Trial Outcomes & Findings for CTLA4-Ig (Abatacept)for Prevention of Abnormal Glucose Tolerance and Diabetes in Relatives At -Risk for Type 1 (NCT NCT01773707)

Last Updated: 2024-06-06

Results Overview

Measured by Oral Glucose Tolerance Test (OGTT): Abnormal Glucose Tolerance is primary endpoint and defined as: 1. Fasting plasma glucose ≥ 110 mg/dL (6.1 mmol/L) and \< 126 mg/dL (7 mmol/L), or 2. 2 hour plasma glucose ≥ 140 mg/dL (7.8 mmol/L) and \< 200 (11.1 mmol/L), or 3. 30, 60, 90 minute plasma glucose during OGTT ≥ 200 mg/dL (11.1 mmol/L)

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

212 participants

Primary outcome timeframe

96 months

Results posted on

2024-06-06

Participant Flow

Participant milestones

Participant milestones
Measure	Abatacept IV Infusion CTLA4-Ig (Abatacept) will be administered as 14 (30 minute) infusions over one year (3 infusions every other week the first month; monthly for the following 11 months) CTLA4-Ig (Abatacept): Given as 30 minute IV infusion	Placebo The placebo arm will receive 14 (30 minute) IV infusions (containing saline) given 3 times (every other week) the first month and monthly for the following 11 months. Placebo: Saline given as 30 minute IV infusion
Overall Study STARTED	101	111
Overall Study COMPLETED	99	108
Overall Study NOT COMPLETED	2	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

CTLA4-Ig (Abatacept)for Prevention of Abnormal Glucose Tolerance and Diabetes in Relatives At -Risk for Type 1

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Abatacept IV Infusion n=101 Participants CTLA4-Ig (Abatacept) will be administered as 14 (30 minute) infusions over one year (3 infusions every other week the first month; monthly for the following 11 months) CTLA4-Ig (Abatacept): Given as 30 minute IV infusion	Placebo n=111 Participants The placebo arm will receive 14 (30 minute) IV infusions (containing saline) given 3 times (every other week) the first month and monthly for the following 11 months. Placebo: Saline given as 30 minute IV infusion	Total n=212 Participants Total of all reporting groups
Age, Continuous	16.3 years n=5 Participants	14.9 years n=7 Participants	15.6 years n=5 Participants
Sex: Female, Male Female	50 Participants n=5 Participants	57 Participants n=7 Participants	107 Participants n=5 Participants
Sex: Female, Male Male	51 Participants n=5 Participants	54 Participants n=7 Participants	105 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	11 Participants n=5 Participants	10 Participants n=7 Participants	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	84 Participants n=5 Participants	98 Participants n=7 Participants	182 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) White	91 Participants n=5 Participants	102 Participants n=7 Participants	193 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Relationship to person with type 1 diabetes Sibling(s)	53 Participants n=5 Participants	56 Participants n=7 Participants	109 Participants n=5 Participants
Relationship to person with type 1 diabetes Identical twin	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Relationship to person with type 1 diabetes Offspring	21 Participants n=5 Participants	14 Participants n=7 Participants	35 Participants n=5 Participants
Relationship to person with type 1 diabetes Parent(s)	14 Participants n=5 Participants	23 Participants n=7 Participants	37 Participants n=5 Participants
Relationship to person with type 1 diabetes Sibling and another first degree relative	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Relationship to person with type 1 diabetes Second degree relative	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Relationship to person with type 1 diabetes Third degree relative	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Autoantibodies positive Anti-GAD65 harmonized	94 Participants n=5 Participants	104 Participants n=7 Participants	198 Participants n=5 Participants
Autoantibodies positive Micro insulin	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Autoantibodies positive Anti-IA-2 harmonized	49 Participants n=5 Participants	61 Participants n=7 Participants	110 Participants n=5 Participants
Autoantibodies positive Autoantibodies (ICA)	76 Participants n=5 Participants	79 Participants n=7 Participants	155 Participants n=5 Participants
Autoantibodies positive Anti-ZnT8	47 Participants n=5 Participants	65 Participants n=7 Participants	112 Participants n=5 Participants
Autoantibodies titer GADA	317 titers n=5 Participants	375 titers n=7 Participants	335 titers n=5 Participants
Autoantibodies titer Micro insulin	0.002 titers n=5 Participants	0.002 titers n=7 Participants	0.002 titers n=5 Participants
Autoantibodies titer Anti-IA-2 harmonized	2 titers n=5 Participants	23 titers n=7 Participants	9 titers n=5 Participants
Autoantibodies titer Autoantibodies (ICA)	40 titers n=5 Participants	40 titers n=7 Participants	40 titers n=5 Participants
Autoantibodies titer Anti-ZnT8	0.013 titers n=5 Participants	0.041 titers n=7 Participants	0.027 titers n=5 Participants
Glycated hemoglobin level	5.1 percentage of glycated hemoglobin n=5 Participants	5.1 percentage of glycated hemoglobin n=7 Participants	5.1 percentage of glycated hemoglobin n=5 Participants
Body Mass Index (BMI)	22.7 kg/m^2 n=5 Participants	21.6 kg/m^2 n=7 Participants	22.1 kg/m^2 n=5 Participants
Body Mass Index (BMI) Z-score	0.668 Z-score n=5 Participants	0.582 Z-score n=7 Participants	0.623 Z-score n=5 Participants
HLA alleles present DR3	47 Participants n=5 Participants	60 Participants n=7 Participants	107 Participants n=5 Participants
HLA alleles present DR4	60 Participants n=5 Participants	63 Participants n=7 Participants	123 Participants n=5 Participants
HLA alleles present Missing	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: 96 months

Population: Relatives of patients with type 1 diabetes who did not have diabetes but were at high risk for development of clinical disease.

Outcome measures

Outcome measures
Measure	Abatacept IV Infusion n=101 Participants CTLA4-Ig (Abatacept) will be administered as 14 (30 minute) infusions over one year (3 infusions every other week the first month; monthly for the following 11 months) CTLA4-Ig (Abatacept): Given as 30 minute IV infusion	Placebo n=111 Participants The placebo arm will receive 14 (30 minute) IV infusions (containing saline) given 3 times (every other week) the first month and monthly for the following 11 months. Placebo: Saline given as 30 minute IV infusion
Time From Randomization to Confirmed Abnormal Glucose Tolerance Test	89.2 months Interval 41.1 to upper quartile range is unknown as it has not been reached	71.6 months Interval 23.7 to upper quartile range is unknown as it has not been reached

SECONDARY outcome

Timeframe: 0 time to 30 months

To Determine whether treatment with Abatacept is superior to placebo with respect to C-peptide response to oral glucose tolerance

Outcome measures

Outcome measures
Measure	Abatacept IV Infusion n=101 Participants CTLA4-Ig (Abatacept) will be administered as 14 (30 minute) infusions over one year (3 infusions every other week the first month; monthly for the following 11 months) CTLA4-Ig (Abatacept): Given as 30 minute IV infusion	Placebo n=111 Participants The placebo arm will receive 14 (30 minute) IV infusions (containing saline) given 3 times (every other week) the first month and monthly for the following 11 months. Placebo: Saline given as 30 minute IV infusion
Change in C-peptide Concentration to Oral Glucose Tolerance Test (OGTT)	2.16 nmol/L Interval 1.61 to 2.5	2.07 nmol/L Interval 1.51 to 2.74

Adverse Events

Abatacept IV Infusion

Serious events: 2 serious events

Other events: 63 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 77 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Abatacept IV Infusion n=101 participants at risk CTLA4-Ig (Abatacept) will be administered as 14 (30 minute) infusions over one year (3 infusions every other week the first month; monthly for the following 11 months) CTLA4-Ig (Abatacept): Given as 30 minute IV infusion	Placebo n=111 participants at risk The placebo arm will receive 14 (30 minute) IV infusions (containing saline) given 3 times (every other week) the first month and monthly for the following 11 months. Placebo: Saline given as 30 minute IV infusion
Surgical and medical procedures Surgical and medical procedures - Other, specify	0.00% 0/101 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.	0.90% 1/111 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.
Nervous system disorders Stroke	0.00% 0/101 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.	0.90% 1/111 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	2.0% 2/101 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.	0.00% 0/111 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.
Infections and infestations Appendicitis	0.00% 0/101 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.	0.90% 1/111 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.

Other adverse events

Additional Information

Dr. Kevan Herold

Yale University

Phone: 203-785-6507

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Abatacept IV Infusion n=101 participants at risk CTLA4-Ig (Abatacept) will be administered as 14 (30 minute) infusions over one year (3 infusions every other week the first month; monthly for the following 11 months) CTLA4-Ig (Abatacept): Given as 30 minute IV infusion	Placebo n=111 participants at risk The placebo arm will receive 14 (30 minute) IV infusions (containing saline) given 3 times (every other week) the first month and monthly for the following 11 months. Placebo: Saline given as 30 minute IV infusion
Infections and infestations Infections and infestations	37.6% 38/101 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.	40.5% 45/111 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.
Gastrointestinal disorders Gastrointestinal Disorders	21.8% 22/101 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.	26.1% 29/111 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.
Musculoskeletal and connective tissue disorders Musculoskeletal and Connective Tissue	18.8% 19/101 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.	13.5% 15/111 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders	15.8% 16/101 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.	13.5% 15/111 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.
General disorders General disorders and administration site	13.9% 14/101 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.	18.0% 20/111 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders	16.8% 17/101 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.	9.0% 10/111 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.
Nervous system disorders Nervous system disorders	12.9% 13/101 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.	7.2% 8/111 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.
Injury, poisoning and procedural complications Injury, poisoning and procedural	14.9% 15/101 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.	7.2% 8/111 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.
Psychiatric disorders Psychiatric disorders	6.9% 7/101 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.	8.1% 9/111 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.
Surgical and medical procedures Surgical and medical procedures	8.9% 9/101 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.	8.1% 9/111 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.
Investigations Investigations	3.0% 3/101 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.	9.0% 10/111 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.
Metabolism and nutrition disorders Metabolism and nutrition disorders	5.0% 5/101 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.	3.6% 4/111 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.
Eye disorders Eye disorders	5.0% 5/101 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.	3.6% 4/111 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.
Reproductive system and breast disorders Reproductive system and breast disorders	3.0% 3/101 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.	2.7% 3/111 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.
Blood and lymphatic system disorders Blood and lymphatic system disorders	3.0% 3/101 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.	6.3% 7/111 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.
Cardiac disorders Cardiac disorders	3.0% 3/101 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.	2.7% 3/111 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.
Vascular disorders Vascular disorders	2.0% 2/101 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.	3.6% 4/111 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.
Endocrine disorders Endocrine disorders	3.0% 3/101 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.	1.8% 2/111 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.
Pregnancy, puerperium and perinatal conditions Pregnancy, puerperium and perinatal	2.0% 2/101 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.	0.00% 0/111 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified	4.0% 4/101 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.	1.8% 2/111 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.
Immune system disorders Immune system disorders	2.0% 2/101 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.	2.7% 3/111 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.
Renal and urinary disorders Renal and urinary disorders	3.0% 3/101 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.	0.90% 1/111 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.
Ear and labyrinth disorders Ear and labyrinth disorders	2.0% 2/101 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.	1.8% 2/111 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.
Hepatobiliary disorders Hepatobiliary disorders	2.0% 2/101 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.	0.00% 0/111 • Baseline Visit through study endpoint, up to 6 years CTCAE; Adverse events were analyzed and published based on organ system class without regard to the specific Adverse Event Term.