A Trial to Compare BioChaperone Insulin Lispro Formulations With US Approved Humalog® and With EU Approved Humalog® in Patients With Type 1 Diabetes Mellitus

NCT04501107 | Completed Phase 1 FDA Drug

• 1 other identifier: CT037-ADO02
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-centre, randomised, double-blind, 4-way crossover, 4-treatment, euglycaemic clamp study in subjects with Type 1 Diabetes Mellitus (T1DM). Each subject will be randomly allocated to one of four treatment sequences. Each sequence comprises one single dose of each of four IMPs. IMP1 and IMP2 are BioChaperone lispro formulations. They have the same composition and correspond to different development stages of a unique product which is BioChaperone insulin lispro; between them, improvements were made to prepare industrial production. Comparators (IMP3 and IMP4) are US-approved Humalog® and EU-approved Humalog®. All IMPs will be dosed at 0.2 U/Kg of insulin lispro on 4 dosing visits separated by a washout period of 5 to 15 days. The trial will compare the characteristics of BioChaperone insulin lispro fully liquid (IMP2) formulation to US-approved Humalog and EU-approved Humalog.

Conditions

Type 1 Diabetes

Outcome Measures

Primary Outcomes (4)

• AUCGIR.0-12h

  Area under the glucose infusion rate-time curve from time 0 until end of clamp

  From t=0 to t=12 hours after IMP administration

• AUCGIR.0-1h

  Area under the glucose infusion rate-time curve from time 0 to 1 hour after IMP administration

  From t=0 to t=1 hour after IMP administration

• AUCLIS.0-12h

  Area under the insulin lispro concentration-time curve from 0 hours to 12 hours after dose administration

  From t=0 to t=12 hours after IMP administration

• AUCLIS.0-1h

  Area under the insulin lispro concentration-time curve from 0 hours to 1 hour after dose administration

  From t=0 to t=1 hour after IMP administration

Secondary Outcomes (7)

• tmax.LIS

  From t=0 to t=12 hours after IMP administration

• Cmax.LIS

  From t=0 to t=12 hours after IMP administration

• AUCLIS.2-6h

  From t=2 to t=6hours after IMP administration

• t50%-LIS (early)

  From t=0 to t=12 hours after IMP administration

• tmax.GIR

  From t=0 to t=12 hours after IMP administration

Study Arms (4)

BioChaperone insulin lispro reconstituted with Humalog® (IMP1)

EXPERIMENTAL

Subcutaneous administration of Biochaperone insulin lispro formulation made from a freeze-dried of BioChaperone reconstituted with Humalog® at a dose of 0.2 U/Kg Body Weight (BW).

Drug: Administration of BioChaperone insulin lispro reconstituted with Humalog® (IMP1)

Ready-to-use BioChaperone insulin lispro (IMP2)

EXPERIMENTAL

Subcutaneous administration of ready-to-use Biochaperone insulin lispro formulation at a dose of 0.2 U/Kg BW.

Drug: Administration of Ready-to-use BioChaperone insulin lispro (IMP2)

US-approved Humalog® (IMP3)

ACTIVE COMPARATOR

Subcutaneous administration of US-approved Humalog® at a dose of 0.2 U/Kg BW.

Drug: Administration of US-approved Humalog® (IMP3)

EU-approved Humalog® (IMP4)

ACTIVE COMPARATOR

Subcutaneous administration of EU-approved Humalog® at a dose of 0.2 U/Kg BW.

Drug: Administration of EU-approved Humalog® (IMP4)

Interventions

Administration of BioChaperone insulin lispro reconstituted with Humalog® (IMP1) DRUG

Administration of IMP1 during a 12-hour euglycaemic clamp.

BioChaperone insulin lispro reconstituted with Humalog® (IMP1)

Administration of Ready-to-use BioChaperone insulin lispro (IMP2) DRUG

Administration of IMP2 during a 12-hour euglycaemic clamp.

Ready-to-use BioChaperone insulin lispro (IMP2)

Administration of US-approved Humalog® (IMP3) DRUG

Administration of IMP3 during a 12-hour euglycaemic clamp.

US-approved Humalog® (IMP3)

Administration of EU-approved Humalog® (IMP4) DRUG

Administration of IMP4 during a 12-hour euglycaemic clamp.

EU-approved Humalog® (IMP4)

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects with type 1 Diabetes Mellitus
• Body Mass Index (BMI) between 18.5 and 28.5 kg/m\^2, both inclusive
• HbA1c \<= 75 mmol/mol (\<=9.0%).
• Fasting negative C-peptide (\<= 0.30 nmol/L).
• Total insulin dose of \< 1.2 (I)U/kg/day.
• Stable insulin regimen (with respect to safety of the subject and scientific integrity of the study) using continuous subcutaneous insulin infusion (CSII) or multiple daily insulin injections (MDI) for at least 2 months.

You may not qualify if:

• Known or suspected hypersensitivity to IMP(s) or related products.
• Receipt of any medicinal product in clinical development within 30 days or at least 5 half-lives of the related substances and their metabolites (whichever is longer) before randomisation in this trial.
• History of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reaction.
• Any history or presence of cancer except basal cell skin cancer or squamous cell skin cancer as judged by the Investigator.
• Any history or presence of clinically relevant comorbidity capable of constituting a risk for the subject when participating in the trial or of interfering with the interpretation of data.
• Signs of acute illness as judged by the Investigator.
• Any serious systemic infectious disease during four weeks prior to first dosing of the trial drug, as judged by the Investigator.
• Clinically significant abnormal screening laboratory tests, as judged by the Investigator.
• Proliferative retinopathy or maculopathy as judged by the Investigator based on a recent (\<1.5 years) ophthalmologic examination.
• Use of oral antidiabetic drugs (OADs) and/or GLP-1 receptor agonists within 3 months prior to screening.

Sponsors & Collaborators

• Adocia: lead

Study Sites (1)

Profil GmbH

Mainz, D-55116, Germany

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Insulin Lispro; signal peptide peptidase; IGF2BP2 protein, human

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Insulin, Short-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Eugen Baumgaertner, MD

  Profil GmbH

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2020
• First Posted: August 6, 2020
• Study Start: August 3, 2020
• Primary Completion: November 3, 2020
• Study Completion: November 3, 2020
• Last Updated: November 30, 2020

Record last verified: 2020-11

Locations

DE (1)