Combination Immunotherapy in Biochemically Recurrent Prostate Cancer

Phase II Trial of Combination Immunotherapy in Biochemically Recurrent Prostate Cancer

Background:

Some people with prostate cancer have a rise in prostate-specific antigen (PSA). This can happen even after treatments like radiation and surgery. Androgen deprivation therapy (ADT) drugs and close monitoring are one standard way to treat this group of people. Another way is to monitor people and their PSA values over time. Researchers want to see if a combination of new drugs can help these people.

Objective:

To see if the combination treatment of PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec vaccinia), CV301, and MSB0011359C (M7824) can induce an anti-tumor impact in people with biochemically recurrent prostate cancer.

Eligibility:

People ages 18 and older with certain kinds of prostate cancer

Design:

Participants will be screened with

• Medical history
• Physical exam
• Blood and urine tests
• A scan of the neck, chest, abdomen, and pelvis
• A bone scan

A sample of tissue that was already taken will be tested. This will confirm the diagnosis, stage, and disease status.

Some participants will have close monitoring with four monthly PSA checks.

All participants will get two study drugs as shots under the skin. They will get the third drug in a vein. They will get the drugs over at least 7 months. Their vital signs will be checked before they get the drugs and for up to 1 hour after.

Participants will have frequent study visits. They will have physical exams, urine and blood tests, and scans.

Participants will return to the clinic about 4 weeks after they stop taking the study drugs. They will have a medical history, physical exam, and blood tests. They may also have long-term follow-up visits.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Biological: Antigen direct immunotherapy: PROSTVAC-V; Biological: Antigen direct immunotherapy: PROSTVAC-F; Drug: MSB0011359C (M7824); Biological: Antigen direct immunotherapy: CV301; Diagnostic test: CT scan of chest; Diagnostic test: CT scan of abdomen/pelvis; Diagnostic test: MRI; Diagnostic test: Bone scan; Diagnostic test: PSMA

Detailed Description

Background:

Androgen deprivation therapy (ADT) and surveillance are treatment options for prostate cancer patients with biochemical progression after localized therapy (i.e., biochemically recurrent [BCR] prostate cancer). The primary goal in these patients is to prevent morbidity from their cancer that results from disease progression and metastatic disease on conventional imaging.

ADT can lower the prostate-specific antigen (PSA) in these patients, but because of its substantial side effect profile and ambiguous long-term impact, it is generally deferred by most patients until there is a rapid escalation in their PSA.

Immunotherapy presents an alternative option for these patients that is especially attractive because it is not associated with substantial toxicity. Also, since immunotherapy can have lasting effects after treatment due to a sustained activated immune response, patients will not be required to take these treatments indefinitely to potentially benefit clinically.

Current and previous clinical trials have demonstrated that single agent immunotherapy can impact PSA in patients in this population.

The focus of this study is to determine if combination immunotherapy with Antigen direct immunotherapy antigen directed immunotherapy can initiate an immune response in the first 4 months that is then augmented by an immune checkpoint inhibitor in the following 3 months.

In addition to PSA responses (the primary metric in this population), safety, changes in immune responses, and PSA kinetics will also be evaluated.

Objectives:

Primary Objectives:

Safety Lead-In: To evaluate the safety and tolerability of combination immunotherapy in participants with castration-resistant prostate cancer

Biochemical Recurrence: To determine if the combination immunotherapy can induce a 30% decline in PSA in 28% of participants with biochemically recurrent prostate cancer.

Eligibility Criteria (for biochemical recurrence):

Histologically confirmed adenocarcinoma of the prostate

Participants with negative computed tomography (CT) Scan and Tc-99m Bone Scan

Participants with a PSA over 0.8 ng/ml for participants following radical prostatectomy or for participants following definitive radiation therapy: a rise in PSA of >= 2 ng/mL above the nadir

Participants with a PSA doubling time of 5-15 months

No history of active autoimmune disease or history of organ compromising autoimmune disease

Eastern Cooperative Oncology Group (ECOG) 0-1

Safety lead-in cohort will evaluate 6 participants with castration resistant prostate cancer

Design:

Three-arm, non-randomized study

Accrual goal is a total of 37 evaluable participants (6 in an initial safety cohort, 6 participants who received M7824 (MSB0011359C) as part of the initial investigation and 25 homogenously treated participants without M7824) to evaluate response

Participants from a previous study (NCT02649439) with nearly identical eligibility can serve as a contemporary control for secondary endpoints

Following the safety lead-in, all participants will be enrolled and may undergo a surveillance period during which up to 4 consecutive monthly PSA values will be captured by the labs.

After surveillance period, if applicable, participants will be treated with 2 Antigen direct immunotherapy's concurrently, Prostvac (rilimogene galvacirepvec/rilimogene glafolivec) and CV301, during months 1-4. For months 5-7, MSB0011359C [an anti-programmed Cell Death Ligand 1 (PD-L1) antibody (avelumab) with TGF(Beta)-Trap molecule] will be added to the regimen.

-Effective with amendment v7/29/2021, MSB0011359C (M7824) will no longer be given as part of the treatment combination for the Biochemical Recurrence cohort (Arms 3)

Participants will be monitored for on-treatment and post-treatment PSA, immune and imaging responses.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

• For Safety Lead-in
• INCLUSION CRITERIA:
• Histopathological documentation of prostate cancer confirmed in either the Laboratory of Pathology at the National Institutes of Health (NIH) Clinical Center, or Walter Reed National Military Medical Center prior to enrollment. If no pathologic specimen is available, participants may enroll with a pathologist's report showing a histologic diagnosis of prostate cancer and a clinical course consistent with the disease.
• Recovery to baseline from acute toxicity related to prior therapy, including surgery and radiation. (28 days removed from last systemic therapy, 14 days removed from last radiation therapy).

• Hepatic function eligibility parameters (within 16 days before starting therapy):

  --Bilirubin less than or equal to upper limit of normal (ULN) (OR in participants with Gilbert's syndrome, a total bilirubin less than or equal to 3.0), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 1.5 times upper limit of normal.

• Adequate renal function defined by an estimated creatinine clearance > 50 mL/min according to the Cockcroft-Gault formula or by measure of creatinine clearance from 24-hour urine collection.
• No other active malignancies within the past 36 months (with the exception of nonmelanoma skin cancers or carcinoma in situ of the bladder) or life-threatening illnesses.
• Willing to travel to the NIH for follow-up visits.
• 18 years of age or older.
• Able to understand and sign informed consent.
• The effects Prostvac (rilimogene galvacirepvec/rilimogene glafolivec) and CV301 on the developing human fetus are unknown. For this reason, men must agree to use highly effective contraception (that is, methods with a failure rate of less than 1% per year) prior to study entry, for the duration of study therapy and at least four months after the last treatment administration. Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform her treating physician immediately.

• Additional Inclusion Criteria Specific to Safety Lead-In Cohort

  • Castrate testosterone level (<50ng/dl or 1.7nmol /L)

  • Progressive disease at study entry defined as one or more of the following criteria occurring in the setting of castrate levels of testosterone:

    • Radiographic progression defined as any new or enlarging bone lesions or growing lymph node disease, consistent with prostate cancer

OR

• For Biochemical Recurrence:

• Prostate-specific antigen (PSA) progression defined by sequence of rising values separated by >1 week (2 separate increasing values over a minimum of 2ng/ml (Prostate Cancer Working Group 2 (PCWG2) PSA eligibility criteria). If participants had been on flutamide, PSA progression is documented 4 weeks or more after withdrawal. For participants on bicalutamide or nilutamide disease progression is documented 6 or more weeks after withdrawal.

  --Participants must agree to continuation of androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone agonist/antagonist or bilateral orchiectomy

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (Karnofsky >80%).
• Hematological eligibility parameters (within 16 days before starting therapy):
• Granulocyte count greater than or equal to 1000/mm^3
• Platelet count greater than or equal to 100 000/mm^3
• Hemoglobin (Hgb) greater than or equal to 9 g/dL
• Prothrombin time (PT) less than or equal to 1.5 x ULN
• Activated partial thromboplastin time (aPTT) less than or equal to 1.5 x ULN

Additional Inclusion Criteria Specific to Biochemical Recurrence Cohort

• Biochemical progression defined as follows:

  • For participants following definitive radiation therapy: a rise in PSA of greater than or equal to 2 ng/mL above the nadir (per Radiation Therapy Oncology Group (RTOG) -American Society for Therapeutic Radiation Oncology (ASTRO) consensus criteria)
  • For participants following radical prostatectomy: rising PSA after surgical procedure (participants must have a PSA greater than or equal to 0.8 ng/mL)
• Participants must have a rising PSA as confirmed by 3 values a minimum of 1 week apart over at least a 1 month period of time.
• Participants must have a PSA doubling time of 5-15 months.
• ECOG performance status of 0-1 (Karnofsky greater than or equal to 80%).
• Negative computed tomography (CT) scan/magnetic resonance imaging (MRI) and bone scan for metastatic prostate cancer.
• Baseline testosterone greater than or equal to 100 ng/dl.
• PSA less than or equal to 30 ng/mL.

• Hematological eligibility parameters (within 16 days before starting therapy):

  • Granulocyte count greater than or equal to 1000/mm3
  • Platelet count greater than or equal to 100 000/mm3
  • Hgb greater than or equal to 10 g/dL

EXCLUSION CRITERIA:

• Immunocompromised status due to:

  • Human immunodeficiency virus (HIV) positivity.

  • Active autoimmune diseases such as Addison's disease, Hashimoto's thyroiditis, systemic lupus erythematosus, Sjogren syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome or active Grave's disease.

    • Participants with a history of autoimmunity that has not required systemic immunosuppressive therapy or does not threaten vital organ function including central nervous system (CNS), heart, lungs, kidneys, skin, and gastrointestinal (GI) tract will be allowed.
    • Participants with diabetes type I, vitiligo, or alopecia are allowed.
  • Other immunodeficiency diseases
  • Splenectomy
• Receipt of any organ transplantation, including allogeneic stem-cell transplantation, but with the exception of transplants that do not require immunosuppression (e.g., corneal transplant, hair transplant).
• Chronic administration (defined as daily or every other day for continued use > 14 days) of systemic corticosteroids within 28 days before the first planned dose of investigational therapy. Use of corticosteroids with minimal systemic absorption (e.g., inhaled steroids, nasal sprays, and topical agents) is allowed.
• Serious intercurrent medical illness that, in the judgment of the investigator, would interfere with participants ability to carry out the treatment program.
• Other medications used for urinary symptoms including 5-alpha reductase inhibitors (finasteride and dutasteride) and alternative medications known to alter PSA (e.g. phytoestrogens and saw palmetto).
• History of prior chemotherapy (chemotherapy allowed for lead-in cohort in castration resistant disease.)
• History of prior immunotherapy within the last 3 years (immunotherapy allowed for lead-in cohort in castration resistant disease.)
• Receipt of an investigational agent within 28 days (or 56 days for an antibody-based therapy) before the first planned dose of study drugs.
• Major surgery within 4 weeks prior to enrollment
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to poxviral Antigen direct immunotherapy's (e.g., vaccinia Antigen direct immunotherapy)
• Previous serious adverse reactions to smallpox vaccination
• History of allergic reactions attributed to monoclonal antibodies (grade 3)
• Known allergy to eggs, egg products, aminoglycoside antibiotics (e.g., gentamicin or tobramycin).
• History of atopic dermatitis or active skin condition (acute, chronic, exfoliative) that disrupts the epidermis
• Unable to avoid close contact or household contact with the following high-risk individuals for three weeks after the Day 1 vaccination: (a) children less than or equal to 3 years of age, (b) pregnant or nursing women, (c) individuals with prior or concurrent extensive eczema or other eczemoid skin disorders, or (d) immunocompromised individuals, such as those with HIV.
• Participants who test positive for hepatitis B virus (HBV) or hepatitis C virus (HCV)
• Clinically significant cardiovascular/cerebrovascular disease as follows: cerebral vascular accident/stroke (< 6 months prior to the first planned dose of study drugs), myocardial infarction (< 6 months prior to the first planned dose of study drugs), unstable angina, congestive heart failure (New York Heart Association Classification Class greater than or equal to II), serious cardiac arrhythmia, or uncontrolled hypertension (systolic blood pressure (SBP)>170/diastolic blood pressure (DBP)>105).
• Participants who have received a red cell transfusion within 2 weeks prior to enrollment.
• Participants unwilling to accept blood products as medically indicated.
• Individual tumor lesion(s) in the liver or chest which are 10 cm or larger.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1/Safety Lead-in Combination Therapy (closed December 2018); Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301+ MSB0011359C (M7824)	Biological: Antigen direct immunotherapy: PROSTVAC-V; Recombinant vaccinia virus vector antigen direct immunotherapy of the genus Orthopoxvirus. Administered by subcutaneous injection.; Other Names: rilimogene galvacirepvec/rilimogene glafolivec vaccinia; Biological: Antigen direct immunotherapy: PROSTVAC-F; Recombinant fowlpox virus vector Antigen direct immunotherapy of the genus Avipoxvirus. Administered by subcutaneous injection.; Other Names: rilimogene galvacirepvec/rilimogene glafolivec fowlpox; Drug: MSB0011359C (M7824); Fully human bifunctional fusion protein that combines immunoglobulin G1 (IgG1) anti-programmed death-ligand 1 (PD-L1) and Transforming growth factor, beta receptor II (TGFbetaRII) as a monoclonal antibody. Administered via intravenous (IV) infusion over 1 hour.; Other Names: M7824; Biological: Antigen direct immunotherapy: CV301; Recombinant vaccinia virus Antigen direct immunotherapy of the genus Avipoxvirus. Administered subcutaneously.; Diagnostic test: CT scan of chest; Screening, prior to Antigen direct immunotherapy, end of study therapy, then every 6 months as long as participants remain in follow-up. And as clinically indicated after one year.; Other Names: Computed tomography; Diagnostic test: CT scan of abdomen/pelvis; Screening, prior to Antigen direct immunotherapy, end of study therapy, then every 6 months as long as participants remain in follow-up. And as clinically indicated after one year.; Diagnostic test: MRI; Screening, prior to Antigen direct immunotherapy, end of study therapy, then every 6 months as long as participants remain in follow-up. And as clinically indicated after one year.; Other Names: Magnetic resonance imaging; Diagnostic test: Bone scan; Screening, prior to Antigen direct immunotherapy, end of study therapy, then every 6 months as long as participants remain in follow-up. And as clinically indicated after one year.
Experimental: 2/Biochemical Recurrence: Combination Therapy + Surveillance (closed); Surveillance followed by Prostvac ( rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301 then Prostvac + CV301 + MSB0011359C (M7824)	Biological: Antigen direct immunotherapy: PROSTVAC-V; Recombinant vaccinia virus vector antigen direct immunotherapy of the genus Orthopoxvirus. Administered by subcutaneous injection.; Other Names: rilimogene galvacirepvec/rilimogene glafolivec vaccinia; Biological: Antigen direct immunotherapy: PROSTVAC-F; Recombinant fowlpox virus vector Antigen direct immunotherapy of the genus Avipoxvirus. Administered by subcutaneous injection.; Other Names: rilimogene galvacirepvec/rilimogene glafolivec fowlpox; Drug: MSB0011359C (M7824); Fully human bifunctional fusion protein that combines immunoglobulin G1 (IgG1) anti-programmed death-ligand 1 (PD-L1) and Transforming growth factor, beta receptor II (TGFbetaRII) as a monoclonal antibody. Administered via intravenous (IV) infusion over 1 hour.; Other Names: M7824; Biological: Antigen direct immunotherapy: CV301; Recombinant vaccinia virus Antigen direct immunotherapy of the genus Avipoxvirus. Administered subcutaneously.; Diagnostic test: CT scan of chest; Screening, prior to Antigen direct immunotherapy, end of study therapy, then every 6 months as long as participants remain in follow-up. And as clinically indicated after one year.; Other Names: Computed tomography; Diagnostic test: CT scan of abdomen/pelvis; Screening, prior to Antigen direct immunotherapy, end of study therapy, then every 6 months as long as participants remain in follow-up. And as clinically indicated after one year.; Diagnostic test: MRI; Screening, prior to Antigen direct immunotherapy, end of study therapy, then every 6 months as long as participants remain in follow-up. And as clinically indicated after one year.; Other Names: Magnetic resonance imaging; Diagnostic test: Bone scan; Screening, prior to Antigen direct immunotherapy, end of study therapy, then every 6 months as long as participants remain in follow-up. And as clinically indicated after one year.; Diagnostic test: PSMA; Biochemical recurrence group only. Screening, prior to Antigen direct immunotherapy therapy, end of study therapy, then every 6 months as long as participants remain in follow-up. And as clinically indicated after one year.; Other Names: prostate-specific membrane antigen positron emission tomography scan
Experimental: 3/Biochemical Recurrence: Combination Antigen Direct Immunotherapy +/- Surveillance; Surveillance as needed followed by Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301	Biological: Antigen direct immunotherapy: PROSTVAC-V; Recombinant vaccinia virus vector antigen direct immunotherapy of the genus Orthopoxvirus. Administered by subcutaneous injection.; Other Names: rilimogene galvacirepvec/rilimogene glafolivec vaccinia; Biological: Antigen direct immunotherapy: PROSTVAC-F; Recombinant fowlpox virus vector Antigen direct immunotherapy of the genus Avipoxvirus. Administered by subcutaneous injection.; Other Names: rilimogene galvacirepvec/rilimogene glafolivec fowlpox; Biological: Antigen direct immunotherapy: CV301; Recombinant vaccinia virus Antigen direct immunotherapy of the genus Avipoxvirus. Administered subcutaneously.; Diagnostic test: CT scan of chest; Screening, prior to Antigen direct immunotherapy, end of study therapy, then every 6 months as long as participants remain in follow-up. And as clinically indicated after one year.; Other Names: Computed tomography; Diagnostic test: CT scan of abdomen/pelvis; Screening, prior to Antigen direct immunotherapy, end of study therapy, then every 6 months as long as participants remain in follow-up. And as clinically indicated after one year.; Diagnostic test: MRI; Screening, prior to Antigen direct immunotherapy, end of study therapy, then every 6 months as long as participants remain in follow-up. And as clinically indicated after one year.; Other Names: Magnetic resonance imaging; Diagnostic test: Bone scan; Screening, prior to Antigen direct immunotherapy, end of study therapy, then every 6 months as long as participants remain in follow-up. And as clinically indicated after one year.; Diagnostic test: PSMA; Biochemical recurrence group only. Screening, prior to Antigen direct immunotherapy therapy, end of study therapy, then every 6 months as long as participants remain in follow-up. And as clinically indicated after one year.; Other Names: prostate-specific membrane antigen positron emission tomography scan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a Toxicity	Percentage of participants with a toxicity assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.	At the end of therapy (7 months)
Prostate Specific Antigen (PSA) Response	Proportion of evaluable participants who experience at least a 30% decline. PSA is a tumor marker in prostate cancer and elevated in participants with this stage of disease. Declines of 30% can be associated with favorable clinical outcomes.	End of treatment (7 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Related and/or Unrelated Grade 3 and Grade 4 Adverse Events.	Number of participants with related and/or unrelated Grade 3 and Grade 4 adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Reporting the grade of adverse events noted in each participant and reporting the fraction with grade 3 and grade 4 adverse events.	6 weeks
Number of Evaluable Participants With Biochemical Recurrence (BCR) With a 20% Change in PSA Doubling Time	PSA Doubling Time (DT) is the time interval (measured in months) it takes for PSA levels to double. PSA DT was calculated using the Memorial Sloan Kettering online PSA Doubling Time calculator. A long PSA DT suggests more indolent disease based on published data. PSA doubling time has been associated with better clinical outcomes in BCR. Note that PSA DT is calculated on a per participant basis and thus will be presented as number of evaluable participants with a change in PSA DT. A change in 20% would be considered meaningful and not due to lab variations. Thus, the data for this outcome is presented as number of evaluable participants experiencing a 20% change in PSA DT.	End of treatment after 7 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)	Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.	Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Ravi A Madan, M.D., National Cancer Institute (NCI)

Publications and helpful links

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2018
• Primary Completion (Actual): June 4, 2024
• Study Completion (Actual): June 4, 2024

Study Registration Dates

• First Submitted: October 18, 2017
• First Submitted That Met QC Criteria: October 19, 2017
• First Posted (Actual): October 20, 2017

Study Record Updates

• Last Update Posted (Actual): June 19, 2025
• Last Update Submitted That Met QC Criteria: June 4, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Immunotherapy; PSA; Checkpoint Inhibitor; Immune Response; Antigen direct immunotherapy
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Immunomodulating Agents; Immunologic Factors
• Other Study ID Numbers: 180005; 18-C-0005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. In addition, all large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).
• IPD Sharing Time Frame: Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol Genomic Data Sharing (GDS) plan for as long as database is active.
• IPD Sharing Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Genomic data are made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No