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 | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10049416 |
E.1.2 | Term | Short-bowel syndrome |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess long-term safety and tolerability of apraglutide in subjects with SBS-IF |
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E.2.2 | Secondary objectives of the trial |
To evaluate markers indicative of clinical effects of apraglutide |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males and females with a diagnosis of SBS-IF secondary to surgical resection of the small intestine, with CIC or stoma, who have completed parent trials TA799-007 or TA799-013 and:
a. Did not meet any stopping criteria.
b. Received a minimum of 70% of the planned doses in the trial (unless an AE precluded the subject from meeting this percentage; in this case, the Investigator will decide if the subject will benefit from enrolling in the trial).
c. Completed the last two scheduled visits of the parent trial. Subjects who were forced to withdraw from TA799-007 or TA799-013 for logistical reasons not related to the efficacy or safety of apraglutide (e.g., hospitalization for a car accident, coronavirus disease (COVID-19) pandemic, emergency surgery, etc.) which resulted in several consecutive missed doses, including the last 2 visits, may be eligible to participate in this trial upon approval by the Medical Monitor.
2. Able to give informed consent and agree to follow the details of participation as outlined in this protocol.
3. Women of childbearing potential must agree to use a highly effective method of contraception during the trial and for 4 weeks after the EOT visit.
4. Male subjects with a female partner of childbearing potential must commit to practice methods of contraception and abstain from sperm donation during the trial and for 2 weeks after the EOT Visit. |
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E.4 | Principal exclusion criteria |
1. Subject not capable of understanding or not willing to adhere to the trial visit schedules and other protocol requirements.
2. Judged not eligible by the Investigator or any other reason. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Adverse events (AEs; system organ class, frequency and severity)
- Occurrence of clinically relevant AEs of special interest (AESIs):
o Injection site reactions
o Gastrointestinal (GI) obstructions
o Gallbladder, biliary and pancreatic disease
o Fluid overload
o Colorectal polyps
o Malignancies
- Clinical chemistry, hematology, hemostasis and urinalysis
- Occurrence of clinically relevant changes in vital signs (systolic and diastolic blood pressure, heart rate)
- Occurrence of clinically relevant changes in electrocardiogram (ECG; intervals and rhythm)
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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) |
- Change from baseline in PS volume at Week 104
- Change from baseline in PS frequency at Week 104
- Change from baseline in PS composition at Week 104
- Change from baseline in PS infusion time at Week 104
- Percentage of subjects reaching enteral autonomy by Week 104
- Change from baseline in body weight at Week 104
- Change from baseline on the Pittsburgh Sleep Quality Index (PSQI) at
Week 104
- Change from baseline on the Patient Global Impression of Change
(PGIC) at Week 104
- Change from baseline on the Patient Global Impression of Severity
(PGIS) at Week 104
- Changes from baseline on Patient Global Impression of Treatment
Satisfaction (PGI-TS) at Weeks 52 and 104
- Changes from baseline on Patient Global Impression of Satisfaction
with Parenteral Support (PGI-SPS) at Weeks 52 and 104
- Changes from baseline on Patient Global Impression of Parenteral
Support Impact (PGI-PSI) at Weeks 52 and 104 |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | No |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
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 |
China |
Israel |
Japan |
Korea, Republic of |
Taiwan |
United States |
France |
Poland |
Sweden |
Spain |
Czechia |
Germany |
Italy |
Belgium |
Denmark |
Norway |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |