E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10009900 |
E.1.2 | Term | Colitis ulcerative |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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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 Long-Term Safety and Efficacy of ABT-494 |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Dose Optimization Substudy: To evaluate the efficacy and safety of dose decrease from upadacitinib 30 mg QD to 15 mg QD among eligible subjects who receive upadacitinib 30 mg QD for 6 consecutive months and are in stable clinical remission. |
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E.3 | Principal inclusion criteria |
1. Subject has not responded at the end of the induction period (Week 8) in Study M14-234 (Substudy 1), who has been an inadequate responder during the maintenance period of Study M14-234 (Substudy 3), or who has responded and successfully completed Study M14-234 substudy 3.
During the COVID-19 pandemic, for subjects with missing endoscopy due to the COVID-19 pandemic in studies M14-234 SS2, SS3 and M14-675 those following subjects may be enrolled if the below criteria is met: Subjects who achieved clinical response defined by Partial Adapted Mayo Score at Week 8 of Studies M14-234 SS2 and M14-675 ● Subjects who achieved clinical response defined by Partial Adapted Mayo Score at Week 16 in the extended treatment period of Studies M14-234 SS2 and M14-675 Note: If endoscopy is missing at Week 8 but can be performed at Week 16, Week 16 endoscopy should be performed. However, the status of clinical response will be defined by Partial Adapted Mayo Score and clinical responders may enter Study M14-533 Cohort 1. ● Subjects who have completed the 52-week treatment in Study M14-234 SS3 if the PI considers it is safe to continue based on phone/video call, subject's medical history and findings from the last endoscopy.
2. Women of childbearing potential (refer to Section 5.2.4) must have a negative urine pregnancy test at Week 0 visit.
3. If female, subject must meet the criteria as stated in Section 5.2.4 of this protocol: Contraception Recommendations
4. Subject is judged to be in otherwise good health as determined by the principal investigator based upon clinical evaluations performed during the preceding studies.
5. Must be able and willing to give written informed consent and to comply with the requirements of this study protocol. |
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E.4 | Principal exclusion criteria |
1. For any reason subject is considered by the investigator to be an unsuitable candidate.
2. Female subject with a positive pregnancy test at Baseline (final visit of the preceding studies) or who is considering becoming pregnant during the study and within 30 days after the last dose of study drug.
3. Subject with an active or recurrent infection that based on the investigator's clinical assessment makes the subject an unsuitable candidate for the study. Subjects with ongoing infections undergoing treatment may be enrolled BUT NOT dosed until the infection has been successfully treated.
4. Current evidence of active tuberculosis; Current evidence of latent tuberculosis and for any reason the subject cannot take full course of TB prophylaxis treatment
5. Subject with a poorly controlled medical condition, such as uncontrolled diabetes, unstable ischemic heart disease, moderate or severe congestive heart failure (New York Heart Association class III or IV), recent cerebrovascular accidents and any other condition which, in the opinion of the investigator or sponsor, would put the subject at risk by participation in this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of adverse events (Aes) will be assessed for both Main Study, Dose Optimization Substudy, and in an integrated manner. Changes in vital signs, physical examination results, and change from the randomization into the Dose Optimization Substudy in clinical laboratory data will be assessed.
Primary endpoint for Efficacy of Dose Optimization Substudy:: Proportion of subjects with clinical remission per Adapted Mayo Score at Week 48 defined as SFS ≤ 1 and not greater than baseline, RBS of 0, endoscopy subscore ≤ 1 without friability, and without corticosteroid use during the 48-week period. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to 288 weeks with the option of continued treatment dependent on country specific regulatory approval and local requirements. |
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E.5.2 | Secondary end point(s) |
The clinical remission or response will be evaluated using the Mayo Scoring System for Assessment of Ulcerative Colitis Activity (Full Mayo score), Adapted Mayo score (Full Mayo score excluding Physician’s Global Assessment), or Partial Mayo score (Full Mayo score excluding endoscopic subscore). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Up to 288 weeks with the option of continued treatment dependent on country specific regulatory approval and local requirements. |
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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 | Yes |
E.6.6 | Pharmacokinetic | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
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 | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 130 |
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 |
Argentina |
Australia |
Brazil |
Canada |
Chile |
China |
Colombia |
Egypt |
Israel |
Japan |
Malaysia |
Mexico |
Singapore |
South Africa |
United States |
European Union |
Switzerland |
Belarus |
Bosnia and Herzegovina |
Russian Federation |
Turkey |
Ukraine |
Serbia |
Croatia |
Latvia |
Norway |
Korea, Republic of |
Puerto Rico |
Taiwan |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | No |
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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The end-of-study is defined as the date of end of study participation (i.e., the last subject's last visit or the actual date of follow-up contact, whichever is later) by the last subject in the last country where the study was conducted. |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 27 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 27 |