A Research Trial of Aralast in New Onset Diabetes (RETAIN) (RETAIN)

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ClinicalTrials.gov Identifier: NCT01183468

Recruitment Status : Terminated (Due to lack of mechanistic signal and competing industry studies)

First Posted : August 17, 2010

Results First Posted : January 16, 2015

Last Update Posted : June 13, 2018

Sponsor:

Collaborators:

Immune Tolerance Network (ITN)

Juvenile Diabetes Research Foundation

Information provided by (Responsible Party):

National Institute of Allergy and Infectious Diseases (NIAID)

Study Type	Interventional
Study Design	Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Diabetes Mellitus, Type 1
Interventions	Biological: Aralast NP 45 mg dose Biological: Aralast NP 90 mg dose Biological: Aralast NP 180 mg dose
Enrollment	17

Participant Flow

Recruitment Details	Twelve of the fifteen centers enrolled a total of 17 newly diagnosed (within 100 days of Visit 0 first low dose infusion) Type 1 Diabetes Mellitus participants.
Pre-assignment Details


Arm/Group Title	Part 1a(Aralast NP)-Subjects Aged 16-35 Yrs	Part 1a (Aralast NP)-Subjects 8-15 Yrs	Part 1b (Aralast NP)-Subjects Aged 18-35 Yrs	Part 1b (Aralast NP)-Subjects 8-17 Yrs
Arm/Group Description	Subjects aged 16-35 years at enroll...	Subjects aged 8-15 years at enrollm...	Aralast NP 90 mg/kg/wk by IV infusi...	Aralast NP 90 mg/kg/wk by IV infusi...
Arm/Group Description	Subjects aged 16-35 years at enrollment with new-onset type 1 diabetes mellitus (T1DM) received Aralast NP 45 mg/kg by intravenous (IV) infusion once a week for 6 weeks. Following the Week 6 infusion, participants underwent a minimum 3-week washout period. After the washout period, each participant proceeded to a high dose of Aralast NP 90 mg/kg by IV infusion for the next 6 weeks, for a total of 12 infusions.	Subjects aged 8-15 years at enrollment with new-onset type 1 diabetes mellitus (T1DM) received Aralast NP 45 mg/kg by IV infusion once a week for 6 weeks. Following the Week 6 infusion, participants underwent a minimum 3-week washout period. After the washout period, each participant proceeded to a high dose of Aralast NP 90 mg/kg by IV infusion for the next 6 weeks, for a total of 12 infusions.	Aralast NP 90 mg/kg/wk by IV infusion once a week for 6 weeks. Following the Week 6 infusion, participants undergo a minimum 3-wk washout period than then, each participant proceeds to high dose Aralast NP 180 mg/kg/wk by IV infusion for the next 6 weeks, for a total of 12 infusions. Aralast NP 90 mg dose: - 90 mg/kg/week Aralast NP 180 mg dose: - 180 mg/kg/week	Aralast NP 90 mg/kg/wk by IV infusion once a week for 6 weeks. Following the Week 6 infusion, participants undergo a minimum 3-wk washout period than then, each participant proceeds to high dose Aralast NP 180 mg/kg/wk by IV infusion for the next 6 weeks, for a total of 12 infusions. Aralast NP 90 mg dose: - 90 mg/kg/week Aralast NP 180 mg dose: - 180 mg/kg/week
Period Title: Overall Study
Started	8	9	0	0
Completed	5	7	0	0
Not Completed	3	2	0	0
Reason Not Completed
Lost to Follow-up	2	1	0	0
Physician Decision	1	0	0	0
Withdrawal by Subject	0	1	0	0

Baseline Characteristics

Arm/Group Title		Part 1a(Aralast NP)-Subjects Aged 16-35 Yrs	Part 1a (Aralast NP)-Subjects 8-15 Yrs	Part 1b (Aralast NP)-Subjects Aged 18-35 Yrs	Part 1b (Aralast NP)-Subjects 8-17 Yrs	Total
Arm/Group Description		Subjects aged 16-35 years at enroll...	Subjects aged 8-15 years at enrollm...	Aralast NP 90 mg/kg/wk by IV infusi...	Aralast NP 90 mg/kg/wk by IV infusi...	Total of all reporting groups
Arm/Group Description		Subjects aged 16-35 years at enrollment with new-onset type 1 diabetes mellitus (T1DM) received Aralast NP 45 mg/kg by intravenous (IV) infusion once a week for 6 weeks. Following the Week 6 infusion, participants underwent a minimum 3-week washout period. After the washout period, each participant proceeded to a high dose of Aralast NP 90 mg/kg by IV infusion for the next 6 weeks, for a total of 12 infusions.	Subjects aged 8-15 years at enrollment with new-onset type 1 diabetes mellitus (T1DM) received Aralast NP 45 mg/kg by IV infusion once a week for 6 weeks. Following the Week 6 infusion, participants underwent a minimum 3-week washout period. After the washout period, each participant proceeded to a high dose of Aralast NP 90 mg/kg by IV infusion for the next 6 weeks, for a total of 12 infusions.	Aralast NP 90 mg/kg/wk by IV infusion once a week for 6 weeks. Following the Week 6 infusion, participants undergo a minimum 3-wk washout period than then, each participant proceeds to high dose Aralast NP 180 mg/kg/wk by IV infusion for the next 6 weeks, for a total of 12 infusions. Aralast NP 90 mg dose: - 90 mg/kg/week Aralast NP 180 mg dose: - 180 mg/kg/week	Aralast NP 90 mg/kg/wk by IV infusion once a week for 6 weeks. Following the Week 6 infusion, participants undergo a minimum 3-wk washout period than then, each participant proceeds to high dose Aralast NP 180 mg/kg/wk by IV infusion for the next 6 weeks, for a total of 12 infusions. Aralast NP 90 mg dose: - 90 mg/kg/week Aralast NP 180 mg dose: - 180 mg/kg/week	Total of all reporting groups
Overall Number of Baseline Participants		8	9	0	0	17
Baseline Analysis Population Description		...
Baseline Analysis Population Description		Enrolled Sample
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	8 participants	9 participants	0 participants	0 participants	17 participants
	<=18 years	4 50.0%	9 100.0%			13 76.5%
	Between 18 and 65 years	4 50.0%	0 0.0%			4 23.5%
	>=65 years	0 0.0%	0 0.0%			0 0.0%
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	8 participants	9 participants	0 participants	0 participants	17 participants
		20.6 (5.7)	10.7 (2.2)			15.4 (6.6)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	8 participants	9 participants	0 participants	0 participants	17 participants
	Female	3 37.5%	3 33.3%			6 35.3%
	Male	5 62.5%	6 66.7%			11 64.7%
Region of Enrollment Measure Type: Number Unit of measure: Participants
United States	Number Analyzed	8 participants	9 participants	0 participants	0 participants	17 participants
United States		8	9			17

Outcome Measures

1.Primary Outcome


Title	C-peptide 2-hour AUC in Response to a Mixed-meal Tolerance Test at Week 52
Description	No results for the primary outcome measure are available since the stu...
Description	No results for the primary outcome measure are available since the study was terminated prior to reaching the outcome measure time frame of 52 weeks.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Enrolled Sample


Arm/Group Title	Part 1a(Aralast NP)-Subjects Aged 16-35 Yrs	Part 1a (Aralast NP)-Subjects 8-15 Yrs	Part 1b (Aralast NP)-Subjects Aged 18-35 Yrs	Part 1b (Aralast NP)-Subjects 8-17 Yrs
Arm/Group Description:	Subjects aged 16-35 years at enroll...	Subjects aged 8-15 years at enrollm...	Aralast NP 90 mg/kg/wk by IV infusi...	Aralast NP 90 mg/kg/wk by IV infusi...
Arm/Group Description:	Subjects aged 16-35 years at enrollment with new-onset type 1 diabetes mellitus (T1DM) received Aralast NP 45 mg/kg by intravenous (IV) infusion once a week for 6 weeks. Following the Week 6 infusion, participants underwent a minimum 3-week washout period. After the washout period, each participant proceeded to a high dose of Aralast NP 90 mg/kg by IV infusion for the next 6 weeks, for a total of 12 infusions.	Subjects aged 8-15 years at enrollment with new-onset type 1 diabetes mellitus (T1DM) received Aralast NP 45 mg/kg by IV infusion once a week for 6 weeks. Following the Week 6 infusion, participants underwent a minimum 3-week washout period. After the washout period, each participant proceeded to a high dose of Aralast NP 90 mg/kg by IV infusion for the next 6 weeks, for a total of 12 infusions.	Aralast NP 90 mg/kg/wk by IV infusion once a week for 6 weeks. Following the Week 6 infusion, participants undergo a minimum 3-wk washout period than then, each participant proceeds to high dose Aralast NP 180 mg/kg/wk by IV infusion for the next 6 weeks, for a total of 12 infusions. Aralast NP 90 mg dose: - 90 mg/kg/week Aralast NP 180 mg dose: - 180 mg/kg/week	Aralast NP 90 mg/kg/wk by IV infusion once a week for 6 weeks. Following the Week 6 infusion, participants undergo a minimum 3-wk washout period than then, each participant proceeds to high dose Aralast NP 180 mg/kg/wk by IV infusion for the next 6 weeks, for a total of 12 infusions. Aralast NP 90 mg dose: - 90 mg/kg/week Aralast NP 180 mg dose: - 180 mg/kg/week
Overall Number of Participants Analyzed	0	0	0	0

No data displayed because Outcome Measure has zero total analyzed.

Adverse Events

Time Frame	Adverse events were collected for 2.5 years, from the start of the study in January 2011 until the last participant completed the study in July 2013.
Adverse Event Reporting Description	Adverse events were collected from the time a participant signed informed consent until the time an event resolved or until 30 days after the participant completed study treatment, whichever came first.

Arm/Group Title	Subjects Aged 16 - 35 Years		Subjects Aged 8 - 15 Years
Arm/Group Description	Subjects aged 16-35 years at enroll...		Subjects aged 8-15 years at enrollm...
Arm/Group Description	Subjects aged 16-35 years at enrollment with new-onset type 1 diabetes mellitus (T1DM) received Aralast NP 45 mg/kg by IV infusion once a week for 6 weeks. Following the Week 6 infusion, participants underwent a minimum 3-week washout period. After the washout period, each participant proceeded to a high dose of Aralast NP 90 mg/kg by IV infusion for the next 6 weeks, for a total of 12 infusions.		Subjects aged 8-15 years at enrollment with new-onset type 1 diabetes mellitus (T1DM) received Aralast NP 45 mg/kg by IV infusion once a week for 6 weeks. Following the Week 6 infusion, participants underwent a minimum 3-week washout period. After the washout period, each participant proceeded to a high dose of Aralast NP 90 mg/kg by IV infusion for the next 6 weeks, for a total of 12 infusions.
All-Cause Mortality
	Subjects Aged 16 - 35 Years		Subjects Aged 8 - 15 Years
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events Serious Adverse Events
	Subjects Aged 16 - 35 Years		Subjects Aged 8 - 15 Years
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/8 (25.00%)		1/9 (11.11%)
Metabolism and nutrition disorders
Diabetic ketoacidosis ^† 1	0/8 (0.00%)	0	1/9 (11.11%)	1
Hypoglycaemia ^† 1	1/8 (12.50%)	1	0/9 (0.00%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal pain ^† 1	1/8 (12.50%)	1	0/9 (0.00%)	0
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA 11.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Subjects Aged 16 - 35 Years		Subjects Aged 8 - 15 Years
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/8 (100.00%)		8/9 (88.89%)
Endocrine disorders
Goitre ^† 1	0/8 (0.00%)	0	1/9 (11.11%)	1
Eye disorders
Blepharitis ^† 1	1/8 (12.50%)	1	0/9 (0.00%)	0
Conjunctivitis ^† 1	0/8 (0.00%)	0	1/9 (11.11%)	2
Gastrointestinal disorders
Abdominal discomfort ^† 1	0/8 (0.00%)	0	1/9 (11.11%)	1
Abdominal pain ^† 1	0/8 (0.00%)	0	1/9 (11.11%)	4
Abdominal pain upper ^† 1	0/8 (0.00%)	0	2/9 (22.22%)	12
Constipation ^† 1	1/8 (12.50%)	1	0/9 (0.00%)	0
Diarrhoea ^† 1	1/8 (12.50%)	1	2/9 (22.22%)	3
Nausea ^† 1	1/8 (12.50%)	1	4/9 (44.44%)	7
Vomiting ^† 1	0/8 (0.00%)	0	4/9 (44.44%)	5
General disorders
Chest pain ^† 1	1/8 (12.50%)	1	2/9 (22.22%)	2
Influenza like illness ^† 1	1/8 (12.50%)	1	1/9 (11.11%)	1
Infusion site haematoma ^† 1	0/8 (0.00%)	0	1/9 (11.11%)	4
Infusion site pain ^† 1	0/8 (0.00%)	0	1/9 (11.11%)	1
Injection site haematoma ^† 1	0/8 (0.00%)	0	1/9 (11.11%)	1
Pyrexia ^† 1	1/8 (12.50%)	1	3/9 (33.33%)	3
Infections and infestations
Ear infection ^† 1	0/8 (0.00%)	0	1/9 (11.11%)	1
Fungal infection ^† 1	1/8 (12.50%)	1	0/9 (0.00%)	0
Gastroenteritis ^† 1	0/8 (0.00%)	0	2/9 (22.22%)	2
Gastroenteritis viral ^† 1	0/8 (0.00%)	0	3/9 (33.33%)	3
Influenza ^† 1	1/8 (12.50%)	1	0/9 (0.00%)	0
Kidney infection ^† 1	0/8 (0.00%)	0	1/9 (11.11%)	1
Nasopharyngitis ^† 1	2/8 (25.00%)	2	2/9 (22.22%)	3
Otitis externa ^† 1	0/8 (0.00%)	0	1/9 (11.11%)	1
Pharyngitis streptococcal ^† 1	1/8 (12.50%)	1	1/9 (11.11%)	1
Pneumonia ^† 1	1/8 (12.50%)	1	1/9 (11.11%)	1
Respiratory tract infection viral ^† 1	0/8 (0.00%)	0	1/9 (11.11%)	1
Sinusitis ^† 1	0/8 (0.00%)	0	1/9 (11.11%)	1
Streptococcal infection ^† 1	0/8 (0.00%)	0	1/9 (11.11%)	1
Tooth infection ^† 1	1/8 (12.50%)	1	0/9 (0.00%)	0
Upper respiratory tract infection ^† 1	0/8 (0.00%)	0	4/9 (44.44%)	10
Urinary tract infection ^† 1	2/8 (25.00%)	9	0/9 (0.00%)	0
Injury, poisoning and procedural complications
Concussion ^† 1	0/8 (0.00%)	0	1/9 (11.11%)	2
Contusion ^† 1	1/8 (12.50%)	1	3/9 (33.33%)	3
Fibula fracture ^† 1	1/8 (12.50%)	1	0/9 (0.00%)	0
Foot fracture ^† 1	0/8 (0.00%)	0	1/9 (11.11%)	1
Hand fracture ^† 1	0/8 (0.00%)	0	1/9 (11.11%)	1
Procedural pain ^† 1	1/8 (12.50%)	3	1/9 (11.11%)	1
Radius fracture ^† 1	1/8 (12.50%)	1	0/9 (0.00%)	0
Upper limb fracture ^† 1	0/8 (0.00%)	0	1/9 (11.11%)	2
Investigations
Fibrin D dimer increased ^† 1	0/8 (0.00%)	0	3/9 (33.33%)	3
Glycosylated haemoglobin increased ^† 1	0/8 (0.00%)	0	2/9 (22.22%)	2
Lymphocyte count decreased ^† 1	1/8 (12.50%)	1	0/9 (0.00%)	0
Lymphocyte count increased ^† 1	1/8 (12.50%)	2	0/9 (0.00%)	0
Neutrophil count decreased ^† 1	1/8 (12.50%)	1	0/9 (0.00%)	0
White blood cell count decreased ^† 1	0/8 (0.00%)	0	1/9 (11.11%)	1
Metabolism and nutrition disorders
Hyperglycaemia ^† 1	0/8 (0.00%)	0	1/9 (11.11%)	4
Hypoglycaemia ^† 1	7/8 (87.50%)	69	8/9 (88.89%)	104
Vitamin D deficiency ^† 1	0/8 (0.00%)	0	1/9 (11.11%)	1
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	3/8 (37.50%)	3	0/9 (0.00%)	0
Back pain ^† 1	1/8 (12.50%)	1	0/9 (0.00%)	0
Muscle spasms ^† 1	0/8 (0.00%)	0	1/9 (11.11%)	1
Musculoskeletal pain ^† 1	0/8 (0.00%)	0	1/9 (11.11%)	1
Myalgia ^† 1	0/8 (0.00%)	0	1/9 (11.11%)	4
Neck pain ^† 1	0/8 (0.00%)	0	1/9 (11.11%)	1
Pain in extremity ^† 1	1/8 (12.50%)	1	0/9 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma ^† 1	0/8 (0.00%)	0	1/9 (11.11%)	2
Nervous system disorders
Dizziness ^† 1	0/8 (0.00%)	0	2/9 (22.22%)	2
Headache ^† 1	2/8 (25.00%)	2	4/9 (44.44%)	77
Sinus headache ^† 1	1/8 (12.50%)	1	0/9 (0.00%)	0
Syncope ^† 1	0/8 (0.00%)	0	1/9 (11.11%)	1
Psychiatric disorders
Panic attack ^† 1	1/8 (12.50%)	1	0/9 (0.00%)	0
Renal and urinary disorders
Hypercalciuria ^† 1	1/8 (12.50%)	1	0/9 (0.00%)	0
Ketonuria ^† 1	0/8 (0.00%)	0	2/9 (22.22%)	4
Nephrolithiasis ^† 1	1/8 (12.50%)	1	0/9 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	3/8 (37.50%)	3	2/9 (22.22%)	4
Nasal congestion ^† 1	3/8 (37.50%)	3	2/9 (22.22%)	2
Oropharyngeal pain ^† 1	0/8 (0.00%)	0	2/9 (22.22%)	9
Respiratory tract congestion ^† 1	1/8 (12.50%)	1	0/9 (0.00%)	0
Rhinitis allergic ^† 1	1/8 (12.50%)	1	1/9 (11.11%)	1
Upper respiratory tract congestion ^† 1	0/8 (0.00%)	0	1/9 (11.11%)	2
Upper-airway cough syndrome ^† 1	1/8 (12.50%)	1	0/9 (0.00%)	0
Skin and subcutaneous tissue disorders
Dry skin ^† 1	0/8 (0.00%)	0	1/9 (11.11%)	1
Eczema ^† 1	0/8 (0.00%)	0	1/9 (11.11%)	1
Rash ^† 1	1/8 (12.50%)	3	3/9 (33.33%)	4
Rash papular ^† 1	1/8 (12.50%)	1	0/9 (0.00%)	0
Rash pruritic ^† 1	0/8 (0.00%)	0	1/9 (11.11%)	2
Skin mass ^† 1	0/8 (0.00%)	0	1/9 (11.11%)	1
Urticaria ^† 1	1/8 (12.50%)	1	0/9 (0.00%)	0
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA 11.1

Limitations and Caveats

This (Part 1) was the drug dosing portion of the study; however, due to lack of a mechanistic signal and competing industry studies, the study was terminated and the trial portion (Part II, NCT01183455) was withdrawn.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Director, Clinical Research Operations Program
Organization:	DAIT/NIAID
Phone:	301-594-7669
EMail:	DAITClinicalTrialsGov@niaid.nih.gov

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ozeri E, Mizrahi M, Shahaf G, Lewis EC. α-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.

Layout table for additonal information

Responsible Party:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT01183468
Other Study ID Numbers:	DAIT ITN041AI Part 1
First Submitted:	August 16, 2010
First Posted:	August 17, 2010
Results First Submitted:	January 6, 2015
Results First Posted:	January 16, 2015
Last Update Posted:	June 13, 2018

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