Triptorelin for Ovary Protection in Childhood Onset Lupus

Systemic Lupus Erythematosus Clinical Trial

Official title:

Triptorelin for Ovary Protection in Childhood Onset Lupus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00124514
• Other study ID #: 2008-1045
• Secondary ID: FD-R-00239
• Status: Completed
• Phase: Phase 2
• Start date: June 2003
• Est. completion date: March 2014

Study information

• Verified date: December 2020
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Other known NCT identifiers

• NCT00088244

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: March 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 9 Years to 21 Years

Eligibility

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.

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Drug:
• Triptorelin pamoate
IM injection given monthly
• Triptorelin Pamoate
IM injection given monthly
• Triptorelin Pamoate
IM injection given monthly
• Triptorelin Pamoate
IM injection given monthly

Other:
• placebo
placebo 0.9% normal saline IM injection

Locations

Country	Name	City	State
Brazil	University of Sao Paulo	São Paulo
United States	Children's Memorial Hospital	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Columbus Children's Hospital	Columbus	Ohio
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Morgan Stanley Children's Hospital of New York	New York	New York
United States	Children's Hospital of Oklahoma	Oklahoma City	Oklahoma
United States	Seattle Children's Hospital	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati	Watson Pharmaceuticals

Countries where clinical trial is conducted

United States,  Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	baseline to week 24
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.	baseline to week 24