Canakinumab for the Treatment of Postprandial Hypoglycemia

NCT05401578 | Recruiting Phase 3 DMC

• 1 other identifier: 2021-02325; kt21Donath2
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 2

Brief Summary

The primary objective of this randomized trial is to test whether a treatment with canakinumab is superior to placebo in patients with postprandial hypoglycemia after bariatric surgery, that is if it improves health related quality of life (mentally or physically) or reduces the risk of hypoglycemic events.

Conditions

Postprandial Hypoglycemia

Keywords

bariatric surgery; IL-1 receptor antagonist; postbariatric hypoglycemia; canakinumab; quality of life

Outcome Measures

Primary Outcomes (3)

• Change in Health related quality of life (mental health)

  Health related quality of life (mental health; as assessed by the SF-36 mental health component score; MCS). The lower the score the more disability.

  At Baseline (study day 1), day 29 (-1 /+2 days) and at Follow- up (day 90 +/- 11 days)

• Change in Health related quality of life (physical health)

  Health related quality of life (physical health; as assessed by the SF-36 physical component score; PCS). The lower the score the more disability.

  At Baseline (study day 1), day 29 (-1 /+2 days) and at Follow- up (day 90 +/- 11 days)

• Number of Hypoglycemic events

  Hypoglycemic events defined as glucose values below 3.0 mmol/l

  From Baseline (study day 1) to day 29 (-1 /+2 days)

Secondary Outcomes (11)

• Change in Postprandial Symptoms of hypoglycemia according to Edinburgh Hypoglycemia Scale (EHSS)

  At Baseline (study day 1), day 29 (-1 /+2 days) and at Follow- up (day 90 +/- 11 days)

• Change in Hypoglycemia unawareness (measured by modified Clarke Score)

  At Baseline (study day 1), day 29 (-1 /+2 days) and at Follow- up (day 90 +/- 11 days)

• Change in Fear of hypoglycemia (measured on a scale of 0 to 10)

  At Baseline (study day 1), day 29 (-1 /+2 days) and at Follow- up (day 90 +/- 11 days)

• Time below range (TBR; % of sensor glucose readings and time between 3.0 and 3.8 mmol/L)

  From Baseline (study day 1) to day 29 (-1 /+2 days)

• Time in hypoglycemia: % of sensor glucose readings and time below 3.0 mmol/L

  From Baseline (study day 1) to day 29 (-1 /+2 days)

Study Arms (2)

Study Intervention: Canakinumab

ACTIVE COMPARATOR

Standard dose of canakinumab (Ilaris®; Novartis Switzerland), i. e. 150 mg subcutaneously. Canakinumab (Ilaris®, Novartis) is a recombinant, human monoclonal IgG1/kappa antibody inhibiting IL-1β by neutralizing its biological activity through binding to the IL-1 receptor.

Drug: Canakinumab

Control Intervention: Placebo (0.9% NaCl)

PLACEBO COMPARATOR

Placebo: 1 ml of 0.9 % NaCl

Drug: Placebo (0.9% NaCl)

Interventions

Canakinumab DRUG

Canakinumab (Ilaris®, Novartis Switzerland) will be used in the recommended standard dose of 150 mg subcutaneously once. Patients will be randomized at visit 2 = Baseline to either placebo (1 ml 0.9 % saline solution s.c.) or treatment with 1 ml 150 mg canakinumab solution s.c. in a 1:1 manner.

Study Intervention: Canakinumab

Placebo (0.9% NaCl) DRUG

1 ml 0.9 % saline solution s.c. Patients will be randomized at visit 2 = Baseline to either placebo (1 ml 0.9 % saline solution s.c.) or treatment with 1 ml 150 mg canakinumab solution s.c. in a 1:1 manner.

Control Intervention: Placebo (0.9% NaCl)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients after bariatric surgery (i.e. sleeve gastrectomy, Roux-en-Y gastric bypass, omega-loop bypass, biliopancreatic diversion) with documented hypoglycemia, i. e. \< 3.0 mmol/l and at least 5 hypoglycemic episodes per week despite dietary modification
• For women with child-bearing potential, willingness to use contraceptive measures adequate to prevent pregnancy during the study
• Informed Consent as documented by signature

You may not qualify if:

• Any type of diabetes mellitus according to ADA criteria
• Intolerance to the study drug
• Signs of current infection
• Any use of immunosuppressive medication
• Use of any drug therapy for postbariatric hypoglycemia apart from acarbose (all remaining drugs have to be discontinued four half-life times before screening phase)
• Neutropenia (leukocyte count \< 1.5 × 109/L or ANC \< 0.5 × 109/L)
• Anemia (hemoglobin \< 11 g/dL for males, \< 10 g/dL for females)
• Clinically significant kidney or liver disease (creatinine \> 1.5 mg/dL, AST/ALT \> 2 × ULN, alkaline phosphatase \> 2 × ULN, or total bilirubin \[tBili\] \> 1.5 × ULN)
• Uncontrolled congestive heart failure
• Uncontrolled malignant disease
• Currently pregnant or breastfeeding
• Known or suspected non-compliance, drug or alcohol abuse
• Meeting the criteria for vulnerability (e.g. participants incapable of judgment or participants under tutelage)
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc.
• Participation in another clinical trial using investigational drugs in the last 30 days or planned participation in the next 60 days

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (2)

University Hospital Basel, Division of Endocrinology, Diabetes and Metabolism

Basel, 4031, Switzerland

RECRUITING

Cantonal Hospital Olten, Division of Endocrinology

Olten, 4600, Switzerland

RECRUITING

MeSH Terms

Conditions

Hypoglycemia

Interventions

canakinumab

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Marc Y Donath, Prof. Dr.

  University of Basel

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marc Y Donath, Prof. Dr.

CONTACT

+41 61 265 25 25; marc.donath@usb.ch

Susanne Ruesch

CONTACT

+41 61 556 5655; susanne.ruesch@usb.ch

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Both subjects and investigators will be blinded. A nurse independent of the research group will be responsible for treatment blinding and preparation of trial drugs throughout the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: National, multicenter, 1:1 randomized, placebo-controlled, parallel-group, double-blind superiority trial

Study Record Dates

• First Submitted: May 23, 2022
• First Posted: June 2, 2022
• Study Start: April 17, 2023
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2026
• Last Updated: January 29, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CH (2)