Safety, Tolerability, PK/PD of FE 203799 in Adults With Lymphomas

NCT03417765 | Withdrawn Phase 1 DMC

• 1 other identifier: GLY-211-2017
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

RATIONALE: The integrity of the intestinal mucosa is a key factor for the preservation of a normal gut function. Damage of the epithelium (i.e. by chemotherapy) results in significant cellular and molecular alterations that ultimately lead to intestinal dysfunction/failure. This intestinal dysfunction manifests as several pathological processes, such as inability to absorb nutrients, intestinal inflammation, immune system dysregulation, and disequilibrium of normal intestinal microbiota leading to increased risk of infection due to bacterial translocation and septicaemia. Gastrointestinal (GI) mucositis is a well-known, frequent and debilitating side effect of most anticancer regimens with a very high incidence in hemato-oncology. The most common symptoms are nausea, vomiting, weight loss, abdominal cramps and pain, diarrhea, and electrolyte imbalance. Patients may also experience ulceration/bleeding and injury of the lining of the entire gastrointestinal tract from the esophagus to the colon. Currently no therapy is available for the prevention or treatment of GI intestinal injury. Treatment of related symptoms is limited to supportive measures to decrease diarrhea and to preventive antibiotic therapy. The GLP-2 analogue, FE 203799, has a favorable pharmacology profile for clinical development in the intended therapeutic indication of myeloablative chemotherapy-induced GI damage. The data collected from animal studies has shown that FE 203799 stimulates the proliferation of the intestinal epithelium and protects the GI mucosa from chemotherapy-induced injury. Hence, the primary pharmacologic activity of FE 203799 would promote a healthy GI microenvironment, thus preventing intestinal dysfunction and related complications. PURPOSE: Prevention by FE 203799 of chemotherapy-induced intestinal damage and related complications in patients with lymphoma receiving Melphalan based (BEAM) myeloablative conditioning regimen followed by hematopoietic stem cell transplantation.

Conditions

Lymphoma, Non-Hodgkin's, Adult; Lymphoma, Hodgkin's, Adult

Keywords

gastrointestinal mucositis; myeloablative chemotherapy; autologous transplantation

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment-emergent adverse events

  Adverse events as assessed by CTCAE v4.03

  Day -8 to Day 100

Secondary Outcomes (19)

• Maximum observed plasma concentration (Cmax) of FE 203799

  Day -8 to Day 13

• Cumulative area under the plasma concentration (AUC) time curve from 0-168 hours of FE 203799

  Day -8 to Day 13

• Cumulative area under the plasma concentration (AUC) from time zero to infinity of FE 203799

  Day -8 to Day 13

• Terminal elimination half-life (T1/2) of FE 203799

  Day -8 to Day 13

• Apparent total body clearance (CL) of the drug from plasma of FE 203799

  Day -8 to Day 13

Study Arms (3)

Cohort A: 5 mg (FE 203799/Placebo)

EXPERIMENTAL

Drug: FE 203799 Drug: BEAM Procedure: myeloablative chemotherapy Procedure: autologous stem cell transplantation

Drug: FE 203799

Cohort B: 10 mg (FE 203799/Placebo)

EXPERIMENTAL

Drug: FE 203799 Drug: BEAM Procedure: myeloablative chemotherapy Procedure: autologous stem cell transplantation

Drug: FE 203799

Cohort C: 25 mg (FE 203799/Placebo)

EXPERIMENTAL

Drug: FE 203799 Drug: BEAM Procedure: myeloablative chemotherapy Procedure: autologous stem cell transplantation

Drug: FE 203799

Interventions

FE 203799 DRUG

GLP-2 analogue, once weekly, subcutaneous administration

Cohort A: 5 mg (FE 203799/Placebo); Cohort B: 10 mg (FE 203799/Placebo); Cohort C: 25 mg (FE 203799/Placebo)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult male and non-pregnant or lactating female patients diagnosed with Hodgkin's lymphoma (HL) or non- Hodgkin's lymphoma (NHL; T- or B-cell variants) based on histological or cytological evidence.
• Patients are eligible to receive myeloablative chemotherapy as per center eligibility criteria, followed by AHSCT.
• Patients between 18 years and 65 years of age with a Hematopoietic Cell Transplant- Co-morbidity Index (HCT-CI) ≤5. Patients between 65 years and 70 years will be eligible if their HCT-CI score is ≤3.
• Patients, or their legal representatives, must have the ability to read, understand and provide written informed consent prior to the initiation of any study related procedures.
• Patients must have chemo-sensitive disease and be in partial or complete remission following the most recent anti-neoplastic therapy regimen, according to the Lugano revision of the International Working Group (IWG) response criteria \[1\].
• Patients must have available a cryopreserved autologous hematopoietic stem cell graft containing ≥ 2.0 x 106 cryopreserved CD34+ cells/kg.
• Patients must have a Karnofsky score ≥ 70%.
• Patients must have adequate hepatic function as evidenced by bilirubin ≤ upper limit of normal (ULN), unless felt to be related to Gilbert's syndrome or hemolysis; patients must also have AST and ALT ≤ 1.5 x ULN and alkaline phosphatase ≤ 2.5 x ULN.
• Patients must have an estimated or measured creatinine clearance ≥ 30 ml/min/1.73 m2 by the Cockcroft-Gault equation.
• Patients must have left ventricular ejection fraction ≥ 50%.
• Patients must have forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and diffusing capacity corrected for hemoglobin (DLCOc) ≥ 50% of predicted.
• Patients must have recovered from the effects of any prior chemotherapy, radiotherapy or surgery; for patients who have been on monoclonal antibody therapy, at least one half-life or 4 weeks (whichever is longer) should have elapsed prior to the first scheduled day of dosing with FE 203799.
• A female recipient of childbearing potential must meet the following criteria:
• Participant has a negative pregnancy test at Screening.
• Participant agrees to use one of the accepted contraceptive regimens from at least 14 days prior to the first administration of the Study Drug, during the study and for at least 90 days after the last dose of the Study Drug. An acceptable method of contraception includes one of the following:

You may not qualify if:

• Patient is unable or unwilling to give informed consent.
• Patients who are unable to comply with the treatment protocol including appropriate supportive care, follow-up and tests.
• Patients with known hypersensitivity to FE 203799, or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions to any drugs.
• Patients with an active infection or with a fever ≥38.5oC within 3 days of the first scheduled day of dosing.
• Patients who had an autologous stem cell transplant within 24 months.
• Patients who had an available cryopreserved autologous graft with a CD34+ cell count of \< 2 x 106/kg.
• Patients undergoing AHSCT for conditions other than lymphoma.
• Presence of a malignancy other than the one for which the transplant is being performed (except for baso-cellular skin carcinoma).
• Patients who are receiving investigational therapies or who have been treated with investigational therapies or investigational devices within 30 days prior to the first scheduled day of dosing with FE 203799.
• Patients with cardiovascular congestive heart failure, unstable angina pectoris, cardiac arrhythmias requiring a pacemaker; myocardial infarction within the past six months; stroke within the past 6 months; or uncontrolled hypertension.
• Patients with mean QTcF values of \>450 msec (in males) or \>470 msec (in females) following ECGs conducted in triplicate 5 minutes apart from each other; patients who are known to have congenital prolonged QT syndromes, including patients who are already on medication known to cause prolonged QT intervals on ECG.
• Presence of out-of-range cardiac interval (PR \< 110 msec, PR \> 220 msec, QRS \< 60 msec, QRS \>119 msec) on the screening ECG or other clinically significant ECG abnormalities.
• Patients with history or presence of GI tract cancer, polyps, ulcerative colitis, Crohn's disease, coeliac disease, tropical sprue, etc.
• Presence of active pancreatic disease.
• Presence of active liver disease (i.e. cirrhosis; bilirubin \> ULN; transaminases \> 1.5 x ULN; alkaline phosphatase \> 2.5 x ULN).

Sponsors & Collaborators

• GlyPharma Therapeutics: lead
• VectivBio AG: collaborator

MeSH Terms

Conditions

Lymphoma; Hodgkin Disease; Mucositis

Interventions

apraglutide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Mouth Diseases; Stomatognathic Diseases

Study Officials

• Tomasz Masior

  VectivBio AG

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: SUPPORTIVE CARE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Placebo-control, ascending dose

Study Record Dates

• First Submitted: November 13, 2017
• First Posted: January 31, 2018
• Study Start: September 1, 2018
• Primary Completion: March 31, 2019
• Study Completion: March 31, 2019
• Last Updated: October 24, 2024

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share