NCT02993926

Brief Summary

The purpose of this study is to evaluate the long-term safety and efficacy of Enantone in the treatment of CPP in Chinese participants.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
108

participants targeted

Target at P50-P75 for all trials

Timeline
Completed

Started Jun 2017

Geographic Reach
1 country

6 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 13, 2016

Completed
2 days until next milestone

First Posted

Study publicly available on registry

December 15, 2016

Completed
6 months until next milestone

Study Start

First participant enrolled

June 24, 2017

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 30, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 30, 2018

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

October 24, 2019

Completed
Last Updated

March 16, 2022

Status Verified

March 1, 2022

Enrollment Period

1.3 years

First QC Date

December 13, 2016

Results QC Date

September 30, 2019

Last Update Submit

March 7, 2022

Conditions

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (4)

  • Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) During Enantone Treatment Phase

    A TEAE is any untoward medical occurrence in a subject administered a medicinal product and which does not necessarily have to have a causal relationship with this treatment. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

    During treatment with and up to 30 days post last dose of Enantone (the mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months)

  • Number of Participants With at Least One Treatment Emergent Adverse (TEAE) and Serious Adverse Event (SAE) During Follow-up Phase

    A TEAE is any untoward medical occurrence in a subject administered a medicinal product and which does not necessarily have to have a causal relationship with this treatment. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

    Mean duration of follow-up=8.75 months (range: 1.9-29.5 months) for No longer treated for CPP group; 10.80 months (range: 2.8-20.5 months) for Treated with Non-Enantone GnRHa group after treatment with Enantone (while on another GnRHa)

  • Percentage of Participants Who Had Regression or No Progression in Tanner Staging at the End of Enantone Treatment Phase

    Tanner Stage is used to measure pubertal development. Female (F) and male (M) participants were evaluated for breast development and genital development respectively and both genders for pubic hair development. Tanner Stage is based on progression through 5-stages. Participants were classified as having progression if either breast/genitals or pubic hair progression were present. Otherwise participant is classified as regression or no progression.

    The mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months

  • Percentage of Participants Who Had Regression or No Progression in Tanner Staging at the End of Follow-Up Phase

    Tanner Stage is used to measure pubertal development. Female (F) and male (M) participants were evaluated for breast development and genital development respectively and both genders for pubic hair development. Tanner Stage is based on progression through 5-stages. Participants were classified as having progression if either breast/genitals or pubic hair progression were present. Otherwise participant is classified as regression or no progression.

    No longer treated for CPP group - Month: 27 (766- 855 days) post last dose of Enantone; Treated with Non-Enantone GnRHa group - Month 21 (586- 675 days) post last dose of Enantone

Secondary Outcomes (6)

  • Percentage of Participants With Post Stimulation Test Peak Values, for Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH), Suppressed Below Upper Limit Value (ULV) at the End of Enantone Treatment Phase

    The mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months

  • Percentage of Participants With Post Stimulation Test Peak Values, for Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH), Suppressed Below Upper Limit Value (ULV) at the End of Follow-Up Phase

    No longer treated for CPP group - Month: 27 (766- 855 days) post last dose of Enantone; Treated with Non-Enantone GnRHa group - Month 21 (586- 675 days) post last dose of Enantone

  • Percentage of Participants With Value, for Estradiol or Testosterone, Suppressed Below Upper Limit Value (ULV) at the End of Enantone Treatment Phase

    The mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months

  • Percentage of Participants With Value, for Estradiol or Testosterone, Suppressed Below Upper Limit Value (ULV) at the End of Follow-Up Phase

    No longer treated for CPP group-Month: 27 (766-855 days) post last dose of Enantone; Treated with Non-Enantone GnRHa group-Month 21 (586-675 days) post last dose of Enantone

  • Percentage of Participants With Decease of Ratio of Bone Age to Chronological Age at the End of Enantone Treatment Phase

    The mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months

  • +1 more secondary outcomes

Study Arms (3)

Treatment Phase: Enantone

Participants with CPP who were treated with Enantone (≥ 30 μg/kg up to 180 μg/kg) for at least 9 continuous months and who initiated and received the last dose of treatment during the index period from 01 September 1998 to 30 September 2018 (the mean duration of Enantone exposure was 22.3 months, ranging from 10.1 to 52.4 months).

Drug: Enantone

Follow Up: Participants No longer Treated for CPP

Participants who had completed their CPP during the treatment phase with Enantone and were no longer on treatment in the follow-up phase (the mean duration of follow up was 8.75 months with a range of 1.9 to 29.5 months).

Follow Up: Treated with Non-Enantone GnRHa after Enantone

Participants who were continuing their CPP treatment with a non-Enantone gonadotropin releasing hormone agonist (GnRHa) after treatment with Enantone in the follow-up phase (the mean duration of follow up while on another GnRHa was 10.80 months with a range of 2.8 to 20.5 months, and the mean duration of follow up after stopping treatment was 4.26 months with a range of 0.0 \[i.e. 1 day\] to 12 months).

Drug: GnRH agonist

Interventions

Enantone suspension for injection

Also known as: Leuprorelin
Treatment Phase: Enantone

A non-Enantone GnRH agonist

Follow Up: Treated with Non-Enantone GnRHa after Enantone

Eligibility Criteria

Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Participants diagnosed with CPP will be observed.

You may qualify if:

  • Has diagnosis of idiopathic CPP.
  • Has been treated with leuprorelin acetate (Enantone) for at least 9 continuous months of therapy with either a stable dose of high dose (greater than or equal to \[\>=\] 90 mcg/kg up to 180 mcg/kg) or low dose (\< 90 mcg/kg down to 30 mcg/kg).
  • Has initiated and completed treatment during the index period from September 1st 1998 to September 30th 2018.
  • Have the following information prior to initiation of enantone and at least one record of each of the following parameters at the end of enantone treatment in the medical records: Tanner staging, estradiol or testosterone level, and FSH and LH level. The participant should have at least one record of bone age prior to the initiation gonadotropin releasing hormone analogs (GnRHa) therapy with enantone to support the diagnosis of CPP. In addition, should have at least one record of bone age during treatment with enantone.

You may not qualify if:

  • Has been treated with leuprorelin acetate or any other GnRHa for conditions other than CPP.
  • Has used any other GnRHa products for CPP treatment prior to initiation of enantone therapy.
  • CPP participants with identified etiology, such as brain tumor or cranial irradiation.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

The Children's Hospital, Zhejiang University School of Medicine

Wuhan, Hubei, 430030, China

Location

Childrens Hospital of Hunan province

Changsha, Hunan, 410007, China

Location

Jiangsu Province Hosptial

Nanjing, Jiangsu, 210036, China

Location

Children's Hospital of Jiangxi province

Nanchang, Jiangxi, 330006, China

Location

Children's Hospital of Shanghai

Shanghai, Shanghai Municipality, 200040, China

Location

The Children's Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310053, China

Location

MeSH Terms

Conditions

Puberty, Precocious

Interventions

LeuprolideGonadotropin-Releasing Hormone

Condition Hierarchy (Ancestors)

Gonadal DisordersEndocrine System Diseases

Intervention Hierarchy (Ancestors)

Pituitary Hormone-Releasing HormonesHypothalamic HormonesPeptide HormonesHormonesHormones, Hormone Substitutes, and Hormone AntagonistsNeuropeptidesPeptidesAmino Acids, Peptides, and ProteinsOligopeptidesNerve Tissue ProteinsProteins

Limitations and Caveats

The enrollment of only 100 participants did not support the performance of subgroup analysis of outcomes by dose. Retrospective observational data is not controlled and therefore robust analysis could not be performed.

Results Point of Contact

Title
Medical Director
Organization
Takeda

Study Officials

  • Medical Director Clinical Science

    Takeda

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
RETROSPECTIVE
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 13, 2016

First Posted

December 15, 2016

Study Start

June 24, 2017

Primary Completion

September 30, 2018

Study Completion

September 30, 2018

Last Updated

March 16, 2022

Results First Posted

October 24, 2019

Record last verified: 2022-03

Data Sharing

IPD Sharing
Will share

Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Shared Documents
STUDY PROTOCOL, SAP, ICF, CSR
Access Criteria
IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/ For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
More information

Locations