1 and IE2: subject is considered a non-responder (composite strategy) 
 Missing data for Day 169: subject is considered a non-responder 
 Continuous endpoints measured through time (SLEDAI-2K total score):
 IE1 and IE2: data after IE1 and IE2 occurs will not be included in the analysis 
(hypothetical strategy) 
 Missing data caused by applying the intercurrent event handling described above 
and other missing data will be handled by the mixed effects models for repeated 
measures (MMRM) analysis 
 Other efficacy endpoints:
 Treatment policy strategy will be applied and all observed data during the 
treatment period will be used regardless of IE1 or IE2 
 Missing data for Day 169 for binary endpoints: subject is considered a non- 
responder for applicable endpoints 
7.5. 
Analysis of Primary Efficacy Endpoints 
7.5.1. 
Main Analysis 
Response rates for subjects in the ALPN-101 group and in the placebo group will be calculated 
and the corresponding 95% CI will be reported for each treatment group. These response 
endpoints will be analyzed through Day 169 for subjects who complete treatment and through 


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the last assessment recorded ≤28 days after treatment discontinuation date for subjects who 
discontinue treatment early. 
For the main analyses of SRI-4 response rate and BICLA response rate, non-responder 
imputation will be used for IE and missing data as described in Section 7.4.2. 
Response rates will be compared using Cochran-Mantel-Haenszel (CMH) test statistic stratified 
by the factors used at randomization. Estimated treatment effect will be reported as the 
difference between the response rate in the ALPN-101 treatment group and the response rate in 
the placebo group. Corresponding 95% CI for the difference in proportions and the two-sided p- 
value for the difference will be reported. 
7.6. 
Analysis of Secondary 
Efficacy Endpoints 
Unless otherwise stated, the mITT population will be the basis for analyses of all efficacy 
endpoints. These data will be analyzed through Week 24 (Day 169) for subjects who complete 
treatment and through the last assessment recorded ≤28 days after treatment discontinuation for 
subjects who discontinue treatment early. 
7.6.1. 
Analysis of Categorical Endpoints 
Analyses of other categorical efficacy endpoints will be conducted using the stratified CMH 
approach described for the efficacy endpoints of primary interest. Response will be summarized 
for each treatment group by visit as the proportion of subjects in the category of interest at the 
specified visit, and across the 24-week treatment period as the proportion of subjects in the 


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category of interest at any time during treatment. The difference in proportions between the 
ALPN-101 treatment group and the placebo group and the associated 95% CI for this difference 
will be reported. 
7.6.2. 
Analysis of Continuous Endpoints 
MMRM will be used for the analysis of continuous longitudinal data. Terms in the model will 
include treatment group, baseline value of the analysis variable, stratification factors 
(concomitant oral immunosuppressive therapy use at enrollment and geographic region), analysis 
visit, and the interactions of treatment-by-visit and baseline value-by-visit as fixed effects. An 
unstructured covariance matrix will be used to model within-subject error. If the model fails to 
converge with an unstructured covariance matrix, a heterogeneous compound symmetric 
structure will be used. Kenward-Roger degrees of freedom, Type III sums of squares, and least 
squares (LS) mean values will be reported for each treatment group and for the difference 
between treatments. Standard errors and 95% CI for the estimated mean difference at each visit 
will be presented. Plots of LS mean values and 95% CIs by visit with separate lines for each 
treatment group will be provided for continuous secondary efficacy endpoints. 
Annualized flare rates and cumulative prednisone-equivalent dose use will be analyzed using an 
analysis of variance model. Terms in the model include treatment group and stratification factors 
(concomitant oral immunosuppressive therapy use at enrollment and geographic region). Type 
III sums of squares, and least squares (LS) mean values will be reported for each treatment group 
and for the difference between treatments. Standard errors and 95% CI for the estimated mean 
difference will be presented. 
7.6.3. 
Analysis of Time-to-Event Endpoints 
Time-to-event analyses, such as time-to-first SLE flare and time-to-first BICLA response, will be 
analyzed using a Cox proportional hazards models adjusted for stratification factors 
(concomitant oral immunosuppressive therapy use at enrollment and geographic region). 
Subjects who do not experience the specified event will be censored on the date at which the last 
non-missing response data were collected. For example, in the time-to-first SLE flare, subjects 
who do not experience flares will be censored on the date of the last available BILAG value. In 
the analysis of time to first BICLA response, subjects who do not achieve a positive BICLA 
response will be censored on the date of their last non-missing BICLA response value. Estimated 
hazard ratios and corresponding 95% CI will be reported. If estimable, median, 25th and 75th 
percentiles of the time to specified event and corresponding 95% CI will be reported. Time to 
event secondary efficacy endpoints will be displayed in Kaplan-Meier curves. 
7.7. 
Estimands for the Primary and Secondary Endpoints 
Estimand definitions for the primary and secondary efficacy endpoints are provided below: 


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Table 2: 
Estimand Attributes Corresponding to the Primary and Secondary Efficacy 
Endpoints 
 
Attributes of the Estimand 
Estimand 
Treatment 
Endpoint 
Population 
Handling of 
Intercurrent 
Events 
Statistical 
Summary 
Primary 
ALPN-101 
vs. Placebo 
Achievement of 
SRI-4 response at 
Day 169 
Subjects with 
moderate to 
severe SLE 
IE1 and IE2: subject 
is considered a non- 
responder 
(composite strategy) 
Missing data: 
subject is 
considered a non- 
responder 
Difference in 
the proportion 
of subjects 
achieving SRI- 
4 response 
Primary 
ALPN-101 
vs. Placebo 
Achievement of 
BICLA response 
at Day 169 
Subjects with 
moderate to 
severe SLE 
IE1 and IE2: subject 
is considered a non- 
responder 
(composite strategy) 
Missing data: 
subject is 
considered a non- 
responder 
Difference in 
the proportion 
of subjects 
achieving 
BICLA 
response 
Secondary 
ALPN-101 
vs. Placebo 
Annualized flare 
rate by BILAG- 
2004 flare index 
through Day 169 
for all flares 
Subjects with 
moderate to 
severe SLE 
All observed data 
used (treatment 
policy strategy) 
Difference in 
the LS means 
for annualized 
flare rate by 
BILAG-2004 
flare index for 
all flares 
Secondary 
ALPN-101 
vs. Placebo 
Time-to-first 
flare by BILAG- 
2004 flare index 
Subjects with 
moderate to 
severe SLE 
All observed data 
used (treatment 
policy strategy) 
Hazard ratio 
for time-to- 
first flare by 
BILAG-2004 
flare index 
Secondary 
ALPN-101 
vs. Placebo 
Achievement of 
LLDAS response 
at Day 169 
Subjects with 
moderate to 
severe SLE 
IE1 and IE2: subject 
is considered a non- 
responder 
(composite strategy) 
Missing data: 
subject is 
considered a non- 
responder 
Difference in 
the proportion 
of subjects 
achieving 
LLDAS 
response 


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Attributes of the Estimand 
Estimand 
Treatment 
Endpoint 
Population 
Handling of 
Intercurrent 
Events 
Statistical 
Summary 
Secondary 
ALPN-101 
vs. Placebo 
Change from 
baseline in 
SLEDAI-2K total 
score at Day 169 
Subjects with 
moderate to 
severe SLE 
All observed data 
used (hypothetical 
strategy) 
Difference in 
the LS means 
for change 
from baseline 
in SLEDAI- 
2K total score 
Secondary 
ALPN-101 
vs. Placebo 
Cumulative 
prednisone- 
equivalent dose 
use through Day 
169 
Subjects with 
moderate to 
severe SLE 
All observed data 
used (treatment 
policy strategy) 
Difference in 
the LS means 
for cumulative 
prednisone- 
equivalent 
dose use 
Secondary 
ALPN-101 
vs. Placebo 
Achievement of 
≥50% reduction 
in CLASI activity 
score at Day 169 
in the subgroup 
of subjects with 
baseline CLASI 
activity score ≥8 
Subjects with 
moderate to 
severe SLE 
IE1 and IE2: subject 
is considered a non- 
responder 
(composite strategy) 
Missing data: 
subject is 
considered a non- 
responder 
Difference in 
the proportion 
of subjects 
achieving 
≥50% 
reduction in 
CLASI 
activity score 
7.8. 
Analysis of Safety Endpoints 
The primary study objective of assessing safety and tolerability of ALPN-101 in subjects with 
active SLE will be assessed using TEAEs, AEIs, SAEs, physical exam findings, vital signs, ECG 
measurements, and laboratory tests. All safety data will be descriptively summarized by 
treatment group. No formal inference is planned. Analyses will be based on subjects in the safety 
population. Individual subjects will only be counted once when calculating the incidence of AEs. 
7.8.1. 
Treatment-Emergent Adverse Events 
AEs will be recorded at all scheduled and unscheduled visits during the study. Summaries will be 
presented for TEAEs. In this study, signs and symptoms of SLE activity are captured in the 
disease activity assessments and will not be reported as AEs. Clinically significant changes in 
physical exam findings, laboratory test results, and ECG results will be recorded and analyzed as 
AEs. The incidence, seriousness, and severity of TEAEs and the relationship of the events to 
study drug will be used to assess safety. 
All AEs terms will be classified using MedDRA and reported based on system organ classes and 
preferred terms. Adverse event severity will be graded using Common Terminology Criteria for 
Adverse Events (CTCAE), version 5.0. AEIs will be reviewed by the medical monitor lead. 
In general, the incidence of AEs will be summarized by the number and the percentage of unique 
subjects in the safety population who experiencing an event. As such, subjects who report the 


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same event on multiple occasions will only be counted once. A by-subject listing of all AEs 
reported will be provided. Rules for the imputation of missing and partial AE dates and missing 
designations of AE severity, relatedness and seriousness are defined in Section 13. 
7.8.2. 
Laboratory Tests 
Safety laboratory tests collected in this study include hematology, serum chemistry, coagulation 
and urinalysis as specified Appendix 15.5. Numeric laboratory results that are reported using 
non-numeric qualifiers, such as less than (<) a certain value or greater than (>) a certain value, 
will be analyzed using the numeric portion of laboratory values minus one or plus one, 
respectively. 
Descriptive summaries of continuous laboratory values and changes in these values from 
baseline will include the number of non-missing observations, mean, SD, median, min and max 
value at each scheduled visit, at the last on-treatment visit and at the end of study visit. Data will 
be summarized in standardized units. 
The severity of laboratory result abnormalities will be graded using the CTCAE grading scale. 
Laboratory values that are within the limits of normal and are not graded as 1-4 will be 
summarized as a normal result with grade equal to 0. Treatment-emergent abnormal laboratory 
values are defined as those reported normal (i.e., grade=0) at baseline and abnormal (grade 1-4) 
after starting study medication. The numbers and percentages of subjects reporting a max (worst) 
treatment-emergent post-baseline grade observed through the end of the study will be 
summarized for each laboratory parameter. Percentages will be based on the number of subjects 
in the safety population with at least one post-baseline value of the respective laboratory 
parameter. 
To examine hepatic laboratory parameters, additional summaries of alanine aminotransferase 
(ALT), aspartate aminotransferase (AST), total bilirubin and alkaline phosphatase (ALP) will be 
presented. The number and percentage of subjects in the safety population who meet the 
following criteria at any time during treatment or follow-up will be summarized: 
 Peak ALT value falling within ranges of central laboratory upper limit of normal 
(ULN) of: 
 >3x ULN and ≤5x ULN 
 >5x ULN and ≤10x ULN 
 >10x ULN and ≤20x ULN 
 >20x ULN 
 Peak AST value falling within ranges of central laboratory ULN of: 
 >3x ULN and ≤5x ULN 
 >5x ULN and ≤10x ULN 
 >10x ULN and ≤20x ULN 
 >20x ULN 
 Peak total bilirubin within ranges of central laboratory ULN of: 


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 <ULN 
 ≥ULN and <2x ULN 
 ≥2x ULN 
 Peak ALP of >1.5 x ULN 
 Simultaneous ALT or AST >3x ULN and total bilirubin >1.5x ULN 
 Simultaneous ALT or AST >3x ULN and total bilirubin >2x ULN 
For qualitative laboratory values such as urinalysis data, shift tables comparing baseline results 
(for example, negative, trace, positive) to the worst post-baseline results will be presented. 
Listings of laboratory results for each subject will be presented by type of laboratory test and 
parameter. Values outside of the corresponding reference range will be flagged in the listings. 
Laboratory values assessed as part of screening (i.e., infectious disease assessments and 
screening biomarker values) and pregnancy test results will be presented in by-subject listings 
but will not be summarized. 
7.8.3. 
Vital Signs 
Vital signs data will be summarized descriptively for the safety population by study visit and by 
measurement time, if applicable. Reported values and changes from baseline in weight, BMI, 
temperature, systolic and diastolic blood pressure, heart rate, and respiratory rate will be 
summarized. The number and percentage of subjects with markedly abnormal vital signs, as 
defined below, will be summarized. Abnormalities of interest include: 
 American Heart Association categories for hypertension: 
 Elevated: systolic blood pressure of ≥120 to ≤129 mmHg with diastolic blood 
pressure <80 mmHg 
 Stage 1 Hypertension: systolic blood pressure of ≥130 to ≤139 mmHg or diastolic 
blood pressure of ≥80 to ≤89 mmHg 
 Stage 2 Hypertension: systolic blood pressure of ≥140 mmHg or diastolic blood 
pressure of ≥90 mmHg 
 Hypertensive Crisis: systolic blood pressure of >180 mmHg and/or diastolic 
blood pressure of >120 mmHg 
 Heart rate (beats per minute, bpm): 
 Abnormally low: a decrease from baseline of ≥15 to a value ≤50 bpm 
 Abnormally high: an increase from baseline of ≥15 to a value ≥120 bpm 
 Temperature (°C): 
 Abnormally high: value ≥38.3°C and ≥0.8°C increase from baseline. 
 Respiratory rate (bpm): 
 Abnormally low: <12 breaths/min 


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 Abnormally high: >25 breaths/min 
All vital signs including the reported values for each parameters and overall interpretations will 
be listed by subject. 
7.8.4. 
Electrocardiogram 
ECG measurements and change from baseline in ECG measurements, including heart rate (bpm), 
QT interval (msec), PR interval (msec), QRS interval (msec), RR interval (msec), QTcB interval 
(msec), and QTcF interval (msec), will be summarized descriptively in the safety population. 
To identify potential clinically significant QTcF results, the numbers and percentages of subjects 
in the safety population who experience confirmed post-baseline absolute QTcF values >450 
msec, >480 msec, and >500 msec will be summarized, as will the numbers and percentages of 
subjects who experience confirmed increases from baseline in QTcF ≥30 msec and ≥60 msec. In 
addition, a shift table comparing the baseline overall ECG interpretations, based on investigator 
interpretation, of normal, abnormal – not clinically significant, and abnormal – clinically 
significant to the investigator interpretation at each post-baseline visit will be presented. 
A listing of ECG measurements and investigator-reported ECG interpretations will be presented. 
7.8.5. 
Physical Examinations 
Complete physical examinations will be performed at intervals designated in the scheduled of 
assessments (Appendix 15.2) and will include examination of head, eyes, ears, nose and throat, 
lungs, abdomen, joints, muscle and soft tissues, neurologic system, skin, and lymph nodes. 
Clinically relevant findings identified during a physical examination will be reported and 
summarized as AEs. 
7.9. 
Analysis of Biomarkers 
Descriptive summaries of the absolute, change from baseline, and percent change from baseline 
 
. Additionally, the incidence of subjects with shifts from abnormal 
baseline values to normal values at EOT in clinical biomarkers will be presented for each 
treatment group. 
7.10. 
Analysis of Pharmacokinetic Endpoints 
ALPN-101 concentration data will be summarized by visit for the PK population. Mean 
concentration data will also be presented graphically. In summaries of concentration data, 
concentrations that are reported below the lower limit of quantitation (BLOQ) will be treated as 
missing. 
The PK data obtained in dense PK subset subjects will be analyzed using non-compartmental 
analysis. The PK parameters including Cmax, AUC, t1/2, and Ctrough will be determined based on 
the available data. Descriptive statistics (n, arithmetic mean, standard deviation, % coefficient of 
variation (CV), min, median, max, geometric mean, and geometric %CV) will be calculated for 
the PK parameters. For individual PK parameter estimation, BLOQ will be treated as missing if 


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the value occurs after Tmax. Investigational population PK modeling and exposure-response 
analysis is outside the scope of this SAP. 
7.11. 
Analysis of Immunogenicity Endpoints 
The incidence of ADA positive to study drug will be summarized by visit and overall for each 
treatment group for the ADA population. The min and max of the ADA titer value will also be 
presented. For subjects who are ADA positive, the incidence of NAb positive will be 
summarized by visit and overall for each treatment group. 


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8. 
CHANGES IN ANALYSIS FROM PROTOCOL 
Analyses described in this plan are consistent with the protocol-specified analyses. Changes 
made to the planned analyses described in this SAP will be documented in an SAP amendment 
or described in the Clinical Study Report. 


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9. 
INTERIM ANALYSIS 
An administrative interim analysis may be performed when approximately 50% of subjects have 
completed assessments through Week 24 (Day 169). 


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10. 
DATA REVIEW COMMITTEE 
Cumulative safety data will be reviewed by a Data Monitoring Committee (DMC), which will 
provide recommendations regarding study conduct, if indicated. Roles and responsibilities of the 
DMC are defined in the DMC charter. The specifications for the presentation of study data in the 
DMC report is defined in a separate analysis plan. 


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11. 
MULTIPLICITY ADJUSTMENT 
No adjustments for multiplicity will be applied in the analyses of data from this first clinical 
study of APN-101 in subjects with active SLE. 


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12. 
VISIT WINDOWS 
All scheduled study visits and corresponding time windows for data analysis are listed in 
Table 3. Similarly, scheduled study visits and analysis windows for data collected at a subset of 
study visits are presented in Table 4 and Table 5. Visit windows for data collection are calculated 
from date of first dose of study drug (Day 1). Unscheduled visits occurring within a defined 
analysis window will be included in an analysis of specified endpoints. Analysis visit windows 
are defined to capture data collected at all scheduled and unscheduled visits on or after the first 
day of the analysis visit window until the day prior to the start of the next window in visit-based 
analyses. 
For analyses of clinical data based on specific visits, if multiple values are recorded within a 
single analysis window, the following rules will be applied for analysis, unless otherwise 
specified for the analysis. 
 If two or more values are recorded within the same analysis window, the non-missing 
value collected closest to the scheduled visit will be used in the analysis. 
 If two values are collected on dates equidistant from the scheduled visit, the non- 
missing observation with the earlier collection date will be used in the analysis. 
 If more than one value is collected on the same day, the non-missing value with the 
earlier collection time will be used in the analysis. 
Unless otherwise noted, PK data will be summarized using nominal visit labels. 
Table 3: 
Visit Windows for Data Collected at All Visits 
 
Visit Number 
Visit 
Label 
Study 
Day 
Protocol Defined Visit 
Window 
Analysis Defined Window 
From 
To 
From 
To 
1 
Baseline 
1 
1 
1 
≤1 
2 
Day 15 
15 
14 
16 
2 
≤21 
3 
Day 29 
29 
27 
31 
22 
≤36 
4 
Day 43 
43 
41 
45 
37 
≤49 
5 
Day 57 
57 
54 
60 
50 
≤64 
6 
Day 71 
71 
68 
74 
65 
≤78 
7 
Day 85 
85 
82 
88 
79 
≤92 
8 
Day 99 
99 
96 
102 
93 
≤106 
9 
Day 113 
113 
110 
116 
107 
≤120 
10 
Day 127 
127 
124 
130 
121 
≤134 
11 
Day 141 
141 
138 
144 
135 
≤148 
12 
Day 155 
155 
152 
158 
149 
≤162 
13 
Day 169/EOT 
169 
166 
172 
163 
≤183 
EOS 
Day 197/EOS 
197 
194 
200 
184 
EOS visit 
date 
Notes:  EOS=End of study; EOT=End of treatment. 


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Table 4: 
Visit Windows for Efficacy Date Collected in a Subset of All Visits 
 
Visit Number 
Visit 
Label 
Study 
Day 
Protocol Defined Visit 
Window 
Analysis Defined Window 
From 
To 
From 
To 
1 
Baseline 
1 
1 
1 
≤1 
2 
Day 15 
15 
14 
16 
2 
≤21 
31 
Day 29 
29 
27 
31 
22 
≤43 
32 
Day 29 
29 
27 
31 
2 
≤43 
5 
Day 57 
57 
54 
60 
44 
≤71 
7 
Day 85 
85 
82 
88 
72 
≤99 
9 
Day 113 
113 
110 
116 
100 
≤128 
11 
Day 141 
141 
138 
144 
129 
≤159 
13 
Day 169/EOT 
169 
166 
172 
160 
≤183 
EOS 
Day 197/EOS 
197 
194 
200 
184 
EOS visit 
date 
1 Indicates Day 29 visit window definition applicable to efficacy assessments scheduled for Day 15 
2 Indicates Day 29 visit window definition applicable to efficacy assessments NOT scheduled for Day 15 
Notes: EOS=End of study; EOT=End of treatment. 
 
There will be no windowing for the SDI endpoint as this endpoint is only collected at Day 1, end 
of treatment, and end of study. 
Table 5: 
Visit Windows for ECG Data 
 
Visit 
Number 
Visit 
Label 
Study 
Day 
Protocol Defined Visit 
Window 
Analysis Defined Window 
From 
To 
From 
To 
1 
Baseline 
1 
1 
1 
≤1 
7 
Day 85 
85 
82 
88 
2 
≤120 
12 
Day 155 
155 
152 
158 
121 
≤176 
EOS 
Day 197/EOS 
197 
194 
200 
177 
EOS visit 
date 


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13. 
DATA HANDLING 
Data handling rules for specific missing efficacy and safety data and missing and partial dates is 
provided below. 
Missing Lab Data for BILAG Renal and Hematological Organ System Scoring: 
In the event there is missing lab data for the renal or hematological BILAG organ systems at a 
particular visit, the preceding visits lab data will be used in the derivation of the renal and 
hematological BILAG grading. If the preceding visits lab data is also missing, then the lab data 
will be missing and a BILAG grade for that organ system will not be derived. 
Missing BILAG D or E Grades After a Missed Visit: 
Due to constraints within the electronic clinical outcome assessment vendor system, BILAG 
grades of D and E cannot be scored after a subject has a missed visit. Organ system grades for 
these non-missing visit cases will be derived by carrying forward the previous non-missing D or 
E grade for these organ systems. This does not apply to grades of A, B, or C. 
Table 6: 
Dummy Coding for Multiple Imputation Modeling 
 
Region 
Strata2d 
Strata3d 
North America/Western Europe 
0 
0 
Eastern Europe 
1 
0 
Asia 
0 
1 


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Region 
Strata2d 
Strata3d 
North America/Western Europe is the reference region 
 
 Step 2: A CMH test will be conducted for each imputed dataset on the Day 169 
endpoint. The Wilson-Hilferty transformation will be applied to the CMH general 
association test statistic to create a normally distributed statistic with a mean=0 and 
standard deviation=1. Generic SAS code is provided below: 
proc freq data=d_log; 
tables strata1n*strata2n*treatment*resp_D169 / CMH; 
ods output CMH=cmh; 
by Imputation; 
run; 
Where strata1n and strata2n are the stratification factors for concomitant oral 
immunosuppressive therapy use at enrollment and geographic region from the 
Interactive Response Technology system for randomization. 
data cmh_wh; set cmh (where=(AltHypothesis=”General Association”)); 
cmh_value_wh=((VALUE/DF)**(1/3) – (1-2/(9*DF)))/SQRT(2/(9*DF)); 
cmh_sterr_wh = 1.0; 
run; 
 
 Step 3: Combine the transformed values from the 100 imputed datasets using PROC 
MIANALYZE. The combined p-value for the CMH test will be obtained as the upper- 
tailed p-value from the test produced by PROC MIANALYZE. 
proc mianalyze data=cmh_wh; 
ods output parameterestimates = est1; 
modeleffects cmh_value_wh; 
stderr cmh_sterr_wh; 
run; 
 
data fin_cmh; set est1; 
if tValue > 0 then Probt_upper = Probt/2; 
else Probt_upper = 1-probt/2; 
run; 
Missing Safety Information: 
For analyses of AE data, events with missing severity grade will be imputed as Grade 3 for 
analysis. Similarly, AEs with missing relationship to study drug will be imputed as drug-related. 
If no designation of event seriousness is available, the AE will be considered serious. 
Missing and Partial Dates: 
Algorithms applied for imputing partial and missing date values are described below: 


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Table 7: 
Imputation of Partial and Missing Date Values 
 
Partial/Missing Start or 
Stop Date 
Imputed Start Date 
Imputed Stop Date 
Missing year, month, and 
day 
Date of randomization visit 
Missing month and day, and 
the year is present 
Date of randomization visit if the 
year is the same as the year 
of randomization date, else January 1 
of the start year. 
December 31 of that year 
Missing day, but year and 
month are present 
Date of randomization visit if the 
year and month are the same as the 
year and month of randomization 
date, else the 1st of the start month. 
Last day of that month 
Missing month, but year and 
day are present 
Assume day is also missing and 
impute as above 
Missing month imputed as 
December 


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14. 
REFERENCES 
Dixon JS. Second-line Agents in the Treatment of Rheumatic Diseases. Informa Health Care, 
1991. 
FACIT-Fatigue Subscale Scoring Guidelines, Version 4. 2003. URL: https://www.FACIT.org 
Franklyn K, Lau CS, Navarra SV, Louthrenoo W, et al. Definition of initial validation of Lupus 
Low Disease Activity State (LLDAS). 2016; 75: 1615-21. URL: 
http://dx.doi.org/10.1136/annrheumdis-2015-207726. 
Gladman D, Ginzler E, Goldsmith C, Fortin P, Liang M, Sanchez-Guerrero J, et al. The 
development and initial validation of the systemic lupus international collaborating 
clinics/American college of rheumatology damage index for systemic lupus erythematosus. 
Arthritis & Rheumatism. 1996 Mar;39(3):363–9 
Gladman DD, Ibañez D, Urowitz MB. Systemic lupus erythematosus disease activity index 
2000. The Journal of Rheumatology. 2002 Feb 1;29(2):288–91. 
URL: https://pubmed.ncbi.nlm.nih.gov/11838846/ 
Gordon C, Sutliffe N, Skan J, Stoll T, Isenberg DA. Definition and treatment of lupus flares 
measured by the BILAG index. Rheumatology. 2003; 42(11): 1372–9. 
URL: https://doi.org/10.1093/rheumatology/keg382. 
Klein R, Moghadam-Kia S, LoMonico J, Okawa J, Coley C, Taylor L, et al. Development of the 
CLASI as a Tool to Measure Disease Severity and Responsiveness to Therapy in Cutaneous 
Lupus Erythematosus. Archives of Dermatology [Internet]. 2011 Feb 1;147(2):203–8. 
URL: https://jamanetwork.com/journals/jamadermatology/fullarticle/426652?resultClick=1 
Meikle AW and Tyler FH. Potency and duration of action of glucocorticoids: Effects of 
hydrocortisone, prednisone and dexamethasone on human pituitary-adrenal function. Am J of 
Med. 1977; 63(2): 200-7. URL: https://doi.org/10.1016/0002-9343(77)90233-9. 
Nayak S, Acharjya B. Deflazacort versus other glucocorticoids: A comparison. Indian J 
Dermatol. 2008; 53(4):167-70. URL: https://doi.org/10.4103/0019-5154.44786. 
Polachek A, Gladman DD, Su J, Urowitz MB. Defining low disease activity in systemic lupus 
erythematosus. Arthritis Care Res. 2017; 69(7): 997-1003. 
URL: https://doi.org/10.1002/acr.23109. 
US Food and Drug Administration. Guidance for Industry on Systemic Lupus Erythematosus: 
Developing Medical Products for Treatment. 2010. 
URL: http://fda.org/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm. 
Ware JE, Kosinski m, Dewey JE. How to Score Version Two of the SF-36® Health Survey. 
Lincoln, RI: QualityMetric Incorporated, 2000. 


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15. 
APPENDICES 
15.1. 
Study Overview 
 
 
Figure 1: 
Study Overview 
Notes: 
ADA=Anti-drug antibodies; CLASI=Cutaneous Lupus Erythematosus Disease Area and Severity Index; BILAG=British Isles Lupus Assessment 
Group; 
 PGA= Physician's Global Assessment; PROs=Patient - Reported Outcomes; PK=Pharmacokinetics; SLE=Systemic 
lupus erythematosus; SLEDAI=SLE Disease Activity Index. 


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15.2. 
Schedule of Assessments 
Table 8: 
Schedule of Procedures and Assessments 
 
Study Period: 
Screen 
Treatment1 
EoT 
EoS2 
Visit: 
1 
1b3 
1c3 
1d3 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
Day: 
-42 to -1 
1 
2 
4 
8 
15 
29 
43 
57 
71 
85 
99 
113 
127 
141 
155 
169 
197 
Visit Window: 
NA 
NA 
NA 
± 1 
± 1 
± 1 
± 2 
± 2 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
Demographics 
X 
Medical History 
X 
5 
X 
Eligibility Review 
4 
X 
5 
X 
Chest X-ray 
6 
X 
Physical Exam7 
X 
5 
X 
8 
X 
8 
X 
8 
X 
8 
X 
8 
X 
8 
X 
8 
X 
8 
X 
8 
X 
8 
X 
8 
X 
8 
X 
X 
Electrocardiogram 
X 
2X9 
2X9 
2X9 
X 
Weight 
X 
5 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signs 
X 
2X9 
2X9 
2X9 
2X9 
2X9 
2X9 
2X9 
2X9 
2X9 
2X9 
2X9 
2X9 
X 
X 
SLE Damage Assessment (SDI) 
5 
X 
X 
X 
Physician SLE Assessment10 
11 
X 
5 
X 
12 
X 
X 
X 
X 
X 
X 
X 
X 
Skin Photography13 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Patient SLE Assessment14 
5 
X 
X 
X 
X 
X 
X 
X 
X 
Safety Lab Evaluations15 
16 
X 
5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Infectious Disease Screen17 
X 
Urine Pregnancy Test18 
X 
5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical Biomarkers of SLE19 
X 
5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PK/ADA
 
2X9 
X 
X 
X 
2X9 
X 
X 
2X9 
X 
X 
(Dense PK Subject Subset)21 
(3X22) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(2X9) 
(X) 
(X) (2X9) 
(X) 
(X) 
(DNA)21 
X 
Randomization 
X 
Study Drug Administration23 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant Medications 
X 
(X) 
(X) 
(X) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events24 
X 
(X) 
(X) 
(X) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


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1 
On the days of study drug administration, all assessments and procedures must be performed prior to dosing except where otherwise specified. 
2 
Assessments should also be performed in the event of early discontinuation. 
3 
Visit held only for subjects in the Dense PK/
ubset. 
4 
Investigator’s screening eligibility assessment must be reviewed and confirmed by Sponsor or designee. 
5 
Perform prior to randomization and study-drug dosing. 
6 
This requirement may be met with documentation of a previous chest x-ray performed within 3 months of Screening. 
7 
Complete physical examination required at Screening, Baseline, and EoS or early discontinuation. 
8 
A problem-oriented exam may be performed at the physician’s discretion; however, at applicable visits, physical examination 
required for SLEDAI and BILAG assessment must be performed. 
9 
Obtain pre-dose, and then at 10 minutes (± 10 min) following completion of infusion. 
10 BILAG, SLEDAI-2K 30 (or SLEDAI-2K on Day 15 per footnote 12), PhGA, CLASI, 
 NOTE: only a subset of these 
will be conducted at Screening (see footnote 11) and Day 15 (see footnote 12). 
11 SLEDAI-2K 30, BILAG, 
and PhGA; lupus history should be recorded at Screening. 
12 SLEDAI-2K, PhGA. 
13 Skin photography should be performed as indicated if any abnormalities are recorded on CLASI. 
14 PtGA, SF-36, FACIT-F (13-item). Note: Patient’s assessments should be completed before physician’s assessment. 
15 Collect blood and urine samples using kit provided by the central laboratory. 
16 In addition to standard safety lab evaluations, includes TSH. 
17 Collect samples using kit provided by the central laboratory. 
18 Perform at the clinical site using provided kit; negative results must be confirmed prior to study drug dosing. 
19 Collect blood samples using kit provided by the central laboratory. 
20 Pharmacokinetics, anti-drug antibodies, 
biomarkers. Please reference Procedures Manual for more 
detailed timepoints and instructions. 
21 In subjects who provide supplemental consent. 
22 Obtain pre-dose, and then at 10 minutes (± 10 min) and 4 hours (± 30 min) following completion of infusion. 
23 Subjects should be observed for at least 2 hours following their first infusion of study drug and for 30 minutes following each subsequent infusion. 
24 For oral mucocutaneous lesions reported as AEIs, photographic documentation should be collected at presentation and in the event of 
significant change (as detailed in the Procedures Manual). 
Abbreviations: ADA, Anti-drug antibodies; AEI, Adverse event of interest: BILAG, British Isles Lupus Assessment Group index; CLASI, 
Cutaneous Lupus Erythematosus Disease Area and Severity Index; EoS, End of study; EoT, End of treatment; FACIT-F, Functional 
Assessment of Chronic Illness Therapy-Fatigue; 
 PhGA, Physician’s Global Assessment of SLE Disease Activity; PK, 
Pharmacokinetics; PtGA, Patient’s Global Assessment of Disease Activity; SDI, Systemic Lupus International Collaborating Clinics/American 
College of Rheumatology (SLICC/ACR) Damage Index; 
SF-36, Short Form-36; SLE, Systemic lupus 
erythematosus; SLEDAI, Systemic Lupus Erythematosus Disease Activity Index; 
 TSH, Thyroid stimulating 
hormone. 


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15.3. 
Disease Assessment Tools 
15.3.1. 
SLEDAI-2K 
The SLEDAI-2K is a global measure of disease activity. The raw data set contains responses for 
24 items, each of which are assigned weighted scores of 1 to 8 points. The total score is the sum 
of the weights of the items which are present at the time of assessment. The range of the 
SLEDAI total score is 0 to 105. 
Weighted SLEDAI-2K scores for the presence of each of the 24 items on the data collection tool 
are shown in below. 
Table 9: 
SLEDAI Weighted Score by Item 
 
Organ System 
Item Name 
Description 
Score 
Neuropsychiatric 
Seizure 
Recent onset, exclude metabolic, infectious or 
drug causes 
8 
Psychosis 
Altered ability to function in normal activity due 
to severe disturbance in perception of reality. 
Include hallucinations, incoherence, marked loose 
associations, impoverished thought content, 
marked illogical thinking, bizarre, disorganized, or 
catatonic behavior. Exclude uraemia and drug 
causes 
8 
Organic Brain 
Syndrome 
Altered mental function with impaired orientation, 
memory, or other intellectual function, with rapid 
onset and fluctuating clinical features, inability to 
sustain attention to environment, plus at least 2 of 
the following: perceptual disturbance, incoherent 
speech, insomnia or daytime drowsiness, or 
increased or decreased psychomotor activity. 
Exclude metabolic, infectious or drug causes 
8 
Cranial Nerve Disorder 
New onset of sensory or motor neuropathy 
involving cranial nerves 
8 
Lupus Headache 
Severe, persistent headache; may be migrainous, 
but must be non-responsive to narcotic analgesia 
8 
CVA 
New onset cerebrovascular accident(s). Exclude 
arteriosclerosis. 
8 
Ophthalmic 
Visual Disturbance 
Retinal changes of SLE. Include cytoid bodies, 
retinal hemorrhages, serous exudates or 
hemorrhages in the choroid, or optic neuritis. 
Exclude hypertension, infection, or drug causes 
8 
Mucocutaneous 
Vasculitis 
Ulceration, gangrene, tender finger nodules, 
periungual infarction, splinter hemorrhages or 
biopsy or angiogram proof of vasculitis 
8 
Rash 
Inflammatory type rash 
2 
Alopecia 
Abnormal, patchy or diffuse loss of hair 
2 
Mucosal ulcers 
Oral or nasal ulcerations 
2 


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Organ System 
Item Name 
Description 
Score 
Musculoskeletal 
Arthritis 
≥2 joints with pain and signs of inflammation 
4 
Myositis 
Proximal muscle aching/weakness, associated with 
elevated creatinine phosphokinase/aldolase, or 
EMG changes or a biopsy showing myositis 
4 
Renal 
Urinary Casts 
Heme-granular or RBC casts 
4 
Hematuria 
>5 RBC/high power field. Exclude stone, infection 
or other cause 
4 
Proteinuria 
>0.5 gram/24 hours 
4 
Pyuria 
>5 WBC/high power field. Exclude infection 
4 
Cardiorespiratory 
Pleurisy 
Pleuritic chest pain or pleural rub with effusion, or 
pleural thickening (requires objective component) 
2 
Pericarditis 
Classic pericardial pain and/or rub, effusion with 
ECG or echocardiogram confirmation 
2 
Hematological 
Low complement 
Decrease in CH50, C3 or C4 below lower limit of 
normal for testing laboratory 
2 
Increased DNA 
Binding 
Increased DNA binding above normal range for 
testing lab 
2 
Thrombocytopenia 
<100 x 109 platelets/L, exclude drug causes 
1 
Leukopenia 
<3 x 109 WBC/L, exclude drug causes 
1 
Constitutional 
Fever 
>38°C Exclude infectious cause 
1 
Source: Gladman, 2000. 
Notes: C3=Complement component 3; C4=Complement component 4; CH50=Total complement; 
CVA=Cerebrovascular accident; ECG=Electrocardiogram; EMG=Electromyogram; RBC=Red blood cell; 
SLE=Systemic lupus erythematosus; WBC=White blood cell. 


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15.3.2. 
BILAG 2004 
The BILAG 2004 index is an 86-item assessment of nine organ domains. The first seven organ 
systems (constitutional, mucocutaneous, neuropsychiatric, musculoskeletal, cardiorespiratory, 
gastrointestinal, and ophthalmic) contain clinical parameters which are assessed by the 
investigator and given scores of 0=not present, 1=improving, 2=same, 3=worse, or 4=new. Renal 
and haematologic scores are based on laboratory values reported at the time of assessment. The 
numeric parameter scores within each organ system are used to assign a letter grade indicating 
disease activity. Table 10 displays each level of organ system grading. 
Table 10: BILAG Organ System Grades 
 
BILAG Grade 
Description 
BILAG A 
Requires disease-modifying treatment such as prednisone >20 mg/day or 
immunosuppressant 
BILAG B 
Mild, reversible problems requiring symptomatic therapy such as anti-malarials, 
NSAIDS, or prednisone ≤20 mg/day 
BILAG C 
Stable, mild disease 
BILAG D 
System previously involved but not currently active 
BILAG E 
System never involved 
Notes:  BILAG=British Isles lupus assessment group; NSAIDS=Non-steroidal anti-inflammatory drugs 
Table 11 lists the grading algorithms for each body system. 


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Table 11: BILAG Grading Algorithms 
 
BILAG Grade 
Organ System 
A 
B 
C 
D 
E 
Constitutional 
Pyrexia recorded as 2 (same), 
3 (worse) or 4 (new) AND 
Any 2 or more of the following recorded 
as 2 (same), 3 (worse) 
or 4 (new): 
 
Weight loss 
 
Lymphadenopathy/ 
splenomegaly 
 
Anorexia 
Pyrexia recorded as 2 (same), 
3 (worse) or 4 (new) OR 
Any 2 or more of the following 
recorded as 2 (same), 3 (worse) 
or 4 (new): 
 
Weight loss 
 
Lymphadenopathy/ 
splenomegaly 
 
Anorexia 
BUT do not fulfill criteria for 
Category A 
Pyrexia recorded as 1 (improving) 
OR 
One or more of the following 
recorded as >0: 
 
Weight loss 
 
Lymphadenopathy/ 
splenomegaly 
 
Anorexia 
BUT does not fulfill criteria for 
category A or B 
Previous 
involvement, 
currently 
inactive 
No previous 
involvement 
Mucocutaneous 
Any of the following recorded as 2 
(Same), 3 (Worse), or 4 (New): 
 
Skin eruption – severe 
 
Angio-oedema – severe 
 
Mucosal ulceration – severe 
 
Panniculitis/ Bullous lupus – 
severe 
 
Major cutaneous 
vasculitis/thrombosis 
Any Category A features recorded 
as 1(Improving) OR 
Any of the following recorded as 2 
(Same), 3 (Worse) or 4 (New): 
 
Skin eruption – mild 
 
Panniculitis/Bullous 
lupus – mild 
 
Digital infarcts or 
nodular vasculitis 
 
Alopecia-severe 
Any Category B features recorded 
as 1(Improving) OR 
Any of the following recorded as 
1(Improving), 
2 (Same), 3 (Worse) or 
4 (New): 
 
Angio-oedema – mild 
 
Mucosal ulceration – 
mild 
 
Alopecia – mild 
 
Periungual 
erythema/chilblains 
 
Splinter haemorrhages 
Previous 
involvement, 
currently 
inactive 
No previous 
involvement 


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BILAG Grade 
Organ System 
A 
B 
C 
D 
E 
Neuropsychiatric 
Any of the following recorded as 2 
(Same), 3 (Worse) or 4 (New): 
 
Aseptic meningitis 
 
Cerebral vasculitis 
 
Demyelinating syndrome 
 
Myelopathy 
 
Acute confusional state 
 
Psychosis 
 
Acute inflammatory 
demyelinating 
polyradiculoneuropathy 
 
Mononeuropathy 
(single/multiplex) 
 
Cranial neuropathy 
 
Plexopathy 
 
Polyneuropathy 
 
Status epilepticus 
 
Cerebellar ataxia 
Any Category A features recorded 
as 1 (Improving) OR 
Any of the following recorded as 2 
(Same), 3 (Worse) or 4 (New): 
 
Seizure disorder 
 
Cerebrovascular disease 
(not due to vasculitis) 
 
Cognitive dysfunction 
 
Movement disorder 
 
Autonomic disorder 
 
Headache severe 
unremitting 
 
Headache due to raised 
intracranial hypertension 
Any Category B features recorded 
as 1 (improving) 
Previous 
involvement, 
currently 
inactive 
No previous 
involvement 
Musculoskeletal 
Any of the following recorded as 2 
(Same), 3 (Worse) or 4 (New): 
 
Myositis-severe 
 
Arthritis (severe) 
Any Category A features recorded 
as 1 (Improving) OR 
Any of the following recorded as 2 
(Same), 3 (Worse) or 4 (New): 
 
Myositis-mild 
 
Arthritis (moderate)/ 
Tendonitis/Tenosynovitis 
Any Category B features recorded 
as 1 (Improving) OR 
The following recorded as 1 
(Improving), 2 (Same), 3 (Worse) 
or 4 (New): 
 
Arthritis (mild)/ 
Arthralgia/ Myalgia 
Previous 
involvement, 
currently 
inactive 
No previous 
involvement 


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BILAG Grade 
Organ System 
A 
B 
C 
D 
E 
Cardiorespiratory 
Any of the following recorded as 2 
(Same), 3 (Worse) or 4 (New): 
 
Myocarditis/Endocarditis + 
Cardiac failure 
 
Arrhythmia 
 
New valvular dysfunction 
 
Cardiac tamponade 
 
Pleural effusion with dyspnoea 
 
Pulmonary 
haemorrhage/vasculitis 
 
Interstitial alveolitis/ 
pneumonitis 
 
Shrinking lung syndrome 
 
Aortitis 
 
Coronary vasculitis 
Any Category A features recorded 
as 1 (Improving) OR 
Any of the following recorded as 2 
(Same), 3 (Worse) or 4 (New): 
 
Pleurisy/Pericarditis 
 
Myocarditis – mild 
Any Category B features recorded 
as 1 (improving) 
Previous 
involvement, 
currently 
inactive 
No previous 
involvement 
Gastrointestinal 
Any of the following recorded as 2 
(Same), 3 (Worse) or 4 (New): 
 
Peritonitis 
 
Lupus enteritis/colitis 
 
Intestinal pseudo-obstruction 
 
Acute lupus cholecystitis 
 
Acute lupus pancreatitis 
Any Category A feature recorded 
as 1 (Improving) OR 
Any of the following recorded as 2 
(Same), 3 (Worse) or 4 (New): 
 
Abdominal serositis or 
ascites 
 
Malabsorption 
 
Protein-losing 
enteropathy 
 
Lupus hepatitis 
Any Category B features recorded 
as 1 (improving) 
Previous 
involvement, 
currently 
inactive 
No previous 
involvement 


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BILAG Grade 
Organ System 
A 
B 
C 
D 
E 
Ophthalmic 
Any of the following recorded as 2 
(Same), 3 (Worse) or 4 (New): 
 
Orbital 
inflammation/myositis/proptosis 
 
Keratitis – severe 
 
Posterior uveitis/retinal 
vasculitis – severe 
 
Scleritis – severe 
 
Retinal/choroidal vaso- 
occlusive disease 
 
Optic neuritis 
 
Anterior ischaemic optic 
neuropathy 
Any Category A features recorded 
as 1 (Improving) OR 
Any of the following recorded as 2 
(Same), 3 (Worse) or 4 (New): 
 
Keratitis – mild 
 
Anterior uveitis 
 
Posterior uveitis/retinal 
vasculitis – mild 
 
Scleritis-mild 
Any Category B features recorded 
as 1 (Improving) OR 
Any of the following recorded as 1 
(Improving), 2 (Same), 3 (Worse) 
or 4 
(New): 
 
Episcleritis 
 
Isolated cotton-wool 
spots (cytoid bodies) 
Previous 
involvement, 
currently 
inactive 
No previous 
involvement 
Renal 
Two or more of the following providing 
1, 4 or 5 is included: 
1. Deteriorating proteinuria (severe): 
a. urine dipstick increased by ≥2 levels 
(only if other methods of urine protein 
estimation not available); or 
b. 24-hour urine protein >1 g that has 
not decreased by ≥25%; or 
c. urine protein-creatinine ratio >100 
mg/mmol that has not decreased by 
≥25%; or 
d. urine albumin-creatinine ratio >100 
mg/mmol that has not decreased by 
≥25% 
2. Accelerated hypertension 
3. Deteriorating renal function (severe): 
a. plasma creatinine >130 μmol/L and 
having risen to >130% of previous 
value; or 
b. GFR having fallen to <67% of 
previous value; or 
One of the following: 
1. One of the Category A features 
2. Proteinuria (not fulfilling 
Category A criteria): 
a. urine dipstick which has risen 
by 1 level to at least 2+ (only 
if other methods of urine 
protein estimation not 
available); or 
b. 24-hour urine protein ≥0.5 g 
that has not decreased by 
≥25%; or 
c. urine protein-creatinine ratio 
≥50 mg/mmol that has not 
decreased by ≥25%; or 
d. urine albumin-creatinine ratio 
≥50 mg/mmol that has not 
decreased by ≥25% 
3. Plasma creatinine >130 μmol/L 
and having risen to ≥115% but 
≤130% of previous value 
One of the following: 
1. Mild/Stable proteinuria: 
a. urine dipstick ≥1+ but not 
fulfilling Category A & B 
criteria (only if other methods 
of urine protein estimation not 
available); or 
b. 24-hour urine protein >0.25 g 
but not fulfilling Category A & 
B criteria; or 
c. urine protein-creatinine ratio 
>25 mg/mmol but not fulfilling 
Category A & B criteria; or 
d. urine albumin-creatinine ratio 
>25 mg/mmol but not fulfilling 
Category A & B criteria 
2. Rising blood pressure (providing 
the recorded values are >140/90 
mm Hg) not fulfilling Category A 
& B criteria, defined as: 
a. systolic rise of ≥30 mmHg; and 
b. diastolic rise of ≥15mmHg 
Previous 
involvement, 
currently 
inactive 
No previous 
involvement 


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BILAG Grade 
Organ System 
A 
B 
C 
D 
E 
c. GFR <50 ml/min per 1.73 m², and 
last time was >50 ml/min per 1.73 m² 
or was not measured. 
4. Active urinary sediment 
5. Histological evidence of active 
nephritis within last 3 months 
6. Nephrotic syndrome 
Haematological 
TTP recorded as 2 (Same), 3 (Worse) or 4 
(New) OR 
Any of the following: 
 
Evidence of haemolysis and 
Haemoglobin <8 g/dl 
 
Platelet count <25 x 109/l 
TTP recorded as 1 (Improving) 
OR 
Any of the following: 
 
Evidence of haemolysis 
and Haemoglobin 8-9.9 
g/dl 
 
Haemoglobin <8 g/dL 
(without haemolysis) 
 
White cell count <1.0 x 
109/L 
 
Neutrophil count <0.5 x 
109/L 
 
Platelet count 25-49 x 
109/L 
Any of the following: 
 
Evidence of haemolysis 
and Haemoglobin 
≥10g/dl 
 
Haemoglobin 8-10.9 g/dl 
 
White cell count 1-3.9 x 
109/L 
 
Neutrophil count 0.5-1.9 
x 109/L 
 
Lymphocyte count <1.0 
x 109/L 
 
Platelet count 50-149 x 
109/l 
 
Isolated Coombs’ test 
positive 
Previous 
involvement, 
currently 
inactive 
No previous 
involvement 
Notes:  BILAG=British Isles Lupus Assessment Group; GFR=Glomerular filtration rate. 


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15.3.3. 
CLASI 
The CLASI assesses activity of disease and damage done by the disease in 13 anatomical 
locations [Klein, 2011]. These locations are: 
 Scalp 
 Ears 
 Nose 
 Rest of face 
 V-area of neck (frontal) 
 Posterior neck and/or shoulders 
 Chest 
 Abdomen 
 Back, buttocks 
 Arms 
 Hands 
 Legs 
 Feet 
To calculate the CLASI activity score, the numeric scores of each anatomical location for degree 
of erythema (0=absent, 1=pink; faint erythema, 2=red, or 3=dark red; 
purple/violaceous/hypertonic) are added to the responses for mucous membrane lesions 
(0=absent, 1=lesion or ulceration), recent hair loss (0=no, 1=yes), and non-scarring alopecia 
(0=absent, 1=diffuse; non-inflammatory, 2=focal or patchy in one quadrant, 3=focal or patchy in 
more than one quadrant). The CLASI activity score ranges from 0 to 70. 
To calculate the CLASI damage score the total numeric scores for dyspigmentation (0=absent, 
1=dyspigmentation) for the 13 anatomical locations is calculated. If the response to the 
dyspigmentation duration question indicates that dyspigmentation usually lasts for at least 12 
months, the total dyspigmentation score is multiplied by two. The resulting dyspigmentation 
score is added to the sum of the scarring scores (0=absent, 1=scarring, 2=severe) for all locations 
except for the scalp. Scalp scarring, scored as part of the alopecia assessment with possible 
values of 0=absent, 3=one quadrant, 4=two quadrants, 5=3 quadrants, or 6=whole skull, is then 
added to compute the total damage score. The CLASI damage score ranges from 0 to 56. 


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15.3.4. 
SLICC/ACR Damage Index 
The SLICC/ACR Damage Index (SDI) measures non-reversible change occurring since the onset 
of SLE and present for at least six months in 12 different organ systems. A total of 39 items 
within 12 organ systems are scored as 0, indicating no damage, or ≥1, indicating damage, for a 
max total score of 47. The SDI organ systems, items and their possible scores are shown in 
Table 12. 
Table 12: SLICC/ACR Organ Systems and Items 
 
Organ System 
Item Name 
Score 
Ocular 
Any cataract ever 
0, 1 
Renal change or optic atrophy 
0, 1 
Neuropsychiatric 
Cognitive impairment 
0, 1 
Seizures requiring therapy ≥6 months 
0, 1 
CVA ever (score 2 if >1) 
0, 1, 2 
Cranial or peripheral neuropathy 
0, 1 
Transverse myelitis 
0, 1 
Renal 
eGFR <50% 
0, 1 
Proteinuria ≥3.5 gm/24 hr 
0, 1 
End-stage renal disease 
3 
Pulmonary 
Pulmonary hypertension 
0, 1 
Pulmonary fibrosis 
0, 1 
Shrinking lung 
0, 1 
Pleural fibrosis 
0, 1 
Pulmonary infarction 
0, 1 
Cardiovascular 
Angina or coronary artery bypass 
0, 1 
Myocardial infarction ever (score 2 if >1) 
0, 1, 2 
Cardiomyopathy 
0, 1 
Valvular disease 
0, 1 
Pericarditis or pericardiectomy 
0, 1 
Peripheral Vascular 
Claudication ≥6 months 
0, 1 
Minor tissue loss 
0, 1 
Significant tissue loss (score 2 if >1 site) 
0, 1, 2 
Venous thrombosis or venous stasis 
0, 1 
Gastrointestinal 
Infarction or resection of bowel (score 2 if >1 site) 
0, 1, 2 
Mesenteric insufficiency 
0, 1 
Chronic peritonitis 
0, 1 
Stricture or upper GI surgery ever 
0, 1 


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Organ System 
Item Name 
Score 
Musculoskeletal 
Atrophy or weakness 
0, 1 
Deforming or erosive arthritis 
0, 1 
Osteoporosis with fracture or vertebral collapse 
0, 1 
Avascular necrosis (score 2 if >1 site) 
0, 1, 2 
Osteomyelitis 
0, 1 
Skin 
Scarring chronic alopecia 
0, 1 
Extensive scarring or panniculum 
0, 1 
Skin ulceration 
0, 1 
Premature gonadal failure 
0, 1 
Diabetes 
0, 1 
Malignancy (score 2 if >1 site) 
0, 1, 2 
Source: Gladman, 1996. 
Notes:  CVA=Cerebrovascular accident; eGFR=Estimated glomerular filtration rate; GI=Gastrointestinal 


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15.3.5. 
FACIT – Fatigue 
The scoring of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) is 
based on guidelines published by the FACIT group [FACIT, 2003]. The following steps are 
required to score the FACIT-F. 
1. The 13 questions constituting the FACIT – fatigue assessment are identified by unique 
item code numbers. Possible responses for each item are 0=“not at all”, 1=“a little bit”, 
2=“somewhat”, 3=“quite a bit”, or 4=‘very much”. 
2. The reported item responses for each question are converted to a final score by 
subtracting the reported response from the reversal factor for the specified item listed in 
Table 13. For example, if a subject’s response to item HI7, “I feel fatigued”, is 4 (very 
much), the item score is equal to 0 (4 – 4). 
3. The resulting item scores are added to derive a total score. 
4. The total score is multiplied by the number of items in the subscale (n=13 for FACIT-F). 
5. Finally, the result of step 4 is divided by the number of items answered to obtain the final 
FACIT-F score. 
The resulting FACIT – F scores range from 0 to 52 with a higher score indicating a better quality 
of life. The final score will be used for all analyses of FACIT – F data. 
Table 13: FACIT – Fatigue Item Scoring 
 
FACIT Item Code 
Item Reversal Factor 
Valid Resulting Item Scores 
HI7 
4 
4, 3, 2, 1, 0 
HI12 
4 
4, 3, 2, 1, 0 
An1 
4 
4, 3, 2, 1, 0 
An2 
4 
4, 3, 2, 1, 0 
An3 
4 
4, 3, 2, 1, 0 
An4 
4 
4, 3, 2, 1, 0 
An5 
0 
0, 1, 2, 3, 4 
An7 
0 
0, 1, 2, 3, 4 
An8 
4 
4, 3, 2, 1, 0 
An12 
4 
4, 3, 2, 1, 0 
An15 
4 
4, 3, 2, 1, 0 
An16 
4 
4, 3, 2, 1, 0 
Source: FACIT, 2003. 
Notes:  FACIT=Functional Assessment of Chronic Illness Therapy. 


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15.3.6. 
Tender and Swollen Joint Count 
For each of 14 anatomical regions, i.e., locations, the presence of tender, swollen or tender and 
swollen joints is recorded. These values are collected separately for the left and right sides of the 
body, i.e., laterality, yielding 28 values. 
Three separate joint count scores (Tender, Swollen and Tender/Swollen) will be derived as 
follows for each visit: 
 If the status variable in the record states “Intentionally left blank”, all joint counts are 
set to missing for that visit. 
 For each location and laterality, if the result contains “Tender”, add 1 to the tender 
joint count. 
 For each location and laterality, if the result contains “Swollen”, add 1 to the swollen 
joint count. 
 For each location and laterality, if the results contains “Tender|Swollen”, add 1 to the 
tender/swollen joint count. 
Results reported as “NA” will not be counted in the total joint count. Responses of “NA” will be 
displayed in the data listing with the reason given for this response. 


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15.3.7. 
SF-36 
The Short Form Health Survey – 36 (SF-36) is a general health patient-reported outcome survey 
containing 36 items. Individual items on the SF-36 have different numbers of valid responses. 
Scores are calculated for the eight subscales and two component scales by transforming 
responses to a 0 to 100 scale. Higher scores indicate better health. Scoring will be performed 
using the vendor software. 


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15.4. 
Randomization Algorithm 
Subjects enrolled in this study were randomly assigned to receive either ALPN-101 or placebo in 
a 1:1 ratio. Randomization was stratified by geographic region and by use of concomitant oral 
immunosuppressant therapy at enrollment using a centralized interactive web-based response 
system. 
Geographic regions include the following: 
 Geographic region 1: Sites located in North America or Western Europe 
 Geographic region 2: Sites located in Eastern Europe 
 Geographic region 3: Sites in Asia 


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15.5. 
Laboratory Assessments 
All per-protocol laboratory assessments will be performed by the central lab per the assessment 
schedule shown in Table 14. Investigators must document their review of each laboratory safety 
report. 
Table 14: Clinical Laboratory Assessments 
 
Assessment 
Parameters 
Safety: 
Hematology 
Platelet count 
RBC count and indices: MCV, MCH, percent reticulocytes 
WBC count with differential; neutrophils, lymphocytes, monocytes, eosinophils, 
basophils 
Absolute neutrophil count and lymphocyte count; CD4 and CD8 lymphocytes 
Hemoglobin 
Hematocrit 
Safety: 
Clinical Chemistry 
Electrolytes: sodium, potassium, chloride, bicarbonate 
Other cations: calcium, magnesium, phosphorus 
Amylase 
Lipase 
Glucose 
CPK 
LDH 
Renal function: creatinine, eGFR 
Liver Function Tests: ALT, albumin, alkaline phosphatase, AST, total and direct 
bilirubin, total protein 
Safety: 
Coagulation 
PT (i.e., INR) , aPTT 
Safety: 
Urinalysis 
Specific gravity, pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, 
leukocyte esterase, microscopic examination if blood or protein is abnormal, UPCR 
Infectious Disease 
Hepatitis B and C viruses, Human Immunodeficiency Virus, tuberculosis, SARS- 
CoV-2 
Other Tests 
TSH, FSH and estradiol (female subjects only, if needed to confirm menopausal 
status) 
Clinical Biomarkers of SLE 
Screening only: ANA, anti-Smith antibodies, anti- SSA antibodies, anti-SSB 
antibodies, anti- RNP antibodies, Scl 70 (topoisomerase 1) antibodies, centromere 
antibodies, anticardiolipin antibodies (IgG and IgM), LAC, anti-beta-2-glycoprotein I 
antibodies 
All applicable visits: hsCRP, complements (C3, C4, CH50), quantitative IgM, IgG, 
IgA, IgE, dsDNA antibodies 
Notes: 
ALT=Alanine aminotransferase; ANA=Anti-nuclear antibodies; aPTT=Activated partial thromboplastin 
time; AST=Aspartate aminotransferase; C3=Complement component 3; C4=Complement component 4; 
CD=Cluster of differentiation; CH50=Total complement; CPK=Creatinine phosphokinase; 
dsDNA=Double stranded DNA eGFR=Estimated glomerular filtration rate; FSH=Follicle stimulating 
hormone; hsCRP=High-sensitivity C-reactive protein; INR=International normalized ratio; LAC=Lupus 
anticoagulant; LDH=Lactate dehydrogenase; MCH=Mean corpuscular hemoglobin; WBC=White blood 
cell; MCV=Mean corpuscular volume; PT=Prothrombin time; RBC=Red blood cell; 


Protocol AIS-A03 
Statistical Analysis Plan 
Confidential 
67 
 
 
RNP=Ribonucleoprotein; Ig=Immunoglobulin; SSA=Sjögren’s syndrome type A; SSB=Sjögren’s 
syndrome type B; TSH=Thyroid stimulating hormone; UPCR=Urine protein-creatinine ratio. 


Protocol AIS-A03 
Statistical Analysis Plan 
Confidential 
68 
 
 
15.6. 
Prednisone-Equivalent Conversion Table 
Table 15: Prednisone-Equivalent Conversion 
 
Glucocorticoid 
Approximate equivalent 
dose (mg) 
Conversion Factor 
Cortisone 
25 
0.20 
Hydrocortisone 
20 
0.25 
Methylprednisolone, Methylprednisolone Sodium 
Succinate, Methylprednisolone Acetate 
4 
1.25 
Prednisolone 
5 
1.00 
Prednisone 
5 
1.00 
Triamcinolone, Triamcinolone Acetonide 
4 
1.25 
Betamethasone, DIPROSPAN /00582101/ 
0.70 
7.15 
Dexamethasone 
0.75 
6.67 
Deflazacort 
6 
0.83 
Fludrocortisone acetate 
2 
2.5 
Sources: Dixon, 1991, Meikle, 1977, Nayak, 2008.