A Study of Ponsegromab in People With Heart Failure

NCT ID: NCT05492500

Last Updated: 2025-06-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

455 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-09-26

Study Completion Date

2025-03-05

Brief Summary

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The primary purpose of this clinical trial is to compare the effects of study medicine (Ponsegromab/PF-06946860) with a placebo (an injection that looks like the study medicine but does not contain the active medicine) to find out if the study medicine is better than the placebo (an injection that looks like the study medicine but does not contain the active medicine) for treatment of symptoms related to heart failure. Participants will not know which treatment group they are assigned to. Most participants in this study will receive the study medicine or placebo by shots under the skin every four weeks. People may be able to participate in this study if they have heart failure. Participants will take part in this study for about 9 months. During this time participants will visit the study clinic once a month.

A separate PK cohort within this clinical trial will receive open-label study medicine (Ponsegromab/PF-06946860) only. Participants in this open-label, PK cohort will not receive placebo. These participants will receive the study medicine by shots under the skin every four weeks. People may be able to participate in this study cohort if they also have heart failure. Participants will take part in the open-label, PK cohort for about 7 months.

Detailed Description

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The primary purpose of this study is to assess the effect of repeated subcutaneous administration of ponsegromab (PF-06946860) compared to placebo on frequency, severity, and burden of symptoms as well as physical limitations in participants with heart failure and different ranges of circulating GDF-15 concentrations. The study will also assess the safety, tolerability, PK, PD, and immunogenicity of ponsegromab.

A separate, open-label, PK cohort, with more frequent PK and GDF-15 collection after single and multiple subcutaneous administration of ponsegromab (PF-06946860), will be enrolled at certain sites to facilitate a more comprehensive assessment of PK characteristics and PK/PD relationship for GDF-15 in participants with heart failure and elevated circulating GDF-15 concentrations.

Conditions

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Heart Failure

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

In the main cohort (Cohort A), ponsegromab will be administered at low, medium and high doses every 4 weeks by subcutaneous injections for a total of 6 doses. Participants will be randomized to 1 of the 3 doses of ponsegromab or placebo.

In optional Cohort C, ponsegromab will be administered at low doses every 4 weeks by subcutaneous injections for a total of 6 doses. Participants will be randomized to the low dose of ponsegromab or placebo.

In optional Cohort D, ponsegromab will be administered at high doses every 4 weeks by subcutaneous injections for a total of 6 doses. Participants will be randomized to the high dose of ponsegromab or placebo.

In a separate open-label, PK cohort (Cohort B), ponsegromab will be administered at low, medium and high doses every 4 weeks by subcutaneous injections for a total of 4 doses. Participants will be randomized to 1 of the 3 doses of ponsegromab. There is no placebo in the open-label, PK cohort.
Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
In the main cohort (Cohort A), Cohort C and Cohort D, investigators, sponsor, participants and other site staff will be blinded to participants' assigned study intervention, including the site staff assigned to prepare and administer the study intervention. Pharmacists and site personnel will be blinded to study intervention versus placebo within each study arm.

The separate PK cohort (Cohort B) will be open-label and study treatment will be prepared and administered as per treatment assignment by qualified personnel. There is no blinding in the open-label, PK cohort (Cohort B).

Study Groups

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Main cohort (Cohort A): ponsegromab low dose

Participants will receive a low dose Q4W SC

Group Type EXPERIMENTAL

Main cohort (Cohort A): Ponsegromab low dose

Intervention Type DRUG

Ponsegromab low dose subcutaneous injection

Main cohort (Cohort A): ponsegromab medium dose

Participants will receive a medium dose Q4W SC

Group Type EXPERIMENTAL

Main cohort (Cohort A): Ponsegromab medium dose

Intervention Type DRUG

Ponsegromab medium dose subcutaneous injection

Main cohort (Cohort A): ponsegromab high dose

Participants will receive a high dose Q4W SC

Group Type EXPERIMENTAL

Main cohort (Cohort A): ponsegromab high dose

Intervention Type DRUG

Ponsegromab high dose subcutaneous injection

Main cohort (Cohort A): placebo

matched placebo

Group Type PLACEBO_COMPARATOR

Main cohort (Cohort A): Matched placebo

Intervention Type OTHER

Matched placebo subcutaneous injection

Open-label, PK Cohort (Cohort B): ponsegromab low dose

Participants will receive a low dose Q4W SC

Group Type EXPERIMENTAL

Open-label, PK Cohort (Cohort B): ponsegromab low dose

Intervention Type DRUG

ponsegromab low dose subcutaneous injection

Open-label, PK Cohort (Cohort B): ponsegromab medium dose

Participants will receive a medium dose Q4W SC

Group Type EXPERIMENTAL

Open-label, PK Cohort (Cohort B): ponsegromab medium dose

Intervention Type DRUG

Ponsegromab medium dose subcutaneous injection

Open-label, PK Cohort (Cohort B): ponsegromab high dose

Participants will receive a high dose Q4W SC

Group Type EXPERIMENTAL

Open-label, PK Cohort (Cohort B): ponsegromab high dose

Intervention Type DRUG

Ponsegromab high dose subcutaneous injection

Optional Cohort C: ponsegromab low dose

Participants will receive a low dose Q4W SC

Group Type EXPERIMENTAL

Optional Cohort C: Ponsegromab low dose

Intervention Type DRUG

Ponsegromab low dose subcutaneous injection

Optional Cohort C: placebo

matched placebo

Group Type PLACEBO_COMPARATOR

Optional Cohort C: Matched placebo

Intervention Type OTHER

Matched placebo subcutaneous injection

Optional Cohort D: ponsegromab high dose

Participants will receive a high dose Q4W SC

Group Type EXPERIMENTAL

Optional Cohort D: Ponsegromab high dose

Intervention Type DRUG

Ponsegromab high dose subcutaneous injection

Optional Cohort D: placebo

matched placebo

Group Type PLACEBO_COMPARATOR

Optional Cohort D: Matched placebo

Intervention Type OTHER

Matched placebo subcutaneous injection

Interventions

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Main cohort (Cohort A): Ponsegromab low dose

Ponsegromab low dose subcutaneous injection

Intervention Type DRUG

Main cohort (Cohort A): Ponsegromab medium dose

Ponsegromab medium dose subcutaneous injection

Intervention Type DRUG

Main cohort (Cohort A): ponsegromab high dose

Ponsegromab high dose subcutaneous injection

Intervention Type DRUG

Main cohort (Cohort A): Matched placebo

Matched placebo subcutaneous injection

Intervention Type OTHER

Open-label, PK Cohort (Cohort B): ponsegromab low dose

ponsegromab low dose subcutaneous injection

Intervention Type DRUG

Open-label, PK Cohort (Cohort B): ponsegromab medium dose

Ponsegromab medium dose subcutaneous injection

Intervention Type DRUG

Open-label, PK Cohort (Cohort B): ponsegromab high dose

Ponsegromab high dose subcutaneous injection

Intervention Type DRUG

Optional Cohort C: Ponsegromab low dose

Ponsegromab low dose subcutaneous injection

Intervention Type DRUG

Optional Cohort C: Matched placebo

Matched placebo subcutaneous injection

Intervention Type OTHER

Optional Cohort D: Ponsegromab high dose

Ponsegromab high dose subcutaneous injection

Intervention Type DRUG

Optional Cohort D: Matched placebo

Matched placebo subcutaneous injection

Intervention Type OTHER

Other Intervention Names

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PF-06946860 low dose PF-06946860 medium dose PF-06946860 high dose Placebo PF-06946860 low dose PF-06946860 medium dose PF-06946860 high dose PF-06946860 low dose Placebo PF-06946860 high dose Placebo

Eligibility Criteria

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Inclusion Criteria

* Male and female participants aged 18 years or older

-. Clinical evidence of HF with each of the following criteria:
1. LVEF \<50% on most recent measurement, within 12 months of screening. Note: An assessment of LVEF in the prior 12 months is not required in situations where LVEF has been persistently \<50% on prior assessments obtained at least 3 months apart (including the most recent measurement).
2. NYHA class II-IV at screening.
3. NT-proBNP ≥400 pg/mL at screening (Note: Does not apply to open-label, PK Cohort \[Cohort B\]).
* Serum GDF-15 concentration ≥2000 pg/mL at screening.
* Cohort D only: Serum GDF-15 concentration \<2000 pg/mL at screening.
* KCCQ-23 CSS \<75 at screening (Note: Does not apply to open-label, PK Cohort \[Cohort B\]).
* Evidence of cachexia or fatigue or functional impairment, as demonstrated by at least one of the following at screening (Note: Does not apply to open-label, PK Cohort \[Cohort B\]):

1. Non-edematous unintentional weight loss ≥5% in the last 6 months or current BMI \<20 kg/m2, associated with subjective fatigue or anorexia; or
2. Fatigue at least 3 times per week AND at least moderately bothersome fatigue in the past 2 weeks based on the KCCQ-23 administered at screening; or
3. A score of \<60 on the Physical Limitations Domain of the KCCQ 23 administered at screening.

Exclusion Criteria

* Acute decompensated HF within 1 month prior to Screening Visit 1 or during the screening period.
* Implantation of a cardiac resynchronization therapy device or valve repair or replacement within 3 months prior to randomization or intent to do so during the trial.

For the open-label, PK cohort (Cohort B) only: implantation of a cardiac resynchronization therapy device more than 1 month prior to randomization is permitted.

* History of heart transplantation, currently listed for heart transplant, current/planned mechanical circulatory support, or current/planned use of intravenous inotropes (eg, dobutamine, milrinone).
* Acute coronary syndrome within 1 month prior to randomization.
* Coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting) within 3 months prior to randomization or intent to undergo coronary revascularization during the trial.

For the open-label, PK cohort (Cohort B) only: coronary revascularization more than 1 month prior to randomization is permitted.

* Untreated indication for an implantable cardiac defibrillator or pacemaker to treat a cardiac rhythm abnormality (ie, tachyarrhythmia or bradyarrhythmia).
* Previous administration with an investigational product (drug or vaccine) within 30 days (or as determined by the local requirement) or 5 half lives (whichever is longer) preceding the first dose of study intervention used in this study. Treatment with an investigational biologic agent within 6 months or 5 half-lives (whichever is longer) of Day 1.
* Previous exposure to ponsegromab in a prior clinical study.
* Renal disease requiring ongoing dialysis.
* Cirrhosis with evidence of portal hypertension not due to HF, or the following LFT abnormalities at the time of screening, confirmed by a repeat test if deemed necessary: AST or ALT level ≥ 3 x ULN, or total bilirubin level ≥ 2 x ULN (unless history of Gilbert's syndrome).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The TIMI Study Group

OTHER

Sponsor Role collaborator

Pfizer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

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Eastern shore Research Institute LLC

Fairhope, Alabama, United States

Site Status

Keck Medical Center of USC

Los Angeles, California, United States

Site Status

MedStar Washington Hospital Center

Washington D.C., District of Columbia, United States

Site Status

Emory University School of Medicine-Grady Campus

Atlanta, Georgia, United States

Site Status

Chicago Medical Research

Hazel Crest, Illinois, United States

Site Status

Reid Physician Associates

Richmond, Indiana, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Traverse Heart & Vascular

Traverse City, Michigan, United States

Site Status

M Health Fairview Clinics and Surgery Center

Minneapolis, Minnesota, United States

Site Status

M Health Fairview University of Minnesota Investigational Drug Services

Minneapolis, Minnesota, United States

Site Status

M Health Fairview University of Minnesota Medical Center-East Bank

Minneapolis, Minnesota, United States

Site Status

University of Minnesota/Lillehei Clinical Research Unit

Minneapolis, Minnesota, United States

Site Status

Saint Luke's Hospital of Kansas City

Kansas City, Missouri, United States

Site Status

Washington University in St. Louis Center for Outpatient Health (COH)

St Louis, Missouri, United States

Site Status

Washington University in St. Louis Center for Advanced Medicine (CAM)

St Louis, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Holy Name Medical Center

Teaneck, New Jersey, United States

Site Status

University of North Carolina Medical Center

Chapel Hill, North Carolina, United States

Site Status

Clinical and Translational Research Center

Chapel Hill, North Carolina, United States

Site Status

South Oklahoma Heart Research, LLC

Oklahoma City, Oklahoma, United States

Site Status

Texas Health Heart & Vascular Specialist (THHVS) #18760

Dallas, Texas, United States

Site Status

Concord Repatriation General Hospital

Concord, New South Wales, Australia

Site Status

Core Research Group

Brisbane, Queensland, Australia

Site Status

The Prince Charles Hospital

Chermside, Queensland, Australia

Site Status

Lyell McEwin Hospital

Elizabeth Vale, South Australia, Australia

Site Status

The Alfred Hospital

Melbourne, Victoria, Australia

Site Status

Fraser Clinical Trials Inc

New Westminster, British Columbia, Canada

Site Status

QEII Health Sciences Centre - Victoria General Site

Halifax, Nova Scotia, Canada

Site Status

Saul Vizel Professional Medicine Corporation dba Vizel Cardiac Research

Cambridge, Ontario, Canada

Site Status

University Hospital - London Health Sciences Centre

London, Ontario, Canada

Site Status

North York Diagnostic and Cardiac Centre

North York, Ontario, Canada

Site Status

Private Practice - Dr. James Cha

Oshawa, Ontario, Canada

Site Status

Kawartha Cardiology Clinical Trials

Peterborough, Ontario, Canada

Site Status

Corcare

Toronto, Ontario, Canada

Site Status

Unity Health Toronto, St. Michael's Hospital

Toronto, Ontario, Canada

Site Status

Community Care Building

Winchester, Ontario, Canada

Site Status

Winchester District Memorial Hospital

Winchester, Ontario, Canada

Site Status

Institut de Cardiologie de Montreal

Montreal, Quebec, Canada

Site Status

Centre Hospitalier de l'Université de Montréal

Montreal, Quebec, Canada

Site Status

Centre intégré de santé et de services sociaux du Bas Saint-Laurent- Hôpital régional de Rimouski

Rimouski, Quebec, Canada

Site Status

CardioVasc HR Inc

Saint-Jean-sur-Richelieu, Quebec, Canada

Site Status

Centre intégré de santé et de services sociaux de Lanaudière - Hopital Pierre-Le Gardeur.

Terrebonne, Quebec, Canada

Site Status

Diex Recherche Trois-Rivieres

Trois-Rivières, Quebec, Canada

Site Status

Guangdong Provincial People's Hospital

Guangzhou, Guangdong, China

Site Status

The First Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, China

Site Status

The Second Xiangya Hospital of Central South University

Changsha, Hunan, China

Site Status

The First Affiliated Hospital of University of South China

Hengyang, Hunan, China

Site Status

China-Japan Union Hospital

Changchun, Jilin, China

Site Status

The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, China

Site Status

Qilu Hospital of Shandong University

Jinan, Shandong, China

Site Status

Zhongshan Hospital,Fudan University

Shanghai, Shanghai Municipality, China

Site Status

Yuncheng Central Hospital

Yuncheng, Shanxi, China

Site Status

Tianjin People' s Hospital

Tianjin, Tianjin Municipality, China

Site Status

Peking University First Hospital

Beijing, , China

Site Status

EDUMED - Jaroměř

Jaroměř, Náchod, Czechia

Site Status

Institut Klinicke a Experimentalni Mediciny

Prague, Praha 4, Czechia

Site Status

Fakultni Nemocnice u sv. Anny v Brne

Brno, South Moravian, Czechia

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Fakultni nemocnice Kralovske Vinohrady

Prague, , Czechia

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Vseobecna fakultni nemocnice v Praze

Prague, , Czechia

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Ustredni vojenska nemocnice

Prague, , Czechia

Site Status

Universitätsklinikum Frankfurt Goethe-Universität

Frankfurt am Main, Hesse, Germany

Site Status

Universitätsmedizin Göttingen - Georg-August-Universität

Göttingen, Lower Saxony, Germany

Site Status

Herz - und Diabeteszentrum Nordrhein - Westfalen, Bad Oeynhausen

Bad Oeynhausen, North Rhine-Westphalia, Germany

Site Status

Hausärztlich-Kardiologisches MVZ am Felsenkeller GmbH/Zentrum für klinische Studien

Dresden, Saxony, Germany

Site Status

Universitätsklinikum Jena

Jena, Thuringia, Germany

Site Status

Universitätsklinikum Jena

Jena, Thuringia, Germany

Site Status

Pécsi Tudományegyetem Klinikai Központ

Pécs, Baranya, Hungary

Site Status

Private Practice - Dr. Lakatos Ferenc

Békéscsaba, Bekes County, Hungary

Site Status

TaNa Med

Mosonmagyaróvár, Győr-Moson-Sopron, Hungary

Site Status

Medifarma 98 Kft

Nyíregyháza, Nyíregyháza, Hungary

Site Status

Somogy Vármegyei Kaposi Mór Oktató Kórház

Kaposvár, Somogy County, Hungary

Site Status

Dél-Pesti Centrumkórház Orszagos Hematologiai es Infektologiai Intezet

Budapest, , Hungary

Site Status

Semmelweis Egyetem

Budapest, , Hungary

Site Status

Kanizsai Dorottya Korhaz

Nagykanizsa, , Hungary

Site Status

Hyogo Prefectural Amagasaki General Medical Center

Amagasaki, Hyōgo, Japan

Site Status

Hyogo Prefectural Harima-Himeji General Medical Center

Himeji, Hyōgo, Japan

Site Status

Higashi Takarazuka Satoh Hospital

Takarazuka, Hyōgo, Japan

Site Status

Iwate Prefectural Central Hospital

Morioka, Iwate, Japan

Site Status

National Hospital Organization Sendai Medical Center

Sendai, Miyagi, Japan

Site Status

Kishiwada Tokushukai Hospital

Kishiwada, Osaka, Japan

Site Status

National Cerebral and Cardiovascular Center

Suita, Osaka, Japan

Site Status

National Hospital Organization Saitama Hospital

Wako, Saitama, Japan

Site Status

Keio University Hospital

Shinjuku-ku, Tokyo, Japan

Site Status

Osaka General Medical Center

Osaka, , Japan

Site Status

Uniwersytecki Szpital Kliniczny w Poznaniu

Poznan, Greater Poland Voivodeship, Poland

Site Status

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu

Wroclaw, Lower Silesian Voivodeship, Poland

Site Status

Uniwersytecki Szpital Kliniczny w Białymstoku

Bialystok, Podlaskie Voivodeship, Poland

Site Status

Kardio Brynow

Katowice, Silesian Voivodeship, Poland

Site Status

Miejski Szpital Zespolony w Olsztynie

Olsztyn, Warmian-Masurian Voivodeship, Poland

Site Status

SPZOZ Centralny Szpital Kliniczny Uniwersytetu Medycznego w Lodzi

Lodz, , Poland

Site Status

Polsko Amerykanskie Kliniki Serca

Tychy, , Poland

Site Status

Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego Centralny Szpital Kliniczny

Warsaw, , Poland

Site Status

CHUAC-Complejo Hospitalario Universitario A Coruña

A Coruña, A Coruña [LA Coruña], Spain

Site Status

CHUS - Hospital Clinico Universitario

Santiago de Compostela, A Coruña [LA Coruña], Spain

Site Status

Parc de Salut Mar - Hospital del Mar

Barcelona, Barcelona [barcelona], Spain

Site Status

Hospital Universitari Vall d'Hebron

Barcelona, Barcelona [barcelona], Spain

Site Status

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Barcelona, Spain

Site Status

Hospital de la Santa Creu i Sant Pau

Barcelona, Catalunya [cataluña], Spain

Site Status

Hospital Universitario Ramón y Cajal

Madrid, Madrid, Comunidad de, Spain

Site Status

Hospital Universitario Puerta de Hierro Majadahonda

Majadahonda, Madrid, Comunidad de, Spain

Site Status

Hospital Clínico Universitario Virgen de la Arrixaca

El Palmar, Murcia, Región de, Spain

Site Status

Hospital Clinico de Valencia

Valencia, Valenciana, Comunitat, Spain

Site Status

Hospital Universitario Virgen Nieves

Granada, , Spain

Site Status

Hospital Universitario La Paz

Madrid, , Spain

Site Status

Hospital Universitario Virgen de la Victoria

Málaga, , Spain

Site Status

Hospital Universitario Central de Asturias

Oviedo, , Spain

Site Status

Hospital Universitario Virgen Del Rocio

Seville, , Spain

Site Status

Hospital General Universitario de Valencia

Valencia, , Spain

Site Status

Hospital Universitari i Politecnic La Fe

Valencia, , Spain

Site Status

Wycombe General Hospital

High Wycombe, Buckinghamshire, United Kingdom

Site Status

Ninewells Hospital and Medical School

Dundee, Dundee CITY, United Kingdom

Site Status

St. George's Hospital

London, England and Wales, United Kingdom

Site Status

Northwick Park Hospital

Harrow, London, CITY of, United Kingdom

Site Status

Glasgow Royal Infirmary

Glasgow, Scotland, United Kingdom

Site Status

Barnet Hospital

Barnet, , United Kingdom

Site Status

Royal Papworth Hospital NHS Foundation Trust

Cambridge, , United Kingdom

Site Status

Golden Jubilee National Hospital

Clydebank, , United Kingdom

Site Status

Lincoln County Hospital

Lincoln, , United Kingdom

Site Status

Liverpool University Hospitals NHS Foundation Trust

Liverpool, , United Kingdom

Site Status

Northern General Hospital

Sheffield, , United Kingdom

Site Status

University Hospital of North Tees

Stockton-on-Tees, , United Kingdom

Site Status

Countries

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United States Australia Canada China Czechia Germany Hungary Japan Poland Spain United Kingdom

Related Links

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https://pmiform.com/clinical-trial-info-request?StudyID=C3651011

To obtain contact information for a study center near you, click here.

Other Identifiers

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2023-509747-27-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

C3651011

Identifier Type: -

Identifier Source: org_study_id

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