This study has been transitioned to CTIS with ID 2024-512890-28-00 check the CTIS register for the current data. The purpose of this study is to assess the efficacy and safety of ianalumab (VAY736) compared to placebo in addition to second-line…
ID
Source
Brief title
Condition
- Platelet disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Time from randomization to treatment failure defined as the time from
randomization until :
- platelet counts below 30 G/L), later than 8 weeks from randomization,
- start of a new ITP treatment due to any reasons, need for a
- rescue treatment (e.g.corticosteroids, IVIG, or platelet transfusion) later
than 8 weeks from randomization,
- ineligibility to taper or inability to discontinue eltrombopag
- death (whatever the cause)
Time to treatment failure (TTF) will be assessed in each treatment group and
each of the two doses of ianalumab (ianalumab+eltrombopag) will be compared to
the control arm (placebo+eltrombopag).
Secondary outcome
• Complete Response (CR) rate at each time point defined as the proportion of
participants with any platelet count of at least 100 G/L in the
absence of rescue treatment or new ITP treatment
• Response rate at each timepoint defined as the proportion of participants
with any platelet count of at least 50 G/L in the absence of rescue
treatment or new ITP treatment
• Complete Response (CR) rate at each time point defined as the proportion of
participants with any platelet count of at least 100 G/L in the
absence of rescue treatment or new ITP treatment
• Response rate at each time point defined as the proportion of participants
with any platelet count of at least 50 G/L in the absence of rescue
treatment or new ITP treatment
• Best response rate over all timepoints defined as proportion of participants
with a best response of either response or complete response
• Time from randomization to date of first response and time from randomization
to date of first complete response
• Duration of response is defined as the time from achievement of response to
treatment failure
• Duration of complete response(CR) is defined as the time from achievement of
CR to loss of CR
• Probability to be in treatment failure-free (as defined for the primary
efficacy endpoint) at the end of the planned treatment period (end of Week
24)
• Frequency of adverse events and other safety parameters
• Number of severe infections and proportion of participants with severe
infection
• Proportion of participants with bleeding events according to WHO Bleeding
Scale
• Number and proportion of participants receiving rescue treatment
• Change from baseline on total score of the PROMIS SF v1.0 Fatigue 13a
• Change from baseline in ITP PAQ domain scores of Symptoms, Fatigue, Bother,
Activity
• B-cell levels:
- Change from baseline in the frequency (% within the CD45) and
absolute number of CD19+ B-cell counts
- Time to first occurrence of B-cell recovery, defined as >=80% of
baseline or >=50 cells/µL
• Immunoglobulins:
- Change from baseline in immunoglobulin levels
• Ianalumab concentration in serum and PK parameters after the first and last
dose in a subset of participants
• Incidence and titer of anti-ianalumab antibodies in serum (Anti-Drug-Antibody
(ADA) assay) over time
Background summary
Immune Thrombocytopenia (ITP) is a rare, acquired, immune-mediated disease of
adults and children, characterized by transient or persistent decrease of the
platelet count and, depending upon the degree of thrombocytopenia, increased
risk of bleeding. Primary ITP is defined by the absence of other causes or
disorders that may be associated with thrombocytopenia. Secondary forms include
thrombocytopenias that are due to an underlying disease or to drug exposure
Currently approved and available second-line therapies, such as TPO-RAs, are
able to induce a high rate of response, but they are required to be taken
life-long in order to maintain response.
Chronic treatment with additional lines of therapy may further lead to a more
treatment-refractory, difficult-to-treat disease over time, with very low
platelet counts and increased bleeding risk. It is therefore important that the
most effective treatment is established in the early phase of the disease
(first- or second-line).
Consequently, there remains a significant unmet medical need for new,
potentially disease-modifying therapies in the early stages of ITP that are
well tolerated, require shorter course of treatment that is more convenient for
patients, and induce a high rate of response, which is also maintained after
end of the treatment period.
Study objective
This study has been transitioned to CTIS with ID 2024-512890-28-00 check the CTIS register for the current data.
The purpose of this study is to assess the efficacy and safety of ianalumab
(VAY736) compared to placebo in addition to second-line eltrombopag in adults
with primary immune thrombocytopenia
Study design
This is a multicenter, randomized, double-blinded phase 3 study to assess the
efficacy and safety of two different doses of ianalumab (3 and 9 milligram
(mg)/ kilogram (kg)) compared to placebo in adults with primary ITP (platelets
count < 30 G/L) treated with eltrombopag. After completion of screening period,
participants will enter 16-week randomized combination treatment period in one
of the following three arms: Arm A (eltrombopag once daily + 4 cycles of
ianalumab 3 mg/kg intravenously every 4 weeks), Arm B (eltrombopag once daily +
4 cycles of ianalumab 9 mg/kg intravenously every 4 weeks), Arm C (eltrombopag
once daily + 4 cycles of placebo intravenously every 4 weeks). After the
16-week of combination treatment period of eltrombopag + ianalumab/placebo,
eltrombopag will be tapered until discontinuation for a maximum of 8-weeks.
After the treatment period, all participants will enter a follow-up period to
be monitored for efficacy and safety or safety only, depending on how the
participant responded to the study treatment. Efficacy and safety follow-up
will last until loss of TFR or up to 39 months after randomization of the last
participant, whichever occurs first. Safety follow-up will be performed for at
least 20 weeks (Short Term Safety Follow-Up (STSFU)) and up to 2 years after
the last ianalumab/placebo dose (Long Term Safety Follow-Up (LTSFU)).
Intervention
VAY736 (ianalumab) 3 or 9 mg/kg or placebo in addition to eltrombopag
Study burden and risks
Potential burden and risk to participants includes potential side effects of
study medications and inconveniences of procedures:
Possible side effects of eltrombopag (as described in the package leaflet).
Possible side effects of ianalumab
- Upper respiratory tract infections
- Urinary tract infections
- Drip-related reactions
- Infection of the lower respiratory tract
- Herpes infection of the mouth or inflammation of the conjunctiva of the eye
Blood tests can hurt or cause bleeding. Sometimes a person gets dizzy or faints.
ECG patches can cause skin irritation
Also the time investment of tests and investigations:
Physical examination, blood pressure/pulse measurement. eye examination, blood
test, urinalysis, EKG, completing questionnaires and pregnancy test (if
participant can become pregnant)
See protocol and investigator's brochure for additional information on risks
and benefits.
Haaksbergweg 16
Amsterdam 1101 BX
NL
Haaksbergweg 16
Amsterdam 1101 BX
NL
Listed location countries
Age
Inclusion criteria
1. Male or female patients aged 18 years and older on the day of signing the
informed consent. 2. A signed informed consent must be obtained prior to
participation in the study. 3. A diagnosis of primary ITP, with insufficient
response to, or relapse after a first-line corticosteroid therapy. 4. Patients
with Platelet count below 30 G/L for whom eltrombopag is clinically indicated
as per physician*s discretion and with no contraindication to receive
eltrombopag.
Exclusion criteria
1. ITP patients who received second-line ITP treatments (other than
corticosteroid therapy ± IVIG) including splenectomy. However, patients exposed
to thrombopoietin receptor agonists (TPO-RAs) for a limited time (max one week)
before screening are eligible.
2. Patients with key lab abnormalities and patients with Evans syndrome or any
other cytopenia (patients with low grade anemia related to bleeding or iron
deficiency are eligible).
3. Patients with history of clinically significant hematological disorders, or
with marked altered hematologic parameters
4. Patients with current or history of life-threatening bleeding
5. Patient that are Human Immunodeficiency Virus (HIV), Hepatitis C Virus
(HCV), HBsAg positive are excluded. Participants who are hepatitis core
antibody (HBcAb) positive are also executed unless all of the following
criteria are met: HbsAg and HBV DNA are negative, participant has no pre
existing liver fibrosis, hepatitis B monitoring is implemented , including
regular ALT testing and HBV DNA testing. Antiviral prophylaxis with entecavir
must be initiated prior randomization and must continue during the treatment
period and at least 12 months after the last dose of ianalumab /placebo. If
antiviral prophylaxis with entecavir is not allowed as per local guidelines or
local clinical practice, clinically contraindicated or not accepted by the
patient, participants who are HBsAg negative and HBcAb positive are not
eligible.
6. Patients with known active or uncontrolled infection requiring systemic
treatment during screening period.
7. Patients with hepatic impairment
8. Patients with concurrent coagulation disorders and/or receiving
anti-platelet or anticoagulant medication with an exemption of low dose of
acetylsalicylic acid (<=150 mg daily).
9. Female patients who are pregnant or nursing
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-512890-28-00 |
| EudraCT | EUCTR2022-001627-32-NL |
| ClinicalTrials.gov | NCT05653219 |
| CCMO | NL82422.056.22 |