Long Term Treatment Effect of the Safety, Tolerability and Efficacy of AAT in Type 1 Diabetes (AAT Extension)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Kamada, Ltd.
Information provided by (Responsible Party):
Rabin Medical Center
ClinicalTrials.gov Identifier:
NCT01661192
First received: August 7, 2012
Last updated: September 12, 2013
Last verified: September 2013
  Purpose

At a previous study the investigators have assessed the safety and efficacy of treatment with AAT(Alpha 1 Antitrypsin)in newly diagnosed type 1 diabetes subjects aiming at beta cells preservation .

Since treatment with AAT is expected to be a chronic treatment; stopping treatment will probably result in eventual loss of the preserved beta-cell function. Indeed, other investigational drugs aiming at beta cells preservation have shown that patients who were initially treated and maintained their initial beta-cell function, required continuation of treatment or they lost the beta-cell function.

Therefore, in this extension study, patients who were previously treated with AAT and maintained clinically significant beta-cell function are offered a continuation of treatment, since they are likely to benefit from use of the medication.

The proposed study is aimed to assess the long term effect of AAT in subjects with type 1 diabetes mellitus: safety and tolerability of treatment, and effect on beta-cell function.

Subjects who have completed all visits of the 008 study will be offered to participate in the extension study.

The study will be consist off two main arms as following:

Arm 1: Subjects who maintained peak stimulated C-peptide secretion ≥ 0.2 nmol/L will continue treatment with AAT for up to 18 treatments according to the dosage group they were allocated to in the 008 study.

Arm 2:

Subjects who have not maintained peak stimulated C-peptide secretion ≥ 0.2nmol/L and subjects with peak stimulated C -peptide secretion ≥ 0.2 nmol/L who are reluctant to receive additional study drug.

Clinical follow up for all subjects in both arms will be for 3 years


Condition Intervention Phase
Type 1 Diabetes
Beta Cell Preservation
Drug: AAT( Alpha 1 Antitrypsin)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Open Label Study (Extension 001)to Evaluate Long Term Treatment Effect of the Safety, Tolerability and Efficacy of Intervenous ALPHA-1 ANTITRYSIN (AAT)Glasia™ in Type 1 Diabetes Mellitus (Extension to KAMADA AAt 008, PHASE I/II Study)

Resource links provided by NLM:


Further study details as provided by Rabin Medical Center:

Primary Outcome Measures:
  • Safety and tolerability of AAT in terms of adverse events and serious adverse events [ Time Frame: At month 36 ] [ Designated as safety issue: Yes ]
    We will assess at each visit until final visit (month 36)the safety and tolerability of study drug in terms of adverse events and serious adverse events

  • Safety and tolerability of the AAT in terms of laboratory values [ Time Frame: At month 36 ] [ Designated as safety issue: Yes ]
    We will assess at each visit until final visit (month 36)the safety and tolerability of study drug in terms of laboratory values


Secondary Outcome Measures:
  • Beta cell function-AUC (Area Under the Curve) of stimulated C-Peptide from stimulated MMTT (mixed meal tolerance test) [ Time Frame: at month 36 ] [ Designated as safety issue: No ]
  • Percentage of patients that maintain stimulated peak C-peptide >=0.2 nmol/L [ Time Frame: at month 36 ] [ Designated as safety issue: No ]
  • Percentage of patients that achieve glycemic target of HbA1c <=7.5% [ Time Frame: At month 36 ] [ Designated as safety issue: No ]
  • Daily insulin dose adjusted to body weight [ Time Frame: At month 36 ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: January 2013
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AAT( Alpha 1 Antitrypsin)
Subjects who maintained peak stimulated C-peptide secretion ≥ 0.2nmol/L will continue treatment with AAT according to the dosage group they were allocated to at the previous study(40mg/kg or 60mg/kg or 80mg/kg), intravenously, once a week for 6 consecutive weeks, at 24-week intervals for a duration of ~54 weeks.
Drug: AAT( Alpha 1 Antitrypsin)
No Intervention: Follow up group
Subjects who have not maintained peak stimulated C-peptide secretion ≥ 0.2nmol/L or subjects with peak stimulated C -peptide secretion ≥ 0.2nmol/L who are reluctant to receive additional study drug, will be followed up only with no administration of investigational product

  Eligibility

Ages Eligible for Study:   10 Years to 25 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject (or parent/guardian) willing and able to sign an informed consent
  • Ability to comply with all study requirements.
  • A patient that participated in Study 008 and received all doses of study medication, per protocol.
  • Evidence of clinically significant residual beta-cell function demonstrated by MMTT peak stimulated C-peptide concentrations ≥ 0.20 nmol/L (Arm 1 only).
  • Age 10-25 (inclusive) years
  • If a female is of childbearing potential, the subject is not pregnant or lactating, and will use oral hormonal contraception or other equally effective contraceptive methods throughout the study.

Exclusion Criteria:

  • IgA (immunoglobulin A ) deficient subjects.
  • Individuals with a history of severe immediate hypersensitivity reactions, including anaphylaxis, to plasma products.
  • History of life threatening allergy, anaphylactic reaction, or systemic response to human plasma derived products.
  • The subject is receiving immunosuppressive or immunomodulating agents or cytotoxic therapy or any medication that in the opinion of the Investigator might interfere with the study.
  • Clinically significant intercurrent illnesses, including (but not limited to): cardiac, hepatic, renal, neurological, hematological, neoplastic, immunological, skeletal or other) that in the opinion of the investigator, could interfere with the safety, compliance or other aspects of this study. Patients with well-controlled, chronic diseases could be possibly included after consultation with the treating physician.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01661192

Locations
Israel
Schneider Children's Medical Center
Petah-Tikva, Israel, 49202
Assaf Haroffeh Medical Center
Zerifin, Israel
Sponsors and Collaborators
Rabin Medical Center
Kamada, Ltd.
Investigators
Principal Investigator: Yael Lebenthal, MD Rabin Medical Center
Principal Investigator: Mariana Rachmiel, MD Assaf Haroffe Medical Center
  More Information

No publications provided

Responsible Party: Rabin Medical Center
ClinicalTrials.gov Identifier: NCT01661192     History of Changes
Other Study ID Numbers: 006971ctil
Study First Received: August 7, 2012
Last Updated: September 12, 2013
Health Authority: Israel: Ministry of Health

Keywords provided by Rabin Medical Center:
Type 1 Diabetes
newly diagnosed
Beta cell preservation

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Alpha 1-Antitrypsin
Protein C Inhibitor
Trypsin Inhibitors
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 09, 2014