Confirmatory Study of 17P vs Vehicle for Prevention of Preterm Birth in Women w/ Previous Spontaneous Preterm Delivery

NCT01004029 | Completed Phase 3 Results DMC

• 1 other identifier: 17P-ES-003
• Study Type: interventional
• Target: 1,740
• Locations: 9 countries
• Sites: 104

Brief Summary

As part of the continuing effort to study the benefit and risks of 17P and preterm delivery, this study is designed as a multi-center, randomized, double-blind, vehicle-controlled clinical trial of 17P for the prevention of preterm birth prior to 35 weeks, 0 days of gestation in women with a singleton pregnancy, aged 18 years or older, with a previous singleton spontaneous preterm delivery. The study also includes a population pharmacokinetic (PK) substudy to assess the hydroxyprogesterone caproate (HPC) exposure-response relationship and the effect of body mass index (BMI) on the PK of 17P.

Conditions

Preterm Birth

Keywords

17P; 17-HPC; 17-OHPC; 17-hydroxyprogesterone caproate; progestogens; preterm birth; recurrent preterm birth; spontaneous preterm birth

Outcome Measures

Primary Outcomes (2)

• Preterm Birth <35 Weeks Gestation

  Determine if treatment with 17P reduces the rate of preterm birth \< 35 weeks, 0 days of gestation in women with a previous singleton spontaneous preterm delivery.

  Up to 35 weeks

• Neonatal Composite Index (NCI)

  The composite index is defined as a liveborn neonate with any of the following occurring at any time during the birth hospitalization up through discharge from the NICU: neonatal death, grade 3 or 4 intraventricular hemorrhage, respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis or proven sepsis.

  Until 28 days of life or discharge from the neonatal intensive care unit (NICU), whichever occurred later.

Secondary Outcomes (5)

• Fetal/Early Infant Death

  Delivery from 16 weeks 0 days through 19 weeks 6 days of gestation; or neonatal death occurring in liveborns born at less than 24 weeks gestation; or stillbirth (antepartum or intrapartum death) from 20 weeks gestation through term).

• Preterm Birth Prior to 32 Weeks Gestation

  Up to 32 weeks

• Preterm Birth Prior to 37 Weeks Gestation

  Up to 37 weeks

• Stillbirths

  20 weeks gestation until term

• Neonatal Deaths With ≥24 Weeks Gestational Age

  Until 28 days of life or discharge from the NICU whichever occurred later.

Study Arms (2)

Vehicle

PLACEBO COMPARATOR

Castor Oil

Drug: Vehicle

Hydroxyprogesterone Caproate Injection (HPC), 250 mg/mL

ACTIVE COMPARATOR

HPC 250 mg/mL in oil

Drug: Hydroxyprogesterone Caproate Injection (HPC), 250mg/mL

Interventions

Hydroxyprogesterone Caproate Injection (HPC), 250mg/mL DRUG

1 mL intramuscular injection every week until 36 weeks, 6 days of gestation or delivery, whichever occurs first.

Also known as: Makena, 17P

Hydroxyprogesterone Caproate Injection (HPC), 250 mg/mL

Vehicle DRUG

Weekly intramuscular injections of 1 mL vehicle inert oil until 36 weeks, 6 days of gestation or delivery, whichever occurs first.

Also known as: Placebo

Vehicle

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Each subject must meet the following criteria to be enrolled in this study:
• Age ≥ 18 years.
• Singleton gestation.
• Project gestational age 16 weeks 0 days of gestation or more and less than or equal to 20 weeks 6 days of gestation at the time of randomization, based on clinical information and evaluation of the first ultrasound.
• Documented history of a previous singleton spontaneous preterm delivery. Spontaneous preterm birth is defined as delivery from 20 weeks 0 days to 36 weeks 6 days of gestation following spontaneous preterm labor or pPROM. Where possible, the gestational age of the previous preterm birth (referred to as the qualifying delivery) should be determined as described in "Gestational Age Determination". If the gestational age at delivery is obtained directly from the medical record and more than one gestational age appears, the latest will be used. As a validation of the gestational age of the previous delivery, if the infant weighed more than 3300 grams (the birth weight 90th percentile for 36 weeks gestational age), this will not qualify as preterm. The previous preterm delivery cannot be an antepartum stillbirth.

You may not qualify if:

• Multifetal gestation.
• Known major fetal anomaly or fetal demise. An ultrasound examination between 14 weeks 0 days through 20 weeks 3 days of gestation must be performed to rule out fetal anomalies.
• Progesterone treatment in any form (i.e., vaginal, oral, intramuscular) during current pregnancy, other than micronized progesterone delivered orally or vaginally provided it is stopped at least 4 weeks prior to the first dose of study medication.
• Heparin therapy during current pregnancy or history of thromboembolic disease.
• Maternal medical/obstetrical complications including:
• Current or planned cerclage
• Hypertension requiring medication
• Seizure disorder
• Subjects with a uterine anomaly (uterine didelphys or bicornate uterus). However, subjects with uterine fibroids are eligible for the study.
• Unwillingness to comply with and complete the study.
• A 14 weeks 0 days through 20 weeks 3 days of gestation ultrasound cannot be arranged before randomization.
• Participation in an antenatal study in which the clinical status or intervention may influence gestational age at delivery.
• Participation in this trial in a previous pregnancy. Women who were screened in a previous pregnancy, but not randomized, do not have to be excluded.
• Known hypersensitivity to hydroxyprogesterone caproate or its components.
• Have any significant medical disorder that, in the opinion of the investigator, would be a contraindication to the use of the drug including those listed in section 5.3.2 of the investigational brochure. Other examples to consider include uncontrolled diabetes, known HIV infection or renal dysfunction.

Sponsors & Collaborators

• AMAG Pharmaceuticals, Inc.: lead
• ResearchPoint Global: collaborator

Study Sites (104)

Drug Research & Analysis Corporation

Montgomery, Alabama, 36106, United States

Location

Tucson Medical Center (Watching Over Mothers and Babies Foundation)

Tucson, Arizona, 85712, United States

Location

Grossmont Center for Clinical Research

La Mesa, California, 91942, United States

Location

Naval Medical Center San Diego - Department of Obstetrics and Gynecology

San Diego, California, 92134-5000, United States

Location

Womens Health Specialists

West Hills, California, 91307, United States

Location

Women's Associates, P.C.

Colorado Springs, Colorado, 80903, United States

Location

Red Rocks OB/GYN - Physician's Research Options, LLC

Lakewood, Colorado, 80228, United States

Location

Visions Clinical Research

Boynton Beach, Florida, 33472, United States

Location

Palm Beach Obstetrics & Gynecology, PA (Altus Research)

Lake Worth, Florida, 33407, United States

Location

Global OB/GYN Centers

Pembroke Pines, Florida, 33024, United States

Location

New Millennium Obstetrics & Gynecology, LLc

Riverdale, Georgia, 30274, United States

Location

Tripler Army Medical Center

Honolulu, Hawaii, 96859, United States

Location

The Women's Clinic

Boise, Idaho, 83712, United States

Location

Rosemark Women Care Specialists

Idaho Falls, Idaho, 83404, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Women's Care Physicians/Obstetrical Specialists, PLLC

Louisville, Kentucky, 40207, United States

Location

Steven Z. Lenowitz, MD, LLC

Bel Air, Maryland, 21014, United States

Location

Female Pelvic Medicine and Urogynecology Institute of Michigan

Grand Rapids, Michigan, 49503, United States

Location

Saginaw Valley Medical Research Group, LLC

Saginaw, Michigan, 48604, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Womack Army Medical Center

Fort Bragg, North Carolina, 28310, United States

Location

Lyndhurst Clinical Research

Winston-Salem, North Carolina, 27103, United States

Location

Triad Research Partners, LLC

Winston-Salem, North Carolina, 27103, United States

Location

Mid Dakota clinicl, PC Center for Women

Bismarck, North Dakota, 58501, United States

Location

HWC Women's Research Center

Englewood, Ohio, 45322, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Temple University School of Medicine

Philadelphia, Pennsylvania, 19140, United States

Location

SC Clinical Research Center, LLC

Columbia, South Carolina, 29201, United States

Location

Greenville Hospital System University Medical Group

Greenville, South Carolina, 29605, United States

Location

Women's Physician's Group, MPLLC

Memphis, Tennessee, 38104, United States

Location

Practice Research Organization, Inc.

Dallas, Texas, 75230, United States

Location

Carl R. Darnall Army Medical Center

Fort Hood, Texas, 76544, United States

Location

San Antonio Military Medical Center

Fort Sam Houston, Texas, 78236, United States

Location

Research Associates Rio Grande Valley

McAllen, Texas, 78503, United States

Location

Tanner Clinic

Layton, Utah, 84041, United States

Location

Mt. Timpanogos Women's Health Care

Pleasant Grove, Utah, 84062, United States

Location

Salt Lake Women's Center, P.C.

Sandy City, Utah, 84070, United States

Location

Naval Medical Center - Portsmouth

Portsmouth, Virginia, 23708, United States

Location

Madigan Army Medical Center

Tacoma, Washington, 98431, United States

Location

Wheaton Franciscan Healthcare - St. Joseph Campus

Milwaukee, Wisconsin, 53210, United States

Location

MHAT "Blagoevgrad", Department of obstetrics and Gynecology

Blagoevgrad, Bulgaria

Location

Medical center "Teodora", LTD

Rousse, Bulgaria

Location

MHAT "Silistra", Obstetrics and Gynecology Department

Silistra, Bulgaria

Location

"Medical institute of Interior ministry", Sofia city PLC, Department of Gynecology

Sofia, Bulgaria

Location

Medical Centre "Avicena" Ltd

Sofia, Bulgaria

Location

SHAT " Sheinovo ",PLS, Maternity Clinic

Sofia, Bulgaria

Location

University of Calgary - Foothills Hospital

Calgary, Alberta, AB T2N 2T9, Canada

Location

Lion's Gate Hospital (University of BC)

North Vancouver, British Columbia, V7M 2H5, Canada

Location

Glazier Medical Centre

Oshawa, Ontario, L1H2J9, Canada

Location

The Ottawa Hospital, General Campus

Ottawa, Ontario, K1H 8L6, Canada

Location

Victory Reproductive Care

Windsor, Ontario, N8W 5R7, Canada

Location

J. Leung Obstetrics and Gynaecology

Windsor, Ontario, N8X 3V6, Canada

Location

Fakultni nemocnice Olomouc

Olomouc, Olomoucký kraj, 77900, Czechia

Location

Fakultni nemocnice Brno

Brno, South Moravian, 62500, Czechia

Location

Nemocnice Ceske Budejovice, a.s. Gynekologicko-pordnicka klinika

České Budějovice, 37001, Czechia

Location

Fakultni nemocnice Hradec Kralove Porodnicka a gynekologicka klinika

Hradec Králové, 500 05, Czechia

Location

Fakultni nemocnice Ostrava Porodnicko-gynekologicka klinika

Ostrava-Poruba, 70852, Czechia

Location

Fakultni nemocnice Pizen Gynekologicko-pordnicka klinika

Plzen-Lochotin, 304 60, Czechia

Location

Debreceni Egyetem Orvos es Egeszsegtudomanyi Centrum, Szuleszeti es Nogyogyaszati Klinika

Debrecen, Hajdú-Bihar, 4032, Hungary

Location

Fovarosi Onkormanyzat Egyesitett Szent Istvan es Szent Laszlo Korhaz-Rendelointezet, Szuleszet - Nogyogyaszat

Budapest, 1097, Hungary

Location

Petz Aladar Megyei Oktato Korhaz, Szuleszet-Nogyogyaszat

Győr, 9024, Hungary

Location

Bacs-Kiskun Megyei Onkormanyzat Korhaza, Svegedi Tudmanyegyetem Altalanos Orvostudomanyi kar Oktato Korhaza

Kecskemét, 6000, Hungary

Location

Josa Andras Oktato Korhaz Egeszsegugyi Szolgaltato Nonprofit Kft.

Nyíregyháza, 4400, Hungary

Location

Szegedi Tudomanyegyetem, Szuleszeti es Nogyogyaszati Klinika

Szeged, 6725, Hungary

Location

Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi

Bologna, 40100, Italy

Location

Azienda Ospedaliera di Bolzano Ospedale Generale Regionale di Bolzano

Bolzano, 39100, Italy

Location

Azienda Ospedaliera di Perugia - Ospedale Santa Maria dell a Misericordia

Perugia, 06132, Italy

Location

Northern State Medical University

Arkhangelsk, 163000, Russia

Location

Northern State Medical University

Arkhangelsk, Russia

Location

Belgorod Regional Clinical Hospital of St.Ioasaf

Belgorod, Russia

Location

State Educational Institution of Higher Professional Education "Kazan State Medical University of RosZdrav"

Kazan', 420012, Russia

Location

Kemerovo State Medical Academy

Kemerovo, Russia

Location

State Educational Institution of Higher Professional Education "Krasnoyarsk State University named After Prof. V.F. Voino-Yasenetsky of Ministry of Health Russia" Department of Perinatology, Obstetrics and Gynecology of Medical Faculty

Krasnoyarsk, 660100, Russia

Location

State Educational Institution of Higher Professional Education "People's Friendship University of Russia" Department of Obstetrics and Gynecology with Course Perinatology

Moscow, 117333, Russia

Location

Russian National Research Medical University named after N.I. Pirogov

Moscow, Russia

Location

Municipal Healthcare Institution "Novosibirsk Municipal Perinatal Centre"

Novosibirsk, 630089, Russia

Location

Rostov Medical State University

Rostov-on-Don, 344029, Russia

Location

State Educational Institution of Higher Professional Education "St. Petersburg l.l Mechnikov State Medical Academy of RosZdrav" Department of Obstetrics, Gynecology and Perinatology

Saint Petersburg, 195257, Russia

Location

State Institution "D.O. Otto Scientific Institute for Obstetrics and Gynecology"

Saint Petersburg, 199034, Russia

Location

Almazov Federal Heart, Blood and Endocrinology Centre

Saint Petersburg, Russia

Location

Regional Perinatal Center

Tomsk, Russia

Location

State Healthcare Institution "Regional Maternity Hospital"

Yaroslavl, 150003, Russia

Location

Federal State Institution "Ural Research Institute of Maternity and Infancy Care of Rosmedtechnologies"

Yekaterinburg, 620028, Russia

Location

Hospital Universitari Vall D'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario Puerta del Mar

Cadiz, 11009, Spain

Location

Hospital Universitario Materno Infantil de Canarias

Las Palmas de Gran Canaria, 35016, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital 12 de Octubre

Madrid, Spain

Location

Hospital Virgen Del Rocio

Seville, Spain

Location

Hospital Universitario La Fe

Valencia, 46009, Spain

Location

"Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

City Clinical Maternity Hospital #1

Chernivtsi, Ukraine

Location

Donets'k Regional Centre of Mother and Child Care

Donets'k, 83114, Ukraine

Location

Ivano-Frankivs'k Regional Prenatal Center, department of pregnant pathology

Ivano-Frankivsk, Ukraine

Location

<<Institute of Pediatrics, Obstetrics and Gynecology of AMS Ukraine>> Department of Rehabilitation and Reproduktive function of Women

Kyiv, 04050, Ukraine

Location

Polyclinic #1, Obolon district of Kyiv, maternity welfare department

Kyiv, 04220, Ukraine

Location

Kyiv City Centre of Reproduction and perinatal medicine, obstetric department

Kyiv, Ukraine

Location

SI "Institute of pediatrics, obstetrics and gynecology of AMS of Ukraine". Department of extragenital pathology and postnatal rehabilitation

Kyiv, Ukraine

Location

Municipal Institution "Maternity Hospital #1"

Odesa, 65039, Ukraine

Location

Ternopil' Municipal Hospital # 2

Ternopil, 46001, Ukraine

Location

Uzhgorod Municipal prenatal Centre, maternity welfare department #2

Uzhhorod, 88017, Ukraine

Location

Clinical Maternity Hospital No 4

Zaporizhzhya, 69065, Ukraine

Location

Department of Obstetrics and Gynecology of Zhaporizhzhya Medical Academy of Postgraduate Education on the Base of Healthcare Institution Maternity Hospital No 3

Zhaporizhzhya, 69071, Ukraine

Location

Related Publications (1)

• Blackwell SC, Gyamfi-Bannerman C, Biggio JR Jr, Chauhan SP, Hughes BL, Louis JM, Manuck TA, Miller HS, Das AF, Saade GR, Nielsen P, Baker J, Yuzko OM, Reznichenko GI, Reznichenko NY, Pekarev O, Tatarova N, Gudeman J, Birch R, Jozwiakowski MJ, Duncan M, Williams L, Krop J. 17-OHPC to Prevent Recurrent Preterm Birth in Singleton Gestations (PROLONG Study): A Multicenter, International, Randomized Double-Blind Trial. Am J Perinatol. 2020 Jan;37(2):127-136. doi: 10.1055/s-0039-3400227. Epub 2019 Oct 25.

  PMID: 31652479 DERIVED

MeSH Terms

Conditions

Premature Birth

Interventions

17 alpha-Hydroxyprogesterone Caproate

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

17-alpha-Hydroxyprogesterone; Hydroxyprogesterones; Progesterone; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Progesterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Clinical Trial Interest
• Organization: Covis Pharma

CTInterest@covispharma.com

1-877-374-4177

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2009
• First Posted: October 29, 2009
• Study Start: October 1, 2009
• Primary Completion: October 1, 2018
• Study Completion: October 1, 2018
• Last Updated: June 1, 2022
• Results First Posted: January 28, 2021

Record last verified: 2022-05

Locations

BU (6); RU (16); IT (3); ES (8); UA (12); CZ (6); HU (6); US (41); CA (6)