| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Relapsed or refractory AML, AML secondary to myeloproliferative neoplasms (MPN), and JAK2 mutationpositive AML. |
| Relapsed or refractory AML, AML secondary to myeloproliferative neoplasms (MPN), and JAK2 mutationpositive AML. |
|
| E.1.1.1 | Medical condition in easily understood language |
| Patients with Acute Myeloid Leukemia (AML). |
| Patients with Acute Myeloid Leukemia (AML). |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10000886 |
| E.1.2 | Term | Acute myeloid leukemia |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Primary Objective for Part A: To determine KRT-232 recommended phase
2 dose (RP2D). Primary Objective for Part B: To determine the rates of
complete remission (CR) and complete remission with partial
hematological improvement (CRh). |
Obiettivo primario della Parte A: determinare la dose raccomandata della fase 2 (RP2D) di KRT-232
Obiettivo primario della Parte B: determinare i tassi di remissione completa (CR) e remissione completa con miglioramento ematologico parziale (CRh) |
|
| E.2.2 | Secondary objectives of the trial |
(Secondary Obj. Part A/Part B): Part A Only-to determine rates complete
remission (CR), complete remission w/partial hematological
improvement (CRh). To determine Overall Response Rate.To determine
rate of return chronic phase MPN w/peripheral blast count <10%. To
determine prop. subjects transition to allogeneic stem cell transplant. To
determine efficacy JAK2 mutational status. To determine Duration of
Response. To determine Progression-Free Survival. To determine Overall
Survival. To determine efficacy KRT-232 in CR and CRh subjects
w/treatment-naïve blast-phase AML vs. subjects w/ blast-phase AML
which has been previously treated. Safety and tolerability of KRT-232. To
monitor PK of KRT-232 and metabolites.
(Exploratory Obj.): To evaluate the combination relative to select
PK,PD,disease markers,markers of resistance in subjects who respond
and in those who relapse on therapy.To determine UGT1A1*28 genotype,
compare KRT-232 and KRT-232 glucuronide plasma conc. across
genotypes. |
(Secondary Obj. Part A/Part B): Part A Only-to determine rates complete
remission (CR), complete remission w/partial hematological
improvement (CRh). To determine Overall Response Rate.To determine
rate of return chronic phase MPN w/peripheral blast count <10%. To
determine prop. subjects transition to allogeneic stem cell transplant. To
determine efficacy JAK2 mutational status. To determine Duration of
Response. To determine Progression-Free Survival. To determine Overall
Survival. To determine efficacy KRT-232 in CR and CRh subjects
w/treatment-naïve blast-phase AML vs. subjects w/ blast-phase AML
which has been previously treated. Safety and tolerability of KRT-232. To
monitor PK of KRT-232 and metabolites.
(Exploratory Obj.): To evaluate the combination relative to select
PK,PD,disease markers,markers of resistance in subjects who respond
and in those who relapse on therapy.To determine UGT1A1*28 genotype,
compare KRT-232 and KRT-232 glucuronide plasma conc. across
genotypes. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Adults = 18 years of age
2. ECOG performance status of 0 to 2
3. Part A: Patients with relapsed or refractory AML, or treatment naïve
AML secondary to MPN. Diagnosis of AML must be according to World
Health Organization (WHO) criteria with at least 20% blasts in the
marrow and/or extramedullary leukemia. Patients with known fms-like
tyrosine kinase 3 (FLT3) mutations must have been treated with a FLT3 inhibitor (unless contraindicated) if FLT3 inhibitors are approved and
available in the country in which the patient is to be treated. Patients
who are known isocitrate dehydrogenase 1 (IDH1) or IDH2 mutation
positive must have been previously treated with an IDH1 or IDH2
inhibitor, respectively, (unless contraindicated) if IDH1 or IDH2
inhibitors are approved and available in the country in which the patient
is to be treated.
4. Part B: Patients with AML secondary to MPN,as defined by =20%
blasts in the bone marrow or peripheral blood,or JAK2 mutation positive
AML.
5. Part B: Patients may have been treated with 0 to 2 prior lines of
therapy for their AML. Patients with known FLT3 mutations must have
been treated with a FLT3 inhibitor (unless contraindicated) if FLT3
inhibitors are approved and available in the country in which the patient
is to be treated. Patients with relapsed or refractory disease who are
known IDH1 or IDH2 mutation positive, must have been previously
treated with an IDH1 or IDH2 inhibitor (respectively) (unless
contraindicated) if IDH1 or IDH2 inhibitors are approved and available in
the country in which the patient is be treated.
6. Adequate hepatic and renal function within 28 days prior to the first
dose of KRT-232.
Hepatic: Direct bilirubin =2.0 times the upper limit of normal (ULN),
unless Gilbert's
Syndrome; aspartate transaminase/serum glutamic oxaloacetic
transaminase (AST/SGOT)
and alanine transaminase/serum glutamic pyruvic transaminase
(ALT/SGPT) =2.5 ULN. Renal: Estimated creatinine clearance =30
mL/min by Cockcroft Gault.
7. Females of childbearing potential and males who have partners of
childbearing potential must agree to use an effective contraception
method during the study. In addition, males must continue to use
contraception for 3 months and 1 week after the last dose of study drug
and females must continue to use contraception for 1 month and 1 week
after the last dose of study drug. Effective birth control includes (a)
combined, estrogen and progestogen containing, hormonal
contraception (oral, intravaginal, transdermal); (b) progestogen-only
hormonal contraception (oral, injectable, implantable); (c) intrauterine
device; (d) intrauterine hormone-releasing system; (e) bilateral tubal
occlusion; (f) vasectomized partner; and (g) sexual abstinence when this
is in line with the preferred and usual lifestyle of the subject. Periodic
abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation
methods) and withdrawal are not acceptable methods of contraception. |
1. Adults = 18 years of age
2. ECOG performance status of 0 to 2
3. Part A: Patients with relapsed or refractory AML, or treatment naïve
AML secondary to MPN. Diagnosis of AML must be according to World
Health Organization (WHO) criteria with at least 20% blasts in the
marrow and/or extramedullary leukemia. Patients with known fms-like
tyrosine kinase 3 (FLT3) mutations must have been treated with a FLT3 inhibitor (unless contraindicated) if FLT3 inhibitors are approved and
available in the country in which the patient is to be treated. Patients
who are known isocitrate dehydrogenase 1 (IDH1) or IDH2 mutation
positive must have been previously treated with an IDH1 or IDH2
inhibitor, respectively, (unless contraindicated) if IDH1 or IDH2
inhibitors are approved and available in the country in which the patient
is to be treated.
4. Part B: Patients with AML secondary to MPN,as defined by =20%
blasts in the bone marrow or peripheral blood,or JAK2 mutation positive
AML.
5. Part B: Patients may have been treated with 0 to 2 prior lines of
therapy for their AML. Patients with known FLT3 mutations must have
been treated with a FLT3 inhibitor (unless contraindicated) if FLT3
inhibitors are approved and available in the country in which the patient
is to be treated. Patients with relapsed or refractory disease who are
known IDH1 or IDH2 mutation positive, must have been previously
treated with an IDH1 or IDH2 inhibitor (respectively) (unless
contraindicated) if IDH1 or IDH2 inhibitors are approved and available in
the country in which the patient is be treated.
6. Adequate hepatic and renal function within 28 days prior to the first
dose of KRT-232.
Hepatic: Direct bilirubin =2.0 times the upper limit of normal (ULN),
unless Gilbert's
Syndrome; aspartate transaminase/serum glutamic oxaloacetic
transaminase (AST/SGOT)
and alanine transaminase/serum glutamic pyruvic transaminase
(ALT/SGPT) =2.5 ULN. Renal: Estimated creatinine clearance =30
mL/min by Cockcroft Gault.
7. Females of childbearing potential and males who have partners of
childbearing potential must agree to use an effective contraception
method during the study. In addition, males must continue to use
contraception for 3 months and 1 week after the last dose of study drug
and females must continue to use contraception for 1 month and 1 week
after the last dose of study drug. Effective birth control includes (a)
combined, estrogen and progestogen containing, hormonal
contraception (oral, intravaginal, transdermal); (b) progestogen-only
hormonal contraception (oral, injectable, implantable); (c) intrauterine
device; (d) intrauterine hormone-releasing system; (e) bilateral tubal
occlusion; (f) vasectomized partner; and (g) sexual abstinence when this
is in line with the preferred and usual lifestyle of the subject. Periodic
abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation
methods) and withdrawal are not acceptable methods of contraception. |
|
| E.4 | Principal exclusion criteria |
1. Patients who are TP53 mutation positive
2. Participants who are either refractory to or relapsed within 90 days of
receiving a regimen containing a cumulative dose of = 18 g/m2 of
cytarabine are not eligible to be treated with cytarabine on this study
but may be treated with decitabine on this study
3. Patients who have received prior treatment with decitabine are not
eligible to receive decitabine in this study but may be treated with
cytarabine on this study
4. Patients who have received an allogeneic HSCT within 90 days of
enrollment or who have active graft-versus-host disease requiring active
therapy and have a donor
5. Patients who are eligible for an allogeneic HSCT per the opinion of the
investigator and have a donor. Patients who are HSCT-eligible in the
opinion of the investigator, but who refuse a transplant, are eligible for
the study.
6. Patients who have received immunosuppressive therapy for graftversus-
host disease within 1 month prior to enrollment into this study
7. Patients with acute promyelocytic leukemia
8. Patients with a history of bleeding diathesis
9. Patients with known active CNS involvement with AML
10. Concurrent anticancer treatment, such as chemotherapy,
cytoreductive therapy, immune therapy, or cytokine therapy within 14
days of the first dose of KRT-232, provided they have recovered from
treatment toxicity. Patients on hydroxyurea may continue therapy with
hydroxyurea until the day before starting therapy on this study. Patients
on FLT3 inhibitors may continue therapy with FLT3 inhibitors until the
day before starting therapy on this study. Subjects on JAK inhibitors
should be tapered off JAK inhibitor therapy prior to starting treatment on
this study per the JAK inhibitor tapering guidelines outlined in Section
7.4.1 of this protocol.
11. Patients previously treated with MDM2 antagonist therapies
12. Patients who have had major surgery within 28 days prior to the first
treatment with KRT-232
13. Women who are pregnant or breastfeeding
14. Uncontrolled intercurrent illness including, but not limited to, known
active hepatitis A, B, or C; known history of human immunodeficiency
virus (HIV)-positive; clinically significant cardiac disease (New York
Heart Association Class III or IV); symptomatic congestive heart failure;
unstable angina pectoris; unstable ventricular arrhythmia; or psychiatric
illness/social situations that would limit compliance with study
requirements
15. Subjects with uncontrolled bacterial, fungal, parasitic, or viral
infection. Subjects with acute bacterial infections requiring antibiotic use
should not enroll until the infection is stable in the judgement of the
treating physician; these patients may be on antibiotics at enrollment.
16. Other malignancy within the last 3 years, other than curatively
treated basal cell or squamous cell skin cancer, carcinoma in situ of the
cervix, organ-confined or treated nonmetastatic prostate cancer with
normal prostate-specific antigen, in situ breast carcinoma after complete
surgical resection, or superficial transitional cell bladder carcinoma
17. Grade 2 or higher QTc prolongation (>480 milliseconds per NCICTCAE
criteria, version 5.0) |
1. Patients who are TP53 mutation positive
2. Participants who are either refractory to or relapsed within 90 days of
receiving a regimen containing a cumulative dose of = 18 g/m2 of
cytarabine are not eligible to be treated with cytarabine on this study
but may be treated with decitabine on this study
3. Patients who have received prior treatment with decitabine are not
eligible to receive decitabine in this study but may be treated with
cytarabine on this study
4. Patients who have received an allogeneic HSCT within 90 days of
enrollment or who have active graft-versus-host disease requiring active
therapy and have a donor
5. Patients who are eligible for an allogeneic HSCT per the opinion of the
investigator and have a donor. Patients who are HSCT-eligible in the
opinion of the investigator, but who refuse a transplant, are eligible for
the study.
6. Patients who have received immunosuppressive therapy for graftversus-
host disease within 1 month prior to enrollment into this study
7. Patients with acute promyelocytic leukemia
8. Patients with a history of bleeding diathesis
9. Patients with known active CNS involvement with AML
10. Concurrent anticancer treatment, such as chemotherapy,
cytoreductive therapy, immune therapy, or cytokine therapy within 14
days of the first dose of KRT-232, provided they have recovered from
treatment toxicity. Patients on hydroxyurea may continue therapy with
hydroxyurea until the day before starting therapy on this study. Patients
on FLT3 inhibitors may continue therapy with FLT3 inhibitors until the
day before starting therapy on this study. Subjects on JAK inhibitors
should be tapered off JAK inhibitor therapy prior to starting treatment on
this study per the JAK inhibitor tapering guidelines outlined in Section
7.4.1 of this protocol.
11. Patients previously treated with MDM2 antagonist therapies
12. Patients who have had major surgery within 28 days prior to the first
treatment with KRT-232
13. Women who are pregnant or breastfeeding
14. Uncontrolled intercurrent illness including, but not limited to, known
active hepatitis A, B, or C; known history of human immunodeficiency
virus (HIV)-positive; clinically significant cardiac disease (New York
Heart Association Class III or IV); symptomatic congestive heart failure;
unstable angina pectoris; unstable ventricular arrhythmia; or psychiatric
illness/social situations that would limit compliance with study
requirements
15. Subjects with uncontrolled bacterial, fungal, parasitic, or viral
infection. Subjects with acute bacterial infections requiring antibiotic use
should not enroll until the infection is stable in the judgement of the
treating physician; these patients may be on antibiotics at enrollment.
16. Other malignancy within the last 3 years, other than curatively
treated basal cell or squamous cell skin cancer, carcinoma in situ of the
cervix, organ-confined or treated nonmetastatic prostate cancer with
normal prostate-specific antigen, in situ breast carcinoma after complete
surgical resection, or superficial transitional cell bladder carcinoma
17. Grade 2 or higher QTc prolongation (>480 milliseconds per NCICTCAE
criteria, version 5.0) |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
• Part A: Dose-limiting toxicities (DLTs) of KRT-232 in combination with
cytarabine and DLTs of KRT-232 in combination with decitabine at each
dose level.
• Part B: Responses will be assessed per the 2017 European
LeukemiaNet (ELN) response criteria (Appendix 3). Blasts in the bone
marrow will be defined morphologically by exam of the aspirate or
biopsy (if aspirate not available). Blasts in the blood will be defined
immunophenotypically. CRh is defined as <5% of blasts by morphology
in the bone marrow, no evidence of disease (blasts in blood by flow
cytometry) and at least partial recovery of peripheral blood counts
(platelets >50,000/µL and ANC >500/ µL). |
• Part A: Dose-limiting toxicities (DLTs) of KRT-232 in combination with
cytarabine and DLTs of KRT-232 in combination with decitabine at each
dose level.
• Part B: Responses will be assessed per the 2017 European
LeukemiaNet (ELN) response criteria (Appendix 3). Blasts in the bone
marrow will be defined morphologically by exam of the aspirate or
biopsy (if aspirate not available). Blasts in the blood will be defined
immunophenotypically. CRh is defined as <5% of blasts by morphology
in the bone marrow, no evidence of disease (blasts in blood by flow
cytometry) and at least partial recovery of peripheral blood counts
(platelets >50,000/µL and ANC >500/ µL). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
• DLTs are defined as the following study treatment-related adverse
events (TEAEs) occurring
in the 1st cycle (i.e., in the first 28 days) of Part A.
• 2017 ELN response criteria will be used to assess the Bone marrow
aspirate and biopsy results. Bone marrow aspirate and biopsy will be
obtained at: Screening; Within 4 days of the end of Cycles 1, 3, 6, 9, 12,15, and 18; Thereafter, within 4 days of the end of every 6th cycle while
on study treatment; At suspected disease progression. |
• DLTs are defined as the following study treatment-related adverse
events (TEAEs) occurring
in the 1st cycle (i.e., in the first 28 days) of Part A.
• 2017 ELN response criteria will be used to assess the Bone marrow
aspirate and biopsy results. Bone marrow aspirate and biopsy will be
obtained at: Screening; Within 4 days of the end of Cycles 1, 3, 6, 9, 12,15, and 18; Thereafter, within 4 days of the end of every 6th cycle while
on study treatment; At suspected disease progression. |
|
| E.5.2 | Secondary end point(s) |
• Responses (in Part A and B) will be assessed per the 2017 European
LeukemiaNet (ELN) response criteria (Appendix 3) to determine rates of
complete remission (CR) and complete remission with partial
hematological improvement (CRh) (in Part A); to determine the overall
response rate (ORR); rate of return to chronic phase MPN with
peripheral blast count <10%; duration of response (DoR); progressionfree
survival (PFS); overall survival (OS); efficacy of KRT-232 in CR and
CRh subjects who have treatment-naïve blastphase AML vs. subjects
who have blast-phase AML which has been previously treated. Blasts in
the bone marrow will be defined morphologically by exam of the aspirate
or biopsy (if aspirate not available). Blasts in the blood will be defined
immunophenotypically. CRh is defined as <5% of blasts by morphology
in the bone marrow, no evidence of disease (blasts in blood by flow
cytometry) and at least partial recovery of peripheral blood counts
(platelets >50,000/µL and ANC >500/ µL).
• Number of subjects who transition to allogeneic transplant
• Efficacy analyses will be evaluated in subjects who are JAK2 V617F
positive and negative
• Safety endpoints will include the following measurements or
assessments: physical examinations; laboratory tests; KRT-232 dose
reductions, interruptions and discontinuations; adverse events (AEs),
serious AEs (SAEs), electrocardiograms (ECGs), vital signs
• KRT-232 and acyl glucuronide metabolite (M1) PK will be monitored on
Cycles 1 and 2 with sparse sampling.
(Exploratory endpoints):
• Biomarkers including but not limited to:
-TP53 mutation status, JAK2 mutations, and other AML-, sAML-, and
MPN-related genes
-TP53-related gene expression: p21 (CDKN1A), MDM2, MDMX (MDM4),
PUMA (BBC3)
-Flow cytometry of peripheral blood blasts
-MIC-1 protein in serum
• UGT1A1*28 genotype (*1*1, *1*28, *28*28) |
• Responses (in Part A and B) will be assessed per the 2017 European
LeukemiaNet (ELN) response criteria (Appendix 3) to determine rates of
complete remission (CR) and complete remission with partial
hematological improvement (CRh) (in Part A); to determine the overall
response rate (ORR); rate of return to chronic phase MPN with
peripheral blast count <10%; duration of response (DoR); progressionfree
survival (PFS); overall survival (OS); efficacy of KRT-232 in CR and
CRh subjects who have treatment-naïve blastphase AML vs. subjects
who have blast-phase AML which has been previously treated. Blasts in
the bone marrow will be defined morphologically by exam of the aspirate
or biopsy (if aspirate not available). Blasts in the blood will be defined
immunophenotypically. CRh is defined as <5% of blasts by morphology
in the bone marrow, no evidence of disease (blasts in blood by flow
cytometry) and at least partial recovery of peripheral blood counts
(platelets >50,000/µL and ANC >500/ µL).
• Number of subjects who transition to allogeneic transplant
• Efficacy analyses will be evaluated in subjects who are JAK2 V617F
positive and negative
• Safety endpoints will include the following measurements or
assessments: physical examinations; laboratory tests; KRT-232 dose
reductions, interruptions and discontinuations; adverse events (AEs),
serious AEs (SAEs), electrocardiograms (ECGs), vital signs
• KRT-232 and acyl glucuronide metabolite (M1) PK will be monitored on
Cycles 1 and 2 with sparse sampling.
(Exploratory endpoints):
• Biomarkers including but not limited to:
-TP53 mutation status, JAK2 mutations, and other AML-, sAML-, and
MPN-related genes
-TP53-related gene expression: p21 (CDKN1A), MDM2, MDMX (MDM4),
PUMA (BBC3)
-Flow cytometry of peripheral blood blasts
-MIC-1 protein in serum
• UGT1A1*28 genotype (*1*1, *1*28, *28*28) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
• 2017 ELN response criteria will be used to assess the Bone marrow
aspirate and biopsy results. Bone marrow aspirate and biopsy will be
obtained at: Screening; Within 4 days of the end of Cycles 1, 3, 6, 9, 12,
15, and 18; Thereafter, within 4 days of the end of every 6th cycle while
on study treatment; At suspected disease progression
• Safety endpoints will be assessed at various timepoints as per the
Schedule of Assessments (Appendix 1 of the Protocol).
• PK: At Cycle 1, Cycle 2, Day 1: Pre-dose and a single point taken
anytime from 0.5 to 6 hours post-dose. At Cycle 1 Day 8: 24 hours
(window ±1 hour) after the Day 7 dose
(Exploratory endpoints):
• Biomarkers and UGT1A1*28 genotype: blood sample collected and
stored at the time points indicated in Table 4. |
• 2017 ELN response criteria will be used to assess the Bone marrow
aspirate and biopsy results. Bone marrow aspirate and biopsy will be
obtained at: Screening; Within 4 days of the end of Cycles 1, 3, 6, 9, 12,
15, and 18; Thereafter, within 4 days of the end of every 6th cycle while
on study treatment; At suspected disease progression
• Safety endpoints will be assessed at various timepoints as per the
Schedule of Assessments (Appendix 1 of the Protocol).
• PK: At Cycle 1, Cycle 2, Day 1: Pre-dose and a single point taken
anytime from 0.5 to 6 hours post-dose. At Cycle 1 Day 8: 24 hours
(window ±1 hour) after the Day 7 dose
(Exploratory endpoints):
• Biomarkers and UGT1A1*28 genotype: blood sample collected and
stored at the time points indicated in Table 4. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description |
| This is a Phase 1b/2 study with a dose-escalation phase (Part A) and an expansion phase (Part B). |
| This is a Phase 1b/2 study with a dose-escalation phase (Part A) and an expansion phase (Part B). |
|
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| KRT-232 combined with Low-Dose Cytarabine (LDAC) or Decitabine in AML Patients. |
| KRT-232 combined with Low-Dose Cytarabine (LDAC) or Decitabine in AML Patients. |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 50 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Austria |
| Belgium |
| France |
| Germany |
| Hungary |
| Israel |
| Italy |
| Korea, Republic of |
| Poland |
| Spain |
| United Kingdom |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The study will be considered complete 2 years after the last subject is
enrolled, at which time subjects who remain on study treatment will be
evaluated for eligibility to enroll in a rollover study. |
The study will be considered complete 2 years after the last subject is
enrolled, at which time subjects who remain on study treatment will be
evaluated for eligibility to enroll in a rollover study. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 6 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 6 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
