Type 1 DiabetesPhase 2AAT ExtensionNCT01661192
Long Term Treatment Effect of the Safety, Tolerability and Efficacy of AAT in Type 1 Diabetes
A Phase 2 study testing AAT( Alpha 1 Antitrypsin) in people with Type 1 Diabetes and Beta Cell Preservation, run by Rabin Medical Center at 2 sites in Israel.
Trial summary
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 . Read more about this study
- Who is it for?
- Ages 10 to 25 years
- Conditions the study is for
- Type 1 Diabetes, Beta Cell Preservation
- What is being tested?
- AAT( Alpha 1 Antitrypsin)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 2 sitesIsrael
- Study dates
- Jan 2013to Jan 2017
- Phase
- Phase 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
- 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
Israel2 sites
Schneider Children's Medical Center
Petah Tikva, 49202
Assaf Haroffeh Medical Center
Tsrifin
About this study
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)
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.
Read more
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
- Conditions
- Type 1 Diabetes, Beta Cell Preservation
- Being tested
- AAT( Alpha 1 Antitrypsin)
- Keywords
- Type 1 Diabetes, newly diagnosed, Beta cell preservation
- 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.
AAT( Alpha 1 Antitrypsin)Drug
| Study group | Role | What they receive |
|---|---|---|
| AAT( Alpha 1 Antitrypsin) | Experimental | 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. Receives: Drug: AAT( Alpha 1 Antitrypsin) |
| Follow up group | No intervention | 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of AAT in terms of adverse events and serious adverse events
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
Measured: At month 36
Safety and tolerability of the AAT in terms of laboratory values
We will assess at each visit until final visit (month 36)the safety and tolerability of study drug in terms of laboratory values
Measured: At month 36
Secondary outcomes (4)
Beta cell function-AUC (Area Under the Curve) of stimulated C-Peptide from stimulated MMTT (mixed meal tolerance test)
Measured: at month 36
Percentage of patients that maintain stimulated peak C-peptide >=0.2 nmol/L
Measured: at month 36
Percentage of patients that achieve glycemic target of HbA1c <=7.5%
Measured: At month 36
Daily insulin dose adjusted to body weight
Measured: At month 36
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2012 (estimated)
- Study startJan 2013
- Primary completionJan 2017
- Study completionJan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 1 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rabin Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Kamada, Ltd.
- Responsible party
- Sponsor
- Investigators
- Yael Lebenthal, MD, Principal investigator, Rabin Medical CenterMariana Rachmiel, MD, Principal investigator, Assaf Haroffe Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01661192
- Sponsor's protocol ID
- 006971ctil
- Acronym
- AAT Extension
- Status last verified
- Jan 2017
- First submitted
- 7 Aug 2012
- Last updated
- 11 Jan 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Brener A, Lebenthal Y, Interator H, Horesh O, Leshem A, Weintrob N, Loewenthal N, Shalitin S, Rachmiel M. Long-term safety of alpha-1 antitrypsin therapy in children and adolescents with Type 1 diabetes. Immunotherapy. 2018 Sep;10(13):1137-1148. doi: 10.2217/imt-2018-0047.
PubMed 30236025
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01661192
- Acronym / sponsor ID
- AAT Extension / 006971ctil
- Conditions
- Type 1 Diabetes, Beta Cell Preservation
- Keywords
- Type 1 Diabetes, newly diagnosed, Beta cell preservation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Rabin Medical CenterUniversity, hospital or other
- Collaborators
- Kamada, Ltd.
- Study start
- Jan 2013
- Primary completion
- Jan 2017 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 9 Aug 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AAT( Alpha 1 Antitrypsin) | Experimental | Drug: 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. |
| Follow up group | No intervention | –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 |
Who may qualify
- Ages
- 10 to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AAT( Alpha 1 Antitrypsin) | Drug | AAT( Alpha 1 Antitrypsin) |
Primary outcome
Safety and tolerability of AAT in terms of adverse events and serious adverse events
Time frame: At month 36
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
We will assess at each visit until final visit (month 36)the safety and tolerability of study drug in terms of laboratory values
4 secondary outcomes
Beta cell function-AUC (Area Under the Curve) of stimulated C-Peptide from stimulated MMTT (mixed meal tolerance test)
Time frame: at month 36
Percentage of patients that maintain stimulated peak C-peptide >=0.2 nmol/L
Time frame: at month 36
Percentage of patients that achieve glycemic target of HbA1c <=7.5%
Time frame: At month 36
Daily insulin dose adjusted to body weight
Time frame: At month 36
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2017.
- Derived from this study: PubMed 30236025Brener A, Lebenthal Y, Interator H, Horesh O, Leshem A, Weintrob N, Loewenthal N, Shalitin S, Rachmiel M. Long-term safety of alpha-1 antitrypsin therapy in children and adolescents with Type 1 diabetes. Immunotherapy. 2018 Sep;10(13):1137-1148. doi: 10.2217/imt-2018-0047.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yael Lebenthal, MD principal investigator
Rabin Medical Center
Mariana Rachmiel, MD principal investigator
Assaf Haroffe Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AAT( Alpha 1 Antitrypsin) in people with Type 1 Diabetes and Beta Cell Preservation, run by Rabin Medical Center 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 6 inclusion and 5 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 11 Jan 2017. 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 phase mean?
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 of AAT in terms of adverse events and serious adverse events (time frame: At month 36). The study lists 2 primary outcomes in all. 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 NCT01661192, 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 11 Jan 2017.