AzTrials
AzTrials

Type 1 Diabetes MellitusPhase 1/2NCT01304537

Study of the Safety and Efficacy of Intravenous Alpha-1 Antitrypsin in Type 1 Diabetes Mellitus

A Phase 1/2 study testing Alpha-1 Antitrypsin 40mg (AAT, Glassia®), Alpha-1 Antitrypsin 60mg (AAT, Glassia®) and Alpha-1 Antitrypsin 80mg (AAT, Glassia®) in people with Type 1 Diabetes Mellitus, run by Kamada, Ltd. at 2 sites in Israel.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Alpha-1 Antitrypsin (AAT), trade name (Glassia ®), is being explored in this phase I/II trial as a potential disease modifying agent in Type 1 Diabetes Mellitus (T1DM) based on its anti-inflammatory properties. AAT is an acute stress reactant protein that increases during inflammation. Read more about this study

Who is it for?
Ages 10 to 25 years
Conditions the study is for
Type 1 Diabetes Mellitus
What is being tested?
Alpha-1 Antitrypsin 40mg (AAT, Glassia®), Alpha-1 Antitrypsin 60mg (AAT, Glassia®) and Alpha-1 Antitrypsin 80mg (AAT, Glassia®)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
2 sitesIsrael
Study dates
Jun 2011to Nov 2012
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 10 to 25 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Subject (or parent/guardian) willing and able to sign an informed consent
  • Age 10-25 (inclusive) years
  • Diagnosed with T1DM within the previous 6 months
  • Level of C-peptide ≥ 0.2 pmol/mL during MMTT(maximal level)
  • Positive for at least one diabetes-related autoantibody(except for insulin autoantibody)
  • No significant abnormalities in serum hematology,serum chemistry according to the Investigator's judgment, taking into considerations the potential effects of the diabetic illness.
Show all 10Show fewer
  • No significant abnormalities in urinalysis according to the Principal Investigator's judgment, taking into considerations the potential effects of the diabetic illness.
  • No significant abnormalities in ECG per investigator judgment
  • Negative for HBsAg and antibodies to HCV, HIV-1
  • Non-pregnant, non-lactating female patients, whose screening pregnancy test is negative and who are using contraceptive methods deemed reliable by the investigator.

Who cannot join

  • Subjects who have received an active/ live virus vaccine within 4 weeks of the screening date
  • Subjects who have received treatment with corticosteroid medication within 2 months prior to screening or any immunosuppressant or cytostatic agent within 6 months prior to screening
  • IgA deficient subjects
  • Individuals with a history of severe immediate hypersensitivity reactions, including anaphylaxis, to plasma products
  • Planned major surgery within the study period
  • 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 and the sponsor.
Show all 15Show fewer
  • Pregnant or lactating women at entry to study and those who are unwilling to agree to continue to use acceptable methods of contraception throughout the study.
  • Presence of psychiatric/ mental disorder or any other medical disorder which might impair the patient's ability to give informed consent or to comply with the requirements of the study protocol.
  • Evidence of ongoing viral infection with HCV, HBV and/or HIV-1.
  • Evidence of alcohol abuse or history of alcohol abuse or illegal and/or legally prescribed drugs.
  • Participation in another interventional clinical trial within 30 days prior to baseline visit.
  • Inability to attend scheduled clinic visits and/or comply with the study protocol.
  • Any other factor that, in the opinion of the investigator, would prevent the patient form complying with the requirements of the protocol.
  • Current use of any medication known to influence glucose tolerance (e.g., beta-blockers, angiotensin-converting enzyme inhibitors, interferons, quinidine anti-malarial drugs, lithium, niacin).
  • Current or prior (within the last 30 days prior to screening visit) use of metformin, sulfonylureas, glinides, thiazolidinediones, exenatide, liraglutide, DPP-IV inhibitors or amylin.

Trial locations and contacts

2 sites in 1 country.

Israel2 sites

  • Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes at Schneider Children's Medical Center of Israel

    Petah Tikva, Israel, 49202

  • Assaf Haroffeh Medical Center

    Tsrifin, Israel, 70300

Other trials in Israel

About this study

Official title: Open Label, Proof of Concept, Phase I/II Study of the Safety, Tolerability and Efficacy of Intravenous Alpha-1 Antitrypsin (AAT) [Trade Name Glassia™] in Type 1 Diabetes Mellitus

Alpha-1 Antitrypsin (AAT), trade name (Glassia ®), is being explored in this phase I/II trial as a potential disease modifying agent in Type 1 Diabetes Mellitus (T1DM) based on its anti-inflammatory properties. AAT is an acute stress reactant protein that increases during inflammation. In T1DM inflammation serves a major role in disease progression.

Read the detailed description

AAT is a protein produced by the human liver and secreted into the blood circulation. AAT, which belongs to a group of serine protease inhibitors (SERPINS) is an acute stress reactant protein that increases during stress conditions, including inflammation. AAT blocks serine proteases that enhance pro-inflammatory mediators (i.e. IL-1 alpha, IL-6, IL-8, TNFalpha) as well as induces production of anti-inflammatory mediators (i.e. IL-10 and IL-1-receptor antagonist).

In Type 1 Diabetes Mellitus (T1DM) inflammation serves a major role in disease progression. The inflammatory signature pattern in these patients appears to have been present years before clinical onset.

Although circulating levels of AAT in T1DM are normal, in majority of cases, the activity of AAT is severely compromised by non-enzymatic glycations, supporting the conclusion that serum protease inhibitory capacity is reduced in T1DM.

It has been shown in different studies, including in vivo and in vitro that AAT has a protective affect on pancreatic islets. This has been demonstrated in both decrease in progression of diabetes in the non-obese diabetic (NOD) mouse as well as during transplantation of islets which presented viability and activity (insulin production) in the presence of AAT. More specifically, islet cells are protected by human AAT from apoptosis, as shown by reduced caspase-3 activity after the addition of human AAT to islet culture media.

Based on the mentioned anti-inflammatory properties of AAT sided to in vivo and in vitro studied indicating that AAT may serve as a disease modifying agent in T1DM, the presented study is suggested.

Being tested
Alpha-1 Antitrypsin 40mg (AAT, Glassia®), Alpha-1 Antitrypsin 60mg (AAT, Glassia®), Alpha-1 Antitrypsin 80mg (AAT, Glassia®)
Medical subject headings
Diabetes Mellitus, Type 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Alpha-1 Antitrypsin 40mg (AAT, Glassia®)Drug

    Each study group will undergo 3 treatment periods:12 weeks, 8 weeks and 4 weeks.

  • Alpha-1 Antitrypsin 60mg (AAT, Glassia®)Drug

    Each study group will undergo 3 treatment periods:12 weeks, 8 weeks and 4 weeks.

  • Alpha-1 Antitrypsin 80mg (AAT, Glassia®)Drug

    Each study group will undergo 3 treatment periods:12 weeks, 8 weeks and 4 weeks.

Study groups in NCT01304537
Study groupRoleWhat they receive
Alpha-1 Antitrypsin 40mg (AAT, Glassia®)ExperimentalSubjects in this arm will receive a dose of 40 mg/kg throughout the study.
Receives: Drug: Alpha-1 Antitrypsin 40mg (AAT, Glassia®)
Alpha-1 Antitrypsin 60mg (AAT, Glassia®)ExperimentalSubjects in this arm will receive a dose of 60 mg/kg throughout the study.
Receives: Drug: Alpha-1 Antitrypsin 60mg (AAT, Glassia®)
Alpha-1 Antitrypsin 80mg (AAT, Glassia®)ExperimentalSubjects in this arm will receive a dose of 80 mg/kg throughout the study.
Receives: Drug: Alpha-1 Antitrypsin 80mg (AAT, Glassia®)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety and Tolerability

    Safety and Tolerability: assessed by vital signs(systolic/diastolic blood pressure and heart rate), physical examination, routine safety lab tests, AEs and SAEs.

    Measured: Approximately 1 year

Secondary outcomes (1)

  1. Efficacy

    Pancreatic beta cell function ; External Insulin dose requirements; Glycosylated hemoglobin (HbA1c) levels.

    Measured: Approximately 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Feb 2011 (estimated)
  2. Study startJun 2011
  3. Primary completionNov 2012
  4. Study completionNov 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01304537
Sponsor's protocol ID
Kamada-AAT (IV) - 008
Status last verified
Feb 2013
First submitted
24 Feb 2011
Last updated
9 Jun 2016
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • Ozeri E, Mizrahi M, Shahaf G, Lewis EC. alpha-1 antitrypsin promotes semimature, IL-10-producing and readily migrating tolerogenic dendritic cells. J Immunol. 2012 Jul 1;189(1):146-53. doi: 10.4049/jimmunol.1101340. Epub 2012 May 25.

    PubMed 22634621

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Alpha-1 Antitrypsin 40mg (AAT, Glassia®), Alpha-1 Antitrypsin 60mg (AAT, Glassia®) and Alpha-1 Antitrypsin 80mg (AAT, Glassia®) in people with Type 1 Diabetes Mellitus, run by Kamada, Ltd. at 2 sites in Israel.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and Tolerability (time frame: Approximately 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01304537, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2016.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in