A Study to Evaluate Safety of Multi-Dose MEDI-545 in Adult Patients With Dermatomyositis or Polymyositis

NCT00533091 | Completed Phase 1 DMC

• 1 other identifier: MI-CP151
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 14

Brief Summary

The primary objective of the study is to evaluate the safety and tolerability of multiple IV doses of MEDI-545 in adult patients with myositis.

Conditions

DERMATOMYOSITIS OR POLYMYOSITIS

Outcome Measures

Primary Outcomes (1)

• The primary endpoints of the study are safety and tolerability of multiple intravenous (IV) doses of MEDI-545 in adult patients with Dermatomyositis or Polymyositis, assessed primarily by summarizing AEs assessing changes in viral cultures and titers.

  12 months

Secondary Outcomes (2)

• The secondary endpoints of the study are the PK and IM of multiple IV doses of MEDI-545.

  12 months

• The third endpoint of the study are the evaluations of disease activities.

  12 months

Study Arms (2)

1

ACTIVE COMPARATOR

MEDI-545

Biological: MEDI-545

2

OTHER

Placebo

Other: Placebo

Interventions

MEDI-545 BIOLOGICAL

MEDI-545 is supplied as a sterile liquid containing 0.75 mL of MEDI-545 solution at a concentration of 100 mg/mL in a 3 mL single-use glass vial. Dosage, frequency and duration: MEDI-545 (0.3, 1.0, 3.0, or 10.0 mg/kg) will be administered via infusion over at least 60 minutes every 2 weeks for 26 weeks.

1

Placebo OTHER

Dosage form: Placebo is supplied as a sterile liquid containing a 0.75 mL solution in a 3 mL single-use vial. Dosage, frequency and duration: Placebo (0.3, 1.0, 3.0, or 10.0 mg/kg) will be administered via infusion over at least 60 minutes every 2 weeks for 12 weeks. Thereafter, subjects will receive MEDI-545, at the dose specified in the dose cohort they are assigned, every 2 weeks for an additional 12 weeks.

2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female adults at least 18 years of age at the time of randomization;
• Written informed consent obtained from the patient or the patient's legal representative prior to receipt of any study medication or beginning study procedures;
• Probable or definite PM or DM according to the Bohan and Peter criteria (Bohan, 1975);
• For patients with PM, documentation of a muscle biopsy result that is consistent with the diagnosis of PM;
• All patients including those with DM must meet at least two of the following criteria:
• Strength in MMT greater ≥ 80/150 but ≤ 125/150 using the MMT-8 muscle group testing;
• Patient Global Activity Assessment by visual analog scale (VAS)≥ 2.0 cm on a 10 cm scale, which is included as part of CLINHAQ;
• Physician Global Activity Assessment by VAS ≥ 2.0 cm on a 10 cm scale, which is included as part of MDAAT;
• CLINHAQ disability index ≥ 0.25;
• Global extramuscular activity assessment ≥ 1.0 cm on a 10-cm VAS scale (this measure is the physician's composite evaluation and is based on assessments of activity scores on the constitutional, cutaneous, skeletal, gastrointestinal, pulmonary and cardiovascular scales of the MDAAT;
• Subjects with PM must have an elevation of serum CK or aldolase at a minimum level of 1.3 x upper limit of normal (ULN) or serum CK or aldolase at least 2-fold higher than the patient's own lowest value since diagnosis;
• For patients randomized to Dose Cohorts 1.2, 3A and 4: median fold overexpression of the top 25 type I IFN inducible genes of four-fold or greater in whole blood at the time of screening; For patients randomized to dose cohort 3B: low or negative expression of type I IFN-inducible genes;
• Sexually active women, unless surgically sterile (including tubal ligation) or at least 2 years postmenopausal, must use an effective method of avoiding pregnancy (including oral, injectable, transdermal, or implanted contraceptives, intrauterine device, diaphragm with spermicide, cervical cap, abstinence, and sterile sexual partner) in addition to the use of condoms (male or female condoms with spermicide) from screening through end of study. Cessation of birth control after this point should be discussed with a responsible physician. Sexually active males, unless surgically sterile, must likewise practice two effective methods of birth control (condom with spermicide or abstinence) and must use such precautions from Study Day 0 through end of study;
• Ability to complete the study period, including follow-up period, of up to 350 days; and
• Willing to forego other forms of experimental treatment during the study.

You may not qualify if:

• Receipt of MEDI-545 in any previous clinical study or prior randomization into the trial;
• History of allergy or reaction to any component of the study drug formulation;
• A history of or a family history of noninflammatory myopathy, scapular winging, atrophy, or hypertrophy of the calf muscles;
• Receiving prednisone \> 35 mg/day (or an equivalent dose of another corticosteroid) within 14 days before Study Day 0;
• Receiving the following dosages of medications within 28 days before Study Day 0: hydroxychloroquine \> 600 mg/day, mycophenolate mofetil \> 3 g/day, methotrexate \> 25 mg/week, azathioprine \> 3 mg/kg/day, or any dose of cyclophosphamide, cyclosporine, or thalidomide;
• Have received fluctuating doses of antimalarials, mycophenolate mofetil, methotrexate, leflunomide, or azathioprine within 28 days before Study Day 0 or fluctuating doses of corticosteroids within 14 days before Study Day 0;
• Have received leflunomide \> 20 mg/day in the 6 months prior to Study Day 0;
• Treatment with any investigational drug therapy within 28 days before Study Day 0 or biologic therapies (eg, rituximab) within 30 days or 5 half-lives of the biologic agent, whichever is longer, before Study Day 0;
• In the investigator's opinion, evidence of clinically significant active infection, including ongoing, chronic infection, within 28 days before Study Day 0;
• A history of severe viral infection as judged by the investigators, including severe infections of either CMV or the herpes family such as disseminated herpes, herpes encephalitis, ophthalmic herpes;
• Herpes zoster ≤ 3 months prior to Study Day 0;
• Evidence of infection with hepatitis B or C virus or HIV-1 or HIV-2, or active infection with hepatitis A, as determined by results of testing at screening;
• Vaccination with live attenuated viruses within 28 days before Study Day 0;
• Pregnancy (sexually active women, unless surgically sterile or at least 2 years post-menopausal, must have a negative serum pregnancy test at screening and a negative urine pregnancy test prior to study drug administration on Study Day 0);
• Breastfeeding or lactating women;

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (14)

Research Site

Scottsdale, Arizona, 85258, United States

Location

Research Site

Stanford, California, 94305, United States

Location

Research Site

Whittier, California, 90606, United States

Location

Research Site

Fort Lauderdale, Florida, 33334, United States

Location

Research Site

Miami, Florida, 33136, United States

Location

Research Site

Evansville, Indiana, 47714, United States

Location

Research Site

Kansas City, Kansas, 66160, United States

Location

Research Site

Baltimore, Maryland, 21224, United States

Location

Research Site

Cumberland, Maryland, 21502, United States

Location

Research Site

Boston, Massachusetts, 02115, United States

Location

Research Site

Lebanon, New Hampshire, 03756, United States

Location

Research Site

Lake Success, New York, 11042, United States

Location

Research Site

Portland, Oregon, 97239, United States

Location

Research Site

Duncansville, Pennsylvania, 16635, United States

Location

Related Publications (1)

• Higgs BW, Zhu W, Morehouse C, White WI, Brohawn P, Guo X, Rebelatto M, Le C, Amato A, Fiorentino D, Greenberg SA, Drappa J, Richman L, Greth W, Jallal B, Yao Y. A phase 1b clinical trial evaluating sifalimumab, an anti-IFN-alpha monoclonal antibody, shows target neutralisation of a type I IFN signature in blood of dermatomyositis and polymyositis patients. Ann Rheum Dis. 2014 Jan;73(1):256-62. doi: 10.1136/annrheumdis-2012-202794. Epub 2013 Feb 23.

  PMID: 23434567 DERIVED

MeSH Terms

Conditions

Dermatomyositis

Interventions

sifalimumab

Condition Hierarchy (Ancestors)

Polymyositis; Myositis; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Study Officials

• Dominique Ethgen, M.D.

  MedImmune LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2007
• First Posted: September 21, 2007
• Study Start: April 1, 2008
• Primary Completion: August 1, 2010
• Study Completion: October 1, 2010
• Last Updated: May 28, 2012

Record last verified: 2012-05

Locations

US (14)