E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
To evaluate the testicular safety of filgotinib in adult males with moderately to severely Active Inflammatory Bowel Disease |
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E.1.1.1 | Medical condition in easily understood language |
Inflammatory Bowel Disease |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045365 |
E.1.2 | Term | Ulcerative colitis |
E.1.2 | System Organ Class | 100000004856 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10013099 |
E.1.2 | Term | Disease Crohns |
E.1.2 | System Organ Class | 100000004856 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
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E.2.2 | Secondary objectives of the trial |
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 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
For a full list please see the study protocol.
- Males between the age of 21 and 65 (inclusive) on the day of signing informed consent
- Documented diagnosis of UC or CD of at least 4 months duration. Documentation must include endoscopic and histopathologic documentation, as follows: a) UC i) Medical record documentation of, or an endoscopy report dated ≥ 4 months before randomization, which shows features consistent with UC, determined by the procedure performing physician, AND ii) Medical record documentation of, or a histopathology report indicating features consistent with UC as determined by the pathologist, AND Note: Subject also needs to have minimum disease extent of 15 cm from the anal verge b) CD i) Medical record documentation of, or an ileocolonoscopy (full colonoscopy with intubation of terminal ileum) reported dated ≥ 4 months before randomization, which shows features consistent with CD, determined by the procedure performing physician, AND ii) Medical record documentation of, or a histopathology report indicating features consistent with, CD as determined by the pathologist
- Moderately to severely active UC, or moderately to severely active CD, assessed locally and defined by: a) UC I) Mayo Clinic Score (MCS; Appendix 3) ≥ 6, PGA of 2 or 3, and endoscopic subscore ≥ 2, at Screening or in the prior 90 days b) CD I) CDAI total score (Appendix 9) ≥ 220, AND ii) Evidence of active inflammation, with a total score of ≥ 6 by the Simple Endoscopic Activity Score in Crohn's Disease (SES-CD; Appendix 10), OR if disease is limited to the ileum and/or right colon, a combined SES-CD score ≥ 4 in these 2 segments, at Screening or in the prior 90 days
- Previously demonstrated an inadequate clinical response, loss of response to, or intolerance of at least one of the following agents (depending on current country treatment recommendations/guidelines): a) corticosteroids b) immunomodulators c) TNFα antagonists d) vedolizumab e) Ustekinumab (criterion applicable only to subjects with CD)
- May be receiving 1 or more of the following drugs (subjects on these therapies must be willing to remain on stable doses for the noted times): a) 5-aminosalicylate (5-ASA) compounds provided the dose prescribed has been stable for at least 4 weeks prior to randomization; dose must remain stable for the first 13 weeks after randomization b) Azathioprine, 6-MP, or MTX provided the dose prescribed has been stable for 4 weeks prior to randomization; dose of MTX must remain stable for 26 weeks and dose of AZA/6-MP must remain stable for first 13 weeks but can be adjusted if indicated between 13 and 26 weeks. c) Corticosteroid therapy (prednisone prescribed at a stable dose ≤ 20 mg/day or budesonide prescribed at a stable dose of ≤ 9 mg/day); dose should not be changed during the first 13 weeks. A steroid taper should only commence after Week 13.
- The mean of 2 separate semen samples collected at the Screening visit must meet the following minimum criteria (in accordance with Section 6.13 and Figure 6-1): 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 normal reference ranges at Screening
- Be up to date on colorectal cancer surveillance as per local guidelines prior to screening. |
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E.4 | Principal exclusion criteria |
For a full list please see the study protocol.
- 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 treatment with antiandrogen therapy (including but not limited to spironolactone or oral ketoconazole), or treatment within 4 weeks of Screening
- Current treatment with testosterone replacement therapy, or treatment within 12 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
- Current use of sulfasalazine or use of sulfasalazine within 26 weeks of Screening; sulfasalazine is not permitted at any point during the study
- Use of any TNFα antagonist or vedolizumab within 8 weeks prior to screening, ustekinumab 12 weeks prior to screening, or any other biologic agent within 8 weeks prior to Screening or within 5 half-lives of the biologic agent prior to screening, whichever is longer
- Currently have complications of CD as any of the following: a) Symptomatic strictures, OR b) Severe (impassable) rectal/anal stenosis, OR c) Fistulae, OR d) Short bowel syndrome, OR e) Any other complications which could preclude the use of the CDAI to assess response to therapy, or would possibly confound the evaluation of benefit from treatment with filgotinib |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the proportion of subjects with a ≥ 50% decrease from baseline in sperm concentration at Week 13. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 70 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
India |
New Zealand |
United States |
Austria |
Poland |
Netherlands |
Romania |
Spain |
Germany |
Portugal |
Russian Federation |
Ukraine |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of Study is reached when the last subject completes the LTE Week 195 visit, or when the last subject completes his last visit, whichever is sooner. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 13 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 16 |