Safety and Efficacy of Efavaleukin Alfa in Subjects With Steroid Refractory Chronic Graft Versus Host Disease

NCT03422627 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 201602832017-000763-33
• Study Type: interventional
• Target: 32
• Locations: 4 countries
• Sites: 14

Brief Summary

Phase 1b: To evaluate the safety and tolerability of multiple ascending doses of efavaleukin alfa in subjects with steroid refractory chronic graft versus host disease (cGVHD). Phase 2: To evaluate the efficacy of efavaleukin alfa in subjects with steroid refractory cGVHD as measured by overall response rate (ORR) at 16 weeks according to the 2014 cGVHD NIH Consensus Criteria. Due to early termination, the Phase 2 portion of this study was not conducted.

Conditions

Chronic Graft Versus Host Disease cGVHD

Outcome Measures

Primary Outcomes (4)

• Phase 1b: Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)

  A DLT was defined as a: * Non-hematological toxicity ≥grade-4(per common terminology criteria for adverse events \[CTCAE\] v4.03) related to efavaleukin alfa. Non-hematological lab abnormalities without clinical significance weren't considered DLTs. * Hematological toxicity ≥grade 4 related to efavaleukin alfa defined as decreases in peripheral counts (absolute neutrophil count or platelets) persisting longer than 72 hrs, as measured by 2 separate results, that were not related to malignant disease relapse, infection, or other etiologies. * Constitutional events (ie, fever, fatigue) ≥grade 3 that were classified as serious adverse events by the investigator and related to efavaleukin alfa. * Infection is considered an expected complication of chronic graft versus host disease (cGVHD) and its treatment. Only grade 4 or 5 infections considered by the investigator to be related to efavaleukin alfa were reviewed by the dose level review meeting to determine whether it was considered a DLT.

  Up to 4 weeks after first dose of study drug administration

• Phase 1b: Number of Participants Who Experienced a Treatment-related Adverse Event (AE)

  A treatment-related AE was any untoward medical occurrence in a clinical study participant deemed to have a possibly causal relationship to the study treatment as determined by the investigator.

  Day 1 until the end of study; median (min, max) duration was 38.01 (3.27, 139.81) weeks

• Phase 1b: Number of Participants Who Experienced a Treatment-emergent AE

  A treatment-emergent AE was any untoward medical occurrence in a clinical study participant that occurred after first dose.

  Day 1 until the end of study; median (min, max) duration was 38.01 (3.27, 139.81) weeks

• Phase 1b: Number of Participants Who Experienced a Treatment-emergent Serious AE

  A treatment-emergent serious AE was any untoward medical occurrence in a clinical study participant that occurred after first dose that resulted in death, was immediately life threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or another medically important serious event.

  Day 1 until the end of study; median (min, max) duration was 38.01 (3.27, 139.81) weeks

Study Arms (2)

Phase 1: Efavaleukin Alfa Multiple Ascending Doses

EXPERIMENTAL

Efavaleukin will be administered as multiple ascending doses (MAD) across cohorts 1-5. Each dosing cohort will consist of between 3 and 6 subjects who will receive efavaleukin alfa subcutaneously (SC) either every week or every 2 weeks plus protocol permitted background therapy for 52 weeks. At the discretion of the Sponsor, following discussion and agreement between the principal investigator and medical monitor, subjects responding to efavaleukin alfa (as assessed by the end of week 50), who wish to continue treatment, may continue to receive efavaleukin alfa treatment at their current dosing regimen.

Drug: Efavaleukin Alfa

Phase 2: RP2D Efavaleukin Alfa

EXPERIMENTAL

The phase 2 portion of this study will be conducted as a single arm, multi-center, open label trial in subjects with steroid refractory chronic graft versus Host Disease (cGVHD). All subjects will receive the recommended phase 2 dose (RP2D) of efavaleukin alfa for up to 52 weeks plus protocol permitted background therapy for cGVHD. Due to early study termination the Phase 2 portion of the study was never opened.

Drug: Efavaleukin Alfa

Interventions

Efavaleukin Alfa DRUG

Phase 1: This study will be conducted as a multiple ascending dose (MAD) study. Each dosing cohort will consist of between 3 and 6 subjects who will receive efavaleukin alfa subcutaneously (SC) either every week or every 2 weeks plus protocol permitted background therapy for 52 weeks. At the discretion of the Sponsor, following discussion and agreement between the principal investigator and medical monitor, subjects responding to efavaleukin alfa (as assessed by the end of week 50), who wish to continue treatment, may continue to receive efavaleukin alfa treatment at their current dosing regimen for up to an additional 208 weeks through an extended dosing period. All subjects who continue to receive efavaleukin alfa during the extended dosing period will be reevaluated every 6 months for their response to treatment. Phase 2: All subjects will receive the recommended phase 2 dose (RP2D) of efavaleukin alfa for 52 weeks.

Also known as: AMG 592

Phase 1: Efavaleukin Alfa Multiple Ascending Doses; Phase 2: RP2D Efavaleukin Alfa

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has provided informed consent prior to initiation of any study specific activities/procedures.
• Subject is an adult ≥ 18 years old at the time of signing the informed consent.
• Subject is a recipient of an allogeneic HSCT.
• Subject has moderate to severe steroid-refractory cGVHD as defined by all of the following criteria:
• Diagnosed with cGVHD per the 2014 cGVHD NIH Consensus Criteria
• Steroid refractory cGVHD, defined as having persistent signs and symptoms of cGVHD despite ≥ 4 weeks of prednisone (or equivalent) dosed at ≥ 0.25 mg/kg/day (or ≥ 0.5 mg/kg every other day).
• Moderate to severe cGVHD (in accordance with 2014 cGVHD NIH Consensus Criteria at screening with involvement of at least one of the following organs at the screening and baseline visits: skin, mouth, eyes, gastrointestinal (GI) tract, liver, lungs, and joint and fascia.
• Subject has received no more than 3 previous treatments for cGVHD, excluding topical agents.
• Treatment with corticosteroids is considered a treatment for cGVHD and should be included in determining the number of previous treatments.
• Lines of therapy consisting of concurrent medications or interventions (eg, tacrolimus and corticosteroids; ECP and corticosteroids) count as 2 separate treatments.
• If cGVHD has worsened during a taper of immunosuppressive agents, restoring the agents to therapeutic level is permitted and does not count as an additional treatment.
• Subject may be receiving corticosteroid therapy provided that the dose is ≤ 1 mg/kg/day of systemic prednisone or equivalent and has been stable for at least 2 weeks prior to first dose of efavaleukin alfa.
• Subject may be receiving other non-corticosteroid immunosuppressive therapies provided that the immunosuppressant dose is stable for at least 2 weeks prior to first dose of efavaleukin alfa. Adjustments to dose of calcineurin inhibitor or sirolimus are allowed only to maintain drug levels within therapeutic range.
• Subject has a Karnofsky performance status score ≥ 50%.
• Subject has an estimated life expectancy of \> 3 months.

You may not qualify if:

• Subject is concurrently receiving treatment with calcineurin-inhibitor plus sirolimus (either agent alone is acceptable).
• Subject has received ibrutinib, imatinib, bortezomib, entospletinib, ruxolitinib or other JAK inhibitor, or treatment with any investigational drug or device within 4 weeks prior to starting efavaleukin alfa.
• Subject has received treatment with T-cell depleting, B-cell depleting or IL-2 signaling targeted medication (eg, ATG, alemtuzumab, basiliximab, denileukin diftitox, IL-2, rituximab) within 12 weeks prior to starting efavaleukin alfa.
• Subject has received treatment with T regulatory cell expanding therapies (ie PUVA, UVB, adoptively transferred T regulatory cells) within 4 weeks prior to starting efavaleukin alfa.
• Subject has received a donor lymphocyte infusion within 12 weeks prior to starting dose of efavaleukin alfa.
• Subject with active morphologic relapse/progression of hematologic malignancy post transplantation. Persistent CLL early after transplantation that subsequently entered remission will not be excluded.
• Subject has a history of malignancy, other than the indication for hematopoietic cell transplantation, with the following exceptions:
• adequately treated nonmelanoma skin cancers without current evidence of disease
• adequately treated cervical carcinoma in situ without current evidence of disease
• adequately treated breast ductal cancer in situ without current evidence of disease
• any malignancy treated with curative intent and with no evidence of active disease present for more than 5 years prior to screening and felt to be at low risk for recurrence by the treating physician
• Subject has a history of thrombotic microangiopathy, hemolytic-uremic syndrome or thrombotic thrombocytopenic purpura.
• Subject has an active infection requiring treatment with IV antibiotics or has been hospitalized for treatment of an active infection in the 4 weeks prior to starting dose of efavaleukin alfa.
• Subject has known history of active tuberculosis.
• Positive test for tuberculosis during screening defined as either:

Sponsors & Collaborators

• Amgen: lead

Study Sites (14)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

The Ohio State University Wexner Medical Center Arthur G James Cancer Hospital and Solove Research

Columbus, Ohio, 43210, United States

Location

Texas Oncology Baylor

Dallas, Texas, 75246, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109-1024, United States

Location

Universitair Ziekenhuis Leuven - Campus Gasthuisberg

Leuven, 3000, Belgium

Location

CHU Grenoble Alpes

Grenoble, 38043, France

Location

Hôpital Saint Louis

Paris, 75475, France

Location

Okayama University Hospital

Okayama, Okayama-ken, 700-8558, Japan

Location

Osaka City University Hospital

Osaka, Osaka, 545-8586, Japan

Location

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

Location

Related Links

• AmgenTrials clinical trials website

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2018
• First Posted: February 6, 2018
• Study Start: April 27, 2018
• Primary Completion: October 13, 2022
• Study Completion: October 13, 2022
• Last Updated: November 22, 2023
• Results First Posted: November 22, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.

Locations

FR (2); BE (1); US (8); JP (3)