Phase 1 Study of BHT-3021 in Subjects With Type 1 Diabetes Mellitus

Sponsor

Bayhill Therapeutics (Industry)

Overall Status

Completed

CT.gov ID

NCT00453375

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

4.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the safety of BHT-3021 injections given weekly for 12 weeks and to evaluate the effect of BHT-3021 on antibody and immune (T cell) responses to autoantigens (e.g. insulin). Changes in pancreatic beta cell function, insulin requirements and blood glucose levels will also be evaluated.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Hypoglycemia	Drug: BHT-3021 Drug: BHT-Placebo	Phase 1

Detailed Description

Type 1 diabetes results from an attack by the body's own immune system on the insulin producing cells in the pancreas. Around 80% of diagnosed patients have detectable antibodies to islet cell self-proteins including, insulin IA-2 and glutamic acid decarboxylase. The drug, BHT-3021 is being studied because an agent that stops autoimmune damage could offer patients benefit.

Study Description: A Randomized, Blinded, Placebo Controlled, Safety and Pharmacodynamic Study of BHT-3021 with Open Label Cross-Over in Subjects with Type I Diabetes Mellitus that will enroll up to 72 subjects in this trial. Subjects will be randomized to BHT-3021 or BHT-placebo in a 2:1 ratio.

The duration of the study is approximately 25 to 37 months depending on treatment assignment:

4 week Screening Period; 12 month Blinded Treatment and Evaluation Period; 12 month Cross-over Treatment and Evaluation Period (BHT-placebo subjects only); 12 month Long Term Follow-Up period.

Study Design

Study Type:

Interventional

Actual Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Randomized, Blinded, Placebo Controlled, Safety and Pharmacodynamic Study of BHT-3021 With Open Label Cross-Over in Subjects With Type I Diabetes Mellitus

Study Start Date :

Oct 1, 2006

Actual Primary Completion Date :

May 1, 2011

Actual Study Completion Date :

May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 BHT-3021	Drug: BHT-3021 Evaluation of up to four dose levels will be given in weekly IM injections for 12 weeks.
Placebo Comparator: 2 BHT-Placebo	Drug: BHT-Placebo Evaluation of up to four dose levels will be given in weekly IM injections for 12 weeks.

Arm

Intervention/Treatment

Experimental: 1

BHT-3021

Drug: BHT-3021

Evaluation of up to four dose levels will be given in weekly IM injections for 12 weeks.

Placebo Comparator: 2

BHT-Placebo

Drug: BHT-Placebo

Evaluation of up to four dose levels will be given in weekly IM injections for 12 weeks.

Outcome Measures

Primary Outcome Measures

The primary endpoint in this study is safety.Safety parameters include: stimulated C-peptide response levels, opthalmologic examination, laboratory assessments, 24-hr urine protein, allergic reactions and adverse events including hypoglycemia. []

Secondary Outcome Measures

The secondary endpoints are pharmacodynamic parameters. Parameters include plasmid levels and insulin mRNA levels in blood and urine, Stimulated C-peptide response and Immunological response. []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Diagnosis of Type 1a Diabetes Mellitus based on ADA Criteria
≤5 years since T1D was diagnosed
≥ 18 years of age
≤ 40 years of age at the time of diagnosis of Type 1a diabetes
Presence of antibodies to at least one of the following antigens:

insulin, GAD-65, or IA-2

Detectable fasting C-peptide level
C-peptide increase during screening mixed meal tolerance test with a minimal stimulated value of ≥ 0.2 pmol/mL
Presence of antibodies to at least one of the following antigens: insulin, GAD-65, or IA-2. If insulin antibody positive only, determination must be within 2 weeks of insulin initiation

Exclusion Criteria:

BMI > 30 kg/m2
Unstable blood sugar control defined as one or more episodes of severe hypoglycemia (defined as hypoglycemia that required the assistance of another person) within the last 30 days
Current use of inhalable insulin
Previous immunotherapy for T1D
Administration of an experimental agent for T1D at any time or use of an experimental device for T1D within 30 days prior to screening, unless approved by the medical monitor
History of any organ transplant, including islet cell transplant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham School of Medicine	Birmingham	Alabama	United States	35294
2	Valley Research	Fresno	California	United States	93720
3	Barbara Davis Center for Childhood Diabetes	Aurora	Colorado	United States	80045
4	Private Practice	Denver	Colorado	United States	80209
5	MedStar Research Institute	Washington	District of Columbia	United States	20003
6	University of Miami, Miller School of Medicine, Diabetes Research Institute	Miami	Florida	United States	33136
7	Private Practice	Wellington	Florida	United States	33414
8	Creighton Diabetes Center	Omaha	Nebraska	United States	68131
9	Diabetes and Glandular Disease Center	San Antonio	Texas	United States	78229
10	Benaroya Research Institute at Virginia Mason	Seattle	Washington	United States	98101-2795
11	Peninsula Clinical Research Centre	Kippa Ring	Queensland	Australia	4021
12	Royal Melbourne Hospital	Parkville	Victoria	Australia	3050
13	Eastern Clinical Research Unit	Ringwood East	Victoria	Australia	3050
14	Fremantle Hospital	Fremantle	Western Australia	Australia	6160
15	Middlemore Hospital	Otahuhu	Auckland	New Zealand	Private Bag 93311
16	Christchurch Hospital	Christchurch	Canterbury	New Zealand	Private Bag 4710
17	Waikato Regional Diabetes Service	Hamilton	Waikato	New Zealand	Private bag 3200
18	The Diabetes Centre	Newtown	Wellington	New Zealand	Private Bag 7902

Sponsors and Collaborators

Bayhill Therapeutics

Investigators

Study Chair: Peter Gottlieb, MD, University of Colorado, Denver
Study Director: Joanne Quan, MD, Bayhill Therapeutics Inc.
Study Chair: Len Harrison, MD, Walter and Eliza Hall Institute of Medical Research