A study looking at the safety and effect of two kinds of Itolizumab in Normal Healthy Subjects.

• Register: ANZCTR
• Last refreshed on: 13 January 2020
• Main ID: ACTRN12616000138482
• Date of registration: 05/02/2016
• Prospective Registration: Yes
• Primary sponsor: Biocon Research Limited
• Public title: A study looking at the safety and effect of two kinds of Itolizumab in Normal Healthy Subjects.
• Scientific title: A Randomized, Double Blind, Placebo Controlled, Single Ascending Dose, Phase I Study of Itolizumab (Bmab 600) Administered Subcutaneously and a Randomized, Partial Blind, Placebo-controlled, Comparative Pharmacokinetic and Safety Study of Two Formulations of Itolizumab Administered Intravenously and a Bioavailability Assessment of Subcutaneous Administration of Itolizumab (Bmab 600) in Normal Healthy Subjects
• Date of first enrolment: 08/03/2016
• Target sample size: 74
• Recruitment status: Stopped early
• URL: https://anzctr.org.au/ACTRN12616000138482.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Randomised controlled trial; Masking: Blinded (masking used);Assignment: Other;Type of endpoint: Pharmacokinetics / pharmacodynamics;
• Phase: Phase 1

Countries of recruitment

Australia

Contacts

• Name: Dr Claire Williams

• Name: Dr Kanhei Charan Sahoo

Key inclusion & exclusion criteria

Inclusion criteria: 1. Male or female between 18 and 50 years of age (inclusive).
2. Healthy with no clinically significant medical problems.
3. BMI between 18 to 30 kg/m2 with weight between 50 to 100 kg (both inclusive).
4. No history of alcohol or drug abuse (Paracetamol, Barbiturates, Benzodiazepines, Cocaine, Methadone, Amphetamines, Methamphetamines, Opiates, Phencyclidine, Tetrahydrocannabinol (cannabis), Tricyclic Antidepressants). Subjects should be enrolled only after passing the urine drug screen (positive test for paracetamol will be allowed).
5. Non smokers or light smokers (Less than 5 cigarettes per day) by history and planned during study.
6. No history of significant allergic diathesis such as urticaria, angioedema or anaphylaxis.
7. No prior exposure to Itolizumab or other biologicals including monoclonal antibodies, fusion proteins etc.
8. Willing and able to sign written, informed consent.
Exclusion criteria: 1. Any significant past or current cardiac, pulmonary, hepatic, renal or other medical condition which in the opinion of the investigator would make participation of the subject in this study medically unsafe or compromise the accuracy of assessment of safety, pharmacokinetic and pharmacodynamic data of the study.
2. Subjects who have abnormal safety labs outside the local lab ranges will be excluded as per PI's discretion based on his/her assessment of clinical significance.
3. Subjects with past medical history of malignancy except basal cell or squamous cell carcinoma of the skin who have had curative surgical treatment and at least 6 months has elapsed since the procedure.
4. A value outside the specified range of 90 mm Hg – 140 mm Hg for systolic blood pressure and 50 mm Hg – 90 mm Hg for diastolic blood pressure (both inclusive) at screening.
5. Subjects who show a positive Quantiferon TB test for tuberculosis will be excluded. Subjects with history of tuberculosis will be excluded irrespective of prior successful treatment.
6. History of clinically significant acute bacterial, viral, or fungal systemic infections in the last 4 weeks prior to screening.
7. Clinical or laboratory evidence of an active infection at the time of screening.
8. Serological evidence of human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or anti-hepatitis C virus (Anti-HCV) at screening.
9. Vaccination within 3 months of screening for the study or requiring vaccination during the study or within 3 months after completion of the study.
10. Females who are pregnant or nursing.
11. Females of childbearing potential (i.e., any woman who is not surgically sterile e.g., hysterectomy, bilateral oophorectomy or more than 2 years post menopause) and all men who, if participating in heterosexual sexual activity that could lead to pregnancy are unable or unwilling to practice medically effective contraception during the study. They should agree to use two reliable methods of contraception (e.g., double-barrier condom plus diaphragm, condom or diaphragm plus stable dose of hormonal contraception) throughout the study period and until 3 months after receiving study drug. Women of childbearing potential will require compulsory pregnancy testing. A negative pregnancy test (serum and urine) will be documented during screening and at Day -1 respectively.
12. Participation in any other drug study within 8 weeks or 5 half lives of the study drug whichever is longer.
13. Unable or unwilling to comply with the protocol requirements for study visits and procedures.
14. Subjects who do not have good venous access for infusion of study drug or for blood sampling.
15. History of hypersensitivity to diphenhydramine or paracetamol.

Age minimum: 18 Years
Age maximum: 50 Years
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Psoriasis;Rheumatoid arthritis;Multiple Sclerosis;
Psoriasis
Rheumatoid arthritis
Multiple Sclerosis

Neurological - Multiple sclerosis

Skin - Dermatological conditions

Inflammatory and Immune System - Rheumatoid arthritis

Intervention(s)

Itolizumab (Bmab 600)
In Stage 1 -escalating single doses administered subcutaneously at 0.8, 1.6, 2.4 and 3.2 mg/kg dose levels.
In Stage 2 – single dose of 0.8mg/kg administered subcutaneously or intravenous infusion at 0.8 mg/kg dose level over 2 hours

Itolizumab (NS0)
Stage 2- single dose administered as intravenous infusion at 0.8 mg/kg dose level over 2 hours.

All doses will be administered in the clinic by study staff.

Primary Outcome(s)

To evaluate the safety and tolerance of ascending, single doses of Itolizumab (Bmab 600) administered subcutaneously in normal healthy subjects.
This will be assessed by monitoring adverse events, physical examination findings including injection site reactions, vital signs, laboratory parameters and electrocardiogram.[For Stage 1, subjects will be assessed at Day 1-5, 8, 11, 15, 29, 43 and Day 57.
For Stage 2, Day 1-5, 6, 8, 11, 15, 29, 43, 57 and Day 75]

To compare the pharmacokinetics (PK) of Itolizumab NS0 and Bmab-600 administered intravenously.
This will be assessed by collecting and analysing blood samples for drug concentrations at various time points.
PK parameters include: Cmax, AUC, Tmax, T1/2[Collection of blood samples at various time points (pre-dose, 1, 1.5, 2, 2.5, 4, 6, 12, 24 hours and Days 3, 4, 5, 6, 8, 11, 15, 29, 43, 57 and 75) ]

Secondary Outcome(s)

To evaluate immunogenicity of single doses of Itolizumab (Bmab 600) administered subcutaneously.
This will be assessed by analysing blood samples for anti-drug antibodies.[Collection of blood samples at various time points (Days 1, 8, 29, 57 and 75) ]

To determine the absolute bioavailability of Itolizumab (Bmab 600) administered subcutaneously.
This will be assessed by analysing blood samples for drug levels and comparing exposure (AUC) after subcutaneous and intravenous administration.[Collection of blood samples at various time points (pre-dose, 1, 1.5, 2, 2.5, 4, 6, 12, 24 hours and Days 3, 4, 5, 6, 8, 11, 15, 29, 43, 57 and 75)]

To characterize the pharmacokinetic (PK) profile of single doses of Itolizumab (Bmab-600) administered subcutaneously.
This will be assessed by collecting and analysing blood samples for Bmab 600 drug concentrations at various time points.
PK parameters include: Cmax, AUC, Tmax, T1/2[Collection of blood samples at various time points (pre-dose, 2, 4, 8, 12, 24 hours and Days 3, 4, 5, 8, 11, 15, 29, 43, 57 and 75). ]

Secondary ID(s)

Bm600-NHV-01-G-01

Source(s) of Monetary Support

Biocon SA

Secondary Sponsor(s)

Novotech (Australia) Pty Limited

Ethics review

Status: Approved
Approval date:
Contact:

Queensland Institute of Medical Research Berghofer Human Research Ethics Committee