A Randomized, Open-label, Single Dose, 3-Period, 6-Sequence Cross-Over Trial to Investigate the Relative Bioavailability of Apraglutide Versus the Reference Formulation Following Subcutaneous Administrations.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

VectivBio AG

Participant type

Healthy volunteers

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

23 May 2023 → 22 Sep 2023

Decision date (initial)

2023-05-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Bioequivalence, Safety, Others, Pharmacokinetic

To assess the relative bioavailability of apraglutide in DCS compared to the reference formulation apraglutide in vials.

Secondary objectives 2

1. To assess the bioequivalence of apraglutide in DCS compared to the reference formulation apraglutide in vials.
2. To assess the safety and tolerability of apraglutide in DCS versus apraglutide in vials.

Conditions and MedDRA coding

Healthy

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Signed and dated Informed Consent Form (ICF) prior to any trial-mandated procedure.
2. Male or female subjects aged from 18.0 to 67.0 years (inclusive) at the time of signing the ICF.
3. Body mass index range from 18.0 to 35.0 inclusive kg/m2 (inclusive).
4. Women of childbearing potential must agree to practice effective contraception and to use a highly effective method of contraception (see Section 7.1.1) during the trial and for 4 weeks after the FU visit.
5. Women of childbearing potential with vasectomized partner. Women considered sterilized or infertile, females who have undergone surgical sterilization (bilateral tubectomy, bilateral tubal occlusion, hysterectomy, or bilateral ovariectomy).
6. Postmenopausal women. Postmenopausal status is defined as no regular menstrual bleeding for at least 12 months prior to inclusion. Menopause will be confirmed by a serum estradiol concentration of <58 pmol/L and a serum follicle-stimulating hormone (FSH) level of >23 IU/L.
7. Male subjects with a female partner of childbearing potential must commit to practice highly effective methods of contraception (e.g., condom, vasectomy) and abstain from sperm donation during the trial and for 4 weeks after the FU visit. Their partners, if they are women of childbearing potential, must agree to practice effective contraception and to use a highly effective method of contraception during the trial and for 4 weeks after the FU visit. See Section 7.1.3.
8. Able to participate, willing to give written informed consent, and comply with the trial restriction.
9. Subject must be healthy, as determined by medical history, complete physical examination (including vital signs and ECG), and safety laboratory tests (general biochemistry, hematology, urinalysis) including negative tests for human immunodeficiency virus (HIV), hepatitis A immunoglobulin (Ig)M, hepatitis B, and hepatitis C.

Exclusion criteria 21

1. Body weight less than 50.0 kg and more than 110.0 kg.
2. History of clinically significant gastro-intestinal, hepatic, bronchopulmonary, neurological, cardiovascular, endocrine, renal, allergic, or psychiatric disease in the opinion of the Investigator.
3. Any clinically relevant abnormal laboratory test results that are not in line with subject status of healthy subject in the opinion of the Investigator.
4. If female of child-bearing potential, a positive blood pregnancy test.
5. Lactating women.
6. Positive urine test for alcohol and drugs of abuse at Screening and on Day -1.
7. Use of prohibited medications excepting the use of paracetamol with a maximum dose of 4 g per day for treatment of AEs and the use of hormonal contraceptives during the study as described in Section 10.2.
8. Known presence or history of intestinal polyps.
9. Known presence or history of any type of cancer.
10. Pancreatic events such as chronic and acute pancreatitis, pancreatic duct stenosis, pancreas infection, and increased blood amylase and lipase (>2.0–5.0 × upper limit of normal range) at Screening and on Day -1 of each period.
11. Participation in an investigational drug or device study within 30 days prior to Screening.
12. Donation of blood over 499 mL within 3 months prior to Screening.
13. Donation of plasma within 2 weeks prior to Screening.
14. Heavy use of tobacco products (i.e., smokes more than 10 cigarettes per day at the time of Screening).
15. Concomitant disease or condition that could interfere with, or for which the treatment of might interfere with, the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the subject in this trial.
16. Any clinically significant illness in the previous 28 days before Day 1 of this study as determined by Investigator
17. Positive results to HIV antigen/antibody combo, hepatitis A virus (HAV) IgM, hepatitis B surface antigen (HBsAg), hepatitis B core antigen (anti-HBc) or hepatitis C virus (HCV) tests.
18. Unwillingness or inability to comply with the study protocol for any other reason.
19. Supine pulse rate less than 40 beats per minute or more than 100 beats per minute at Screening. Supine systolic blood pressure below 90 mmHg or higher than 140 mmHg. Supine diastolic blood pressure below 45 mmHg or higher than 90 mmHg at Screening
20. Any known skin condition that can affect SC dosing or interpretation of injectireactions.
21. History of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for males (1 drink = 5 ounces [150 mL] of wine, or 12 ounces [360 mL] of beer, or 1.5 ounces [45 mL] of hard liquor) within 3 months of Screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Maximum concentration (Cmax).
2. Area under the curve to infinity (AUC0-inf) or the area under the curve from time zero to the last quantifiable concentration (AUClast [also called AUC0-t]), if AUC0-inf cannot be correctly estimated.

Secondary endpoints 3

1. Time of maximum plasma concentration (tmax).
2. Terminal elimination rate constant (λz).
3. Terminal half-life (t1/2).

Investigational products

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

Test 3

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

Federico Bolognani, Head of Clinical Development

Public contact point

Organisation

VectivBio AG

Contact name

Clinical Trial Information Desk

Third parties 2

Locations

1 EU/EEA country · 1 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 3 files

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

Application history

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