ALPN-101 (Acazicolcept) in Systemic Lupus Erythematosus

Alpine Immune Sciences Inc, A Subsidiary of Vertex76 enrolled

Overview

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)

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Systemic Lupus Erythematosus

Interventions

ALPN-101DRUG

Intravenous infusion via an infusion pump.

PlaceboDRUG

Intravenous infusion via an infusion pump.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Key Inclusion Criteria Summary * SLE onset ≥ 6 months prior to Screening * Positive ANA and/or elevated anti-dsDNA and/or elevated anti-Smith antibody test * Active lupus at Screening and Baseline, as defined per-protocol and confirmed by the study's medical monitor, including a SLEDAI score at Screening of ≥ 6 and a clinical score at Baseline of ≥ 4 * Standard lupus medications must be stable prior to Screening Key Exclusion Criteria Summary: * Life-threatening or organ system-threatening lupus activity that is anticipated to require increased treatment during the study * Proteinuria consistent with nephrotic syndrome * Active lupus-related neuropsychiatric disease * Drug-induced lupus * Recent or serious ongoing infection; risk or history of serious infection * Receipt of live vaccination within 8 weeks of Day 1, or expected to require live vaccination during the study * Prior diagnosis of, or fulfills diagnostic criteria for, another rheumatic disease that overlaps with lupus or another autoimmune or inflammatory disease that may confound clinical assessments or increase subject risk in the study * Diagnosis of, or fulfills diagnostic criteria for fibromyalgia * Functional class IV * Serious lupus disease activity, which warrants immediate immunosuppressive therapy not appropriate for the study or which makes the possibility of receiving placebo or investigational agent an inappropriate risk

Locations (46)

Outcomes

Primary Outcomes

Safety and Tolerability as Assessed by Number of Participants With Treatment- Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Time frame: Day 1 up to Safety follow-up (up to 28 weeks)

Percentage of Participants Achieving a Systemic Lupus Erythematosus (SLE) Responder Index (SRI)-4

The SRI-4 is a composite index of SLE disease improvement that consists of scores derived from the SLE Disease Activity Index 2000 (SLEDAI-2K), the British Isles Lupus Assessment Group (BILAG) 2004 Index, and the Physician's Global Assessment (PGA). Participants classified as responder if they met all of the following criteria: 1) ≥ 4-point reduction in the SLEDAI-2K total score; 2) no new severe disease activity (BILAG A organ score) or more than 1 new moderate organ score (BILAG B) compared with baseline; and 3) No worsening from baseline in participants' lupus disease activity (i.e., increase of ≥0.3 0 on a 3-point scale) in PGA. The SLEDAI-2K total score falls between 0 and 105, with higher scores representing increased disease activity. SLEDAI-2K: assesses improvement in disease activity (range: 0 to 105; higher score = higher severity). BILAG: assesses disease extent, severity (range: A\[severe\] to E\[no disease\]). PGA: assesses worsening in participant's general health.

Time frame: At Day 169

Percentage of Participants Achieving a British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) Response

The BICLA is a responder index developed to measure response to therapy, and it includes scores from the BILAG, SLEDAI-2K, and Physician's Global Assessment (PGA). BICLA response is defined as: 1) at least 1 gradation of improvement in baseline BILAG 2004 scores in all body systems with moderate disease activity at entry (eg, all B \[mild disease\] scores falling to C \[Stable and mild\], or D \[no activity\]); 2) no new BILAG A or more than 1 new BILAG B scores; 3) no worsening of total SLEDAI-2K score from baseline; 4) ≤ 10% deterioration in PGA score. The PGA is measured on a 0 to 100 mm scale with score 0 indicates No Disease Activity and score 100 indicates the most Severe Disease Activity.

Time frame: At Day 169

Secondary Outcomes

Data from ClinicalTrials.gov

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Investigational Site (107)

Anniston, Alabama, United States

Investigational Site (189)

Phoenix, Arizona, United States

Investigational Site (155)

Los Angeles, California, United States

Investigational Site (109)

San Diego, California, United States

Investigational Site (169)

Santa Barbara, California, United States

Investigational Site (106)

DeBary, Florida, United States

Investigational Site (120)

Hialeah, Florida, United States

Investigational Sites (134)

Miami, Florida, United States

Investigational Site (152)

Ormond Beach, Florida, United States

Investigational Site (133)

Plantation, Florida, United States

...and 36 more locations

Annualized Flare Rate by British Isles Lupus Assessment Group (BILAG)-2004 Flare Index

The BILAG-2004 index covers 86 questions item assessed across 9 organ systems. Each question is answered as 0-not present, 1-improving, 2- same, 3-worse, to 4-new. The BILAG-2004 index categorizes disease activity in each organ system into five different levels from A to E. Grade A represents requires disease-modifying treatment, Grade B represents mild, reversible problems requiring symptomatic therapy, Grade C indicates mild stable disease, and grade D implies no disease activity, but suggests the organ system had previously been affected. Grade E indicates no current or previous disease activity. Higher scores indicate more severe disease activity. Annualized flare rate is defined as the number of flares observed during the treatment period divided by the flare exposure time in days multiplied by 365.25.

Time frame: From Baseline to Day 169

Time-to-first Flare by BILAG-2004 Flare Index

Time-to-first SLE flare is defined as the number of days from the administration of first dose to the first occurrence of flare. A flare was defined as having an adjudicated BILAG A or B score in any of the 8 organ systems during treatment. The BILAG disease activity index evaluates SLE activity in 8 organ systems, using a separate alphabetic score (A to E) assigned to each organ system defined as follows. BILAG A: Disease sufficiently active requiring disease modifying treatment (prednisone greater than 20 mg daily or immunosuppressants); BILAG B: Disease less active than in "A", mild reversible problems requiring only symptomatic therapy such as antimalarials, NSAIDs, or prednisone less than 20 mg day; BILAG C: Stable mild disease; BILAG D: System previously affected but now inactive; BILAG E: System never involved.

Time frame: From Baseline to Day 169

Percentage of Participants Achieving a Lupus Low Disease Activity State (LLDAS)

The LLDAS is a composite measure designed to identify patients achieving a state of low disease activity. LLDAS was defined as SLE disease activity index (SLEDAI-2k \<=4, with no activity in major organ systems (CNS, vascular, renal, cardiorespiratory and constitutional); where "no activity" is defined as all items of SLEDAI-2K within these major organ systems equal to 0; No new features of lupus disease activity compared to previous occurred visit, where the "new feature" is defined as any of the SLEDAI-2K 24 items changed from 0 to greater than 0; PGA (scale 0-3 higher scores = higher severity), \<=1; current prednisolone (or equivalent) dose \<=7.5 mg daily; and allowance for maintenance doses of immunosuppressive drugs and approved biological agents.

Time frame: At Day 169

Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Total Score

SLEDAI-2K score is a disease activity score used to identify patients with more active disease at enrolment in study. Total score is defined as the sum of the weighted scores of each individual item within each organ system class. For each system organ with baseline score \>0, improvement in SLEDAI-2K improvement is achieved by meeting all the following criteria: * Reduction in system organ scores among participants with baseline SLEDAI-2K scores greater than 0 * No early discontinuation of study drug * No use of restricted medications beyond the protocol-allowed threshold before assessment SLEDAI-2K uses a weighted checklist to assign a numerical score based on the presence or absence of 24 symptoms. Each symptom present is assigned between 1 and 8 points based on its usual clinical importance, yielding a total score that ranges from 0 points (no symptoms) to 105 points (presence of all defined symptoms).

Time frame: From Baseline to Day 169

Cumulative Prednisone-equivalent Dose Use Through Day 169

Time frame: From Baseline through Day 169

Percentage of Participants With ≥ 50% Reduction In CLASI Activity Score In Participants With Baseline CLASI Activity Score ≥ 8

CLASI is an validated measurement instrument for lupus erythematosus developed for use in clinical studies that consists of separate scores for the activity of the disease. CLASI Activity is scored based on erythema, scale/hyperkeratosis, mucous membrane involvement, acute hair loss and nonscarring alopecia. The total CLASI activity score ranges from 0-70, with higher scores indicating more severe skin disease.

Time frame: From Baseline to Day 169