Systemic Lupus Erythematosus
Conditions
Keywords
SLE, Lupus, Ovarian damage, Menopause
Brief 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
Detailed description
Lupus is an autoimmune disease that may harm all organs in the body and especially affects the kidney, brain, skin and lungs. Cyclophosphamide is a very effective medication to treat lupus, but it can damage the ovaries (pair of reproductive organs). Only female lupus patients may participate in this study.
Interventions
IM injection given monthly
IM injection given monthly
OTHERplacebo
placebo 0.9% normal saline IM injection
Sponsors
Watson Pharmaceuticals
Children's Hospital Medical Center, Cincinnati
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
9 Years to 21 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose of Triptorelin for Ovarian Suppression | baseline to week 24 | Dose escalation was initiated If COS was not maintained with the 1st dose of study drug. Subsequent doses were increased by 25% or at least 20μg/kg dose. This procedure of dose increases by 25% or at least 20μg/kg dose was repeated until COS was maintained. Absolute max dose 7.8mg. Triptorelin (T1-T4) groups were pooled for analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Length of Time of Triptorelin Treatment to Achieve Ovarian Suppression | baseline to week 24 | Time to ovarian suppression, based on suppressed LH levels, after the initial dose of triptorelin. Due to the dose escalation during the study, Triptorelin (T1-T4) groups were pooled for analysis. |
Countries
Brazil, United States
Participant flow
Pre-assignment details
130 patients were screened for the study and 31 were randomized to one of 5 arms to start. The arms determined the starting dose of Triptorelin. All arms participated in dose escalation until the subjects reached and maintained COS. 2 subjects withdrew prior to start of study procedures.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Normal Saline
placebo: placebo 0.9% normal saline IM injection | 6 |
| Triptorelin T1 Triptorelin Pamoate 25 μg/kg body weight | 9 |
| Triptorelin T2 Triptorelin Pamoate 50 μg/kg body weight | 8 |
| Triptorelin T3 Triptorelin Pamoate 75 μg/kg body weight | 6 |
| Triptorelin T4 Triptorelin Pamoate 100 μg/kg body weight | 2 |
| Total | 31 |
Baseline characteristics
| Characteristic | Placebo | Triptorelin T1 | Triptorelin T2 | Triptorelin T3 | Triptorelin T4 | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 17.9 years STANDARD_DEVIATION 2.1 | 15.9 years STANDARD_DEVIATION 2.6 | 16.5 years STANDARD_DEVIATION 2.2 | 13.0 years STANDARD_DEVIATION 2.1 | 12.50 years STANDARD_DEVIATION 0 | 15.4 years STANDARD_DEVIATION 4.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 1 Participants | 4 Participants | 4 Participants | 2 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 8 Participants | 4 Participants | 2 Participants | 0 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 5 Participants | 0 Participants | 2 Participants | 1 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 5 Participants | 3 Participants | 6 Participants | 4 Participants | 1 Participants | 19 Participants |
| Sex: Female, Male Female | 6 Participants | 9 Participants | 8 Participants | 6 Participants | 2 Participants | 31 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 25 |
| other Total, other adverse events | 3 / 6 | 6 / 25 |
| serious Total, serious adverse events | 3 / 6 | 4 / 25 |
Outcome results
Primary
Dose of Triptorelin for Ovarian Suppression
Dose escalation was initiated If COS was not maintained with the 1st dose of study drug. Subsequent doses were increased by 25% or at least 20μg/kg dose. This procedure of dose increases by 25% or at least 20μg/kg dose was repeated until COS was maintained. Absolute max dose 7.8mg. Triptorelin (T1-T4) groups were pooled for analysis.
Time frame: baseline to week 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Dose of Triptorelin for Ovarian Suppression | NA μg/kg |
| Triptorelin (T1-T4) | Dose of Triptorelin for Ovarian Suppression | 120 μg/kg |
Secondary
Length of Time of Triptorelin Treatment to Achieve Ovarian Suppression
Time to ovarian suppression, based on suppressed LH levels, after the initial dose of triptorelin. Due to the dose escalation during the study, Triptorelin (T1-T4) groups were pooled for analysis.
Time frame: baseline to week 24
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Length of Time of Triptorelin Treatment to Achieve Ovarian Suppression | NA days |
| Triptorelin (T1-T4) | Length of Time of Triptorelin Treatment to Achieve Ovarian Suppression | 18 days |