Mycophenolate Mofetil in Systemic Sclerosis

March 29, 2011 updated by: Boston University

Phase I, Open-label Study of Mycophenolate Mofetil In Systemic Sclerosis

This is a research study of an investigational product called Mycophenolate mofetil (MMF). The study is designed to establish the safety and potential benefit of MMF. MMF has proven one of the most effective medications to date for SLE and associated nephritis. It also appears to be active in polymyositis and dermatomyositis. This medication inhibits inosine monophosphate dehydrogenase, the rate-limiting enzyme in synthesis of guanosine nucleotides. It blocks the type II isoform found in activated lymphocytes more potently than the type I isoform inhibiting both T- and B-lymphocytes. In SSc, MMF has been tried after anti-thymocyte globulin in one small open label study with efficacy with a significant improvement in skin score. We will test the safety and efficacy of MMF in SSc. All study patients will receive the study medication. The effect of the study medication will be examined in two subgroups of patients: those with early or progressive skin disease (skin substudy) and those with muscle disease (muscle substudy). The change in modified Rodnan skin score (MRSS) and creatinine phosphokinase (CK) for, respectively, the skin and muscle substudies at 6 months after treatment will be compared to baseline values.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Systemic sclerosis (SSc) is an autoimmune/connective tissue disease with complex pathogenesis involving immune system dysregulation, leading to fibrosis. Inflammatory and autoimmune aspects of this disease overlap systemic lupus erythematosus (SLE), a disease shown clearly to respond to MMF. Activated T-cells, the probable target of MMF in SLE, likely also play an important role in SSc pathogenesis. Evidence for this includes the similarity of SSc skin disease to chronic graft versus host disease, a disease in which T-cells play a critical role. MMF has proven one of the most effective medications to date for SLE and associated nephritis [1]. It also appears to be active in polymyositis and dermatomyositis, disease that also show significant overlap with SSc [2]. Myositis can also be a feature of SSc, suggesting that his disease manifestation might be particularly likely to respond to MMF. MMF inhibits inosine monophosphate dehydrogenase, the rate-limiting enzyme in synthesis of guanosine nucleotides. It blocks the type II isoform found in activated lymphocytes more potently than the type I isoform inhibiting both T- and B-lymphocytes [3]. In SSc, mycophenolate has been tried after anti-thymocyte globulin in one small open label study with efficacy with a significant improvement in skin score [4]. However, MMF has not been tried alone inSSc and has not been tried in muscle disease associated with SSc. In this study, we will test the safety and efficacy of MMF in SSc. In this study all study patients will receive the medication.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Boston University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Must meet the American College of Rheumatology criteria for systemic sclerosis with diffuse cutaneous disease or muscle involvement
  • Patients must also meet one of the following criteria:

SKIN SUBSTUDY (20 patients)

  • Be within 1 1/2 years of first non-Raynaud's disease manifestation.
  • How progression of skin disease at some time over the past 6 months prior to study entry based on either documented increase in skin score or new areas of skin involvement or progression (no more than 10 patients total recruited)

OR, MUSCLE SUBSTUDY (10 patients)

  • Have a serum creatinine phosphokinase (CK) greater than 2 times the upper limit of normal

    • Patients entering the study on the basis of elevated CK must also have subjective and/or objective weakness; clinical evidence of cardiac, pulmonary or gastrointestinal disease as a complication of the patient¿s systemic sclerosis; or progressive skin disease.
    • The total number of patients entered in criteria 2a and 2b (skin substudy) will be 20. Patients meeting both criteria 2c. and either 2a or 2b will first be recruited into the muscle substudy (by criteria 2c) until 10 patients have been recruited.
    • Male or female patients >18 years of age.
    • Able and willing to give written informed consent and comply with the requirements of the study protocol
    • Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for 6 weeks after completion of treatment.
    • Adequate renal function as indicated by Cr less than or equal to 3.0
    • Adequate liver function, as indicated by SGOT and SGPT less than 2.5 times the upper limit of normal.
    • Negative serum pregnancy test (for women of child bearing age)

Exclusion Criteria:

  • Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer).
  • Ongoing use of high dose steroids (>10mg/day) or unstable steroid dose in the past 4 weeks.
  • Receipt of a live vaccine within 4 weeks prior to randomization.
  • Previous Treatment with MMF
  • Treatment with immunosuppressive, cytotoxic or anti-fibrotic drug within 4 weeks of screening other than anti-malarial. This includes cyclophosphamide, azathioprine (Immuran), methotrexate or other immunosuppressive or cytotoxic medication.
  • Treatment with cholestyramine within 1 week of trial entry.
  • History of HIV, Hepatitis B and/or Hepatitis C, or evidence of Hepatitis B or C at screening.
  • Moderate to severe hepatic impairment, Child-Pugh Class B or C.
  • History of recurrent significant infection or history of recurrent bacterial infections.
  • Known active bacterial, viral fungal mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with i.v. antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening.
  • Active gastrointestinal bleeding within 4 weeks of study entry or active serious gastrointestinal disease.
  • Pregnancy (a negative serum pregnancy test will be performed for all women of childbearing potential within 14 days of treatment).
  • Concomitant malignancies or previous malignancies within the last five years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
  • A history of phenylketonuria, hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase, Lesch-Nyhan or Kelley-Seegmiller syndrome
  • Allergy to polysorbate 80/Tween
  • Subjects who are breastfeeding
  • Moderately severe renal dysfunction as indicated by Cr >3.0, dipstick protein >3+, or patient on dialysis.
  • Hemoglobin: < 8.5 gm/dL
  • Platelets: < 100,000/mm
  • AST or ALT >2.5 x Upper limit of normal unless related to muscle disease.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: A
Mycophenolate
Drug: Mycophenolate Mofetil
Mycophenolate 3000 mg each day
Other Names:
  • Cellcept

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Skin Study: The primary evaluation of response will be improvement of the modified Rodnan skin score @ 6 months. Improvement of skin score, correlates with improvement in joint function, functional status and physician's global assessment.
Time Frame: 6 months
6 months
Muscle Sub Study:The primary evaluation of response will be the CK at 6 months compared to baseline.Improvement after 6 months of tx compared to baseline CK will suggest efficacy
Time Frame: 6 months
6 months
Safety evaluation.
Time Frame: 6 months
6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Secondary evaluations of response. Scleroderma Health Assessment Questionnaire (SHAQ): The SHAQ will be evaluated at study entry compared to 6 and 12 months.
Time Frame: 6 months
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Boston University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Aspreva Pharmaceuticals

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Robert Lafyatis, MD, Boston University School od Medicine Rheumatology Section

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2006

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2011

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 7, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 7, 2007

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 9, 2007

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 31, 2011

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 29, 2011

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • H-25973

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings