TUC3PII-01_TU2670 Phase IIa Clinical Study

A Phase IIa, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Proof of Concept Study to Evaluate the Efficacy and Safety of Orally Administered TU2670 in Subjects With Mod to Severe Endometriosis-Associated Pain

This Protocol for TU2670 is to investigate the efficacy, safety, pharmacokinetics (PK), and pharmacodynamics (PD) of multiple doses of TU2670 in subjects with moderate to severe endometriosis-associated pain.

Study Overview

• Status: Completed
• Conditions: Endometriosis
• Intervention / Treatment: Drug: Placebo Comparator: Placebo; Drug: Active Comparator: TU2670 320mg; Drug: Active Comparator: TU2670 240mg; Drug: Active Comparator: TU2670 120mg

Detailed Description

Treatment Groups and Duration:

Following a washout period of up to 12 weeks, subjects will enter a screening period of up to 12 weeks including an observation period consisting of a complete menstrual cycle.

Subjects will be randomly assigned in a 1:1:1:1 ratio to receive either 12 weeks of TU2670 320 mg QD, TU2670 240 mg QD, TU2670 120 mg QD, or matching placebo. TU2670 or a matching placebo will be administered in the clinic on Day 1. Subjects in the PK subset population will also receive the following additional doses in the clinic: Day 2 (after collection of the 24-hour PK sample); the dose on the day scheduled for subsequent serial PK sample collection (Week 4 or Week 5); and the next scheduled dose (after collection of the 24-hour PK sample). All other doses can be taken by the subject at home. Following the end of treatment, subjects will be followed up for safety for 12 weeks.

Statistical Methods:

All formal statistical tests will be done at the 5% 2-sided significance level. Point estimates will have 2 sided 95% confidence intervals (CIs) where applicable.

Where appropriate, variables will be summarized descriptively (frequency and percent will be summarized for categorical variables; n (number of available subjects), mean, standard deviation [SD], median, minimum, and maximum will be presented for continuous variables) by study visit and by treatment group.

Statistical summaries will be presented for the changes from baseline to each time point in efficacy endpoints that it is applicable.

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czechia
  • Brno, Czechia, 62500
    • University Hospital Brno
  • Olomouc, Czechia, 77900
    • NEUMED gynekologická ambulance
  • Prague, Czechia, 18100
    • Nemocnice Na Bulovce
  • Hradec Kralove
    • Hradec Králové, Hradec Kralove, Czechia, 50005
      • University hospital Hradec Králové
  • Nachod
    • Náchod, Nachod, Czechia, 54701
      • Kestr-gyn s.r.o., Gynekologicka ambulance
  • Praha
    • Praha 10, Praha, Czechia, 10034
      • Fakultní Nemocnice Královské Vinohrady
  • Praha 1
    • Praha, Praha 1, Czechia, 11000
      • OB/GYN
  • Praha 2
    • Praha, Praha 2, Czechia, 128 08
      • Vseobecna fakultni nemocnice v Praze, Dept. of Gynekologicko- porodnickaklinika 1.LF UK
• Italy
  • Florence, Italy, 50129
    • University of Florence
  • Milano, Italy, 20122
    • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico di Milano
  • Modena, Italy, 41124
    • AZIENDA Ospedaliero Univeritaria Di Modena
  • Roma, Italy, 00168
    • Fondazione Policlinico Universitario A. Gemelli IRCCS
  • Torino, Italy, 10126
    • P.O. Sant'Anna
  • Verona, Italy, 37126
    • Azienda Ospedaliera Universitaria Integrata Verona
  • Cagliari
    • Monserrato, Cagliari, Italy, 09042
      • Università degli Studi di Cagliari - Policlinico Universitario Duilio Casula
  • Tuscany
    • Siena, Tuscany, Italy, 53100
      • Azienda Ospedaliero-Universitaria Senese
• Poland
  • Białystok, Poland, 15267
    • Klinika Leczenia Niepłodności, Ginekologii i Położnictwa Bocian
  • Katowice, Poland, 40611
    • Provita Sp. z o.o.
  • Poznań, Poland, 60529
    • Klinika Leczenia Niepłodności, Ginekologii i Położnictwa Bocian, Fertility Clinic
  • Dolnośląskie
    • Wrocław, Dolnośląskie, Poland, 53333
      • Dolnośląskie Centrum Ginekologii
  • Kujawsko-pomorskie
    • Bydgoszcz, Kujawsko-pomorskie, Poland, 85090
      • IN VIVO Sp. z o.o.
  • Lodzkie
    • Rzeszów, Lodzkie, Poland, 95030
      • Gameta Hospital
  • Lubelskie
    • Lublin, Lubelskie, Poland, 20362
      • Komed Centra Kliniczne
  • Podkarpackie
    • Rzeszów, Podkarpackie, Poland, 35-302
      • Hospital Pro-Familia
  • Podlaskie
    • Białystok, Podlaskie, Poland, 15224
      • Prywatna Klinika Położniczo-Ginekologiczna Sp. z o.o.
  • Silesia
    • Katowice, Silesia, Poland, 40065
      • Centrum Medyczne Mikołowska
  • Wielkopolska
    • Skorzewo, Wielkopolska, Poland, 60185
      • Examen sp z o.o.
• Russian Federation
  • Moscow, Russian Federation, 127473
    • Moscow State University of Medicine and Dentistry
  • Moscow, Russian Federation, 115280
    • State Institution of Healthcare Moscow City Clinical Hospital # 13 of Moscow Department
  • Moscow, Russian Federation, 115409
    • FSHI Clinical Hospital #85 of FMBA
  • Saint Petersburg, Russian Federation, 194291
    • SBIH Leningrad Regional Clinical Hospital
  • Sverdlovskaya Oblast
    • Ekaterinburg, Sverdlovskaya Oblast, Russian Federation, 620146
      • Ural Research Institution of Maternity and Child Care of Russian Public Health Ministry
• Ukraine
  • Kiev, Ukraine, 04053
    • State Scientific Institution Center for Innovative Medical Technologies of the National Academy of Sciences of Ukraine
  • Kyiv, Ukraine, 04112
    • Kyiv city clinical hospital #9, Department of gynecology
  • Lviv, Ukraine, 79005
    • Lviv City Clinical Hospital #4
  • Lviv, Ukraine, 79010
    • Danylo Halytskyy Lviv national medical university
  • Vinnytsia, Ukraine, 21001
    • Private Small-Scale Enterprise Medical Centre Pulse
  • Ivano-Frankivsk
    • Ivano-Frankivs'k, Ivano-Frankivsk, Ukraine, 76018
      • Ivano-Frankivsk National Medical University on the basis of the municipal non-profit enterprise Ivano-Frankivsk Regional Perinatal Center of the Regional Council
  • Vinnitsia
    • Vinnytsia, Vinnitsia, Ukraine, 21019
      • Communal non-commercial enterprise Vinnytsia City Clinical Hospital "Center of Mother and the Child
  • Zaporizhzhya Oblast
    • Zaporizhzhya, Zaporizhzhya Oblast, Ukraine, 69065
      • Communal Nonprofit Enterprise Maternity Hospital#4 of Zaporizhzhya Municipal Council

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Independent Ethics Committee (IEC)-approved written informed consent/assent and privacy language as per national regulations must be voluntarily obtained from the subject.
• Premenopausal female subject, 18 to 45 years, inclusive
• Subject has moderate to severe endometriosis-related pain

Exclusion Criteria:

• Subject has used hormonal contraceptives or other drugs with effects on gynecological endocrinology within 12 weeks
• Subject has been nonresponsive to GnRH-agonist or antagonist therapy for the management of endometriosis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 4 Placebo capsules	Drug: Placebo Comparator: Placebo; 4 x placebo capsules, QD
Active Comparator: TU2670 High Dose; 320mg, QD	Drug: Active Comparator: TU2670 320mg; 320mg (80mg x 4), QD
Active Comparator: TU2670 Medium Dose; 240 mg, QD	Drug: Active Comparator: TU2670 240mg; 240mg (80mg x 3 + placebo x 1), QD
Active Comparator: TU2670 Low Dose; 120 mg, QD	Drug: Active Comparator: TU2670 120mg; 120mg (80mg x 1 + 20mg x 2 + placebo x 1), QD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall pelvic pain	Change from baseline to 12 weeks of treatment of the mean dysmenorrhea score (defined as mean overall pelvic pain score on menstrual bleeding days) as measured by the Numeric Rating Scale(minimum 0, maximum 10, higher score mean a worse outcome) over the past month.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mean Numeric Rating Scale pain score	Change from baseline to 12 weeks of treatment of the mean Numeric Rating Scale pain score(minimum 0, maximum 10, higher score mean a worse outcome) for non-menstrual pelvic pain (mean Numeric Rating Scale pain score on non menstrual bleeding days)	12 weeks
mean overall pelvic pain Numeric Rating Scale pain score	Change from baseline to 12 weeks of treatment of the mean overall pelvic pain Numeric Rating Scale pain score (mean Numeric Rating Scale pain score(minimum 0, maximum 10, higher score mean a worse outcome) over all 28 days)	12 weeks
mean Numeric Rating Scale dyspareunia score	Change from baseline to 12 weeks of treatment of the mean Numeric Rating Scale((minimum 0, maximum 10, higher score mean a worse outcome) dyspareunia score	12 weeks
rescue medication	Change from baseline to 12 weeks of treatment of the use of protocol-defined rescue medication (ie, ibuprofen)	12 weeks
Time to increase of dose of rescue medication	Time to increase of dose of rescue medication from 0 week to 12 weeks	12 weeks
Time to decrease of dose of rescue medication	Time to decrease of dose of rescue medication from 0 week to 12 weeks	12 weeks
Modified Biberoglu and Behrman sign and symptom scores	Change from baseline to 12 weeks of treatment of the Modified Biberoglu and Behrman (mB&B) sign and symptom scores(minimum 0, maximum 3, higher score mean a worse outcome)	12 weeks
Patient Global Impression of Change	Patient Global Impression of Change (minimum 1, maximum 7, higher score mean a worse outcome) at 12 weeks of treatment	12 weeks
Endometriosis Health Profile-5	Change from baseline to 12 weeks of treatment in the Endometriosis Health Profile-5 score(minimum 1(Never), maximum 5(Always), higher score mean a worse outcome)	12 weeks
36-Item Short Form Health Survey	Change from baseline to 12 weeks of treatment of the 36-Item Short Form Health Survey(Scoring meaning is different from the questions but usually lower score mean a worse outcome)	12 weeks
Work Productivity and Activity Impairment Questionnaire: General Health	Change from baseline to 12 weeks of treatment of the Work Productivity and Activity Impairment Questionnaire: General Health (Scoring meaning is different from the questions)	12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone mineral density loss	Change from baseline to 12 weeks of treatment of the bone mineral density as assessed by dual-energy X-ray absorptiometry (DXA)	12 weeks

Collaborators and Investigators

• Sponsor: TiumBio Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2021
• Primary Completion (Actual): January 23, 2024
• Study Completion (Actual): August 5, 2024

Study Registration Dates

• First Submitted: October 25, 2021
• First Submitted That Met QC Criteria: November 16, 2021
• First Posted (Actual): December 1, 2021

Study Record Updates

• Last Update Posted (Actual): August 13, 2024
• Last Update Submitted That Met QC Criteria: August 11, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Endometriosis
• Other Study ID Numbers: TUC3PII-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No