Type 1 Diabetes MellitusPhase 2NCT02093221
Study of Human Plasma-Derived Alpha1-Proteinase Inhibitor in Subjects With New-Onset Type 1 Diabetes Mellitus
A Phase 2 study testing 180 mg/kg Alpha1-PI and 90 mg/kg Alpha1-PI in people with Type 1 Diabetes Mellitus, run by Grifols Therapeutics LLC at 36 sites in United States.
Trial summary
This is a multicenter, randomized, partial-blinded, five-arm, placebo-controlled study of human plasma-derived alpha1-proteinase inhibitor (alpha1-PI) in children (ages 6-11 years old) and teens/adults (ages 12-35 years old) with new onset Type 1 Diabetes Mellitus (T1DM). Currently enrolling ages 12-35 only. Read more about this study
- Who is it for?
- Ages 6 to 35 years
- Conditions the study is for
- Type 1 Diabetes Mellitus
- What is being tested?
- 180 mg/kg Alpha1-PI and 90 mg/kg Alpha1-PI
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 76 participants
- Where
- 36 sitesUnited States
- Study dates
- Mar 2014to Jun 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 6 to 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnosis of T1DM according to the ADA criteria.
- Current use of injected insulin therapy and one positive result on testing for any of the following antibodies (If not currently on insulin therapy, must have positive result for at least two of the below antibodies):
- Anti-islet-cell antibodies (islet cell antigen 512, insulinoma associated protein 2),
- Anti-glutamic acid decarboxylase antibodies, or
- Anti-insulin antibodies (unless received insulin therapy for > 7 days).
- Body Mass Index (BMI) ≤ 28 kg/m2 for adults (≥ 20 years of age) OR ≤ 90th percentile in accordance with the Centers for Disease Control BMI assessment for children and teens (2 through 19 years old).
Who cannot join
- History of or current diabetic retinopathy, neuropathy, or nephropathy.
- Known thrombophilia or history of thrombosis.
- Malignant disease (including malignant melanoma; however, other forms of skin cancer are allowed) within five years of randomization.
- Active Hepatitis A virus, Hepatitis B virus, Hepatitis C virus, or Human Immunodeficiency Virus infection.
- History of anaphylaxis or severe systemic response to any plasma-derived alpha1-PI preparation or other blood product(s).
- Known selective or severe Immunoglobulin A deficiency.
Show all 12Show fewer
- Elevated liver enzymes (aspartate transaminase, alanine aminotransferase, and alkaline phosphatase) equal to or greater than 2.5 times the upper limit of normal.
- Therapy with exenatide or any other agents that stimulate pancreatic β cell regeneration or insulin secretion, or any antidiabetic agents (oral or parenteral) other than insulin within one month prior to screening.
- Use of omega-3 fatty acid supplements, including fish oil, within seven days prior to screening.
- Current or planned therapy with inhaled insulin, if it becomes available.
- Chronic use of systemic steroids, with the exception of inhaled steroids, above a stable dose equivalent to 5 mg/day prednisone (e.g., 10 mg every 2 days) within 4 weeks prior to randomization. It is recommended to maintain the same dose throughout the study. (Note: Subjects with autoimmune conditions (i.e., asthma) necessitating treatment with systemic short-term corticosteroids and administered a rapid taper are eligible per protocol with the caveat that the tapering is complete or decreased to the minimum requirement (i.e., 5 mg/day) at least 1 week prior to the Baseline visit (when randomization occurs) to ensure the subject is stable. For longer term steroid usage, please consult the Grifols Medical Monitor before considering the subject for study participation.)
- Treatment with immunosuppressants or cytostatic agents within 6 months of randomization.
Trial locations and contacts
36 sites in 1 country.
36 sites in 1 country
United States36 sites
University of New Mexico, Health Sciences Center
Albuquerque, New Mexico, 87131-0001
Atlanta Diabetes Associates
Atlanta, Georgia, 30309
Barry J. Reiner MD, LLC.
Baltimore, Maryland, 21229
Women and Children's Hospital
Buffalo, New York, 14222
Cook County Hospital
Chicago, Illinois, 60612
Endocrinology Associates Inc
Columbus, Ohio, 43201
Ohio State University
Columbus, Ohio, 43210
Research Institute of Dallas
Dallas, Texas, 75231
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Wayne State University
Detroit, Michigan, 48201
Rocky Mountain Diabetes and Osteoporosis Center
Idaho Falls, Idaho, 83404
Methodist Research Institute
Indianapolis, Indiana, 46202
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
Solutions Through Advanced Research Inc.
Jacksonville, Florida, 32258
Clinica Medica San Miguel
Los Angeles, California, 90015
University of Louisville
Louisville, Kentucky, 40202
CCM Clinical Research
Miami, Florida, 33133
Advanced Pharma CR LLC
Miami, Florida, 33136
Morristown Medical Center
Morristown, New Jersey, 07962
Yale New Haven Hospital
New Haven, Connecticut, 06511
Christiana Care Health Services
Newark, Delaware, 19713
Pediatric Endocrinology, Genetics & Metabolism
Oklahoma City, Oklahoma, 73112
Diabetes Associates Medical Group
Orange, California, 92868
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19106
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
WakeMed Children's Hospital
Raleigh, North Carolina, 27610
Rapid City Regional Hospital/Health Clinical Research
Rapid City, South Dakota, 57701
Children's Hospitals and Clinics of Minnesota
Saint Paul, Minnesota, 55102
Northeast Clinical Research of San Antonio LLC
San Antonio, Texas, 78154
University of Texas Health Science Center
San Antonio, Texas, 78229
Consano Clinical Research
San Antonio, Texas, 78232
Rady Children's Hospital San Diego
San Diego, California, 92123
Metabolic Institute of America
Tarzana, California, 91356
University of Arizona
Tucson, Arizona, 85724
Ronald H Chochinov MD
Ventura, California, 93003
UMass Memorial Medical Center
Worcester, Massachusetts, 01655
About this study
Official title: A Multicenter, Randomized, Partial-Blinded, Placebo-Controlled Study to Evaluate the Safety and Efficacy of a Human Plasma-Derived Alpha1-Proteinase Inhibitor in Subjects With New-Onset Type 1 Diabetes Mellitus
This is a multicenter, randomized, partial-blinded, five-arm, placebo-controlled study of human plasma-derived alpha1-proteinase inhibitor (alpha1-PI) in children (ages 6-11 years old) and teens/adults (ages 12-35 years old) with new onset Type 1 Diabetes Mellitus (T1DM). Currently enrolling ages 12-35 only. Once 25 patients are randomized and data is reviewed enrollment will be opened to the child cohort. The purpose of this study is to evaluate the safety and efficacy of four dosing regimens of human plasma-derived alpha1-PI in T1DM.
- Conditions
- Type 1 Diabetes Mellitus
- Being tested
- 180 mg/kg Alpha1-PI, 90 mg/kg Alpha1-PI, Placebo
- Keywords
- Type 1 Diabetes Mellitus, Alpha1-Proteinase Inhibitor, Beta Cell, Alpha1-Antitrypsin
- Medical subject headings
- Diabetes Mellitus, Type 1, alpha 1-Antitrypsin Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
180 mg/kg Alpha1-PIBiological
Also called Alpha1-antitrypsin, Prolastin-C, Alpha1-Proteinase Inhibitor (human), Modified Process, Alpha-1 MP
90 mg/kg Alpha1-PIBiological
Also called Alpha1-antitrypsin, Prolastin-C, Alpha1-Proteinase Inhibitor (human), Modified Process, Alpha-1 MP
PlaceboBiological
| Study group | Role | What they receive |
|---|---|---|
| Alpha1-PI 180 mg/kg/wk, 26 weeks | Experimental | 180 mg/kg weekly infusions of Alpha1-PI for 26 weeks. Receives: Biological: 180 mg/kg Alpha1-PI |
| 90 mg/kg/wk Alpha1-PI, 26 weeks | Experimental | 90 mg/kg weekly infusions of Alpha1-PI for 26 weeks. Receives: Biological: 90 mg/kg Alpha1-PI |
| Placebo, 26 weeks | Placebo comparator | Weekly infusions of placebo for 26 weeks. Receives: Biological: Placebo |
| 180 mg/kg/wk Alpha1-PI, 13 weeks | Experimental | 180 mg/kg weekly infusions of Alpha1-PI for 13 weeks. Receives: Biological: 180 mg/kg Alpha1-PI |
| 90 mg/kg/wk Alpha1-PI, 13 weeks | Experimental | 90 mg/kg weekly infusions of Alpha1-PI for 13 weeks Receives: Biological: 90 mg/kg Alpha1-PI |
| Placebo, 13 weeks | Placebo comparator | Weekly infusions of placebo for 13 weeks. Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Mixed Meal Tolerance Test (MMTMT) Stimulated C-peptide 2 Hour Area Under the Concentration-time Curve (AUC)
C-peptide concentration during MMTT with high protein energy drink. "Dose" for time frame refers to intake of high protein energy drink.
Measured: Baseline, Week 52 (pre-high protein drink and 15, 30, 60, 90, 120 minutes post-drink)
Secondary outcomes (5)
Change From Baseline for MMTT Stimulated C-peptide 2h AUC
Measured: Baseline, Weeks 14, 27, 39, 69, 87, and 104 (pre-high protein drink and 15, 30, 60, 90, 120 minutes post-drink)
Change From Baseline for HbA1c Levels
Measured: Baseline, Weeks 14, 27, 39, 52, 69, 87, and 104
Number of Subjects With Overall Severe Hypoglycemic Episodes
Severe hypoglycemia defined according the ADA Workgroup on Hypoglycemia definition, as follows: An event requiring assistance of another person to actively administer carbohydrate, glucagons, or other resuscitative actions.
Measured: 104 weeks
Change From Baseline for Mean Daily Insulin Dose Requirements
Measured: Baseline, Weeks 2, 4, 14, 27, 39, 52, 69, 87, and 104
Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime
For each visit, the mean daily glucose levels were calculated over the previous 3-7 days prior to the study visit from blood glucose levels recorded daily prior to meals and bedtime.
Measured: Baseline, Weeks 2, 4, 14, 27, 39, 52, 69, 87, and 104
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2014 (estimated)
- Study startMar 2014
- Primary completionJan 2017
- Study completionJun 2017
Why it stopped: Wk 52 primary endpoint results would be unaffected by follow-up data so trial was discontinued prior to wk 104. No safety data was collected after wk 52.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 1 Diabetes MellitusStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- Grifols Therapeutics LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02093221
- Sponsor's protocol ID
- GTI1302
- Status last verified
- Aug 2018
- First submitted
- 11 Mar 2014
- Last updated
- 5 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Lagarde WH, Courtney KL, Reiner B, Steinmann K, Tsalikian E, Willi SM. Human plasma-derived alpha1 -proteinase inhibitor in patients with new-onset type 1 diabetes mellitus: A randomized, placebo-controlled proof-of-concept study. Pediatr Diabetes. 2021 Mar;22(2):192-201. doi: 10.1111/pedi.13162. Epub 2020 Dec 13.
PubMed 33244872
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Partial-Blinded, Placebo-Controlled Study to Evaluate the Safety and Efficacy of a Human Plasma-Derived Alpha1-Proteinase Inhibitor in Subjects With New-Onset Type 1 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT02093221
- Acronym / sponsor ID
- GTI1302
- Conditions
- Type 1 Diabetes Mellitus
- Keywords
- Type 1 Diabetes Mellitus, Alpha1-Proteinase Inhibitor, Beta Cell, Alpha1-Antitrypsin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Wk 52 primary endpoint results would be unaffected by follow-up data so trial was discontinued prior to wk 104. No safety data was collected after wk 52.
- Enrolment
- 76 participants (actual)
- Lead sponsor
- Grifols Therapeutics LLCIndustry (pharma, biotech, devices)
- Study start
- Mar 2014
- Primary completion
- Jan 2017 (actual)
- Study completion
- Jun 2017 (actual)
- First posted
- 20 Mar 2014 (estimated)
- Results
- Posted 19 Apr 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multicenter, randomized, partial-blinded, five-arm, placebo-controlled study of human plasma-derived alpha1-proteinase inhibitor (alpha1-PI) in children (ages 6-11 years old) and teens/adults (ages 12-35 years old) with new onset Type 1 Diabetes Mellitus (T1DM). Currently enrolling ages 12-35 only. Once 25 patients are randomized and data is reviewed enrollment will be opened to the child cohort. The purpose of this study is to evaluate the safety and efficacy of four dosing regimens of human plasma-derived alpha1-PI in T1DM.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Alpha1-PI 180 mg/kg/wk, 26 weeks | Experimental | Biological: 180 mg/kg Alpha1-PI180 mg/kg weekly infusions of Alpha1-PI for 26 weeks. |
| 90 mg/kg/wk Alpha1-PI, 26 weeks | Experimental | Biological: 90 mg/kg Alpha1-PI90 mg/kg weekly infusions of Alpha1-PI for 26 weeks. |
| Placebo, 26 weeks | Placebo comparator | Biological: PlaceboWeekly infusions of placebo for 26 weeks. |
| 180 mg/kg/wk Alpha1-PI, 13 weeks | Experimental | Biological: 180 mg/kg Alpha1-PI180 mg/kg weekly infusions of Alpha1-PI for 13 weeks. |
| 90 mg/kg/wk Alpha1-PI, 13 weeks | Experimental | Biological: 90 mg/kg Alpha1-PI90 mg/kg weekly infusions of Alpha1-PI for 13 weeks |
| Placebo, 13 weeks | Placebo comparator | Biological: PlaceboWeekly infusions of placebo for 13 weeks. |
Who may qualify
- Ages
- 6 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- Diagnosis of T1DM according to the ADA criteria.
- Current use of injected insulin therapy and one positive result on testing for any of the following antibodies (If not currently on insulin therapy, must have positive result for at least two of the below antibodies):
- Body Mass Index (BMI) ≤ 28 kg/m2 for adults (≥ 20 years of age) OR ≤ 90th percentile in accordance with the Centers for Disease Control BMI assessment for children and teens (2 through 19 years old).
Key exclusion criteria (12 listed)
- History of or current diabetic retinopathy, neuropathy, or nephropathy.
- Known thrombophilia or history of thrombosis.
- Malignant disease (including malignant melanoma; however, other forms of skin cancer are allowed) within five years of randomization.
- Active Hepatitis A virus, Hepatitis B virus, Hepatitis C virus, or Human Immunodeficiency Virus infection.
- History of anaphylaxis or severe systemic response to any plasma-derived alpha1-PI preparation or other blood product(s).
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 |
|---|---|---|
| 180 mg/kg Alpha1-PIAlso: Alpha1-antitrypsin, Prolastin-C, Alpha1-Proteinase Inhibitor (human), Modified Process, Alpha-1 MP | Biological | 180 mg/kg/wk Alpha1-PI, 13 weeks, Alpha1-PI 180 mg/kg/wk, 26 weeks |
| 90 mg/kg Alpha1-PIAlso: Alpha1-antitrypsin, Prolastin-C, Alpha1-Proteinase Inhibitor (human), Modified Process, Alpha-1 MP | Biological | 90 mg/kg/wk Alpha1-PI, 13 weeks, 90 mg/kg/wk Alpha1-PI, 26 weeks |
| Placebo | Biological | Placebo, 13 weeks, Placebo, 26 weeks |
Primary outcome
Change From Baseline in Mixed Meal Tolerance Test (MMTMT) Stimulated C-peptide 2 Hour Area Under the Concentration-time Curve (AUC)
Time frame: Baseline, Week 52 (pre-high protein drink and 15, 30, 60, 90, 120 minutes post-drink)
C-peptide concentration during MMTT with high protein energy drink. "Dose" for time frame refers to intake of high protein energy drink.
5 secondary outcomes
Change From Baseline for MMTT Stimulated C-peptide 2h AUC
Time frame: Baseline, Weeks 14, 27, 39, 69, 87, and 104 (pre-high protein drink and 15, 30, 60, 90, 120 minutes post-drink)
Change From Baseline for HbA1c Levels
Time frame: Baseline, Weeks 14, 27, 39, 52, 69, 87, and 104
Number of Subjects With Overall Severe Hypoglycemic Episodes
Time frame: 104 weeks
Change From Baseline for Mean Daily Insulin Dose Requirements
Time frame: Baseline, Weeks 2, 4, 14, 27, 39, 52, 69, 87, and 104
Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime
Time frame: Baseline, Weeks 2, 4, 14, 27, 39, 52, 69, 87, and 104
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33244872Lagarde WH, Courtney KL, Reiner B, Steinmann K, Tsalikian E, Willi SM. Human plasma-derived alpha1 -proteinase inhibitor in patients with new-onset type 1 diabetes mellitus: A randomized, placebo-controlled proof-of-concept study. Pediatr Diabetes. 2021 Mar;22(2):192-201. doi: 10.1111/pedi.13162. Epub 2020 Dec 13.
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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.
The record lists no contact. Use the official record to reach the sponsor.
36 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 180 mg/kg Alpha1-PI and 90 mg/kg Alpha1-PI in people with Type 1 Diabetes Mellitus, run by Grifols Therapeutics LLC at 36 sites in United States.
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 12 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: stopped early, as of the sponsor's last update on 5 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 36 sites in United States. 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. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 19 Apr 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change From Baseline in Mixed Meal Tolerance Test (MMTMT) Stimulated C-peptide 2 Hour Area Under the Concentration-time Curve (AUC) (time frame: Baseline, Week 52 (pre-high protein drink and 15, 30, 60, 90, 120 minutes post-drink)). 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 NCT02093221, 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 5 Sep 2018.