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

Primary Purpose

Multiple Sclerosis, Chronic Progressive, Multiple Sclerosis, Relapsing-Remitting

Status

Unknown status

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

RTL1000 (recombinant T cell receptor ligand)

RTL1000 Placebo

About this trial

This is an interventional treatment trial for Multiple Sclerosis, Chronic Progressive focused on measuring multiple sclerosis, chronic-progressive, relapsing-remitting

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Yale Center for MS Treatment and Research
Indiana University, Dept. of Neurology
University of Kansas Medical Center, Landon Center on Aging
University of Maryland School of Medicine
MS Center of Oregon Health & Science University
MS Center at Evergreen

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm Description

Outcomes

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT00411723

First Posted

December 12, 2006

Last Updated

February 19, 2009

Sponsor

Artielle ImmunoTherapeutics

1. Study Identification

Unique Protocol Identification Number

NCT00411723

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2009

Overall Recruitment Status

Unknown status

Study Start Date

December 2006 (undefined)

Primary Completion Date

February 2009 (Actual)

Study Completion Date

May 2009 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor

Artielle ImmunoTherapeutics

4. Oversight

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Sclerosis, Chronic Progressive, Multiple Sclerosis, Relapsing-Remitting

Keywords

multiple sclerosis, chronic-progressive, relapsing-remitting

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

34 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Title

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

RTL1000 (recombinant T cell receptor ligand)

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

RTL1000 Placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

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.

Time Frame

Day 28

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials: