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.
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Lymphoma, Non-Hodgkin's, Adult Lymphoma, Hodgkin's, Adult | Drug: FE 203799 | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 0 participants |
Allocation: | Randomized |
Intervention Model: | Sequential Assignment |
Intervention Model Description: | Placebo-control, ascending dose |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Masking Description: | Double-blind |
Primary Purpose: | Supportive Care |
Official Title: | Double-blind, Placebo Controlled, Ascending Dose, Randomized Phase 1B/2A Study, Investigating Safety, Tolerability, PK/PD of FE 203799 in Lymphoma Patients, Undergoing Myeloablative Chemotherapy Before Autologous Transplantation |
Estimated Study Start Date : | September 1, 2018 |
Estimated Primary Completion Date : | March 31, 2019 |
Estimated Study Completion Date : | March 31, 2019 |
Arm | Intervention/treatment |
---|---|
Experimental: Cohort A: 5 mg (FE 203799/Placebo)
Drug: FE 203799 Drug: BEAM Procedure: myeloablative chemotherapy Procedure: autologous stem cell transplantation
|
Drug: FE 203799
GLP-2 analogue, once weekly, subcutaneous administration
|
Experimental: Cohort B: 10 mg (FE 203799/Placebo)
Drug: FE 203799 Drug: BEAM Procedure: myeloablative chemotherapy Procedure: autologous stem cell transplantation
|
Drug: FE 203799
GLP-2 analogue, once weekly, subcutaneous administration
|
Experimental: Cohort C: 25 mg (FE 203799/Placebo)
Drug: FE 203799 Drug: BEAM Procedure: myeloablative chemotherapy Procedure: autologous stem cell transplantation
|
Drug: FE 203799
GLP-2 analogue, once weekly, subcutaneous administration
|
Ages Eligible for Study: | 18 Years to 70 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
A female recipient of childbearing potential must meet the following criteria:
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:
A male patient, with sexual partners who are pregnant, possibly pregnant, or who could become pregnant, agrees to use one of the accepted contraceptive regimens throughout the entire duration of the study and until at least 3 months after the last drug administration. An acceptable method of contraception includes one of the following:
Exclusion Criteria:
Principal Investigator: | Silvy Lachance, MD, PhD | Hôpital Maisonneuve Rosemont, Montréal, QC, Canada | |
Study Director: | Micheline St-John, BSc | JSS Research |
Tracking Information | |||||||
---|---|---|---|---|---|---|---|
First Submitted Date ICMJE | November 13, 2017 | ||||||
First Posted Date ICMJE | January 31, 2018 | ||||||
Last Update Posted Date | October 26, 2020 | ||||||
Estimated Study Start Date ICMJE | September 1, 2018 | ||||||
Estimated Primary Completion Date | March 31, 2019 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
Incidence of treatment-emergent adverse events [ Time Frame: Day -8 to Day 100 ] Adverse events as assessed by CTCAE v4.03
|
||||||
Original Primary Outcome Measures ICMJE | Same as current | ||||||
Change History | |||||||
Current Secondary Outcome Measures ICMJE |
|
||||||
Original Secondary Outcome Measures ICMJE | Same as current | ||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||
Descriptive Information | |||||||
Brief Title ICMJE | Safety, Tolerability, PK/PD of FE 203799 in Adults With Lymphomas | ||||||
Official Title ICMJE | Double-blind, Placebo Controlled, Ascending Dose, Randomized Phase 1B/2A Study, Investigating Safety, Tolerability, PK/PD of FE 203799 in Lymphoma Patients, Undergoing Myeloablative Chemotherapy Before Autologous Transplantation | ||||||
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. |
||||||
Detailed Description |
OUTLINE: Multi-center, double-blind, placebo-controlled, ascending dose, randomized Phase IB/2A study to assess the safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) profile of s.c. FE 203799 in patients diagnosed with Hodgkin's lymphoma (HL) or non-Hodgkin's lymphoma (NHL) undergoing Melphalan-based myeloablative chemotherapy (BEAM) followed by autologous human stem cell transplantation (AHSCT). In addition, the impact of FE 203799 on post-transplantation outcomes will be assessed. These outcomes include assessment of intestinal mucosal injury and inflammation, incidence of infection and bacteremia, development of neutropenic fever, assessment of nutritional parameters, modification of the composition of the gut microbiome, recovery of the hematopoietic system and quality of life. More specifically: - PRIMARY OBJECTIVE: Safety and tolerability of s.c. FE 203799 - SECONDARY OBJECTIVES:
METHODOLOGY - STUDY DESIGN The patient population will consist of adult female and male Hodgkin's or non-Hodgkin's lymphomas patients who are eligible to receive BEAM as conditioning regimen followed by autologous type AHSCT using peripheral blood or bone marrow stem cells. At the time of enrollment, patients must be in complete or partial remission following their most recent anti-neoplastic therapy. Patients are required to have available a cryopreserved autologous stem cell graft with a minimum CD34+ cell dose of 2 x 106 cells/kg. Three ascending dose levels of FE 203799 will be investigated (5 mg, 10 mg and 25 mg), with 16 patients required per dose cohort. Patients in each dose cohort will be randomized to FE 203799 vs. Placebo in a 3:1 ratio (12 patients per dose level receiving FE 203799, and 4 patients receiving Placebo), in a double-blind manner. Randomization will occur during the screening period upon confirmation that the patient has met all inclusion and exclusion criteria. A total of 48 subjects, completing the study, is targeted for enrollment. The study will be conducted in approximately 10 clinical centers. Eligibility will be determined at the Screening Visit following signature of the informed consent form (ICF). The inclusion and exclusion criteria will be used to qualify the patient for study entry. Within each cohort, patients will receive 4 doses of the Study Drug (FE 203799 or Placebo). As such, patients will be required to be dosed with the Study Drug the day prior the initiation of the BEAM regimen and subsequently on a weekly basis for 3 consecutive weeks after initiation of chemotherapy. Assessments performed prior to the first dose, will be considered as Baseline. Serial blood samples for determination of the plasma concentration of FE 20799/Placebo, as well as the plasma levels of citrulline and C-Reactive protein (CRP) will be obtained at pre-specified time points. During the Study, patients will be hospitalized during the duration of the conditioning chemotherapy to approximately 3 or 4 weeks post-transplantation depending on their recovery and physical condition. All patients who received at least one treatment, will be required to return to the hospital for the End of Study Visit (Day 30 ±5 post-transplantation) and for two additional follow-up safety visits on Days 45 (±5) and 100 (±5) post-transplantation. A Data Monitoring Committee (DMC) will convene at pre-determined timepoints, or as needed. The grading of adverse events (AEs) will be based on the Common Terminology Criteria for Adverse Events version 4.03 (CTCAE v4.03) (Grade 1 to 5). |
||||||
Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 1 Phase 2 |
||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Sequential Assignment Intervention Model Description: Placebo-control, ascending dose Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)Masking Description: Double-blind Primary Purpose: Supportive Care
|
||||||
Condition ICMJE |
|
||||||
Intervention ICMJE | Drug: FE 203799
GLP-2 analogue, once weekly, subcutaneous administration
|
||||||
Study Arms ICMJE |
|
||||||
Publications * | Not Provided | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
|||||||
Recruitment Information | |||||||
Recruitment Status ICMJE | Withdrawn | ||||||
Actual Enrollment ICMJE |
0 | ||||||
Original Estimated Enrollment ICMJE |
48 | ||||||
Estimated Study Completion Date ICMJE | March 31, 2019 | ||||||
Estimated Primary Completion Date | March 31, 2019 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
|
||||||
Sex/Gender ICMJE |
|
||||||
Ages ICMJE | 18 Years to 70 Years (Adult, Older Adult) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||
Listed Location Countries ICMJE | Not Provided | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT03417765 | ||||||
Other Study ID Numbers ICMJE | GLY-211-2017 | ||||||
Has Data Monitoring Committee | Yes | ||||||
U.S. FDA-regulated Product |
|
||||||
IPD Sharing Statement ICMJE |
|
||||||
Responsible Party | VectivBio AG ( GlyPharma Therapeutics ) | ||||||
Study Sponsor ICMJE | GlyPharma Therapeutics | ||||||
Collaborators ICMJE | VectivBio AG | ||||||
Investigators ICMJE |
|
||||||
PRS Account | VectivBio AG | ||||||
Verification Date | October 2018 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |