Long-term Safety and Tolerability of Atacicept (Long-term Follow-Up of Participant Who Participated in ADDRESS II)

NCT02070978 | Terminated Phase 2 Results DMC

• 2 other identifiers: 700461-0242013-002758-62
• Study Type: interventional
• Target: 253
• Locations: 17 countries
• Sites: 84

Brief Summary

This is a multicenter, double-blind, Phase 2b, long-term extension (LTE) to the ADDRESS II core trial (EMR 700461-023) (NCT01972568), to evaluate long-term safety and tolerability of atacicept in participants with systemic lupus erythematosus (SLE). Participants who completed the 24-week core study ADDRESS II core study (NCT01972568) and thus not met any of the discontinuation criteria were invited to enter this long-term extension (LTE) study NCT02070978.

Conditions

Lupus Erythematosus, Systemic

Keywords

Lupus Erythematosus, Systemic; Atacicept 75 and 150 mg; LTE

Outcome Measures

Primary Outcomes (2)

• Number of Participants With at Least One Serious Adverse Event (SAE) During the Treatment Period

  An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. An AE was considered as 'treatment emergent' if it occurred after the first drug administration of each period or if it was present prior to drug administration but exacerbated after the drug administration. Treatment- Emergent adverse events (TEAEs) during the treatment period exclude those ongoing at the time of study entry into 024 LTE Day 1 and exclude the safety follow-up period.

  Baseline (LTE Day 1) up to maximum treatment duration of 143.7 weeks

• Number of Participants Who Prematurely Discontinued the Treatment Due to Adverse Event (AE)

  An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. TEAEs were defined as events with an onset date on or after the date of first dose of study treatment in the core study and ongoing at the 024 LTE study entry, occurring during the 024 LTE study and the Safety follow-up Period.

  Baseline (Day 1 of Core study) up to maximum duration of 167.7 weeks

Secondary Outcomes (16)

• Change From Baseline in Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index Organ Damage Scores

  Baseline: Day 1 (Core Study), Day 1 (LTE Study), Week 24, Week 48, Week 72 and Week 96

• Change From Baseline in Disease Activity as Measured by British Isles Lupus Assessment Group (BILAG) 2004 Score

  Baseline: Core study Screening, LTE Day 1, Week 24, Week 48, Week 72 and Week 96

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

  Baseline: Screening Visit (Core Study); LTE Day 1, Week 24, Week 48, Week 72 and Week 96

• Change From Baseline in Disease Activity as Measured by SLEDAI-2K Responder Index-50 (SRI-50) Score

  Baseline: Screening Visit (Core Study); LTE Day 1, Week 24, Week 48, Week 72 and Week 96

• Change From Baseline in Disease Activity as Measured by Physician's Global Assessment (PGA) Score

  Baseline: Screening Visit (Core Study); LTE Day1, Week 24, Week 48, Week 72 and Week 96

Study Arms (3)

Atacicept 75 mg

EXPERIMENTAL

Drug: Atacicept 75 mg

Atacicept 150 mg

EXPERIMENTAL

Drug: Atacicept 150 mg

Placebo/Atacicept 150 mg

EXPERIMENTAL

Drug: Atacicept 150 mg

Interventions

Atacicept 75 mg DRUG

Participants who received atacicept 75 milligram (mg) as once-weekly subcutaneous injection in the core study ADDRESS II continued to receive this dose during this LTE study. Participants in this reporting arm received the medication up to a maximum of 143.7 weeks.

Atacicept 75 mg

Atacicept 150 mg DRUG

Participants who received placebo in the core study ADDRESS II switched to receive atacicept 150 mg as once-weekly subcutaneous injection for up to a maximum of 97.7 weeks during this LTE study.

Placebo/Atacicept 150 mg

Eligibility Criteria

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

You may qualify if:

• Participants who had completed the 24-week treatment period of study EMR-700461-023 (ADDRESS II core trial)
• Women of childbearing potential who had a negative pregnancy test

You may not qualify if:

• Active neurological symptoms of SLE that were deemed severe or progressive
• Diagnosis of any demyelinating disease, such as, but not restricted to, multiple sclerosis (MS) or optic neuritis
• Pregnancy
• Active clinically significant viral, bacterial, or fungal infection, or any major episode of infection that in the investigator's opinion makes the participants unsuitable to continued participation in the study

Sponsors & Collaborators

• EMD Serono: lead

Study Sites (84)

Pinnacle Research Group LLC

Anniston, Alabama, 36207, United States

Location

University of Alabama at Birmingham - (UAB)

Birmingham, Alabama, 35294, United States

Location

Wallace Rheumatic Study Center

Beverly Hills, California, 90211, United States

Location

Southern California Permenent Medical Group

Fontana, California, 92335, United States

Location

East Bay Rheumatology Medical Group, Inc.

San Leandro, California, 94578, United States

Location

Clinical Research of West Florida - Corporate

Clearwater, Florida, 33765, United States

Location

Clinical Research of West Florida, Inc.

Tampa, Florida, 33603, United States

Location

McIlwain Medical Group, PA

Tampa, Florida, 33613, United States

Location

AA MRC LLC Ahmed Arif Medical Research Center

Grand Blanc, Michigan, 48439, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Clayton Medical Associates, P.C.

St Louis, Missouri, 63117, United States

Location

Rutgers New Jersey Medical School

Newark, New Jersey, 07103, United States

Location

The Feinstein Institute for Medical Research

Manhasset, New York, 11031, United States

Location

Hospital for Special Surgery

New York, New York, 10021, United States

Location

DJL Clinical Research, PLLC

Charlotte, North Carolina, 28210, United States

Location

MetroHealth System

Cleveland, Ohio, 44109, United States

Location

Arthritis & Rheumatology Center of Oklahoma

Oklahoma City, Oklahoma, 73103, United States

Location

OMRF

Oklahoma City, Oklahoma, 73104, United States

Location

Clinical Research Center of Reading LLC

Wyomissing, Pennsylvania, 19610, United States

Location

Medical University of South Carolina (MUSC)

Charleston, South Carolina, 29425, United States

Location

Austin Regional Clinic, P.A.

Austin, Texas, 78731, United States

Location

Little River Arthritis & Osteoporosis Clinic

Waco, Texas, 76708, United States

Location

Instituto CAICI

Rosario, Santa Fe Province, S2000PBJ, Argentina

Location

Centro Medico Privado de Reumatologia

San Miguel de Tucumán, Tucumán Province, T4000AXL, Argentina

Location

Centro Integral de Reumatologia

San Miguel de Tucumán, Tucumán Province, T4000DVB, Argentina

Location

Investigaciones Clinicas Tucuman

San Miguel de Tucumán, Tucumán Province, T4000ICL, Argentina

Location

Organizacion Medica de Investigacion (OMI)

Ciudad Autonoma Buenos Aires, C1015ABO, Argentina

Location

APRILLUS

Ciudad Autonoma Buenos Aires, C1046AAQ, Argentina

Location

Atencion Integral en Reumatologia (AIR)

Ciudad Autonoma Buenos Aires, C1426AAL, Argentina

Location

Hospital Privado Centro Medico de Cordoba

Córdoba, X5016KEH, Argentina

Location

Cordis S.A.

Salta, A4400ANW, Argentina

Location

Centro Polivalente de Asistencia e Inv. Clinica CER

San Juan, 5400, Argentina

Location

Centro de Pesquisas em Diabetes Ltda.

Porto Alegre, Rio Grande do Sul, 90035-170, Brazil

Location

MHAT "Eurohospital" - Plovdiv, OOD

Plovdiv, 4002, Bulgaria

Location

Medical Center "Teodora", EOOD

Rousse, 7000, Bulgaria

Location

MHAT - Ruse, AD

Rousse, 7002, Bulgaria

Location

UMHAT "Sv. Ivan Rilski", EAD

Sofia, 1431, Bulgaria

Location

DCC "Sveta Anna", EOOD

Sofia, 1750, Bulgaria

Location

Medical Center "Nov Rehabilitatsionen Tsentar", EOOD

Stara Zagora, 6000, Bulgaria

Location

MHAT-Targovishte, AD

Targovishte, 7700, Bulgaria

Location

Corporacion de Beneficencia Osorno

Osorno, 5290000, Chile

Location

Quantum Research Santiago

Puerto Varas, 5550170, Chile

Location

Centro Medico Prosalud

Santiago, 7500000, Chile

Location

Biomedica

Santiago, 7500710, Chile

Location

Centro de Estudios Reumatologicos

Santiago, 7501126, Chile

Location

CINVEC - Centro de Investigacion Clinica V Region

Viña del Mar, Chile

Location

Revmatologicky Ustav

Prague, 128 50, Czechia

Location

Revmatologicka ambulance

Uherské Hradiště, 686 01, Czechia

Location

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz

Mainz, Rhineland-Palatinate, 55131, Germany

Location

Charite Universitaetsmedizin Berlin - Campus Charite Mitte

Berlin, 13353, Germany

Location

Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Hospital Universitario de Saltillo "Dr. Gonzalo Valdés Valdés"

Saltillo, Coahuila, 25000, Mexico

Location

Morales Vargas Centro de Investigacion, S.C.

León, Guanajuato, 37000, Mexico

Location

Icle S.C.

Guadalajara, Jalisco, 44600, Mexico

Location

Unidad de Investigacion en Enfermedades Cronico Degenerativas SC

Guadalajara, Jalisco, 44620, Mexico

Location

Clinstile, S.A. de C.V.

Mexico City, Mexico City, 06700, Mexico

Location

Clinica de Enfermedades Cronicas y de Procedimientos Especiales, S.C.

Morelia, Michoacán, 58249, Mexico

Location

Accelerium S. de R.L. de C.V.

Monterrey, Nuevo León, 64000, Mexico

Location

Centro Multidisciplinario para el desarrollo Especializado de la Investigacion Clinica en Yucatan

Mérida, Yucatán, 97130, Mexico

Location

Investigacion y Biomedicina de Chihuahua, S.C.

Chihuahua City, 31000, Mexico

Location

Hogar Clínica San Juan de Dios - Arequipa

Arequipa, 00000, Peru

Location

Clinica Medica Cayetano Heredia

Lima, Lima 31, Peru

Location

Invest Clinicas Sac Inst de Ginecologia y Reproduccion

Lima, Lima 33, Peru

Location

Angeles University Foundation Medical Center

Angeles City, Pampanga, 2009, Philippines

Location

Mary Mediatrix Medical Center

Batangas, 4127, Philippines

Location

Davao Doctors Hospital

Davao City, 8000, Philippines

Location

Iloilo Doctors Hospital

Iloilo City, 5000, Philippines

Location

Szpital Uniwersytecki nr 2 im.dr J. Biziela

Bydgoszcz, 85-168, Poland

Location

FSBEI HE " First Moscow State Medical University n.a. I.M. Sechenov" of the MoH of the RF

Moscow, 119992, Russia

Location

SBIH of Republic Kareliya "Republican Hospital n.a. V.A. Baranov"

Petrozavodsk, 185019, Russia

Location

SPb SBIH "Clinical Rheumatological Hospital # 25"

Saint Petersburg, 190068, Russia

Location

SIH "Saratov City Clinical Hospital # 12"

Saratov, 410039, Russia

Location

SBIH of Vladimir region "Regional Clinical Hospital"

Vladimir, 600023, Russia

Location

SBHI of Yaroslavl Region "Clinical Hospital # 8"

Yaroslavl, 150003, Russia

Location

Naidoo, A

Durban, KwaZulu-Natal, 4319, South Africa

Location

Winelands Medical Research Centre

Stellenbosch, Western Cape, 7600, South Africa

Location

Seoul National University Hospital

Seoul, Gyeonggi-do, 110744, South Korea

Location

Ajou University Hospital

Suwon, Gyeonggi-do, 16499, South Korea

Location

Konkuk University Medical Center

Seoul, 05030, South Korea

Location

Hospital Clinico Universitario de Valladolid

Valladolid, 47005, Spain

Location

Queen's Hospital

Romford, Essex, RM7 0AG, United Kingdom

Location

University College London Hospitals

London, Greater London, NW1 2PG, United Kingdom

Location

Guy's Hospital

London, Greater London, SE1 7EH, United Kingdom

Location

Related Publications (1)

• Wallace DJ, Isenberg DA, Morand EF, Vazquez-Mateo C, Kao AH, Aydemir A, Pudota K, Ona V, Aranow C, Merrill JT. Safety and clinical activity of atacicept in the long-term extension of the phase 2b ADDRESS II study in systemic lupus erythematosus. Rheumatology (Oxford). 2021 Nov 3;60(11):5379-5389. doi: 10.1093/rheumatology/keab115.

  PMID: 33547784 DERIVED

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

TACI receptor-IgG Fc fragment fusion protein

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Limitations and Caveats

The study was terminated early due to shortage of drug supply and there were many fewer number of participants remaining in each dosage group after Week 72 preluding meaningful inferences.

Results Point of Contact

• Title: Communication Center
• Organization: Merck KGaA Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  EMD Serono, Inc., Rockland MA, a subsidiary of Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2014
• First Posted: February 25, 2014
• Study Start: July 29, 2014
• Primary Completion: April 5, 2016
• Study Completion: February 9, 2018
• Last Updated: March 21, 2019
• Results First Posted: March 21, 2019

Record last verified: 2019-03

Locations

US (23); GB (3); ME (9); CL (6); BU (7); PH (4); RU (6); ES (1); PL (1); DE (2); ZA (2); BR (1); AR (10); KR (3); CZ (2); PE (3); IT (1)