Triptorelin for Ovary Protection in Childhood Onset Lupus
Condition: Systemic Lupus Erythematosus
MeSH terms: Lupus Erythematosus, Systemic
Intervention: Triptorelin pamoate; Triptorelin Pamoate; Triptorelin Pamoate; Triptorelin Pamoate; placebo
Intervention description: IM injection given monthly; IM injection given monthly; IM injection given monthly; IM injection given monthly; placebo 0.9% normal saline IM injection
Intervention MeSH terms: Triptorelin Pamoate
Phase: Phase 2
Study type: Interventional
Primary purpose: Diagnostic
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 31.0
Sex: Female
Minimum age: 9 Years
Maximum age: 21 Years
Healthy volunteers: No
Keywords: SLE; Lupus; Ovarian damage; Menopause

Summary:

      The purpose of this study is to test the safety of triptorelin when used for the protection
      of the ovaries (pair of female reproductive organs) during cyclophosphamide therapy for
      systemic lupus erythematosus (SLE; lupus) and to see what effects (good or bad) it has on
      patients. The study will be done with female patients who have been diagnosed with systemic
      lupus erythematosus, are younger than 21 years of age, and require intravenous
      cyclophosphamide to control the disease. Each patient will be in the study for approximately
      23 months, until 4 months after the intravenous cyclophosphamide treatment has been
      completed.

      This study is currently being conducted at 3 sites across the United States and Brazil (Los
      Angeles, Cincinnati and San Paulo Brazil). A total of 50 patients will participate in this
      study.

      Each patient will be randomized (assigned) to one of 5 groups. Randomization means that
      patients are put into a group completely by chance. It is like flipping a coin. Neither the
      patient nor the study staff knows what group the patient is in. The patient has a 20% chance
      of being placed in any group.

      This is a dose escalation study, each patient will receive the first dose of the study drug
      (T1 - T4, placebo). If a patient has complete ovarian suppression on day 27 after the initial
      injection of study drug, then she will remain on this weight-adjusted dose of study drug
      throughout the study. The dose will be increased up for a weight gain of 5kg or greater. The
      dose will not be adjusted downward for a weight loss. If COS was not maintained with the 1st
      dose of study drug, then the subsequently injected 2nd dose will be increased by 25% or at
      least 20 microgram/kg/dose. The maximal dose of 150 microgram/kg/dose will not be exceeded.
      The absolute maximum dose is 20 mg.

      Funding Source: FDA OOPD and Watson Pharmaceuticals
    

Eligibility criteria:

        Inclusion Criteria:

          -  Females under the age of 21 and non-pregnant

          -  Tanner stage of 2 or above as determined by physical examination of breast stage

          -  Diagnosis with SLE using the updated American College of Rheumatology (ACR)
             Classification Criteria for SLE 1

          -  Severe SLE requiring cyclophosphamide therapy

          -  Bone mineral density z-score > - 2.0

          -  Must be using a medically acceptable form of birth control during the study and must
             not be pregnant at the screening visit

          -  No clinically significant abnormal findings other than those consistent with the
             diagnosis of childhood-onset SLE (cSLE) on the physical examination, medical history
             or clinical laboratory results during screening

          -  Currently on any combination of medication but must not have been treated with more
             than one dose of cyclophosphamide or other gonadotoxic medications in the past

          -  Voluntary consent or, if under the age of consent, assent to participate in this study
             with permission by a legal guardian

        Exclusion Criteria:

          -  Male patients of any age

          -  Female patients with a Tanner stage of 1

          -  Positive blood pregnancy test at screening or taking oral or injectable birth-control
             medications

          -  Prior exposure to more than one dose of gonadotoxic medications including
             cyclophosphamide

          -  History of allergic or adverse response to triptorelin

          -  Diagnosed with hypogonadism prior to cyclophosphamide exposure

          -  Acutely life-threatening disease activity that prohibits inclusion in a clinical trial

          -  History of clinically significant gastrointestinal tract, renal, hepatic, endocrine,
             oncologic, pulmonary (asthma accepted), or cardiovascular disease; or a history of
             tuberculosis, epilepsy, diabetes, depression, psychosis, or any other non-cSLE
             condition, which in the opinion of the physician, would jeopardize the safety of the
             subject or impact the validity of the study results

          -  Patient age 18 years of younger with severe depression as defined by a CDI (Children's
             Depression Inventory) score of > 23 or a patient age 19 to 21 years with severe
             depression as defined by a BDI (Beck's Depression Inventory) score > 29

          -  Patient admits to suicidal thoughts at screening visit

          -  Bone mineral density lower than z = -2.0.