A Phase 1 Study to Evaluate Multiple Doses of golimumab in Participants At-Risk for Developing Type-1 Diabetes.

Phase 1

• Conditions: A Phase 1b Study to Evaluate SIMPONI® (golimumab) Therapy in Children, Adolescents and Young Adults with Pre-Symptomatic Type 1 Diabetes; MedDRA version: 20.0Level: PTClassification code 10067584Term: Type 1 diabetes mellitusSystem Organ Class: 10027433 - Metabolism and nutrition disorders; Therapeutic area: Body processes [G] - Immune system processes [G12]

• Registration Number: EUCTR2017-000225-12-FI
• Lead Sponsor: Janssen Biologics BV

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-06-08
• Last Update Posted: 17 May 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

-Is male or female.
-Is 6 to 21 years of age, inclusive, with minimal weight of 30 kg.
-Is positive for at least 2 of the following diabetes-related autoantibodies obtained at study screening:
•Glutamic acid decarboxylase-65 (GADA-65) Autoantibodies
•Insulinoma-associated 2 Autoantibodies (IA-2A)
•Zinc Transporter-8 (ZnT8)
•Islet Cell Cytoplasmic Autoantibodies (ICA)
•Insulin Autoantibodies (IAA)
Participants with a confirmed documented history of at leas 2 positive diabetes-related autoantibodies but who screen positive on only 1 autoantibody are considered to have met this inclusion criterion 3.
-Has a plasma glucose of 7.8 to 11.0 mmol/L (140 to 199 mg/dL) at the 120 minute timepoint of a 2h-OGTT, OR have a plasma glucose of >200 mg/dL (>11.1 mmol/L) at the 30, 60, or 90 minute timepoint of a 2h OGTT OR have a HbA1c =5.7% but <6.5% (=32 to <48 mmol/mol) evaluated at screening.
-Is medically stable on the basis of physical examination, medical history, laboratory results, and vital signs performed at screening. Any abnormalities must be consistent with the underlying pre-symptomatic stage of illness in the study population and this determination must be recorded in the participant's source documents and initialed by the investigator.

Are the trial subjects under 18? yes
Number of subjects for this age range: 15
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 5
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

-Has a current or prior diagnosis of diabetes mellitus (Type 1, Type 2, or gestational) or meet the metabolic criteria diagnostic of diabetes mellitus obtained at screening including: HbA1c =6.5% (48 mmol/mol), or Fasting plasma glucose =7.0 mmol/L (126 mg/dL) (fasting: no intake =8 hours), or Plasma glucose =11.1 mmol/L (200 mg/dL) 2 hours post OGTT, or Random plasma glucose =11.1 mmol/L (200 mg/dL) in those with symptoms consistent with hyperglycemia crisis. In the absence of unequivocal hyperglycemia, results should be confirmed by repeat testing.
-Has a history of moderate or severe progressive or uncontrolled liver or renal insufficiency, significant cardiac (including congestive heart failure), vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, or psychiatric disease (such as serious depression, including suicidality).
-Has a presence or history of malignancy.
-Has a presence or history of lymphoproliferative disease including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location (eg, nodes in the posterior triangle of the neck, infraclavicular, epitrochlear, or periaortic areas), or clinically significant hepatomegaly or splenomegaly.
-Has an immune deficiency syndrome (eg, severe combined immunodeficiency syndrome, T-cell deficiency syndromes, B-cell deficiency syndromes, or chronic granulomatous disease), or bone marrow or organ transplantation, or a disease associated with lymphopenia.
-Has other autoimmune diseases (eg, RA, pJIA, PsA, AS, multiple sclerosis, celiac disease, systemic lupus erythematosus) excluding clinically stable autoimmune thyroiditis whether treated or untreated.
-Has a concomitant diagnosis or history of demyelinating disease, such as but not limited to multiple sclerosis or Guillain-Barre Syndrome.
-Has known or suspected intolerance or hypersensitivity to human proteins, antibody fragments, or monoclonal antibodies, including golimumab or its excipients, or known allergies or severe sensitivity to latex (refer to the golimumab and VarioJect Investigator's Brochures).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary end point(s): Safety Endpoints<br>-Proportion of participants with treatment-emergent AEs and serious adverse events (SAE) through Week 26 and Week 52.<br>-Proportion of participants with treatment-emergent infections through Week 26 and Week 52.<br>-Proportion of participants with study treatment injection site reactions throughout the study.<br>-Related AE’s and SAE’s reported at the final safety contact point at Week 78.;Timepoint(s) of evaluation of this end point: Safety endpoint assessed at Week 26, 52 and 78.;Main Objective: The primary objective is to determine the safety and tolerability of golimumab in children, adolescents, and young adults with pre-symptomatic Stage 2 T1D.;Secondary Objective: The secondary objective is to assess the PK and immunogenicity of golimumab in children, adolescents, and young adults with pre-symptomatic Stage 2 T1D.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Pharmacokinetic and Immunogenicity<br>-Summary of serum golimumab concentrations and the PK profile after induction and maintenance dosing.<br>-Incidence and titers of antibodies to golimumab.;Timepoint(s) of evaluation of this end point: Endpoint assessed at week 52.