Study to Evaluate the Effect of Filgotinib on Semen Parameters in Adult Males With Active Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, or Non-radiographic Axial Spondyloarthritis (MANTA-RAy)

A Randomized, Double-blind, Placebo-controlled Phase 2 Study to Evaluate the Effect of Filgotinib on Semen Parameters in Adult Males With Active Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis or Non-radiographic Axial Spondyloarthritis

The primary objective of this study is to evaluate the effect of filgotinib on semen parameters in adult males with active rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or non-radiographic axial spondyloarthritis.

Results of this study may be pooled with the results of a separate study being conducted in participants with inflammatory bowel disease (Protocol GS-US-418-4279; NCT03201445) with the same objective.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis; Psoriatic Arthritis; Ankylosing Spondylitis; Non-Radiographical Axial Spondyloarthritis
• Intervention / Treatment: Drug: Filgotinib; Drug: Placebo; Drug: Standard of Care

• Study Type: Interventional
• Enrollment (Actual): 109
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Pleven, Bulgaria, 5800
    • Medical Center Medconsult Pleven Ood
  • Plovdiv, Bulgaria, 4000
    • UMHAT Sv. Georgi, EAD
  • Plovdiv, Bulgaria, 4002
    • MHAT "Eurohospital" - Plovdiv, OOD
  • Plovdiv, Bulgaria, 4000
    • UMHAT Pulmed OOD
  • Ruse, Bulgaria, 7000
    • Medical Center Teodora, EOOD
  • Sevlievo, Bulgaria, 5400
    • Medizinski Zentar-1-Sevlievo EOOD
  • Sofia, Bulgaria, 1504
    • DCC 17 - Sofia EOOD
  • Sofia, Bulgaria, 1407
    • Medical Center Excelsior, OOD
  • Sofia, Bulgaria, 1431
    • DCC Alexandrovska, EOOD
  • Sofia, Bulgaria, 1431
    • UMHAT Sv. Ivan Rilski, EAD
  • Sofia, Bulgaria, 1606
    • Meditsinski Centar - Izgrev EOOD
  • Sofia, Bulgaria, 1784
    • MC Synexus - Sofia, EOOD
• Czechia
  • Brno, Czechia, 60200
    • CCR Brno s.r.o.
  • Ostrava, Czechia, 702 00
    • Vesalion s.r.o.
  • Ostrava, Czechia, 702 00
    • CCBR Ostrava s.r.o
  • Ostrava, Czechia, 708 00
    • MUDr. Rosypalova s.r.o.
  • Pardubice, Czechia, 530 02
    • Bioclinica Pardubice
  • Praha, Czechia, 128 52
    • Revmatologicky ustav
  • Praha, Czechia, 10000
    • Clintrial s.r.o.
  • Praha, Czechia, 140 59
    • Thomayerova nemocnice
  • Praha, Czechia, 14000
    • MUDr Zuzana Stejfova Revmatologicka ambulance
  • Praha, Czechia, 14800
    • Affidea Praha s.r.o.
  • Uherské Hradiště, Czechia, 68601
    • Medical Plus S.R.O.
• Estonia
  • Tallinn, Estonia, 13419
    • North Estonia Medical Centre Foundation
  • Tallinn, Estonia, 10117
    • OU Innomedica
  • Tallinn, Estonia, 10128
    • Center For Clinical And Basic Research
  • Tartu, Estonia, 50106
    • Clinical Research Centre
  • Tartu, Estonia, 50406
    • MediTrials OÜ
• Georgia
  • Tbilisi, Georgia, 0159
    • Tbilisi Heart and Vascular Clinic Ltd
  • Tbilisi, Georgia, 0159
    • Chapidze Emergency Cardiology Center
  • Tbilisi, Georgia, 0159
    • Institute of Clinical Cardiology Ltd
  • Tbilisi, Georgia, 0159
    • National Institute of Endocrinology
  • Tbilisi, Georgia, 0160
    • Aversi ClinicLtd.
  • Tbilisi, Georgia, 0179
    • Clinic on Mtskheta Street
  • Tbilisi, Georgia, 0186
    • Consilium Medulla-multiprofile clinic Ltd
  • Tbilisi, Georgia, 0186
    • Medicore Ltd.
• Latvia
  • Ādaži, Latvia, LV2164
    • M&M center
• Poland
  • Bydgoszcz, Poland, 85-168
    • Szpital Uniwersytecki nr 2 im. dr J. Biziela
  • Bydgoszcz, Poland, 85-065
    • Nasz Lekarz Ośrodek Badań Klinicznych
  • Katowice, Poland, 40-282
    • Silmedic sp. z o.o
  • Knurów, Poland, 44-190
    • Indywidualna Specjalistyczna Praktyka Lekarska Maciej Zymla
  • Lublin, Poland, 20-607
    • Zespol Poradni Specjalistycznych REUMED
  • Poznań, Poland, 60-529
    • SOLUMED Centrum Medyczne
  • Poznań, Poland, 60-773
    • Centrum Badan Klinicznych S.C.
  • Poznań, Poland, 61-113
    • Ai Centrum Medyczne Sp. Z O.O. Sp.K.
  • Sochaczew, Poland, 96-500
    • RCMed
  • Warsaw, Poland, 00-874
    • Medycyna Kliniczna
  • Warszawa, Poland, 03-291
    • Centrum Medyczne AMED
  • Łódź, Poland, 91-363
    • Centrum Medyczne AMED
• Spain
  • Santiago, Spain, 15702
    • Clinica Gaias
• Ukraine
  • Dnipro, Ukraine, 49102
    • CI Dnipropetrovsk CMCH #4 RC
  • Ivano-Frankivs'k, Ukraine, 76008
    • Regional CH Dep of Rheumatology SHEI Ivano-Frankivsk NMU
  • Kharkiv, Ukraine, 61039
    • GI L.T.Malaya Therapy National Institute of the NAMS of Ukraine
  • Kharkiv, Ukraine, 61124
    • CHI Kharkiv City Clinical Hospital #13
  • Kherson, Ukraine, 73000
    • CI A.and O. Tropiny City Clinical Hospital
  • Kyiv, Ukraine, 02091
    • Med Center 'Ok!Clinic+' of International Institute of Clinical Trials LLC
  • Kyiv, Ukraine, 03680
    • SI NSС M.D. Strazhesko Institute of Cardiology of NAMSU
  • Kyiv, Ukraine, 01023
    • Medical Center of Limited Liability Company Medical Clinic Blagomed
  • Kyiv, Ukraine, 04050
    • Limited Liability Company Medical Center Concilium Medical
  • Kyiv, Ukraine, 04050
    • LLC Treatment-Diagnostic Center ADONIS plus
  • Luts'k, Ukraine, 43005
    • Volyn Regional Clinical Hospital
  • Lviv, Ukraine, 79000
    • Lviv Regional Clinical Hospital Dept of Rheumatology NMU
  • Lviv, Ukraine, 79049
    • Mil&Med Cl C of Lviv of the St Border Service of Ukraine
  • Odesa, Ukraine, 65000
    • Center of Reconstructive & Restorative Medicine of Odessa National Medical University
  • Poltava, Ukraine, 36011
    • M.V. Sklifosovskyi Poltava RCH Dept of Rheumatology HSEIU UMSA
  • Ternopil, Ukraine, 46002
    • Ternopil University Hospital, Dept. of Rheumatology, SHEI I.Ya.Horbachevskyi Ternopil SMU
  • Vinnytsia, Ukraine, 21001
    • Private Small Enterprise Medical Center Pulse
  • Vinnytsia, Ukraine, 21018
    • Vinnytsia M.I.Pyrogov RCH Dept of cardiology NMU
  • Vinnytsia, Ukraine, 21029
    • MCIC Health Clinic BO LTD TDC Slaomed
  • Zaporizhzhya, Ukraine, 69035
    • CI CCH #6 Dept of Therapy ZSMU
  • Zaporizhzhya, Ukraine, 69600
    • CI Zaporizhzhia Regional Clinical Hospital of ZRC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Diagnosis of active rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or, non-radiographic axial spondyloarthritis for at least 12 weeks prior to screening, meeting the corresponding specific disease classification criteria as specified in the protocol

Key Exclusion Criteria:

• Previously documented problems with male reproductive health
• Prior diagnosis of male infertility
• Use of any prohibited concomitant medication as outlined by protocol

Note: Other protocol-defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Filgotinib; Participants received filgotinib 200 milligrams (mg) tablet, orally, once daily up to Week 13 in the double-blind (DB) phase. At Week 13, participants who were arthritis responders, were unblinded and received open-label (OL) treatment filgotinib 200 mg, tablet, orally, once daily up to approximately 143 weeks (until Week 156) in the extension (EXT) phase and participants who were arthritis nonresponders discontinued blinded study drug and started standard of care (SOC) treatment in the EXT phase. Participants on DB treatment or OL filgotinib who entered the monitoring phase (if their sperm parameters met ≥50% decrease threshold in pre-specified semen parameters) discontinued the study drug and started SOC for up to 52 weeks.	Drug: Filgotinib; 200-mg tablet administered orally once daily; Other Names: GS-6034; Jyseleca®; Drug: Standard of Care; Locally approved treatment, accepted by medical experts as a proper treatment for rheumatic conditions, prescribed according to best clinical practice, with no known testicular toxicity.
Placebo Comparator: Placebo; Participants received placebo (matched to filgotinib) tablet, orally, once daily up to Week 13 in the DB phase. At Week 13, participants were unblinded and started SOC treatment in the EXT phase for up to approximately 143 weeks (until Week 156). Participants who entered the monitoring phase (if their sperm parameters met ≥50% decrease threshold in pre-specified semen parameters) continued on SOC treatment.	Drug: Placebo; Placebo to match filgotinib tablet administered orally once daily; Drug: Standard of Care; Locally approved treatment, accepted by medical experts as a proper treatment for rheumatic conditions, prescribed according to best clinical practice, with no known testicular toxicity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a ≥ 50% Decrease From Baseline in Sperm Concentration at Week 13	Baseline for sperm/semen parameters was the mean of 2 evaluable semen samples at screening. The normal range for sperm concentration is ≥15 million sperms/mL. Percentage change = ([mean at Week 13 - baseline] / baseline) × 100; value at Week 13 was the mean of 2 evaluable samples collected at Week 13.	Baseline to Week 13

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a ≥ 50% Decrease From Baseline in Sperm Concentration at Week 26	Arthritis responder: For rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and non-radiographic axial spondyloarthritis (nrAxSpA), a participant with an improvement in the Physician's Global Assessment of Disease Activity (PhGADA) of at least 20% compared with baseline (Day 1) at the specified assessment time. Arthritis nonresponder: For RA, PsA, AS, or nrAxSpA, a participant who did not fulfill the definition of arthritis responder at the specified assessment timepoint. PhGADA: Physician measured the participant's disease severity on a visual analogue scale (VAS) ranged from 0 (no disease)-100 (worst disease) millimeters (mm). Baseline value for sperm/semen parameters was the mean of 2 evaluable semen collections at the screening visit. The normal range for sperm concentration is ≥15 million sperms/mL. Percentage change = ([mean at Week 26 - baseline] / baseline) × 100; value at Week 26 was the mean of 2 evaluable samples collected at Week 26.	Baseline to Week 26
Change From Baseline in Sperm Total Motility at Week 13	The normal range for sperm total motility is ≥40%.	Baseline, Week 13
Change From Baseline in Sperm Total Motility at Week 26	Arthritis responder: For RA, PsA, AS, and nrAxSpA, a participant with an improvement in the PhGADA of at least 20% compared with baseline (Day 1) at the specified assessment time. Arthritis nonresponder: For RA, PsA, AS, or nrAxSpA, a participant who did not fulfill the definition of arthritis responder at the specified assessment timepoint. PhGADA: Physician measured the participant's disease severity on a VAS ranged from 0 (no disease)-100 (worst disease) mm. The normal range for sperm total motility is ≥40%.	Baseline, Week 26
Change From Baseline in Total Sperm Count at Week 13	The normal range for total sperm count is ≥ 39 million sperms/ejaculate.	Baseline, Week 13
Change From Baseline in Total Sperm Count at Week 26	Arthritis responder: For RA, PsA, AS, and nrAxSpA, a participant with an improvement in the PhGADA of at least 20% compared with baseline (Day 1) at the specified assessment time. Arthritis nonresponder: For RA, PsA, AS, or nrAxSpA, a participant who did not fulfill the definition of arthritis responder at the specified assessment timepoint. PhGADA: Physician measured the participant's disease severity on a VAS ranged from 0 (no disease)-100 (worst disease) mm. The normal range for total sperm count is ≥ 39 million sperms/ejaculate.	Baseline, Week 26
Change From Baseline in Sperm Concentration at Week 13	The normal range for sperm concentration is ≥15 million sperms/mL.	Baseline, Week 13
Change From Baseline in Sperm Concentration at Week 26	Arthritis responder: For RA, PsA, AS, and nrAxSpA, a participant with an improvement in the PhGADA of at least 20% compared with baseline (Day 1) at the specified assessment time. Arthritis nonresponder: For RA, PsA, AS, or nrAxSpA, a participant who did not fulfill the definition of arthritis responder at the specified assessment timepoint. PhGADA: Physician measured the participant's disease severity on a VAS ranged from 0 (no disease)-100 (worst disease) mm. The normal range for sperm concentration is ≥15 million sperms/mL.	Baseline, Week 26
Change From Baseline in Ejaculate Volume at Week 13	The normal range for ejaculate volume is ≥1.5 mL.	Baseline, Week 13
Change From Baseline in Ejaculate Volume at Week 26	Arthritis responder: For RA, PsA, AS, and nrAxSpA, a participant with an improvement in the PhGADA of at least 20% compared with baseline (Day 1) at the specified assessment time. Arthritis nonresponder: For RA, PsA, AS, or nrAxSpA, a participant who did not fulfill the definition of arthritis responder at the specified assessment timepoint. PhGADA: Physician measured the participant's disease severity on a VAS ranged from 0 (no disease)-100 (worst disease) mm. The normal range for ejaculate volume is ≥1.5 mL.	Baseline, Week 26
Change From Baseline in Percent Normal Sperm Morphology at Week 13	The normal range for percent normal sperm morphology is ≥30% normal sperms.	Baseline, Week 13
Change From Baseline in Percent Normal Sperm Morphology at Week 26	Arthritis responder: For RA, PsA, AS, and nrAxSpA, a participant with an improvement in the PhGADA of at least 20% compared with baseline (Day 1) at the specified assessment time. Arthritis nonresponder: For RA, PsA, AS, or nrAxSpA, a participant who did not fulfill the definition of arthritis responder at the specified assessment timepoint. PhGADA: Physician measured the participant's disease severity on a VAS ranged from 0 (no disease)-100 (worst disease) mm. The normal range for percent normal sperm morphology is ≥30% normal sperms.	Baseline, Week 26

Collaborators and Investigators

• Sponsor: Galapagos NV
• Collaborators: Gilead Sciences
• Investigators: Study Director: Galapagos Study Director, Galapagos NV

Publications and helpful links

General Publications

• Hellstrom WJG, Dolhain RJEM, Ritter TE, Watkins TR, Arterburn SJ, Dekkers G, Gillen A, Tonussi C, Gilles L, Oortwijn A, Van Beneden K, de Vries DE, Sikka SC, Vanderschueren D, Reinisch W. MANTA and MANTA-RAy: Rationale and Design of Trials Evaluating Effects of Filgotinib on Semen Parameters in Patients with Inflammatory Diseases. Adv Ther. 2022 Jul;39(7):3403-3422. doi: 10.1007/s12325-022-02168-4. Epub 2022 May 25.

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2019
• Primary Completion (Actual): August 14, 2020
• Study Completion (Actual): May 10, 2023

Study Registration Dates

• First Submitted: April 19, 2019
• First Submitted That Met QC Criteria: April 19, 2019
• First Posted (Actual): April 24, 2019

Study Record Updates

• Last Update Posted (Actual): August 1, 2023
• Last Update Submitted That Met QC Criteria: July 13, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Infections; Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Psoriasis; Bone Diseases, Infectious; Ankylosis; Arthritis; Arthritis, Rheumatoid; Arthritis, Psoriatic; Spondylitis; Spondylarthritis; Spondylitis, Ankylosing; Axial Spondyloarthritis; Non-Radiographic Axial Spondyloarthritis
• Other Study ID Numbers: GLPG0634-CL-227; 2018-003933-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes