A Study to Evaluate Long-term Safety in Participants Who Have Participated in Other Luspatercept (ACE-536) Clinical Trials

NCT ID: NCT04064060

Last Updated: 2025-11-12

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

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

665 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-08-12

Study Completion Date

2028-05-12

Brief Summary

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A Phase 3b, open-label, single-arm, rollover study to evaluate the long-term safety of luspatercept, to the following participants:

* Participants receiving luspatercept on a parent protocol at the time of their transition to the rollover study, who tolerate the protocol-prescribed regimen in the parent trial and, in the opinion of the investigator, may derive clinical benefit from continuing treatment with luspatercept
* Participants in the follow-up phase previously treated with luspatercept or placebo in the parent protocol will continue into long-term post-treatment follow-up in the rollover study until the follow-up commitments are met
* The study design is divided into the Transition Phase, Treatment Phase and Follow-up Phase. Participants will enter transition phase and depending on their background will enter either the treatment phase or the Long-term Post-treatment Follow-up (LTPTFU) phase
* Transition Phase is defined as one Enrollment visit
* Treatment Phase: For participants in luspatercept treatment the dose and schedule of luspatercept in this study will be the same as the last dose and schedule in the parent luspatercept study. This does not apply to participants that are in long-term follow-up from the parent protocol
* Follow-up Phase includes:

\- 42 Day Safety Follow-up Visit
* During the Safety Follow up, the participants will be followed for 42 days after the last dose of luspatercept, for the assessment of safety-related parameters and adverse event (AE) reporting

\- Long-term Post-treatment Follow-up (LTPTFU) Phase
* Participants will be followed for overall survival every 6 months for at least 5 years from first dose of luspatercept in the parent protocol, or 3 years of post-treatment from last dose, whichever occurs later, or until death, withdrawal of consent, study termination, or until a subject is lost to follow-up. Participants will also be monitored for progression to AML or any malignancies/pre-malignancies. New anticancer or disease related therapies should be collected at the same time schedule

Participants transitioning from a parent luspatercept study in post-treatment follow-up (safety or LTPTFU) will continue from the same equivalent point in this rollover study.

The ACE-536-LTFU-001 rollover study will be terminated, and relevant participants will discontinue from the study when all participants fulfill 5 years on the study, including treatment and follow-up.

Detailed Description

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Conditions

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Myelodysplastic Syndromes (MDS) Beta-thalassemia Myeloproliferative Neoplasm(MPN)-Associated Myelofibrosis

Keywords

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ACE-536 Luspatercept MDS Beta-thalassemia Myeloproliferative neoplasm (MPN)-associated myelofibrosis

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ACE-536

Luspatercept will be administered as a subcutaneous (SC) injection to participants by the study staff at the clinical site and administration will be documented in the subject's source record.

Group Type EXPERIMENTAL

Luspatercept

Intervention Type DRUG

Luspatercept (ACE-536), an erythroid maturation agent, is a recombinant fusion protein consisting of a modified form of the extracellular domain (ECD) of the human activin receptor type IIB (ActRIIB) linked to the human immunoglobin G 1 (IgG1) Fc domain. ActRIIB receptor and its ligands are members of the transforming growth factor-β (TGF-β) superfamily. Members of the TGF-β superfamily ligands, through their binding to activin receptors, are involved in modulating the differentiation of late-stage erythrocyte precursors (normoblasts) in the bone marrow. Luspatercept for injection is formulated as a sterile, preservative-free, lyophilized cake/powder. Luspatercept for injection is available in 25 mg and 75 mg vials and when reconstituted with water for injection, each consists of 50 mg/mL luspatercept in a 10 mM citrate buffer-based solution

Interventions

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Luspatercept

Luspatercept (ACE-536), an erythroid maturation agent, is a recombinant fusion protein consisting of a modified form of the extracellular domain (ECD) of the human activin receptor type IIB (ActRIIB) linked to the human immunoglobin G 1 (IgG1) Fc domain. ActRIIB receptor and its ligands are members of the transforming growth factor-β (TGF-β) superfamily. Members of the TGF-β superfamily ligands, through their binding to activin receptors, are involved in modulating the differentiation of late-stage erythrocyte precursors (normoblasts) in the bone marrow. Luspatercept for injection is formulated as a sterile, preservative-free, lyophilized cake/powder. Luspatercept for injection is available in 25 mg and 75 mg vials and when reconstituted with water for injection, each consists of 50 mg/mL luspatercept in a 10 mM citrate buffer-based solution

Intervention Type DRUG

Other Intervention Names

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ACE-536

Eligibility Criteria

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Inclusion Criteria

Participants must meet all the following criteria to be enrolled in this study:

1. Participant is ≥ 18 years at the time of signing the informed consent form (ICF).
2. Participant is willing and able to adhere to the study visit schedule and other protocol requirements.
3. Participant has been participating in a luspatercept trial and continues to fulfill all the requirements of the parent protocol and the participant has been either:

1. Assigned to luspatercept treatment, continues to receive clinical benefit in the opinion of the investigator and should continue to receive luspatercept treatment, OR
2. Assigned to placebo arm in the parent protocol (at the time of unblinding or in follow-up) and should cross over to luspatercept treatment, OR
3. Assigned to the Follow-up Phase of the parent protocol, previously treated with luspatercept or placebo in the parent protocol who shall continue into LTPTFU phase in the rollover study until the follow-up commitments are met (unless requirements are met as per parent protocol to crossover to luspatercept treatment).
4. Participant understands and voluntarily signs an informed consent document prior to any study-related assessments or procedures being conducted.
5. Participant demonstrates compliance, as assessed by the investigator, with the parent study protocol requirements.
6. Applies to on treatment Participants only- females of childbearing potential (FCBP) defined as a sexually mature woman who:

1\) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy or amenorrhea due to other medical reasons does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months) must:

1. Have two negative pregnancy tests as verified by the investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study therapy. This applies even if the participant practices true abstinence from heterosexual contact.
2. Agrees to use, and be able to comply with highly effective, contraception without interruption, 35 days prior to starting investigational product (IP), during the study therapy (including dose interruptions), and for 84 days after discontinuation of study therapy.

7\. Applies to on treatment participants only- Male participants must:

a. Agrees to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 84 days following investigational product discontinuation even if he has undergone a successful vasectomy.

Exclusion Criteria

The presence of any of the following will exclude a participant from enrollment:

1. Applies to on treatment participants only- Concomitant use of any medications/procedures that are prohibited in the parent luspatercept protocol.
2. Participant has met one or more criteria for study discontinuation as stipulated in the parent luspatercept protocol.
3. Applies to on treatment participants only- More than 26 days between last luspatercept dose in the parent protocol and first dose into ACE-536-LTFU-001 protocol unless dose delay or dose discontinuation criteria met.
4. Applies to on treatment participants only- Pregnant or breastfeeding females.
5. Participant has any significant medical condition, laboratory abnormality, psychiatric illness, or is considered vulnerable by local regulations (eg, imprisoned or institutionalized) that would prevent the subject from participating in the study.
6. Participant has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
7. Participant has any condition that confounds the ability to interpret data from the study.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Celgene

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

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Childrens Hospital Los Angeles RHU

Los Angeles, California, United States

Site Status RECRUITING

Local Institution - 971

Oakland, California, United States

Site Status COMPLETED

Local Institution - 978

Stanford, California, United States

Site Status COMPLETED

Local Institution - 975

Tampa, Florida, United States

Site Status COMPLETED

Local Institution - 970

Chicago, Illinois, United States

Site Status COMPLETED

Local Institution - 973

Boston, Massachusetts, United States

Site Status COMPLETED

Local Institution - 961

Detroit, Michigan, United States

Site Status COMPLETED

Local Institution - 969

New York, New York, United States

Site Status COMPLETED

Local Institution - 967

Cleveland, Ohio, United States

Site Status ACTIVE_NOT_RECRUITING

Local Institution - 972

Philadelphia, Pennsylvania, United States

Site Status COMPLETED

Vanderbilt - Ingram Cancer Center

Nashville, Tennessee, United States

Site Status WITHDRAWN

The University of Texas - MD Anderson Cancer Center

Houston, Texas, United States

Site Status WITHDRAWN

Local Institution - 100

South Brisbane, Queensland, Australia

Site Status COMPLETED

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status RECRUITING

Local Institution - 102

Clayton, Victoria, Australia

Site Status COMPLETED

Royal Prince Alfred Hospital

Camperdown, , Australia

Site Status RECRUITING

Local Institution - 182

Brasschaat, , Belgium

Site Status COMPLETED

Local Institution - 180

Bruges, , Belgium

Site Status COMPLETED

Local Institution - 183

Ghent, , Belgium

Site Status COMPLETED

Local Institution - 184

Leuven, , Belgium

Site Status COMPLETED

Local Institution - 220

Boulevard, Sofia, Bulgaria

Site Status COMPLETED

Local Institution - 221

Plovdiv, , Bulgaria

Site Status COMPLETED

Local Institution - 262

Toronto, Ontario, Canada

Site Status COMPLETED

Local Institution - 260

Toronto, Ontario, Canada

Site Status COMPLETED

Local Institution - 263

Toronto, Ontario, Canada

Site Status COMPLETED

Local Institution - 131

Beijing, Beijing Municipality, China

Site Status WITHDRAWN

Local Institution - 135

Guangzhou, Guangdong, China

Site Status WITHDRAWN

Local Institution - 132

Shanghai, Shanghai Municipality, China

Site Status WITHDRAWN

Local Institution - 134

Chengdu, Sichuan, China

Site Status WITHDRAWN

Local Institution - 130

Tianjin, Tianjin Municipality, China

Site Status WITHDRAWN

Local Institution - 133

Hangzhou, Zhejiang, China

Site Status WITHDRAWN

Local Institution - 305

Angers, , France

Site Status COMPLETED

Local Institution - 300

Créteil, , France

Site Status COMPLETED

Local Institution - 310

La Tronche, , France

Site Status COMPLETED

Local Institution - 306

Lille, , France

Site Status COMPLETED

Local Institution - 301

Marseille, , France

Site Status COMPLETED

Local Institution - 302

Paris, , France

Site Status COMPLETED

Local Institution - 307

Pessac, , France

Site Status WITHDRAWN

Local Institution - 304

Pierre-Bénite, , France

Site Status COMPLETED

Local Institution - 308

Strasbourg, , France

Site Status COMPLETED

Local Institution - 309

Toulouse, , France

Site Status COMPLETED

Local Institution - 303

Tours, , France

Site Status WITHDRAWN

Local Institution - 341

Berlin, , Germany

Site Status COMPLETED

Local Institution - 348

Dresden, , Germany

Site Status COMPLETED

Local Institution - 345

Düsseldorf, , Germany

Site Status COMPLETED

Local Institution - 346

Düsseldorf, , Germany

Site Status COMPLETED

Local Institution - 343

Halle, , Germany

Site Status COMPLETED

Local Institution - 342

Hamburg, , Germany

Site Status COMPLETED

Local Institution - 344

Hanover, , Germany

Site Status COMPLETED

Local Institution - 349

Leipzig, , Germany

Site Status WITHDRAWN

Local Institution - 340

Mainz, , Germany

Site Status COMPLETED

Local Institution - 347

München, , Germany

Site Status COMPLETED

Aghia Sophia' Children's General Hospital of Athens

Athens, , Greece

Site Status RECRUITING

Laiko General Hospital of Athens - Center of Thalassemia

Athens, , Greece

Site Status RECRUITING

Local Institution - 384

Athens, , Greece

Site Status COMPLETED

Local Institution - 383

Rio Patras, , Greece

Site Status COMPLETED

Local Institution - 381

Thessaloniki, , Greece

Site Status COMPLETED

Local Institution - 425

Afula, , Israel

Site Status COMPLETED

Local Institution - 420

Haifa, , Israel

Site Status COMPLETED

Local Institution - 422

Jerusalem, , Israel

Site Status COMPLETED

Local Institution - 424

Jerusalem, , Israel

Site Status COMPLETED

Local Institution - 421

Nahariya, , Israel

Site Status COMPLETED

Local Institution - 423

Petah Tikva, , Israel

Site Status COMPLETED

Local Institution - 478

Florence, Tuscany, Italy

Site Status ACTIVE_NOT_RECRUITING

Local Institution - 471

Florence, Tuscany, Italy

Site Status ACTIVE_NOT_RECRUITING

Local Institution - 470

Allessandria, , Italy

Site Status COMPLETED

Local Institution - 464

Bologna, , Italy

Site Status COMPLETED

Local Institution - 466

Brindisi, , Italy

Site Status COMPLETED

Local Institution - 477

Cagliari, , Italy

Site Status COMPLETED

Local Institution - 462

Ferrara, , Italy

Site Status COMPLETED

Ente Ospedaliero Ospedali Galliera - Centro della Microcitemia e delle Anemie Congenite

Genoa, , Italy

Site Status RECRUITING

Local Institution - 473

Lecce, , Italy

Site Status COMPLETED

Maggiore Polyclinic Hospital, IRCCS Ca' Granda

Milan, , Italy

Site Status RECRUITING

Local Institution - 479

Modena, , Italy

Site Status COMPLETED

AORN A Cardarelli

Napoli, , Italy

Site Status RECRUITING

AOU dell'Universita degli Studi della Campania Luigi Vanvitelli

Napoli, , Italy

Site Status RECRUITING

Azienda Ospedaliero Universitaria S. Luigi Gonzaga

Orbassano, , Italy

Site Status RECRUITING

Local Institution - 469

Pavia, , Italy

Site Status COMPLETED

Local Institution - 468

Reggio Calabria, , Italy

Site Status COMPLETED

Local Institution - 465

Roma, , Italy

Site Status COMPLETED

Local Institution - 474

Rozzano, , Italy

Site Status WITHDRAWN

Local Institution - 472

Varese, , Italy

Site Status COMPLETED

Local Institution - 463

Verona, , Italy

Site Status COMPLETED

Local Institution - 610

Nagoya, Aichi-ken, Japan

Site Status COMPLETED

Local Institution - 601

Kamogawa, Chiba, Japan

Site Status COMPLETED

Matsuyama Red Cross Hospital

Matsuyama, Ehime, Japan

Site Status RECRUITING

Ogaki Municipal Hospital

Ōgaki, Gifu, Japan

Site Status RECRUITING

Japanese Red Cross Society Himeji Hospital

Himeji, Hyōgo, Japan

Site Status RECRUITING

Local Institution - 605

Hitachi, Ibaraki, Japan

Site Status ACTIVE_NOT_RECRUITING

Kitasato University Hospital

Sagamihara, Kanagawa, Japan

Site Status RECRUITING

Local Institution - 0979

Sendai, Miyagi, Japan

Site Status WITHDRAWN

Tohoku University Hospital

Sendai, Miyagi, Japan

Site Status RECRUITING

Local Institution - 611

Nagasaki, Nagasaki, Japan

Site Status WITHDRAWN

Japanese Red Cross Medical Center

Shibuya City, Tokyo, Japan

Site Status RECRUITING

NTT Medical Center Tokyo

Shinagawa City, Tokyo, Japan

Site Status RECRUITING

Local Institution - 612

Chiba, , Japan

Site Status COMPLETED

Shonan Kamakura General Hospital

Kamakura, , Japan

Site Status RECRUITING

Osaka Metropolitan University Hospital

Osaka, , Japan

Site Status RECRUITING

Local Institution - 604

Osaka, , Japan

Site Status ACTIVE_NOT_RECRUITING

Chronic Care Center

Hazmiyeh, , Lebanon

Site Status RECRUITING

Local Institution - 545

Johor Bahru, Johor, Malaysia

Site Status COMPLETED

Hospital Sultanah Bahiyah

Alor Star, Kedah, Malaysia

Site Status RECRUITING

University Malaya Medical Centre

Kuala Lumpur, Kuala Lumpur, Malaysia

Site Status RECRUITING

Hospital Raja Permaisuri Bainun

Ipoh, Perak, Malaysia

Site Status RECRUITING

Queen Elizabeth Hospital

Kota Kinabalu, Sabah, Malaysia

Site Status RECRUITING

Hospital Umum Sarawak

Kuching, Sarawak, Malaysia

Site Status RECRUITING

Local Institution - 580

Amsterdam, , Netherlands

Site Status COMPLETED

Local Institution - 681

Barakaldo, , Spain

Site Status COMPLETED

Local Institution - 686

Barcelona, , Spain

Site Status COMPLETED

Local Institution - 685

Barcelona, , Spain

Site Status COMPLETED

Local Institution - 687

Madrid, , Spain

Site Status COMPLETED

Local Institution - 682

Oviedo, , Spain

Site Status COMPLETED

Local Institution - 684

Salamanca, , Spain

Site Status COMPLETED

Local Institution - 680

Seville, , Spain

Site Status COMPLETED

Local Institution - 683

Valencia, , Spain

Site Status COMPLETED

Local Institution - 720

Gothenburg, , Sweden

Site Status COMPLETED

Local Institution - 722

Lund, , Sweden

Site Status COMPLETED

Local Institution - 721

Stockholm, , Sweden

Site Status COMPLETED

Local Institution - 760

Kaohsiung, San Ming Dist., , Taiwan

Site Status COMPLETED

China Medical University Hospital

Taichung, , Taiwan

Site Status RECRUITING

Local Institution - 761

Taipei, , Taiwan

Site Status COMPLETED

Chulalongkorn University Faculty of Medicine - King Chulalongkorn Memorial Hospital

Bangkok, , Thailand

Site Status RECRUITING

Siriraj Hospital Mahidol University

Bangkok, , Thailand

Site Status RECRUITING

Chiang Mai University - Maharaj Nakorn Chiang Mai Hospital

Chiang Mai, , Thailand

Site Status RECRUITING

University Hospital Farhat Hached

Sousse, , Tunisia

Site Status RECRUITING

Bone Marrow Transplant Center

Tunis, , Tunisia

Site Status RECRUITING

Aziza Othmana Hospital

Tunis, , Tunisia

Site Status RECRUITING

Military Hospital of Tunis

Tunis, , Tunisia

Site Status RECRUITING

Local Institution - 881

Adana, , Turkey (Türkiye)

Site Status COMPLETED

Local Institution - 885

Ankara, , Turkey (Türkiye)

Site Status COMPLETED

Local Institution - 882

Istanbul, , Turkey (Türkiye)

Site Status COMPLETED

Local Institution - 884

Istanbul, , Turkey (Türkiye)

Site Status COMPLETED

Local Institution - 880

Izmir, , Turkey (Türkiye)

Site Status COMPLETED

Local Institution - 883

Mersin, , Turkey (Türkiye)

Site Status COMPLETED

Local Institution - 925

Aberdeen, , United Kingdom

Site Status COMPLETED

Local Institution - 921

Leeds, , United Kingdom

Site Status WITHDRAWN

Local Institution - 923

London, , United Kingdom

Site Status COMPLETED

Whittington Hospital

London, , United Kingdom

Site Status RECRUITING

University College London Hospitals NHS Foundation Trust - University College Hospital

London, , United Kingdom

Site Status RECRUITING

Local Institution - 928

London, , United Kingdom

Site Status COMPLETED

Local Institution - 924

London, , United Kingdom

Site Status COMPLETED

Local Institution - 929

Oxford, , United Kingdom

Site Status WITHDRAWN

Local Institution - 926

Sutton in Ashfield, , United Kingdom

Site Status WITHDRAWN

Countries

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United States Australia Belgium Bulgaria Canada China France Germany Greece Israel Italy Japan Lebanon Malaysia Netherlands Spain Sweden Taiwan Thailand Tunisia Turkey (Türkiye) United Kingdom

Central Contacts

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BMS Study Connect Contact Center www.BMSStudyConnect.com

Role: CONTACT

Phone: 855-907-3286

Email: [email protected]

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Thomas Coates, Site 968

Role: primary

Devendra Hiwase, Site 103

Role: primary

Joy Ho, Site 101

Role: primary

Antonis Kattamis, Site 382

Role: primary

Maria Dimopoulou, Site 380

Role: primary

Manuela Balocco, Site 476

Role: primary

Maria Domenica Cappellini, Site 467

Role: primary

Paolo Ricchi, Site 475

Role: primary

Silverio Perrotta, Site 461

Role: primary

Giovanni Battista Ferrero, Site 460

Role: primary

Tomoaki Fujisaki, Site 606

Role: primary

Hiroshi Kosugi, Site 608

Role: primary

Yasushi Hiramatsu, Site 614

Role: primary

Takahiro Suzuki, Site 603

Role: primary

Koichi Onodera, Site 607

Role: primary

Nobuhiro Tsukada, Site 602

Role: primary

Motoshi Ichikawa, Site 600

Role: primary

Shuku sato, Site 613

Role: primary

Yasuhiro Nakashima, Site 609

Role: primary

Ali Taher, Site 500

Role: primary

Hong Keng Liew, Site 542

Role: primary

Ping Chong Bee, Site 544

Role: primary

Kamini Kirubamoorthy, Site 546

Role: primary

Lily Wong, Site 543

Role: primary

Lee Ping Chew, Site 540

Role: primary

Ching-Tien Peng, Site 762

Role: primary

Pranee Sutcharitchan, Site 800

Role: primary

Vip Viprakasit, Site 802

Role: primary

Adisak Tantiworawit, Site 801

Role: primary

Khelif Abderahim, Site 840

Role: primary

Monia Ouederni, Site 841

Role: primary

Karima Kacem, Site 842

Role: primary

Fehmi M'Sadk, Site 843

Role: primary

Emma Drasar, Site 920

Role: primary

John Porter, Site 922

Role: primary

Related Links

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Other Identifiers

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U1111-1235-8123

Identifier Type: REGISTRY

Identifier Source: secondary_id

2022-502498-40

Identifier Type: OTHER

Identifier Source: secondary_id

ACE-536-LTFU-001

Identifier Type: -

Identifier Source: org_study_id