Semaglutide in Auto-HSCT (PROTECT)

Semaglutide Treatment for PRevention Of Toxicity in High-dose Chemotherapy With Autologous Haematopoietic Stem Cell Transplantation

The primary objective of this clinical trial is to ievaluate the effect of semaglutide (GLP-1 receptor agonist) in reducing intensity of gastrointestinal (GI) mucositis in patients undergoing high-dosage chemotherapy followed by autologous (auto) haematopoietic stem cell transplantation (HSCT). The secondary objective is to evaluate the effect and safety of semaglutide in reducing gut barrier injury and systemic inflammation in patients undergoing auto-HSCT.

Study design:

The study is designed as a randomized, double-blind, placebo-controlled, phase 2, two-centre investigator-initiated clinical study.

Patients referred for treatment with high-dose chemotherapy and auto-HSCT will be randomized in a 1:1 manner to receive either semaglutide or placebo. The study includes a run-in period 3 to 4-week low-dose period with semaglutide subcutaneously (s.c.) 0.25 mg once-weekly (QW) prior to high-dose chemotherapy treatment followed by a period of 4 to 5 weeks with semaglutide 0.5 mg QW. Total duration of treatment with investigational drug will be 8 weeks. Total study duration for the individual patients will be 20-22 weeks, including a 2-4-week screening period and 10 weeks of follow-up.

Study population:

A planned total number of 40 patients will be randomized.

Study Overview

• Status: Not yet recruiting
• Conditions: Inflammation; Chemotherapeutic Toxicity; Intestinal Mucositis
• Intervention / Treatment: Drug: Semaglutide Pen Injector [Ozempic]; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Maria Ebbesen Sørum, MD, PhD; Phone Number: 004540638545; Email: maria.ebbesen.soerum@regionh.dk
• Study Contact Backup: Name: Klaus Müller, DMSc; Phone Number: 004525325559; Email: klaus.mueller@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Referral for auto-HSCT for relapsed diffuse large B-cell lymphoma or follicular lymphoma
• Age ≥ 18 years
• BMI ≥ 18.5
• ECOG performance status* ≤ 2
• Literate in Danish and/or English

Exclusion Criteria:

• Diabetes
• Inflammatory bowel disease
• Previous or current gastrointestinal malignancy
• Personal or family history of medullary thyroid carcinoma or MEN syndrome
• Genetic disorders with defective tissue repair (e.g., Fanconi anaemia)
• History of pancreatitis (acute or chronic)
• Renal impairment measured as eGFR value of < 30 ml/min/1.73 m2
• Impaired liver function, defined as alanine aminotransferase ≥ 2.5 times upper normal limit at screening
• Known or suspected hypersensitivity to semaglutide or other GLP-1RA
• Pregnant or nursing females

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Semaglutide; Semaglutide active drug 0.25-0.5mg, once-weekly, injection	Drug: Semaglutide Pen Injector [Ozempic]; Semaglutide active drug
Placebo Comparator: Placebo; Semaglutide placebo, once-weekly, injection	Drug: Placebo; semaglutide placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
gastrointestinal mucositis severity	mean severity grade (0-II)	from day of stem cell infusion (day 0) to week +3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CRP increment	AUC	from day of stem cell infusion (day 0) to week +3
Quality of life general	evaluated by EORTC QLQ-C30 questionnaire. The QLQ-C30 summary score is calculated as the mean of the combined 13 QLQ-C30 scale and item scores (excluding global QoL and financial impact). Final scoring range: 0-100 with a higher score indicating a better quality of life	change from baseline (start of high-dose chemotherapy) to study week 9 and 18
Quality of life - high-dose chemotherapy treatment specific	evaluated by EORTC QLQ-HDC29 questionnaire. The QLQ HDC29 module includes 29 items, consisting of 6 multi-item scales and 8 singleitems. Final scoring range: 0-100 with a higher score indicating a better quality of life	change from baseline (start of high-dose chemotherapy) to study week 9 and 18
Safety profile evaluated by number of SARs	SAR will be estimated according to ICH-GCP guidelines	Start of study drug treatment (week 1) until study week 10

Collaborators and Investigators

• Sponsor: Klaus Gottlob Müller
• Collaborators: Novo Nordisk A/S; Independent Research Fund Denmark

Study record dates

Study Major Dates

• Study Start (Estimated): August 12, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: May 14, 2024
• First Submitted That Met QC Criteria: June 3, 2024
• First Posted (Actual): June 10, 2024

Study Record Updates

• Last Update Posted (Actual): June 10, 2024
• Last Update Submitted That Met QC Criteria: June 3, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Growth factor; Gut epithelial barrier; Chemotherapy-induced toxicity
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Stomatognathic Diseases; Mouth Diseases; Inflammation; Mucositis; Hypoglycemic Agents; Physiological Effects of Drugs; Glucagon-Like Peptide-1 Receptor Agonists; Semaglutide
• Other Study ID Numbers: U1111-1277-7868; 2022-502139-20-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No