Long-term safety of apraglutide in short bowel syndrome

Overview

Sponsor-declared trial summary

Key facts

Sponsor

VectivBio AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

14 Jun 2021 → ongoing

Decision date (initial)

2024-07-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

VectivBio AG

External identifiers

EU CT number

2023-510389-28-00

EudraCT number

2020-005513-41

WHO UTN

U1111-1301-8440

ClinicalTrials.gov

NCT05018286

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Pharmacokinetic, Therapy, Safety, Efficacy

To assess long-term safety and tolerability of apraglutide in subjects with SBS-IF

Secondary objectives 1

1. To evaluate markers indicative of clinical effects of apraglutide

Conditions and MedDRA coding

short bowel syndrome

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. 1. Males and females with a diagnosis of SBS-IF secondary to surgical resection of the small intestine, with CIC or stoma, who were trial subjects of TA799-007 or TA799-013 (parent trials) and: a. Did not meet any stopping criteria b. For those subjects who completed a parent trial, they have 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. For those subjects who completed a parent trial, they have 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 d. When the required number of trial-completed subjects is achieved in a parent trial, the remaining subjects still on treatment may prematurely discontinue the parent trial and roll over into TA799-012 (before completing all the parent trial visits). Criterion “d” was not applicable to sites in France
2. 2. Able to give informed consent and agree to follow the details of participation as outlined in this protocol
3. 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/early termination visit. Such methods include combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable); intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner. To be considered sterilized or infertile, females must have undergone surgical sterilization (bilateral tubectomy, hysterectomy or bilateral ovariectomy) or be postmenopausal (defined as at least 12 months amenorrhea without an alternative medical cause, may be confirmed with follicle-stimulating hormone [FSH] test in case of doubt). Women who do not engage in heterosexual intercourse will be allowed to join the trial without contraception following a thorough discussion with the Investigator to determine if this is feasible for the subject. The following methods are not considered acceptable methods of contraception: calendar, ovulation, symptothermal, post-ovulation methods, withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method
4. 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/early termination visit. Nevertheless, if their partners are women of childbearing potential, they must agree to practice contraception and use a highly effective method of contraception during the trial and for 4 weeks after the EOT/early termination visit. Such methods include combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable); intrauterine device; intrauterine hormone-releasing system, bilateral tubal occlusion

Exclusion criteria 3

1. 1. Subject not capable of understanding or not willing to adhere to the trial visit schedules and other protocol requirements
2. 2. Subject not undergoing a baseline colonoscopy (if anatomically feasible) or CT/MRI colonography and not having had all identified colonic or rectal polyps removed
3. 3. Judged not eligible by the Investigator for any other reason

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. 1. Adverse events (AEs; system organ class, frequency and severity)
2. 2. 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
3. 3. Clinical chemistry, hematology, hemostasis and urinalysis
4. 4. Occurrence of clinically relevant changes in vital signs (systolic and diastolic blood pressure, heart rate)
5. 5. Occurrence of clinically relevant changes in electrocardiogram (ECG; intervals and rhythm)

Secondary endpoints 14

1. 1. Change from baseline in PS volume at Weeks 52, 104, 152, 216, 264 and 312
2. 2. Change from baseline in PS frequency at Weeks 52, 104, 152, 216, 264 and 312
3. 3. Change from baseline in PS composition at Weeks 52, 104, 152, 216, 264 and 312
4. 4. Change from baseline in PS infusion time at Weeks 52, 104, 152, 216, 264 and 312
5. 5. Percentage of subjects reaching enteral autonomy by Weeks 52, 104, 152, 216, 264 and 312
6. 6. Change from baseline in body weight at Weeks 52, 104, 152, 216, 264 and 312
7. 7. Change from baseline on the Pittsburgh Sleep Quality Index (PSQI) at Weeks 52, 104, 152, 216, 264 and 312
8. 8. Change from baseline on the Patient Global Impression of Change (PGIC) at Weeks 52, 104, 152, 216, 264 and 312
9. 9. Change from baseline on the Patient Global Impression of Severity (PGIS) at Weeks 52, 104, 152, 216, 264 and 312
10. 10. Changes from baseline on Patient Global Impression of Treatment Satisfaction (PGI-TS) at Weeks 52, 104, 152, 216, 264 and 312
11. 11. Changes from baseline on Patient Global Impression of Satisfaction with Parenteral Support (PGI-SPS) at Weeks 52, 104, 152, 216, 264 and 312
12. 12. Changes from baseline on Patient Global Impression of Parenteral Support Impact (PGI-PSI) at Weeks 52, 104, 152, 216, 264 and 312
13. 13. Change from baseline on the Short Form (36) Health Survey (SF-36) at Weeks 52, 104, 152, 216, 264 and 312
14. 14. Change from baseline on the EuroQoL-5 dimension - 5 level survey (EQ-5D-5L) at Weeks 52, 104, 152, 216, 264 and 312

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

VectivBio AG

Sponsor organisation

VectivBio AG

Address

Aeschenvorstadt 36

City

Basel

Postcode

4051

Country

Switzerland

Scientific contact point

Organisation

VectivBio AG

Contact name

Clinical Trial Information Desk

Public contact point

Organisation

VectivBio AG

Contact name

Clinical Trial Information Desk

Third parties 13

Sponsor responsibilities

Article 77 compliance

VectivBio AG

Contact point sponsor

VectivBio AG

Article 77 implementation

VectivBio AG

Locations

11 EU/EEA countries · 36 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 67 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications