Triptorelin for Ovary Protection in Childhood Onset Lupus
Study Details
Study Description
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Triptorelin T1 Triptorelin Pamoate 25 μg/kg body weight |
Drug: Triptorelin pamoate
IM injection given monthly
Other Names:
|
| Experimental: Triptorelin T2 Triptorelin Pamoate 50 μg/kg body weight |
Drug: Triptorelin Pamoate
IM injection given monthly
Other Names:
|
| Experimental: Triptorelin T3 Triptorelin Pamoate 75 μg/kg body weight T3 |
Drug: Triptorelin Pamoate
IM injection given monthly
Other Names:
|
| Experimental: Triptorelin T4 Triptorelin Pamoate 100 μg/kg body weight T4 |
Drug: Triptorelin Pamoate
IM injection given monthly
Other Names:
|
| Placebo Comparator: Placebo Normal Saline |
Other: placebo
placebo 0.9% normal saline IM injection
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Children's Hospital of Los Angeles | Los Angeles | California | United States | 90027 |
| 2 | Children's Memorial Hospital | Chicago | Illinois | United States | 60614 |
| 3 | Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601 |
| 4 | Morgan Stanley Children's Hospital of New York | New York | New York | United States | 10032 |
| 5 | Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | United States | 45229 |
| 6 | Columbus Children's Hospital | Columbus | Ohio | United States | 43205 |
| 7 | Children's Hospital of Oklahoma | Oklahoma City | Oklahoma | United States | 73104 |
| 8 | Seattle Children's Hospital | Seattle | Washington | United States | 98105 |
| 9 | Children's Hospital of Wisconsin | Milwaukee | Wisconsin | United States | 53226 |
| 10 | University of Sao Paulo | São Paulo | Brazil |
Sponsors and Collaborators
- Children's Hospital Medical Center, Cincinnati
- Watson Pharmaceuticals
Investigators
- Principal Investigator: Hermine I Brunner, M.D. M.Sc., Children's Hospital Medical Center, Cincinnati
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2008-1045
- FD-R-00239
- NCT00088244
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 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. |
| Arm/Group Title | Placebo | Triptorelin T1 | Triptorelin T2 | Triptorelin T3 | Triptorelin T4 |
|---|---|---|---|---|---|
| Arm/Group Description | Normal Saline | Triptorelin Pamoate 25 μg/kg body weight starting dose Dose escalation initiated if COS was not maintained with the 1st dose of study drug. The subsequently injected 2nd dose was increased by 25% or at least 20 μg/kg dose. This procedure of dose increases repeated until COS was maintained. | Triptorelin Pamoate 50 μg/kg body weight starting dose Dose escalation initiated if COS was not maintained with the 1st dose of study drug. The subsequently injected 2nd dose was increased by 25% or at least 20 μg/kg dose. This procedure of dose increases repeated until COS was maintained. | Triptorelin Pamoate 75 μg/kg body weight starting dose Dose escalation initiated if COS was not maintained with the 1st dose of study drug. The subsequently injected 2nd dose was increased by 25% or at least 20 μg/kg dose. This procedure of dose increases repeated until COS was maintained. | Triptorelin Pamoate 100 μg/kg body weight starting dose Dose escalation initiated if COS was not maintained with the 1st dose of study drug. The subsequently injected 2nd dose was increased by 25% or at least 20 μg/kg dose. This procedure of dose increases repeated until COS was maintained. |
| Period Title: Overall Study | |||||
| STARTED | 6 | 9 | 8 | 6 | 2 |
| COMPLETED | 2 | 7 | 7 | 5 | 1 |
| NOT COMPLETED | 4 | 2 | 1 | 1 | 1 |
Baseline Characteristics
| Arm/Group Title | Placebo | Triptorelin T1 | Triptorelin T2 | Triptorelin T3 | Triptorelin T4 | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Normal Saline placebo: placebo 0.9% normal saline IM injection | Triptorelin Pamoate 25 μg/kg body weight | Triptorelin Pamoate 50 μg/kg body weight | Triptorelin Pamoate 75 μg/kg body weight | Triptorelin Pamoate 100 μg/kg body weight | Total of all reporting groups |
| Overall Participants | 6 | 9 | 8 | 6 | 2 | 31 |
| Age (years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [years] |
17.9
(2.1)
|
15.9
(2.6)
|
16.5
(2.2)
|
13.0
(2.1)
|
12.50
(0)
|
15.4
(4.1)
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
6
100%
|
9
100%
|
8
100%
|
6
100%
|
2
100%
|
31
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||||
| Hispanic or Latino |
4
66.7%
|
1
11.1%
|
4
50%
|
4
66.7%
|
2
100%
|
15
48.4%
|
| Not Hispanic or Latino |
2
33.3%
|
8
88.9%
|
4
50%
|
2
33.3%
|
0
0%
|
16
51.6%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | ||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
1
12.5%
|
0
0%
|
0
0%
|
1
3.2%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
1
16.7%
|
5
55.6%
|
0
0%
|
2
33.3%
|
1
50%
|
9
29%
|
| White |
5
83.3%
|
3
33.3%
|
6
75%
|
4
66.7%
|
1
50%
|
19
61.3%
|
| More than one race |
0
0%
|
0
0%
|
1
12.5%
|
0
0%
|
0
0%
|
1
3.2%
|
| Unknown or Not Reported |
0
0%
|
1
11.1%
|
0
0%
|
0
0%
|
0
0%
|
1
3.2%
|
Outcome Measures
| Title | Dose of Triptorelin for Ovarian Suppression |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Placebo | Triptorelin (T1-T4) |
|---|---|---|
| Arm/Group Description | Normal Saline placebo: placebo 0.9% normal saline IM injection | Due to the dose escalation during the study, Triptorelin (T1-T4) groups were pooled for analysis. |
| Measure Participants | 4 | 21 |
| Number [μg/kg] |
NA
|
120
|
| Title | Length of Time of Triptorelin Treatment to Achieve Ovarian Suppression |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Placebo | Triptorelin |
|---|---|---|
| Arm/Group Description | Normal Saline placebo: placebo 0.9% normal saline IM injection | Triptorelin Pamoate Due to the dose escalation during the study, Triptorelin (T1-T4) groups were pooled for analysis. |
| Measure Participants | 4 | 21 |
| Median (Inter-Quartile Range) [days] |
NA
|
18
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | Due to the dose escalation during the study, Triptorelin (T1-T4) groups were pooled for analysis. | |||
| Arm/Group Title | Placebo Group | Triptorelin | ||
| Arm/Group Description | Normal Saline placebo: placebo 0.9% normal saline IM injection | Triptorelin Pamoate Due to the dose escalation during the study, Triptorelin (T1-T4) groups were pooled for analysis. | ||
All Cause Mortality |
||||
| Placebo Group | Triptorelin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/6 (0%) | 0/25 (0%) | ||
Serious Adverse Events |
||||
| Placebo Group | Triptorelin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/6 (50%) | 4/25 (16%) | ||
| Blood and lymphatic system disorders | ||||
| Neutropenia | 0/6 (0%) | 0 | 1/25 (4%) | 1 |
| General disorders | ||||
| Oedema peripheral | 0/6 (0%) | 1/25 (4%) | 2 | |
| Chest pain | 0/6 (0%) | 0 | 1/25 (4%) | 1 |
| Infections and infestations | ||||
| Infection | 1/6 (16.7%) | 1 | 1/25 (4%) | 1 |
| Herpes zoster | 1/6 (16.7%) | 1 | 2/25 (8%) | 2 |
| Gastroenteritis | 0/6 (0%) | 0 | 1/25 (4%) | 1 |
| Cellulitis | 0/6 (0%) | 0 | 1/25 (4%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Systemic lupus erythematosus | 1/6 (16.7%) | 1 | 0/25 (0%) | 0 |
| Nervous system disorders | ||||
| Neuropsychiatric lupus | 0/6 (0%) | 0 | 1/25 (4%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Cutaneous vasculitis | 0/6 (0%) | 0 | 1/25 (4%) | 1 |
| Vascular disorders | ||||
| Hypertension | 1/6 (16.7%) | 1 | 0/25 (0%) | 0 |
| Diffuse vasculitis | 0/6 (0%) | 0 | 1/25 (4%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| Placebo Group | Triptorelin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/6 (50%) | 6/25 (24%) | ||
| Blood and lymphatic system disorders | ||||
| Leukopenia | 0/6 (0%) | 0 | 2/25 (8%) | 2 |
| Lymphopenia | 0/6 (0%) | 0 | 2/25 (8%) | 2 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 0/6 (0%) | 0 | 2/25 (8%) | 2 |
| General disorders | ||||
| Fatigue | 1/6 (16.7%) | 1 | 1/25 (4%) | 1 |
| Oedema | 0/6 (0%) | 0 | 2/25 (8%) | 2 |
| Investigations | ||||
| White blood cell count decreased | 0/6 (0%) | 0 | 2/25 (8%) | 2 |
| Nervous system disorders | ||||
| Headache | 2/6 (33.3%) | 2 | 3/25 (12%) | 4 |
| Paraesthesia | 1/6 (16.7%) | 1 | 2/25 (8%) | 2 |
| Psychiatric disorders | ||||
| Insomnia | 0/6 (0%) | 0 | 3/25 (12%) | 4 |
| Suicidal ideation | 1/6 (16.7%) | 1 | 0/25 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 1/6 (16.7%) | 1 | 3/25 (12%) | 4 |
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 0/6 (0%) | 0 | 2/25 (8%) | 2 |
| Vascular disorders | ||||
| Hot flush | 1/6 (16.7%) | 1 | 5/25 (20%) | 5 |
| Hypertension | 0/6 (0%) | 0 | 4/25 (16%) | 4 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Hermine Brunner |
|---|---|
| Organization | cincinnatichildrens |
| Phone | 5136367982 |
| hermine.brunner@cchmc.org |
- 2008-1045
- FD-R-00239
- NCT00088244