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Efficacy of Extracorporeal Photopheresis (ECP) in the Treatment of Type 1 Diabetes Mellitus (OPERA)

Primary Purpose

Type 1 Diabetes

Status

Recruiting

Phase

Early Phase 1

Locations

United Arab Emirates

Study Type

Interventional

Intervention

ECP regular-intensity arm

ECP accelerated-intensity arm

T1DM standard of care

About this trial

This is an interventional treatment trial for Type 1 Diabetes focused on measuring Type 1 diabetes, Extracorporeal photopheresis, ECP

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria
- Confirmed and documented diagnosis of T1DM. Patients must have:
- A documented history of T1DM within the first 3 years of onset.
- Should be on a multiple dose injection (MDI) therapy.
- C-Peptide levels of ˂ 0.7 ng/mL.
- HbA1C ≥ 6.5% to ≤ 10%.
- Evidence of pancreatic autoimmunity, if available (positive anti-glutamic acid decarboxylase [GAD]; Islet antigen 2 [anti-IA2]; and/or zinc transporter 8 [ZnT8] antibodies).
- Male or female aged ≥ 18 to ≤ 50 years.
- Weight > 40 kg.
- Hematocrit ≥ 32%.
- Platelet count ≥ 100 x10^9/L (with or without transfusion support).
- Willingness to participate in all OPERA Study tests, visits, and ECP procedures, as outlined in the informed consent.
- Willingness to use at least one reliable method of birth control (e.g. abstinence, oral contraceptives, intrauterine devices, barrier method with spermicide, or surgical sterilization) throughout the study for all men and women of childbearing potential.
- The patient agrees to participate in the trial, and signs the OPERA Study informed consent form.
Exclusion Criteria
- Pediatric aged < 18 or ˃ 50 years.
- Clinical diagnosis of type 2 diabetes mellitus (T2DM).
- Inability to tolerate fluid changes associated with ECP (e.g. inadequate renal, hepatic, pulmonary and cardiac function leading to enable patient to tolerate extracorporeal volume shifts associated with ECP).
- Hypersensitivity or allergy to citrate products.
- Hypersensitivity or allergy to psoralen compounds such as Methoxsalen (8-Methoxypsoralen, 8-MOP).
- Aphakia (8-MOP is contraindicated because of the significantly increased risk of retinal damage due to the absence of lenses).
- Presence of comorbidities that may result in photosensitivity (systemic lupus erythematosus, porphyries, albinism, etc.).
- Suspected or diagnosed Diabetic Ketoacidosis (DKA) at the moment of the screening visit.
- Uncontrolled infection requiring treatment at study entry.
- Laboratory evidence of any of the following:
- White Blood Cell (WBC) count < 3.00 x10^9/L.
- Serum transaminase levels > x2 upper normal limit (UNL).
- Hematocrit < 32%.
- Platelet count < 100 x10^9/L (with or without transfusion support).
- Diagnostic of Hepatitis B Virus (HBV) infection.
- Diagnostic of Human Immunodeficiency Virus (HIV) infection or Acquired Immunodeficiency Syndrome (AIDS).
- Pregnant or lactating women.
- Have participated in other clinical trial in the past 3 months.
- Organ transplants in the past 3 months.
- Current diagnosis of cancer.
- Inability to comply with all OPERA Study tests, visits, and procedures (including ECP).
- Inability to provide informed consent.

Sites / Locations

Abu Dhabi Stem Cells CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Group A (ECP regular-intensity arm)

Group B (ECP accelerated-intensity arm)

Arm Description

ECP in a regular-intensity arm plus T1DM standard of care

ECP in an accelerated-intensity arm plus T1DM standard of care

Outcomes

Primary Outcome Measures

Tolerability to ECP procedures

Rate of tolerability of the ECP will be assessed by the number of ECP discontinuation due to adverse events (AE), or withdrawal of participants of the Study due to serious adverse events (SAEs)

Incidence of adverse events (AEs)

Incidence of treatment-emergent adverse events (TEAEs), adverse events of special interest (AESIs), and serious adverse events (SAEs): Proportion of participants with AEs as assessed by CTCAE v5.0

Exogenous insulin use

Rate of modification in exogenous insulin requirements compared with baseline. Marker for efficacy of treatment: reducing insulin dose

HbA1c levels

Rate of modification in HbA1c levels compared with baseline. Marker for efficacy of treatment: decreasing for a target HbA1c level of 48 mmol/mol [6.5%]

C-peptide levels

Rate of modification in C-Peptide levels compared with baseline. Marker for efficacy of treatment: increasing C-Peptide levels of ≥ 0.7 ng/mL

Clinically important hypoglycemic episodes

Frequency of clinically important hypoglycemic episodes (described in Protocol). Marker for efficacy of treatment: requiring decrease of insulin dose)

Secondary Outcome Measures

Immune response profile (cellular)

CD3, CD4, CD8, CD11c, CD14, CD16, CD19, CD20, CD25, CD27, CD28, CD38, CD45, CD45RA, CD45RO, CD56, CD57, CD66b, CD123, CD127, CD161, CD294, CCR4, CCR6, CCR7, CXCR3, CXCR5, will be assessed for identification of immune cells and subsets analyses

Serum IgG levels

Serum IgG concentration will be assessed for characterization of the humoral response profile

Serum IgA levels

Serum IgA concentration will be assessed for characterization of the humoral response profile

Serum IgM levels

Serum IgM concentration will be assessed for characterization of the humoral response profile

Full Information

NCT ID

NCT05413005

First Posted

June 7, 2022

Last Updated

October 28, 2022

Sponsor

Abu Dhabi Stem Cells Center

1. Study Identification

Unique Protocol Identification Number

NCT05413005

Brief Title

Efficacy of Extracorporeal Photopheresis (ECP) in the Treatment of Type 1 Diabetes Mellitus

Acronym

OPERA

Official Title

A Randomized, Open-label, Pilot Study Evaluating the Efficacy of Extracorporeal Photopheresis (ECP) in the Treatment of Type 1 Diabetes Mellitus

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Recruiting

Study Start Date

September 5, 2022 (Actual)

Primary Completion Date

October 1, 2023 (Anticipated)

Study Completion Date

January 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Abu Dhabi Stem Cells Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

OPERA Study is a randomized, open-label, prospective, pilot, and a monocentric clinical trial involving outpatients within Abu Dhabi Stem Cells Center (ADSCC) with a confirmed diagnosis of type 1 diabetes mellitus (T1DM). The patients will be randomly allocated (1:1) in a parallel assignment involving two groups of participants: Group A (Regular-intensity arm): Extracorporeal Photopheresis (ECP) on a regular-intensity regimen described in the Protocol as add-on T1DM standard of care, or Group B (Accelerated-intensity arm): ECP on an accelerated regimen plus T1DM standard of care.

Detailed Description

The standard of care is defined as per the "DOH Standards for diagnosis, management and data reporting for diabetes" in combination with the DOH recommended NICE (UK National Institute for Health and Care Excellence) guidelines "Type 1 diabetes in adults: diagnosis and management (NG17)". OPERA Study will be fully conducted in ADSCC, including the patient assessment and inclusion, randomization, ECP procedures, and follow-up consultations, according to this Protocol and GCP principles. All patients will receive T1DM standard of care, plus additional ECP protocols on two regimens of investigational interventions. The primary objective is the safety assessment of ECP, to be assessed by the tolerability to the ECP procedures, incidence of treatment-emergent adverse events (TEAEs), adverse events of special interest (AESIs), and serious adverse events (SAEs) assessed by the CTCAE v5.0, and the WHO-UMC causality assessment system. The other primary objective is the preliminary efficacy assessment of the ECP as an add-on treatment to the standard of care for T1DM patients, assessed by the exogenous insulin use, HbA1c levels, C-peptide levels, and clinically important hypoglycemic episodes. The secondary objective is the assessment of the immune response profile in T1DM patients receiving standard of care and additional ECP procedures. The trial is approved by the institutional ADSCC Research Ethics Committee (REC) and written informed consent will be obtained from all patients. OPERA Study will be conducted following the principles of the Declaration of Helsinki and ICH-GCP guidelines.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 1 Diabetes

Keywords

Type 1 diabetes, Extracorporeal photopheresis, ECP

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Parallel Assignment

Model Description

The patients will be randomly allocated (1:1) in a parallel assignment involving two groups of participants: Group A (Regular-intensity arm): ECP on a regular-intensity regimen described in the Protocol as add-on T1DM standard of care, or Group B (Accelerated-intensity arm): ECP on an accelerated regimen plus T1DM standard of care.

Masking

None (Open Label)

Allocation

Randomized

Enrollment

10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Group A (ECP regular-intensity arm)

Arm Type

Experimental

Arm Description

ECP in a regular-intensity arm plus T1DM standard of care

Arm Title

Group B (ECP accelerated-intensity arm)

Arm Type

Experimental

Arm Description

ECP in an accelerated-intensity arm plus T1DM standard of care

Intervention Type

Combination Product

Intervention Name(s)

ECP regular-intensity arm

Other Intervention Name(s)

Extracorporeal photochemotherapy, Extracorporeal photoimmunotherapy

Intervention Description

Weeks 1-8: Once every 2 weeks: weeks 1, 3, 5, 7 (cryo-ECP bags infused twice-a-week) Weeks 9-16: Once per month: weeks 9, 13 (cryo-ECP bags infused once-a-week) Weeks 17-24: One: week 17 (cryo-ECP bags infused every two weeks)

Intervention Type

Combination Product

Intervention Name(s)

ECP accelerated-intensity arm

Other Intervention Name(s)

Extracorporeal photochemotherapy, Extracorporeal photoimmunotherapy

Intervention Description

Weeks 1-8: Once every week: weeks 1- 7 (cryo-ECP bags infused twice-a-week) Weeks 9-16: Cryo-ECP bags infused once-a-week Weeks 17-24: Cryo-ECP bags infused every two weeks

Intervention Type

Biological

Intervention Name(s)

T1DM standard of care

Other Intervention Name(s)

Multiple Dose Injection (MDI) therapy

Intervention Description

The standard of care is defined as per the "DOH Standards for diagnosis, management and data reporting for diabetes" in combination with the DOH recommended NICE guidelines "Type 1 diabetes in adults: diagnosis and management (NG17)"

Primary Outcome Measure Information:

Title

Tolerability to ECP procedures

Description

Rate of tolerability of the ECP will be assessed by the number of ECP discontinuation due to adverse events (AE), or withdrawal of participants of the Study due to serious adverse events (SAEs)

Time Frame

Weeks 0 - 24

Title

Incidence of adverse events (AEs)

Description

Incidence of treatment-emergent adverse events (TEAEs), adverse events of special interest (AESIs), and serious adverse events (SAEs): Proportion of participants with AEs as assessed by CTCAE v5.0

Time Frame

Weeks 0 - 24

Title

Exogenous insulin use

Description

Rate of modification in exogenous insulin requirements compared with baseline. Marker for efficacy of treatment: reducing insulin dose

Time Frame

Baseline, months 3, 6, and 12

Title

HbA1c levels

Description

Rate of modification in HbA1c levels compared with baseline. Marker for efficacy of treatment: decreasing for a target HbA1c level of 48 mmol/mol [6.5%]

Time Frame

Baseline, months 3, 6, and 12

Title

C-peptide levels

Description

Rate of modification in C-Peptide levels compared with baseline. Marker for efficacy of treatment: increasing C-Peptide levels of ≥ 0.7 ng/mL

Time Frame

Baseline, months 3, 6, and 12

Title

Clinically important hypoglycemic episodes

Description

Frequency of clinically important hypoglycemic episodes (described in Protocol). Marker for efficacy of treatment: requiring decrease of insulin dose)

Time Frame

Baseline - Month 12

Secondary Outcome Measure Information:

Title

Immune response profile (cellular)

Description

Time Frame

Baseline, months 3, 6, and 12

Title

Serum IgG levels

Description

Serum IgG concentration will be assessed for characterization of the humoral response profile

Time Frame

Baseline, months 3, 6, and 12

Title

Serum IgA levels

Description

Serum IgA concentration will be assessed for characterization of the humoral response profile

Time Frame

Baseline, months 3, 6, and 12

Title

Serum IgM levels

Description

Serum IgM concentration will be assessed for characterization of the humoral response profile

Time Frame

Baseline, months 3, 6, and 12

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria Confirmed and documented diagnosis of T1DM. Patients must have: A documented history of T1DM within the first 3 years of onset. Should be on a multiple dose injection (MDI) therapy. C-Peptide levels of ˂ 0.7 ng/mL. HbA1C ≥ 6.5% to ≤ 10%. Evidence of pancreatic autoimmunity, if available (positive anti-glutamic acid decarboxylase [GAD]; Islet antigen 2 [anti-IA2]; and/or zinc transporter 8 [ZnT8] antibodies). Male or female aged ≥ 18 to ≤ 50 years. Weight > 40 kg. Hematocrit ≥ 32%. Platelet count ≥ 100 x10^9/L (with or without transfusion support). Willingness to participate in all OPERA Study tests, visits, and ECP procedures, as outlined in the informed consent. Willingness to use at least one reliable method of birth control (e.g. abstinence, oral contraceptives, intrauterine devices, barrier method with spermicide, or surgical sterilization) throughout the study for all men and women of childbearing potential. The patient agrees to participate in the trial, and signs the OPERA Study informed consent form. Exclusion Criteria Pediatric aged < 18 or ˃ 50 years. Clinical diagnosis of type 2 diabetes mellitus (T2DM). Inability to tolerate fluid changes associated with ECP (e.g. inadequate renal, hepatic, pulmonary and cardiac function leading to enable patient to tolerate extracorporeal volume shifts associated with ECP). Hypersensitivity or allergy to citrate products. Hypersensitivity or allergy to psoralen compounds such as Methoxsalen (8-Methoxypsoralen, 8-MOP). Aphakia (8-MOP is contraindicated because of the significantly increased risk of retinal damage due to the absence of lenses). Presence of comorbidities that may result in photosensitivity (systemic lupus erythematosus, porphyries, albinism, etc.). Suspected or diagnosed Diabetic Ketoacidosis (DKA) at the moment of the screening visit. Uncontrolled infection requiring treatment at study entry. Laboratory evidence of any of the following: White Blood Cell (WBC) count < 3.00 x10^9/L. Serum transaminase levels > x2 upper normal limit (UNL). Hematocrit < 32%. Platelet count < 100 x10^9/L (with or without transfusion support). Diagnostic of Hepatitis B Virus (HBV) infection. Diagnostic of Human Immunodeficiency Virus (HIV) infection or Acquired Immunodeficiency Syndrome (AIDS). Pregnant or lactating women. Have participated in other clinical trial in the past 3 months. Organ transplants in the past 3 months. Current diagnosis of cancer. Inability to comply with all OPERA Study tests, visits, and procedures (including ECP). Inability to provide informed consent.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Yandy M Castillo-Aleman, MD

Phone

+97126655155

Ext

104

yandy.castillo@adscc.ae

First Name & Middle Initial & Last Name or Official Title & Degree

Muhammad M Alam, MBBS

Phone

+97126655155

Ext

104

muhammad.alam@adscc.ae

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yandy M Castillo-Aleman, MD

Organizational Affiliation

Abu Dhabi Stem Cells Center

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Rene A Rivero-Jimenez, PhD

Organizational Affiliation

Abu Dhabi Stem Cells Center

Official's Role

Study Chair

Facility Information:

Facility Name

Abu Dhabi Stem Cells Center

City

Abu Dhabi

ZIP/Postal Code

4600

Country

United Arab Emirates

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yandy M Castillo-Aleman, MD

Phone

+97126655155

Ext

104

yandy.castillo@adscc.ae

First Name & Middle Initial & Last Name & Degree

Muhammad M Alam, MBBS

Phone

+97126655155

Ext

104

muhammad.alam@adscc.ae

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Efficacy of Extracorporeal Photopheresis (ECP) in the Treatment of Type 1 Diabetes Mellitus

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