Clinical trial NCT04409080: REGN7257 in Adult Patients With Severe Aplastic Anemia That Is Refractory to or Relapsed on Immunosuppressive Therapy
Official title: A Phase 1/2 Study of REGN7257 (Anti-Interleukin 2 Receptor Subunit Gamma [IL2RG] Monoclonal Antibody) in Patients With Severe Aplastic Anemia That Is Refractory to or Relapsed on Immunosuppressive Therapy
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE1
PHASE2
Conditions: Severe Aplastic Anemia (SAA)
Keywords: Immunosuppressive therapy (IST)
Refractory
Relapsed
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2020-06-01
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study is researching an experimental drug called REGN7257 (called "study drug"). The study is focused on patients who have severe aplastic anemia (SAA), a disease of the bone marrow resulting in an impairment of the production of blood cells.

The main purpose of this two-part study (Part A and Part B) is to test how safe and tolerable REGN7257 is in patients with SAA in which other Immunosuppressive therapies (ISTs) have not worked well.

The study is looking at several other research questions to better understand the following properties of REGN7257:

* Side effects that may be experienced by participants taking REGN7257
* How REGN7257 works in the body
* How much REGN7257 is present in blood after dosing
* If REGN7257 works to raise levels of certain blood counts after treatment
* How quickly REGN7257 works to raise levels of certain blood counts
* In patients for whom REGN7257 works to raise levels of certain blood counts after treatment, how many continue to show such a response throughout the study
* If REGN7257 works to lower the number of platelet and red blood cell transfusions needed
* How REGN7257 changes immune cell counts and composition
* How the body reacts to REGN7257 and if it produces proteins that bind to REGN7257 (this would be called the formation of anti-drug antibodies \[ADA\])


Eligibility criteria: Key Inclusion Criteria:

1. Part A: SAA that is IST-refractory or IST-relapsed, as defined in the protocol
2. Part B: SAA that is IST-relapsed, as defined in the protocol
3. Hematopoietic stem cell transplantation (HSCT) is not available or suitable as a treatment option or has been refused by the patient
4. Adequate hepatic and renal function as defined in the protocol

Key Exclusion Criteria:

1. Diagnosis of Fanconi anemia or other congenital bone marrow failure syndrome as defined in the protocol
2. Evidence of myelodysplastic syndrome as defined in the protocol
3. Paroxysmal nocturnal hemoglobinuria (PNH) with evidence of clinically significant hemolysis (eg, treatment indicated) or history of PNH-associated thrombosis
4. Treatment with a T cell-depleting agent (eg, ATG or alemtuzumab) within 6 months prior to dosing
5. Treatment with a calcineurin inhibitor (eg, cyclosporine) within 4 weeks prior to dosing for patients enrolled in Part A
6. Treatment with eltrombopag or investigational thrombopoietin receptor agonist, Granulocyte Colony-Stimulating Factor (G-CSF), or an androgen (eg, danazol), within 2 weeks prior to dosing
7. HIV, hepatitis B or hepatitis C positive by serological testing at the screening visit as defined in the protocol
8. Active tuberculosis, latent tuberculosis infection (LTBI) or history incompletely-treated tuberculosis or LTBI
9. Active infection as defined in the protocol

Note: Other protocol-defined inclusion/ exclusion criteria apply

Primary outcomes:
measure: Incidence of adverse events (AEs)
timeFrame: 12 months post-treatment, approximately 52 weeks
measure: Incidence of serious adverse events (SAEs)
timeFrame: 12 months post-treatment, approximately 52 weeks
measure: Incidence and severity of treatment-emergent adverse events (TEAEs)
timeFrame: 12 months post-treatment, approximately 52 weeks
measure: Incidence of serious adverse events (SAEs)
timeFrame: Through the end of study visit, approximately 78 weeks
measure: Incidence and severity of treatment-emergent adverse events (TEAEs)
timeFrame: Through the end of study visit, approximately 78 weeks
measure: Overall response rate (ORR)
timeFrame: At 6 months, approximately 26 weeks
Secondary outcomes:
measure: ORR
timeFrame: At 3 months, approximately 12 weeks
measure: Complete response (CR)
timeFrame: At 3 months, approximately 12 weeks
measure: Partial response (PR)
timeFrame: At 3 months, approximately 12 weeks
measure: Time to best response
timeFrame: Up to 12 months
measure: Time to best response
timeFrame: Up to 18 months
measure: Time to first response
timeFrame: Up to 12 months
measure: Time to first response
timeFrame: Up to 18 months
measure: Any clinical response
timeFrame: Until the end of study, approximately week 52
measure: Any clinical response
timeFrame: Until the end of study, approximately week 78
measure: Platelet transfusions per month over time
timeFrame: Up to 12 months
measure: Platelet transfusions per month over time
timeFrame: Up to 18 months
measure: Red blood cell transfusions per month over time
timeFrame: Up to 12 months
measure: Red blood cell transfusions per month over time
timeFrame: Up to 18 months
measure: Changes in lymphocyte cell counts
timeFrame: Up to 12 months
measure: Changes in lymphocyte cell counts
timeFrame: Up to 18 months
measure: Changes in neutrophil cell counts
timeFrame: Up to 12 months
measure: Changes in neutrophil cell counts
timeFrame: Up to 18 months
measure: Changes in hemoglobin cell counts
timeFrame: Up to 12 months
measure: Changes in hemoglobin cell counts
timeFrame: Up to 18 months
measure: Changes in reticulocyte cell counts
timeFrame: Up to 12 months
measure: Changes in reticulocyte cell counts
timeFrame: Up to 18 months
measure: Changes in platelet cell counts
timeFrame: Up to 12 months
measure: Changes in platelet cell counts
timeFrame: Up to 18 months
measure: Changes in the whole blood immune cell subsets (T cells)
timeFrame: Up to 12 months
measure: Changes in the whole blood immune cell subsets (T cells)
timeFrame: Up to 18 months
measure: Changes in the whole blood immune cell subsets (B cells)
timeFrame: Up to 12 months
measure: Changes in the whole blood immune cell subsets (B cells)
timeFrame: Up to 18 months
measure: Changes in the whole blood immune cell subsets [Natural killer (NK) cells]
timeFrame: Up to 12 months
measure: Changes in the whole blood immune cell subsets (NK cells)
timeFrame: Up to 18 months
measure: Drug concentrations in serum over time
timeFrame: Up to 12 months
measure: Drug concentrations in serum over time
timeFrame: Up to 18 months
measure: Incidence of treatment-emergent anti-drug antibody (ADA) over time
timeFrame: Up to 12 months
measure: Incidence of treatment-emergent ADA over time
timeFrame: Up to 18 months
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Paris
country: France
facility: Hopital Saint-Louis - APHP
state: Ile-de-France
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Hospital
state: Gyeonggi
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul Capital Area
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul Capital Area
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Marys Hospital
state: Seoul Capital Area
city: Seoul
country: Korea, Republic of
facility: Ewha Womans University Medical Centre
state: Seoul Capital Area
city: Leeds
country: United Kingdom
facility: St James's University Hospital
state: West Yorkshire
city: London
country: United Kingdom
facility: King's College Hospital, London
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: