Safety Study of RTL1000 (Recombinant T Cell Receptor Ligand) in Subjects With Multiple Sclerosis

Sponsor

Artielle ImmunoTherapeutics (Industry)

Overall Status

Unknown status

CT.gov ID

NCT00411723

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

5.7

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RTL1000 is a new agent that has not been previously tested in humans. It is thought that RTL may specifically control the abnormal immune response or attack against the insulation on the nerves that occurs in multiple sclerosis.

The purpose of this study is to evaluate the possible side effects of a single intravenous dose of RTL1000 in subjects with multiple sclerosis. Some subjects will also be asked to participate in one or both of two substudies, one to test blood samples to see how the body's immune system responds after administration of RTL1000, and the other to test blood samples to see how the body absorbs and eliminates the RTL1000.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis, Chronic Progressive Multiple Sclerosis, Relapsing-Remitting	Drug: RTL1000 (recombinant T cell receptor ligand) Drug: RTL1000 Placebo	Phase 1

Detailed Description

This is a double-blind, placebo-controlled treatment protocol with up to six treatment cohorts, each of which receives a single intravenous infusion of an escalating dose of RTL1000. Each dosing group will have six subjects: two who will receive a single dose of placebo and four who will receive a single dose of RTL1000. Subjects are observed in the hospital during the infusion and for 24 hours afterward, and are then followed weekly for 28 days and at 1 and 2 months post-infusion to evaluate safety parameters.

Objectives of the study are to evaluate the safety profile of a single dose of RTL1000 administered by intravenous infusion, to evaluate the pharmacokinetic profile of RTL1000 in a subset of subjects, and to evaluate the feasibility of assessing immunologic parameters in a subset of subjects.

Endpoints include vital signs, electrocardiogram and physical examination results, adverse events, and serious adverse events and safety laboratory parameters (e.g., clinical chemistries and hematology values). Disease parameters, such as neurological findings, expanded disability status scale (EDSS), 25-ft timed walk, 9-hole peg test, and magnetic resonance imaging (MRI) will be measured to ensure that study treatment does not make disease worse. Subjects will also be tested at the beginning and end of the study for antibodies to the drug and its components.

Study Design

Study Type:

Interventional

Actual Enrollment :

34 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

Phase 1 Safety Study of RTL1000 (Recombinant T Cell Receptor Ligand) in Subjects With Multiple Sclerosis

Study Start Date :

Dec 1, 2006

Actual Primary Completion Date :

Feb 1, 2009

Anticipated Study Completion Date :

May 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: RTL1000 (recombinant T cell receptor ligand) Dosage form: IV infusion. Dosage: Single dose @ 2, 6, 20, 60, 100 or 200mg. Duration: 1 - 2 hours.
Placebo Comparator: 2	Drug: RTL1000 Placebo Dosage form: IV infusion. Dosage: Same volume as Experimental. Frequency: Single dose. Duration: 1 - 2 hours.

Arm

Intervention/Treatment

Experimental: 1

Drug: RTL1000 (recombinant T cell receptor ligand)

Dosage form: IV infusion. Dosage: Single dose @ 2, 6, 20, 60, 100 or 200mg. Duration: 1 - 2 hours.

Placebo Comparator: 2

Drug: RTL1000 Placebo

Dosage form: IV infusion. Dosage: Same volume as Experimental. Frequency: Single dose. Duration: 1 - 2 hours.

Outcome Measures

Primary Outcome Measures

Adverse events, safety, laboratory parameters, vital signs, ECG and physical exam results. Disease parameters (neurologic exam, EDSS, 25 foot timed walk, 9-hole PEG test, MRI). Antibodies to drug. [Day 28]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

A specific blood cell type called HLA-DR2 may be required in order for RTL1000 to work. For that reason, all subjects will be tested for HLA-DR2 and only those subjects who test positive (about 50%) will undergo further tests to determine if they meet inclusion and exclusion criteria.

Inclusion criteria:

Fulfill McDonald criteria for multiple sclerosis
Confirmed diagnosis of chronic progressive or relapsing-remitting multiple sclerosis
EDSS score of 0.0 to 6.5
No clinical exacerbations within the 8 weeks before administration of RTL1000
HLA-DR2 positive, as confirmed by study reference laboratory
Negative serum pregnancy test within 7 days of administration of RTL1000 and negative urine pregnancy test on Day 0 for all women of childbearing potential
Agreement of sexually active men and women of childbearing potential to practice a medically-approved form of contraception
Capable of and willing to provide written informed consent

Exclusion Criteria:

Exposure to alemtuzumab or dacluzimab any time in the 6 months before administration of RTL1000
Exposure to natalizumab or other drugs targeting alpha-4 integrin in the 6 months before RTL1000 administration or more than 3 doses of natalizumab or these drugs at any time.
Any prior exposure to RTL1000
Exposure to other MS disease-modifying drugs (e.g., recombinant interferon beta and glatiramer acetate), immunosuppressant agents, or systemic corticosteroids (other than replacement doses) within the 4 weeks prior to RTL1000 administration
Exposure to chemotherapeutic immunosuppressants, including azathioprine, mycophenolate mofetil, methotrexate, cladribine, mitoxantrone, or cyclophosphamide, during the six months prior to administration of RTL1000
Total lymphoid irradiation or bone marrow transplantation at any time
Known or suspected allergy to gadolinium
Contraindication to MRI (e.g., subject has a pacemaker or other contraindicated implanted metal devices or has claustrophobia that cannot be medically managed)
Clinically significant abnormalities in laboratory findings for hematologic, hepatic, and renal function at screening.
Significant medical diseases or conditions, including poorly controlled hypertension, cardiovascular disease, inflammatory disorders, immunodeficiency (e.g., HIV infection), renal failure, liver dysfunction, cancer (except treated basal cell carcinoma), or active infection.
History of, or current, psychiatric illness likely to interfere with ability to comply with protocol requirements or give informed consent
History of alcohol or drug abuse likely to interfere with ability to comply with protocol requirements
Pregnancy or lactation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale Center for MS Treatment and Research	New Haven	Connecticut	United States	06510
2	Indiana University, Dept. of Neurology	Indianapolis	Indiana	United States	46202
3	University of Kansas Medical Center, Landon Center on Aging	Kansas City	Kansas	United States	66160
4	University of Maryland School of Medicine	Baltimore	Maryland	United States	21201
5	MS Center of Oregon Health & Science University	Portland	Oregon	United States	97239
6	MS Center at Evergreen	Kirkland	Washington	United States	98034

Sponsors and Collaborators

Artielle ImmunoTherapeutics

Investigators

Principal Investigator: Jana Preiningerova, M.D., Yale Center for MS Treatment and Research
Principal Investigator: David Mattson, M.D., Ph.D., University of Indiana, Department of Neurology
Principal Investigator: Sharon Lynch, M.D., University of Kansas Medical Center, Landon Center on Aging
Principal Investigator: Christopher Bever, Jr., M.D., M.B.A., University of Maryland School of Medicine
Principal Investigator: Theodore R Brown, M.D., MS Center at Evergreen
Principal Investigator: Vijayshree Yadav, M.D., MS Center of Oregon Health and Science University