Evaluation of the Efficacy and Safety of Two Dosing Regimens of Olokizumab (OKZ), Compared to Placebo, in Subjects With Rheumatoid Arthritis (RA) Who Were Taking an Existing Medication Called a Tumour Necrosis Factor Alpha Inhibitor But Had Active Disease

NCT ID: NCT02760433

Last Updated: 2023-09-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 368 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-25
• Study Completion Date: 2019-10-01

Brief Summary

The purpose of this study was to determine how effective and safe the study drug Olokizumab was in patients with Rheumatoid Arthritis (RA) who had been already receiving, but not fully responding to treatment with an existing medication called a tumour necrosis factor alpha inhibitor

The primary objective of this study was to evaluate the efficacy of olokizumab (OKZ) 64 mg administered subcutaneously (SC) once every 2 weeks (q2w) or once every 4 weeks (q4w) relative to placebo in subjects with moderately to severely active rheumatoid arthritis (RA) inadequately controlled by TNF-α inhibitor (TNFi) therapy.

Detailed Description

The goal of this Phase III study was to assess the efficacy, safety and tolerability of OKZ in subjects with moderately to severely active RA who had responded inadequately to TNFi therapy. The primary endpoint of the trial was assessed at Week 12. Olokizumab was expected to reduce the disease activity and improve physical function. The study was expected to provide safety information in a large group of subjects over at least a 24 week period.

This was a randomized, double-blind, parallel-group, placebo-controlled, multicenter study. This study included a 4-week Screening Period, a double-blind Treatment Period from Week 0 to Week 24, and a Safety FollowUp Period from Week 24 to Week 44.

A total of 350 subjects were planned to be randomized.Subjects were assessed for eligibility to enter the study during a 4-week Screening Period. Eligible subjects were randomized at Visit 2 in a 2:2:1 ratio in one of 3 treatment groups (planned 140, 140, and 70 subjects per group, respectively) :

1. Olokizumab 64 mg q4w: SC injection of OKZ 64 mg q4w (alternating with SC injection of placebo OKZ q4w to maintain blinding) + MTX for 24 weeks,

2. Olokizumab 64 mg q2w: SC injection of OKZ 64 mg q2w + MTX for 24 weeks or

3. Placebo: SC injection of placebo q2w + MTX for 16 weeks.

Subjects who received placebo were re-randomized at Week 16 to receive 64 mg OKZ q4w + Methotrexate or 64 mg OKZ q2w +Methotrexate for 8 weeks.

Throughout the double-blind Treatment Period, all subjects were required to remain on a stable dose of background MTX with a stable route of administration. Concomitant treatment with folic acid was required for all subjects. The last dose of OKZ was administered at Week 20 for subjects receiving OKZ 64 mg q4w and at Week 22 for subjects receiving OKZ 64 mg q2w.

Following Visit 2 (randomization; Week 0), subjects returned to the study site at least every 2 weeks through Week 24 for response and safety assessments.

At Week 14, subjects who did not improve by at least 20% in both swollen and tender joint counts were classified as nonresponders and were administered sulfasalazine and/or hydroxychloroquine as rescue medication in addition to the assigned treatment.

After completion of the 24-week double-blind Treatment Period, subjects either rolled over into the long-term open-label extension (OLE) study or entered the Safety Follow-Up Period. During the Safety Follow-Up Period, subjects returned for visits +4, +8, and +22 weeks after the last dose of study treatment.

Subjects who discontinued randomized treatment prematurely were required to come for the End of Treatment (EoT) Visit 2 weeks after the last study treatment administration and then continue with the scheduled study visits.

Adverse events (AEs) were assessed throughout the study (starting when the subject signed the informed consent form) and evaluated using the Common Terminology Criteria for Adverse Events Version 4.0. There was ongoing monitoring of safety events, including laboratory findings, by the Sponsor or the Sponsor's designee. In addition, safety was assessed throughout the study by an independent Data Safety Monitoring Board and potential major adverse cardiac events were evaluated by an independent Cardiovascular Adjudication Committee.

The study was conducted at 123 sites across 11 countries globally (in US,EU, Russian Federation, Asia, Latin America)

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Arm 1: Olokizumab q4w

Olokizumab 64mg subcutaneous q4w + placebo + Methotrexate

Olokizumab 64 mg subcutaneous q4w + placebo+ concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular) in order to maintain the blind, subjects randomized to receive OKZ q4w received placebo injections at the alternate q4w interval (e.g., Week 2, Week 6, etc.)

Group Type: EXPERIMENTAL

Olokizumab

Intervention Type: DRUG

160 mg/mL sterile solution for SC injection in a 2 mL clear Type I glass vial

Placebo

Intervention Type: DRUG

sodium chloride 0.9% solution provided as either a 10 mL vial or ampoule, depending on market availability. Each placebo will be packed into a cardboard carton to contain 1 vial or ampoule

Arm 2: Olokizumab q2w

Olokizumab 64mg subcutaneous q2w + Methotrexate

64 mg Olokizumab administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular)

Group Type: EXPERIMENTAL

Olokizumab

Intervention Type: DRUG

160 mg/mL sterile solution for SC injection in a 2 mL clear Type I glass vial

Arm 3: Placebo q2w

Placebo q2w subcutaneous + Methotrexate

Placebo administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular)

Starting at Week 16, all subjects in the placebo group were randomized in a blinded fashion to receive either OKZ 64 mg q2w or OKZ 64 mg q4w; equal numbers of subjects were planned to be assigned to each OKZ treatment group.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

sodium chloride 0.9% solution provided as either a 10 mL vial or ampoule, depending on market availability. Each placebo will be packed into a cardboard carton to contain 1 vial or ampoule

Interventions

Olokizumab

160 mg/mL sterile solution for SC injection in a 2 mL clear Type I glass vial

Intervention Type: DRUG

Placebo

sodium chloride 0.9% solution provided as either a 10 mL vial or ampoule, depending on market availability. Each placebo will be packed into a cardboard carton to contain 1 vial or ampoule

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Subjects may be enrolled in the study only if they meet all of the following criteria.

• Subjects willing and able to sign informed consent
• Subjects must have a diagnosis of adult onset RA classified by ACR/EULAR 2010 revised classification criteria for RA for at least 24 weeks prior to Screening.

(If the subject was diagnosed according to ACR 1987 criteria previously, the Investigator may classify the subject per ACR 2010 retrospectively, using available source data.)

• Treatment with oral, SC, or intramuscular (IM) MTX for at least 12 weeks prior to Screening at a dose of 15 to 25 mg/week (or ≥10 mg/week if there is documented intolerance to higher doses)

• The dose and means of administering MTX must have been stable for at least 6 weeks prior to Screening.
• Subjects must be willing to take folic acid or equivalent throughout the study.
• Subjects must have moderately to severely active RA disease as defined by all of the following:

• ≥6 tender joints (68 joint count) at Screening and baseline; and
• ≥6 swollen joints (66 joint count) at Screening and baseline; and
• C-reactive protein (CRP) above Upper limit of normal (ULN) at Screening based on the central laboratory results.
• Subjects must have a documented inadequate response to treatment (i.e., TNFi failure) with ≥1 licensed TNFi following at least 12 weeks of therapy with that agent. Inadequate response to treatment is classified as either:

• Primary failure: The absence of any documented clinically significant response; or
• Secondary failure: Documented initial response with subsequent loss of that response or partial response

Exclusion Criteria

• Diagnosis of any other inflammatory arthritis or systemic rheumatic disease (e.g., gout, psoriatic or reactive arthritis, Crohn's disease, Lyme disease, juvenile idiopathic arthritis, or systemic lupus erythematosus) (However, subjects may have secondary Sjogren's syndrome or hypothyroidism.)
• Subjects who are Steinbrocker class IV functional capacity (incapacitated, largely or wholly bed-ridden or confined to a wheelchair, with little or no self-care)
• Prior exposure to any licensed or investigational compound directly or indirectly targeting Interleukin (IL) 6 or IL 6R (including tofacitinib or other Janus kinases and spleen tyrosine kinase [SYK] inhibitors)
• Prior treatment with cell depleting therapies including anti CD20 or investigational agents (e.g., CAMPATH, anti CD4, anti CD5, anti CD3, and anti CD19) with the exception of rituximab, which is allowed if it was discontinued at least 24 weeks prior to baseline (rituximab should not be discontinued to facilitate a subject's participation in the study, but should instead have been previously discontinued as part of a subject's medical management of RA).
• Prior use of bDMARDs, within the following windows prior to baseline (bDMARDs should not be discontinued to facilitate a subject's participation in the study, but should instead have been previously discontinued as part of a subject's medical management of RA):

1. 4 weeks for etanercept and anakinra

2. 8 weeks for infliximab

3. 10 weeks for adalimumab, certolizumab, and golimumab

4. 12 weeks for abatacept

• Use of parenteral and/or intra-articular glucocorticoids within 4 weeks prior to baseline
• Use of oral glucocorticoids greater than 10 mg/day prednisone (or equivalent) or change in dosage within 2 weeks prior to baseline
• Prior documented history of no response to hydroxychloroquine and sulfasalazine
• Prior use of cDMARDs (other than MTX) within the following windows prior to baseline (cDMARDs should not be discontinued to facilitate a subject's participation in the study, but should instead have been previously discontinued as part of a subject's medical management of RA):

1. 4 weeks for sulfasalazine, azathioprine, cyclosporine, hydroxychloroquine, chloroquine, gold, penicillamine, minocycline, or doxycycline

2. 12 weeks for leflunomide unless the subject has completed the following elimination procedure at least 4 weeks prior to baseline: Cholestyramine at a dosage of 8 grams 3 times daily for at least 24 hours, or activated charcoal at a dosage of 50 grams 4 times daily for at least 24 hours

3. 24 weeks for cyclophosphamide

• Vaccination with live vaccines in the 6 weeks prior to baseline or planned vaccination with live vaccines during the study
• Participation in any other investigational drug study within 30 days or 5 times the terminal half-life of the investigational drug, whichever is longer, prior to baseline
• Other treatments for RA (e.g., Prosorba Device/Column) within 6 months prior to baseline
• Use of intra-articular hyaluronic acid injections within 4 weeks prior to baseline
• Use of non steroidal anti inflammatory drugs (NSAIDs) on unstable dose or switching of NSAIDs within 2 weeks prior to baseline
• Previous participation in this study (randomized) or another study of OKZ
• Subjects with concurrent acute or chronic viral Hepatitis B or C infection as detected by blood tests at Screening (e.g., positive for hepatitis B surface antigen [HBsAg], total hepatitis B core antibody [anti-HBc], or hepatitis C virus antibody [HCV Ab])

a) subjects who are positive for hepatitis B surface antibodies (anti-HBs), but negative for HBsAg and anti-HBc, will be eligible.

• Subjects with HIV infection
• Subjects with:

1. Suspected or confirmed current active tuberculosis (TB) disease or a history of active TB disease.

2. Close contact (i.e., sharing the same household or other enclosed environment, such as a social gathering place, workplace, or facility, for extended periods during the day) with an individual with active TB within 1.5 years prior to Screening

• Concurrent malignancy or a history of malignancy within the last 5 years (with the exception of successfully treated carcinoma of the cervix in situ and successfully treated basal cell carcinoma and squamous cell carcinoma not less than 1 year prior to Screening [and no more than 3 excised skin cancers within the last 5 years prior to Screening])
• Subjects with any infection requiring oral antibiotic or antiviral therapy in the 2 weeks prior to Screening or at baseline, injectable anti-infective therapy in the last 4 weeks prior to baseline, or serious or recurrent infection with history of hospitalization in the 6 months prior to baseline
• Subjects with evidence of disseminated herpes zoster infection, zoster encephalitis, meningitis, or other non-self-limited herpes zoster infections in the 6 months prior to baseline
• Subjects with planned surgery during the study or surgery ≤ 4 weeks prior to Screening and from which the subject has not fully recovered, as judged by the Investigator
• Subjects with diverticulitis or other symptomatic GI conditions that might predispose the subject to perforations, including subjects with history of such predisposing conditions (e.g., diverticulitis, GI perforation, or ulcerative colitis)
• Pre-existing central nervous system demyelinating disorders (e.g., multiple sclerosis and optic neuritis)
• History of chronic alcohol or drug abuse as judged by the Investigator
• Subjects with a known hypersensitivity to any component of the OKZ drug product or placebo
• Subjects with a known hypersensitivity or contraindication to any component of the rescue medication
• History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
• Female subjects who are pregnant, currently lactating, have lactated within the last 12 weeks, or who are planning to become pregnant during the study or within 6 months of the last dose of study treatment
• Female subjects of childbearing potential (unless permanent cessation of menstrual periods, determined retrospectively after a woman has experienced 12 months of natural amenorrhea as defined by the amenorrhea with underlying status [e.g., correlative age] or 6 months of natural amenorrhea with documented serum follicle-stimulating hormone levels >40 mIU/mL and estradiol <20 pg/mL) who are not willing to use a highly effective method of contraception during the study and for at least 6 months after the last administration of study treatment

OR

Male subjects with partners of childbearing potential not willing to use a highly effective method of contraception during the study and for at least 3 months after the last administration of study treatment.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Quintiles, Inc.

INDUSTRY

Sponsor Role: collaborator

OCT Clinical Trials

OTHER

Sponsor Role: collaborator

Mene Research

OTHER

Sponsor Role: collaborator

R-Pharm International, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mikhail Samsonov

Role: STUDY_DIRECTOR

R-Pharm

Locations

Arizona Arthritis & Rheumatology Associates, P.C.

Phoenix, Arizona, United States

CHI St. Vincent Hot Springs

Hot Springs, Arkansas, United States

Medvin Clinical Research

Covina, California, United States

TriWest Research Associates, LLC

El Cajon, California, United States

Saint Jude Heritage Medical Grp

Fullerton, California, United States

С V Mehta MD Med Corp.

Hemet, California, United States

Advanced Medical Research, LLC

Lakewood, California, United States

Stanford University School of Medicine

Palo Alto, California, United States

Riverside Medical Clinic

Riverside, California, United States

East Bay Rheumatology Medical Group, Inc.

San Leandro, California, United States

Inland Rheumatology Clinical Trials, Inc.

Upland, California, United States

Denver Arthritis Clinic

Denver, Colorado, United States

Javed Rheumatology Associates

Newark, Delaware, United States

RASF - Clinical Research Center

Boca Raton, Florida, United States

Suncoast Research Group LLC

Miami, Florida, United States

Omega Research Consultants

Orlando, Florida, United States

Family Clinical Trials, LLC.

Pembroke Pines, Florida, United States

AdventHealth Medical Group, PA

Tampa, Florida, United States

Institute of Arthritis Research

Idaho Falls, Idaho, United States

University of Kansas Hospital

Kansas City, Kansas, United States

Graves Gilbert Clinic

Bowling Green, Kentucky, United States

The Arthritis & Diabetes Clinic, Inc.

Monroe, Louisiana, United States

Klein and Associates, M.D., P.A.

Hagerstown, Maryland, United States

The Center for Rheumatology and Bone Research

Wheaton, Maryland, United States

Clinical Pharmacology Study Group

Worcester, Massachusetts, United States

Glacier View Research Instutute-Rheumatology

Kalispell, Montana, United States

Arthritis & Osteoporosis Associates, PA

Freehold, New Jersey, United States

Lovelace Scientific Resources, Inc.

Albuquerque, New Mexico, United States

NYU Langone Ambulatory Care

New York, New York, United States

Medication Management, LLC

Greensboro, North Carolina, United States

Cape Fear Arthritis Care

Leland, North Carolina, United States

Carolina Arthritis Associates

Wilmington, North Carolina, United States

Trinity Medical Group

Minot, North Dakota, United States

Cincinnati Rheumatic Disease Study Group

Cincinnati, Ohio, United States

STAT Research, Inc.

Dayton, Ohio, United States

Clinical Research Source, Inc.

Perrysburg, Ohio, United States

Arthritis Group

Philadelphia, Pennsylvania, United States

Low Country Research Center

Charleston, South Carolina, United States

Amarillo Center for Clinical Research

Amarillo, Texas, United States

Austin Regional Clinic, P.A.

Austin, Texas, United States

Accurate Clinical Research, Inc.

Baytown, Texas, United States

Precision Comprehensive Clinical Research Solutions

Grapevine, Texas, United States

Therapeutic Concepts Rheumatology, LLC

Houston, Texas, United States

Rheumatology Clinic of Houston, P.A.

Houston, Texas, United States

Accurate Clinical Research, Inc.

Houston, Texas, United States

Pioneer Research Solutions, Inc.

Houston, Texas, United States

Accurate Clinical Research, Inc.

League City, Texas, United States

Endocrinology, Internal Medicine

Lubbock, Texas, United States

Dr. Alex De Jesus Rheumatology, P.A.

San Antonio, Texas, United States

Advanced Rheumatology of Houston

Woodville, Texas, United States

Centro de Investigaciones Medicas Mar del Plata

Mar del Plata, Buenos Aires, Argentina

Instituto de Investigaciones Clinicas

Mar del Plata, Buenos Aires, Argentina

Instituto de Investigaciones Clinicas Quilmes

Quilmes, Buenos Aires, Argentina

Clinica de Higado y Aparato Digestivo

Rosario, Santa Fe Province, Argentina

Sanatorio San Martin

Venado Tuerto, Santa Fe Province, Argentina

Centro Medico Privado de Reumatologia

San Miguel de Tucumán, Tucumán Province, Argentina

Centro de Investigaciones Reumatológicas

San Miguel de Tucumán, Tucumán Province, Argentina

Atencion Integral en Reumatologia (AIR)

Ciudad Autonoma Buenos Aires, , Argentina

Organizacion Medica de Investigacion (OMI)

Ciudad Autonoma Buenos Aires, , Argentina

APRILLUS

Ciudad Autonoma Buenos Aires, , Argentina

Instituto Centenario

Ciudad Autonoma Buenos Aires, , Argentina

Hospital Privado Centro Medico de Cordoba S.A

Córdoba, , Argentina

Centro Polivalente de Asistencia e Inv. Clinica CER

San Juan, , Argentina

HUWC - UFC - Hospital Universitário Walter Cantídio - Universidade Federal do Ceará

Fortaleza, Ceará, Brazil

CEDOES - Diagnóstico e Pesquisa

Vitória, Espírito Santo, Brazil

CIP - Centro Internacional de Pesquisa

Goiânia, Goiás, Brazil

CMiP - Centro Mineiro de Pesquisa

Juiz de Fora, Minas Gerais, Brazil

CETI - Centro de Estudos em Terapias Inovadoras Ltda.

Curitiba, Paraná, Brazil

Hospital Bruno Born

Lajeado, Rio Grande do Sul, Brazil

LMK Serviços Médicos S/S Ltda

Porto Alegre, Rio Grande do Sul, Brazil

Faculdade de Medicina do ABC

Santo André, São Paulo, Brazil

Centro Multidisciplinar de Estudos Clínicos - CEMEC

São Bernardo do Campo, São Paulo, Brazil

Clínica de Neoplasias Litoral Ltda.

Santa Catarina, , Brazil

CPCLIN - Centro de Pesquisas Clínicas Ltda.

São Paulo, , Brazil

Associação de Assistência à Criança Deficiente - AACD

São Paulo, , Brazil

Centro de Reumatologia y Ortopedia SAS

Barranquilla, , Colombia

Centro de Investigacion en Reumatologia y Especialidades Medicas SAS. CIREEM

Bogotá, , Colombia

Medicity S.A.S.

Bucaramanga, , Colombia

Clinica de Artritis Temprana S.A.

Cali, , Colombia

Revmatologie MUDr. Klara Sirova s.r.o.

Ostrava - Moravska Ostrava, , Czechia

CCR Czech, a.s.

Pardubice, , Czechia

MEDICAL PLUS s.r.o.

Uherské Hradiště, , Czechia

PV - Medical, s.r.o.

Zlín, , Czechia

Kerckhoff-Klinik gGmbH

Bad Nauheim, Hesse, Germany

SMO.MD GmbH

Magdeburg, Saxony-Anhalt, Germany

HRF Hamburger Rheuma Forschungszentrum

Hamburg, , Germany

Clinexpert Egeszsegugyi Szolg. es Ker. Kft.

Budapest, , Hungary

Obudai Egeszsegugyi Centrum

Budapest, , Hungary

MAV Korhaz és Rendelointezet

Szolnok, , Hungary

Vital Medical Center

Veszprém, , Hungary

Clinica de Investigacion en Reumatologia y Obesidad S.C.

Guadalajara, Jalisco, Mexico

Centro de Estudios de Investigacion Basica y Clinica SC

Guadalajara, Jalisco, Mexico

Centro de Investigacion Clínica GRAMEL S.C

Mexico City, Mexico City, Mexico

Clinstile, S.A. de C.V.

Mexico City, Mexico City, Mexico

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

Monterrey, Nuevo León, Mexico

Universidad Autonoma de Nuevo Leon, Hospital Universitario Dr. Jose Eleuterio Gonzalez

Monterrey, Nuevo León, Mexico

Centro de Alta Especialidad en Reumatología e Investigación del Potosí, S.C.

San Luis Potosí City, San Luis Potos, Mexico

Investigacion y Biomedicina de Chihuahua, S.C.

Chihuahua City, , Mexico

Szpital Uniwersytecki nr 2 im.dr J. Biziela

Bydgoszcz, , Poland

McBk S.C.

Grodzisk Mazowiecki, , Poland

Centrum Medyczne AMED

Lodz, , Poland

Szpital Wojewodzki im. Prymasa Kardynala Stefana Wyszynskiego

Sieradz, , Poland

Samodzielny Publiczny ZOZ Tomaszow Lubelski

Tomaszów Lubelski, , Poland

McM Polimedica

Warsaw, , Poland

State Budgetary Healthcare Institution "City Clinical Hospital # 15 n.a O.M. Filatov" of Moscow Healtheare Department

Moscow, Moscow Oblast, Russia

City Clinical Hospital #1

Novosibirsk, Novosibirsk Oblast, Russia

Diagnostic Center Ultramed

Omsk, Omsk Oblast, Russia

SBHI of the Republic of Karelia "Republican Hospital named after V.A.Baranov"

Petrozavodsk, Republic of Karelia, Russia

Rostov State Medical Unversity

Rostov-on-Don, Rostov Oblast, Russia

SBHI of Stavropol Region "Stavropol Regional Clinical Hospital"

Stavropol, Stavropol Kray, Russia

Regional Clinical Hospital

Vladimir, Vladimirskaya Oblast’, Russia

FSBSI "Scientific Research Institute of Rheumatology n.a. V.A. Nasonova"

Moscow, , Russia

Ajou University Hospital

Suwon, Gyeonggi-do, South Korea

Chonnam National University Hospital

Gwangju, , South Korea

Hallym University Sacred Heart Hospital

Gyeonggi-do, , South Korea

Severance Hospital, Yonsei University

Seoul, , South Korea

Countries

United States; Argentina; Brazil; Colombia; Czechia; Germany; Hungary; Mexico; Poland; Russia; South Korea

References

Feist E, Fatenejad S, Grishin S, Korneva E, Luggen ME, Nasonov E, Samsonov M, Smolen JS, Fleischmann RM. Olokizumab, a monoclonal antibody against interleukin-6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by tumour necrosis factor inhibitor therapy: efficacy and safety results of a randomised controlled phase III study. Ann Rheum Dis. 2022 Dec;81(12):1661-1668. doi: 10.1136/ard-2022-222630. Epub 2022 Sep 15.

Reference Type: DERIVED

PMID: 36109142 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2015-005308-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CL04041025

Identifier Type: -

Identifier Source: org_study_id