ALPN-101 (Acazicolcept) in Systemic Lupus Erythematosus

NCT04835441 | Completed Phase 2 Results FDA Drug

• 1 other identifier: AIS-A03
• Study Type: interventional
• Target: 76
• Locations: 7 countries
• Sites: 46

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)

Conditions

Systemic Lupus Erythematosus

Keywords

CD28; ICOS; Autoimmune disease; Immune system disease; Immunosuppressive agent

Outcome Measures

Primary Outcomes (3)

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

  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.

  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.

  At Day 169

Secondary Outcomes (6)

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

  From Baseline to Day 169

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

  From Baseline to Day 169

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

  At Day 169

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

  From Baseline to Day 169

• Cumulative Prednisone-equivalent Dose Use Through Day 169

  From Baseline through Day 169

Study Arms (2)

ALPN-101 (Acazicolcept)

EXPERIMENTAL

Participants received a weight-based dose of 3 milligrams/kilogram (mg/kg) ALPN-101 once every 2 weeks (Q2W) up to 24 weeks.

Drug: ALPN-101

Placebo

PLACEBO COMPARATOR

Participants received placebo matched to ALPN-101 up to 24 weeks.

Drug: Placebo

Interventions

ALPN-101 DRUG

Intravenous infusion via an infusion pump.

Also known as: Acazicolcept

ALPN-101 (Acazicolcept)

Placebo DRUG

Intravenous infusion via an infusion pump.

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Alpine Immune Sciences Inc, A Subsidiary of Vertex: lead

Study Sites (46)

Investigational Site (107)

Anniston, Alabama, 36207, United States

Location

Investigational Site (189)

Phoenix, Arizona, 85037, United States

Location

Investigational Site (155)

Los Angeles, California, 90022, United States

Location

Investigational Site (109)

San Diego, California, 92020, United States

Location

Investigational Site (169)

Santa Barbara, California, 93108, United States

Location

Investigational Site (106)

DeBary, Florida, 32713, United States

Location

Investigational Site (120)

Hialeah, Florida, 33016, United States

Location

Investigational Sites (134)

Miami, Florida, 33165, United States

Location

Investigational Site (152)

Ormond Beach, Florida, 32174, United States

Location

Investigational Site (133)

Plantation, Florida, 33324, United States

Location

Investigational Site (190)

Tamarac, Florida, 33321, United States

Location

Investigational Site (163)

Tampa, Florida, 33606, United States

Location

Investigational Site (173)

Idaho Falls, Idaho, 83404, United States

Location

Investigational Site (156)

Skokie, Illinois, 60076, United States

Location

Investigational Site (138)

Grand Blanc, Michigan, 48439, United States

Location

Investigational Site (164)

Las Vegas, Nevada, 89128, United States

Location

Investigational Site (175)

Brooklyn, New York, 11220, United States

Location

Investigational Site (115)

Manhasset, New York, 11030, United States

Location

Investigational Site (179)

Charlotte, North Carolina, 28277, United States

Location

Investigational Site (112)

Crossville, Tennessee, 38555, United States

Location

Investigational Site (186)

Memphis, Tennessee, 38119, United States

Location

Investigational Site (171)

Baytown, Texas, 77521, United States

Location

Investigational Site (143)

Bellaire, Texas, 77401, United States

Location

Investigational Site (118)

Colleyville, Texas, 76034, United States

Location

Investigational Site (166)

Fort Worth, Texas, 76107, United States

Location

Investigational Site (121)

Houston, Texas, 77089, United States

Location

Investigational Site (104)

Mesquite, Texas, 75150, United States

Location

Investigational Site (162)

San Antonio, Texas, 78215, United States

Location

Investigational Site (127)

San Antonio, Texas, 78229, United States

Location

Investigational Site (149)

Marseille, 13285, France

Location

Investigational Site (128)

Paris, France

Location

Investigational Site (161)

Paris, France

Location

Investigational Site (181)

Budapest, Hungary

Location

Investigational Site (180)

Gyula, Hungary

Location

Investigational Site (183)

Székesfehérvár, Hungary

Location

Investigational Site (160)

Elblag, Poland

Location

Investigational Site (110)

Krakow, 30-363, Poland

Location

Investigational Site (108)

Poznan, 60-848, Poland

Location

Investigational Site (119)

Poznan, 61-397, Poland

Location

Investigational Site (165)

Wroclaw, 50-244, Poland

Location

Investigational Site (191)

Caguas, 00725, Puerto Rico

Location

Investigational Site (187)

San Juan, 00914, Puerto Rico

Location

Investigational Site (137)

A Coruña, 15006, Spain

Location

Investigational Site (139)

Seville, 41010, Spain

Location

Investigational Site (184)

Taichung, Taiwan

Location

Investigational Site (182)

Taipei, Taiwan

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Autoimmune Diseases; Immune System Diseases

Interventions

ALPN-101

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Medical Monitor
• Organization: Vertex Pharmaceuticals Incorporated

medicalinfo@vrtx.com

617-341-6777

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2021
• First Posted: April 8, 2021
• Study Start: June 22, 2021
• Primary Completion: July 9, 2024
• Study Completion: July 9, 2024
• Last Updated: August 15, 2025
• Results First Posted: August 15, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

PR (2); ES (2); TW (2); PL (5); US (29); FR (3); HU (3)