The study is to gather evidence of LFG316 efficacy in treatment of transplant associated microangiopathy (TAM) after hematopoetic precursor cell transplantation.

• Register: EUCTR
• Last refreshed on: 3 July 2017
• Main ID: EUCTR2014-004972-49-DE
• Date of registration: 13/10/2015
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: The study is to gather evidence of LFG316 efficacy in treatment of transplant associated microangiopathy (TAM) after hematopoetic precursor cell transplantation.
• Scientific title: A randomized, open label, controlled, multiple dose study to evaluate the clinical efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics of LFG316 in patients with transplant associated microangiopathy after hematopoietic precursor cell transplantation - CLFG316X2202
• Date of first enrolment: 07/03/2016
• Target sample size: 40
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-004972-49
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Standard of care Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

France, Germany, United Kingdom, United States

Contacts

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma AG

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma AG

Key inclusion & exclusion criteria

Inclusion criteria:
1.Written informed consent/assent before any study-specific screening procedures.
For pediatric patients, consent will be obtained from parent(s) or legal guardian(s) and the
signature of at least 1 parent or guardian will be required. Investigators will also obtain
assent of patients according to local, regional or national guidelines.
2. Patients after allogeneic stem cell transplantation from a related or unrelated, HLAmatched
or mismatched donor with the diagnosis of transplant related microangiopathy.
Patients having received any of the following stem cell sources are eligible: G-CSF Mobilized
peripheral blood stem cells, G-CSF bone marrow, umbilical cord blood.
3. Male and female TAM patients = 2 years old at the time of first dose administration.
Patients < 12 years old can only be included in the study after first IA has shown that it is
safe and well tolerated in patients = 12 years old (Section 3.5).
4. The presence of TAM as per below diagnostic criteria at baseline (or screening if baseline visit is skipped). All the criteria have to be met for the patients included in the study: ? Elevated lactate dehydrogenase (any elevation above normal range)
? Thrombocytopenia with platelet count < 50x10e9/L or more than 50% decrease in
platelet count from the highest value achieved after transplant
? Anemia below lower limit of normal or anemia requiring transfusion support as per
center standard
? Schistocytes on peripheral blood smear (>2 per HPF) OR histologic evidence of
microangiopathy
? Absence of coagulopathy (no uncompensated disseminated intravascular coagulation, DIC) at screening
5. The presence of TAM high risk features at baseline (or screening if baseline visit is
skipped): Patients = 16 years must have a Lansky score of = 70 and patients > 16 must
have Karnofsky score = 70% and/or proteinuria (> 30 mg/dL) measured in two urine spot analyses.
6. Hypertension, defined for adults by SBP = 160 mmHg and/or DBP = 100 mmHg at baseline
(or screening if baseline visit is skipped), and for pediatric patients by blood pressure
greater than the 95th percentile for age, sex, and height (see Table 16-1). Additionally,
patients who were started on antihypertensive medication after HSCT or who have received additional antihypertensive medication after HSCT will be eligible, even if they don’t have elevated blood pressure
7. Able to receive antibiotic prophylaxis against N. meningitides for the
duration of the study.
8. Meningococcal vaccine(s) prior to LFG316 treatment if prior
vaccination cannot be confirmed. The choice of vaccine(s) should take
into account the serotypes prevalent in the geographic areas in which
study patients will be enrolled. In case vaccination is not possible or will
result in an unfavorable risk benefit ratio as judged by the investigator,
vaccination can
be postponed until deemed likely to be effective.
9. Patients <18 years old should receive vaccination for the prevention
of S. pneumoniae and H. influenzae type b prior to LFG316
administration. In case vaccination is not possible or will result in an
unfavorable risk benefit ratio as judged by the investigator, vaccination
can be postponed until deemed likely to be effective.
10. Weight of at least 10kg.
Are the trial subjects under 18? yes
Number of subjects for this age range: 10
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects fo
Exclusion criteria:
1.Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or until the expected PD effect has returned to baseline, whichever is longer; or even longer if required by local regulations.
Concomitant investigational treatment, including treatment in the context of a clinical trial with marketed drugs (off-label) may be acceptable but requires approval by the sponsor on the case by case basis.

2. Known hypersensitivity to any constituent of the study medication.
3. Patients with steroid refractory graft versus host disease (SRGvHD). SRGvHD is defined as progression (=increase in overall grade) after 5 days on =2mg/kg methylprednisolone or equivalent OR no improvement
(no decrease in overall grade) after 10 days on = 2mg/kg methylprednisolone or equivalent. If patients are receiving steroids forGvHD prophylaxis as per center standard, progression after 5 days and no response after 10 days after doubling the steroid dose will be regarded as steroid refractory.

4. Patients with ALT > 10x ULN at screening.
5. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of
gestation, confirmed by a positive hCG laboratory test (at screening or baseline).
6. Women of child-bearing potential, defined as all women
physiologically capable of becoming pregnant, unless they are using
highly effective methods of contraception during dosing and for 45 days
after stopping study medication. Highly effective contraception methods
include:
? Total abstinence (when this is in line with the preferred and usual
lifestyle of the subject. Periodic abstinence (i.e., calendar, ovulation,
symptothermal, postovulation methods) and withdrawal are not
acceptable methods of contraception.
? Female sterilization (have had surgical bilateral oophorectomy (with
or without hysterectomy), total hysterectomy or tubal ligation at least
six weeks before taking study treatment. In case of oophorectomy alone,
only when the reproductive status of the woman has been confirmed by
follow up hormone level assessment.
? Male sterilization (at least 6 m prior to screening). The vasectomized
male partner should be the sole partner for that subject.
? Use of oral, injected or implanted hormonal methods of contraception
or placement of an intrauterine device (IUD) or intrauterine system
(IUS) or other forms of hormonal contraception that have comparable
efficacy (failure rate <1%), for example hormone vaginal ring or
transdermal hormone contraception.
? In case of use of oral contraception women should have been stabile
on the same pill for a minimum of 3 months before taking study
treatment.
7. Sexually active males unwilling to use a condom during intercourse
while taking drug and for 45 days after stopping investigational
medication. A condom is required to be used also by vasectomized men
in order to prevent delivery of the drug via seminal fluid. Male patients
should not father a child in this period.
8. Positive HIV (ELISA and Western blot) test result (checked at
screening). Historical local data will be acceptable if it the test was done
within one month before start of HSCT conditioning and not more than 3
months before study visit 3.
9. A positive Hepatitis B surface antigen or Hepatitis C test result at
screening. Historical local data will be acceptable if it the test was done
within one month before start of H

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Transplant associated microangiopathy (TAM)
MedDRA version: 19.0 Level: LLT Classification code 10050444 Term: Microangiopathy NOS System Organ Class: 100000004866

Intervention(s)

Product Code: LFG316
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: NA
Current Sponsor code: LFG316
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Product Code: LFG316
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: NA
Current Sponsor code: LFG316
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Main Objective: To assess the hematological response rate in
patients with TAM receiving LFG316
compared to standard of care (SoC)

Primary end point(s): Hematological response at 17 weeks where a
patient is considered to be a responder if both
of the following criteria are met:
1. Schistocytes <2/microscopic high power field
(HPF).
2.Transfusion independent (no need for
TAM-related transfusions (platelets and
erythrocytes))

Timepoint(s) of evaluation of this end point: 17 weeks

Secondary Objective: To assess the safety and tolerability of
LFG316 in patients with TAM
To describe the pharmacokinetics of total
LFG316
To evaluate non-relapse mortality in TAM
patients treated with LFG316 as compared to
patients on SoC
To assess complete response rate at 17 weeks
in TAM patients treated with LFG316
compared to patients receiving standard of
care

Secondary Outcome(s)

Secondary end point(s): All safety parameters including: blood
chemistry, hematology, proteinuria, body
height/weight, urinalysis, ECG evaluation,
Adverse events, body temperature, blood
pressure, physical examination, pulse rate,
Lansky/Karnofsky score
Serum total LFG316 concentrations
Non-relapse mortality is any death not
considered to be related to a relapse of
underlying disease
Complete response is defined
as hematological response and no proteinuria
as determined by
? proteinuria <30mg/dL and
? eGFR doubled or not less than 0.85 x
lower limit of normal

Timepoint(s) of evaluation of this end point: 45weeks

Secondary ID(s)

CLFG316X2202

Source(s) of Monetary Support

Novartis Pharma Services AG