A study evaluating the effect of filgotinib on sperm parameters in adult males with active rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or non-radiographic axial spondyloarthritis.

• Register: EUCTR
• Last refreshed on: 2 August 2021
• Main ID: EUCTR2018-003933-14-BG
• Date of registration: 27/03/2019
• Prospective Registration: Yes
• Primary sponsor: Galapagos NV
• Public title: A study evaluating the effect of filgotinib on sperm parameters in adult males with active rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or non-radiographic axial spondyloarthritis.
• Scientific title: 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.
• Date of first enrolment: 21/06/2019
• Target sample size: 250
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-003933-14
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: yes; Other trial design description: Open label after week 13; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Bosnia and Herzegovina, Bulgaria, Czech Republic, Czechia, Estonia, Georgia, Germany, India, Latvia, Moldova, Republic of, Poland, Romania, Russian Federation, Spain, Ukraine

Contacts

• Name: Clinical Trial Information Desk
• Affiliation: Galapagos NV

• Name: Clinical Trial Information Desk
• Affiliation: Galapagos NV

Key inclusion & exclusion criteria

Inclusion criteria:
- Male between the ages of 21 and 65 (inclusive) on the day of signing informed consent.
- Diagnosis of rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS) or non-radiographic axial spondyloarthritis (nrAxSpA) for at least 12 weeks prior to screening, meeting the corresponding specific classification criteria:
a) RA, American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) 2010
b) PsA, Classification criteria for Psoriatic Arthritis (CASPAR) criteria
c) AS or nrAxSpA, Assessment of Spondyloarthritis International Society (ASAS) criteria for axial spondyloarthritis
- For RA, PsA, AS, or nrAxSpA, meets the following criteria:
a) RA:
i) Inadequate response or intolerant to an =12-week course of csDMARD or biological DMARD (bDMARD) therapy for RA
ii) Have a Clinical Disease Activity Index (CDAI) >10 at screening
b) PsA
i) Inadequate response or intolerant =12-weeks’ course of csDMARD or bDMARD therapy for PsA
ii) Have a Disease Activity in Psoriatric Arthritis (DAPSA) score >14 at screening
c) Axial Spondyloarthritis (applicable to those with diagnosis of AS or nrAxSpA)
i) Inadequate response or intolerant to at least 2 non-steroidal anti-inflammatory drugs (NSAIDs), which may include cyclooxygenase-2 (COX-2 inhibitors) prescribed for a total period of =4 weeks OR to an at least 12 weeks’ course of csDMARD or bDMARD therapy for spondyloarthritis
ii) Have a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) =4 at screening
iii) At screening, subjects should have a C-reactive protein (CRP) >0.3 mg/dL OR sacroiliitis according to the modified New York (NY) criteria OR a history of active inflammation on magnetic resonance imaging (MRI) consistent with sacroiliitis within two year of screening
- If using csDMARD therapy, subjects are permitted to use one of the following drugs, alone or in combination and must have been on a stable dose of the drug for at least 4 weeks prior to Baseline and remain on a stable dose for the first 13 weeks in the study (stable dose in all cases is defined as no change in prescription):
a) MTX oral or parenteral up to 25 mg/week (with concomitant use of folic or folinic acid supplementation as per local standard of care)
b) Leflunomide (LEF) up to 20 mg/day orally
c) Hydroxychloroquine up to 400 mg/day or chloroquine up to 250 mg/day orally
d) Apremilast orally up to 30 mg twice daily orally
Note that sulfasalazine is not permitted at any time, beginning 26 weeks prior to Screening until the end of the study, and cannot be included in the standard of care arthritis regimen, due to its potential impact on semen parameters
- The mean of 2 separate semen samples collected at Screening must meet the following minimum criteria: semen volume = 1.5 mL, total sperm per ejaculate = 39 million, sperm concentration = 15 million per mL, sperm total motility = 40% and normal sperm morphology = 30%
- LH, FSH, inhibin B, and total testosterone values within 20% of laboratory reference ranges at Screening

This list only contains the key inclusion criteria.


Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 250
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- Previously documented problems with male reproductive health including, but not limited to, known hypothalamic-pituitary disorders (eg, pituitary macroadenomas, pituitary infarction, hyperprolactinemia, panhypopituitarism), primary hypogonadism (eg, cryptorchidism, Klinefelter’s syndrome)
- Prior diagnosis of male infertility (including reduced fertility), or history of anti-sperm antibodies
- Clinically significant (per judgment of investigator) varicocele or spermatocele
- History of radiation to the testicles
- History of clinically significant trauma to, or surgery on, the testicles, including vasectomy
- Current prior treatment with antiandrogen therapy (including but not limited to spirinolactone, oral ketoconazole, or cyproterone acetate), or treatment within 4 weeks of Screening
- Presence of disorders of sperm transport, including but not limited to retrograde ejaculation and immotile cilia syndrome.
- Clinically significant urinary tract infection, prostatitis, epididymitis, including sexually transmitted infection within 4 weeks of Screening
- Any sexual dysfunction of a nature that would prevent sperm collection in accordance with protocol guidance (phosphodiesterase inhibitors, however, are permitted during the study)

This list only contains the key exclusion criteria.


Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis and Non-radiographic Axial Spondyloarthritis
MedDRA version: 23.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
MedDRA version: 20.0 Level: PT Classification code 10002556 Term: Ankylosing spondylitis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
MedDRA version: 21.0 Level: LLT Classification code 10037160 Term: Psoriatic arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
MedDRA version: 20.0 Level: LLT Classification code 10076297 Term: Non-radiographic axial spondyloarthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Product Name: Filgotinib
Product Code: GLPG0634
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: FILGOTINIB
Other descriptive name: FILGOTINIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Proportion of subjects with a = 50% decrease from Baseline in sperm concentration at Week 13.

Main Objective: To evaluate the effect of filgotinib on testicular function as defined by the proportion of subjects with a = 50% decrease from Baseline in sperm concentration at Week 13

Secondary Objective: - To evaluate the effect of filgotinib on testicular function as defined by the proportion of subjects with a = 50% decrease from Baseline in sperm concentration at Week 26
- To evaluate the effect of filgotinib on sperm total motility at Weeks 13 and 26
- To evaluate the effect of filgotinib on total sperm count at Weeks 13 and 26
- To evaluate the effect of filgotinib on the change from Baseline in sperm concentration at Weeks 13 and 26
- To evaluate the effect of filgotinib on ejaculate volume at Weeks 13 and 26
- To evaluate the effect of filgotinib on sperm morphology at Weeks 13 and 26

Timepoint(s) of evaluation of this end point: At baseline and at week 13.

Secondary Outcome(s)

Secondary end point(s): - The proportion of subjects with a = 50% decrease from Baseline in sperm concentration at Week 26
- Change from Baseline in percent motile sperm at Weeks 13 and 26
- Change from Baseline in total sperm count at Weeks 13 and 26
- Change from Baseline in sperm concentration at Weeks 13 and 26
- Change from Baseline in ejaculate volume at Weeks 13 and 26
- Change from Baseline in percent normal sperm morphology at Weeks 13 and 26

Timepoint(s) of evaluation of this end point: At baseline, at week 13 and at week 26

Secondary ID(s)

2018-003933-14-LV

GLPG0634-CL-227

Source(s) of Monetary Support

Galapagos NV

Ethics review

Status: Approved
Approval date: 21/06/2019
Contact: