Velusetrag for the Treatment of Chronic Intestinal Pseudo-Obstruction (CIPO).

NCT05724069 | Completed Phase 2 Results

• 1 other identifier: VE-CIP2001/2021
• Study Type: interventional
• Target: 17
• Locations: 3 countries
• Sites: 4

Brief Summary

This is a phase II, multicenter, double-blind, placebo-controlled trial to evaluate the efficacy and safety of velusetrag once a day, compared to placebo, in subjects with CIPO.

Conditions

Chronic Intestinal Pseudo-obstruction

Outcome Measures

Primary Outcomes (1)

• Mean Change in Weekly Global Gastrointestinal Symptoms Average Index Score (WGGSAIS).

  Mean change in weekly global gastrointestinal symptoms average index score (WGGSAIS) from pretreatment (PRE) to the end of each treatment period (EOT). The weekly global gastrointestinal symptoms average index score is obtained by averaging the scores for each of the 4 symptoms, abdominal pain, bloating, nausea and vomiting, assessed using a subject's e-diary. Each symptom was rated using a recall period of 7 days and a Likert scale with the following categories: 0=none, 1=mild, 2=moderate, 3=severe, 4=very severe according to its influence on usual activity. The WGGSAIS thus ranges between 0 and 4 with lower scores representing better health.

  4 weeks. The change is derived as the end of treatment period minus the pre-treatment value of the period, for each period.

Study Arms (4)

Sequence A

OTHER

Eligible subjects will be treated for 4 periods with either velusetrag 15 mg once a day (2 periods) or placebo (2 periods), with a wash-out period of 2 weeks between treatment periods. The progression order of this sequence is: velusetrag first intervention 4 weeks, 2 weeks of wash-out period, then second intervention of placebo for 4 weeks, 2 weeks of wash-out period, then third intervention of velusetrag for other 4 weeks, 2 weeks of wash-out period and last 4 weeks of placebo as fourth intervention.

Drug: Velusetrag 15 mg once daily for 4 weeks.; Drug: Placebo once daily for 4 weeks.

Sequence B

OTHER

Eligible subjects will be treated for 4 periods with either velusetrag 15 mg once a day (2 periods) or placebo (2 periods), with a wash-out period of 2 weeks between treatment periods. The progression order of this sequence is: placebo first intervention 4 weeks, 2 weeks of wash-out period, then second intervention of velusetrag for 4 weeks, 2 weeks of wash-out period, then third intervention of placebo for other 4 weeks, 2 weeks of wash-out period and last 4 weeks of velusetrag as fourth intervention.

Drug: Velusetrag 15 mg once daily for 4 weeks.; Drug: Placebo once daily for 4 weeks.

Sequence C

OTHER

Eligible subjects will be treated for 4 periods with either velusetrag 15 mg once a day (2 periods) or placebo (2 periods), with a wash-out period of 2 weeks between treatment periods. The progression order of this sequence is: velusetrag first intervention 4 weeks, 2 weeks of wash-out period, then second intervention of placebo for 4 weeks, 2 weeks of wash-out period, then third intervention of placebo for other 4 weeks, 2 weeks of wash-out period and last 4 weeks of velusetrag as fourth intervention.

Drug: Velusetrag 15 mg once daily for 4 weeks.; Drug: Placebo once daily for 4 weeks.

Sequence D

OTHER

Eligible subjects will be treated for 4 periods with either velusetrag 15 mg once a day (2 periods) or placebo (2 periods), with a wash-out period of 2 weeks between treatment periods. The progression order of this sequence is: placebo first intervention 4 weeks, 2 weeks of wash-out period, then second intervention of velusetrag for 4 weeks, 2 weeks of wash-out period, then third intervention of velusetrag for other 4 weeks, 2 weeks of wash-out period and last 4 weeks of placebo as fourth intervention.

Drug: Velusetrag 15 mg once daily for 4 weeks.; Drug: Placebo once daily for 4 weeks.

Interventions

Velusetrag 15 mg once daily for 4 weeks. DRUG

Subjects will be randomly allocated in a blinded fashion to 1 out of the 4 treatment sequences (each sequence include 4 periods, 2 periods with velusetrag and 2 periods with placebo). There will be a wash-out period between each treatment period.

Sequence A; Sequence B; Sequence C; Sequence D

Placebo once daily for 4 weeks. DRUG

Subjects will be randomly allocated in a blinded fashion to 1 out of the 4 treatment sequences (each sequence include 4 periods, 2 periods with velusetrag and 2 periods with placebo). There will be a wash-out period between each treatment period.

Sequence A; Sequence B; Sequence C; Sequence D

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with history of chronic idiopathic intestinal pseudo-obstruction or CIPO secondary to neurodegenerative or demyelinating disease.
• Subjects with estimated oral caloric intake of at least 30% of the daily age- and sex-recommended caloric intake.
• Subjects with at least 2 out of 4 CIPO gastrointestinal symptoms each of the 2 with a score ≥3 (on a 0 to 4 scale) at Day -1
• Subjects accepting to provide and legally capable of providing free and informed consent to all procedures included in the protocol.
• All sexually active male participants who are partner of women of childbearing potential must use condom during intercourse until the 90th day after the end of the entire study.
• Female participants are eligible if they are: i) of non-childbearing potential or ii) of childbearing potential with a negative pregnancy test result at screening and randomization AND agreeing to use a highly effective method of contraception (i.e., with failure rate of less than 1% per year) until the end of the entire study.

You may not qualify if:

• Subjects with primary CIPO or CIPO secondary to other known endocrine/metabolic, autoimmune diseases and neurologic conditions other than neurodegenerative or demyelinating diseases.
• Subjects with conditions characterized by mechanical intestinal obstruction.
• Nasogastric tube, gastrostomy tube, or jejunostomy feeding tube in place at randomization or planned throughout the duration of the study, or artificial food need scale stage 3.
• Presence of untreated clinically relevant thyroid dysfunction or known thyroid dysfunction not well controlled by treatment deemed clinically significant by the Investigator.
• Subjects with history of diabetes at screening.
• Clinically significant ECG abnormalities at screening and randomization.
• Screening ECG with a QTcF \>450 msec in males or \>470 msec in females or family history of sudden cardiac death.
• Subjects requiring a low galactose diet.
• Hypersensitivity or documented intolerance to lactulose, lactose or any excipient of the lactulose preparation to be used for L-BT.
• History of sensitivity to velusetrag, or any of the velusetrag or placebo excipients.
• Use of scopolamine or erythromycin within 2 weeks prior to screening and/or planned throughout the duration of the study.
• Use of 5-HT4 receptor agonists within 5 days prior to randomization and/or planned throughout the duration of the study
• Use of opioids within 8 weeks from screening and/or planned throughout the duration of the study.
• Received strong cytochrome P450-isozyme 3A4 (CYP3A4) inhibitors within 2 weeks prior to screening and/or planned throughout the duration of the study.
• Received strong P-glycoprotein (P-gp) transporter inhibitors within 2 weeks prior to Screening and/or planned throughout the duration of the study.

Sponsors & Collaborators

• Alfasigma S.p.A.: lead

Study Sites (4)

UZ Leuven Gasthuisberg Campus

Leuven, B3000, Belgium

Location

Policlinico S.Orsola-Malpighi

Bologna, 40128, Italy

Location

Aou Arcispedale Sant'Anna Di Cona

Cona, 30010, Italy

Location

Hospital General Vall Hebron

Barcelona, 08035, Spain

Location

Related Publications (1)

• Malagelada C, De Giorgio R, Cogliandro RF, Alcala-Gonzalez L, Costanzini A, Scuderi V, Manzoni S, Pasquali E, Tack J, Stanghellini V. Clinical Trial: Efficacy and Safety of Velusetrag in Chronic Intestinal Pseudo-Obstruction: A Randomized, Phase 2, Placebo-Controlled, Crossover, Multiple (n = 1), Proof-of-Concept Study. Neurogastroenterol Motil. 2026 Jan;38(1):e70246. doi: 10.1111/nmo.70246.

  PMID: 41553253 DERIVED

MeSH Terms

Interventions

TD-5108

Results Point of Contact

• Title: Sara Manzoni
• Organization: Alfasigma

sara.manzoni@alfasigma.com

3473778218

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2023
• First Posted: February 13, 2023
• Study Start: December 15, 2021
• Primary Completion: April 12, 2023
• Study Completion: April 12, 2023
• Last Updated: August 3, 2025
• Results First Posted: August 3, 2025

Record last verified: 2025-07

Locations

BE (1); IT (2); ES (1)