This study is an open-label, non-randomized extension to study CCDZ173X2201. It aims to provide treatment with CDZ173 to patients withAPDS/PASLI who participated in study CCDZ173X2201 or who were treated previously with PI3Kδ inhibitors…
ID
Source
Brief title
Condition
- Immunodeficiency syndromes
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To evaluate the long term safety and tolerability of CDZ173 in patients with
APDS/PASLI
Secondary outcome
- To evaluate the long term efficacy of CDZ173 to modify healthrelated quality
of life in patients with APDS/PASLI.
- To evaluate the long term efficacy of CDZ173 by means of biomarkers
reflecting the efficacy of CDZ173 to reduce systemic inflammatory components of
the disease in patients with APDS/PASLI.
- To characterize the pharmacokinetics (trough concentrations) of CDZ173 in
patients with APDS/PASLI.
- To evaluate the pharmacokinetics and relative bioavailability of CDZ173
film-coated tablets compared to CDZ173 hard-gelatin capsules
Background summary
This study is designed to evaluate CDZ173, a selective PI3Kδ inhibitor, in
patients with genetically activated PI3Kδ, i.e., patients with APDS/PASLI.
Mutations in the p110δ subunit of the PI3K kinase that recruit the kinase PI3K
to the plasma membrane independent of exogenous activation have been recently
described, hence resulting in a gain-of-function of PI3Kδ. Less than 100
patients have been described to date. This rare disease has been named
*Activated PI3Kδ Syndrome* (APDS) or *p110δ-activating mutation causing
senescent T cells, lymphadenopathy and immunodeficiency* (PASLI). The clinical
phenotype frequently includes massive lymphoproliferation/lymphadenopathy,
recurrent oto-sino-pulmonary infections, increased risk for autoimmune
diseases, inability of successful vaccination, and risk of lymphomas. Current
treatment options are only symptomatic. CDZ173 is a small molecule inhibitor of
p110δ that inhibits the overactive function of the mutated PI3K.
Study objective
This study is an open-label, non-randomized extension to study CCDZ173X2201. It
aims to provide treatment with CDZ173 to patients with
APDS/PASLI who participated in study CCDZ173X2201 or who were treated
previously with PI3Kδ inhibitors other than CDZ173, and to obtain long term
safety, tolerability, efficacy and pharmacokinetic data of CDZ173 in this
patient population.
Study design
Patients can be enrolled in this extension study either directly at the EOT or
EOS visit of the study CCDZ173X2201 or later in time. Patients who were treated
previously with PI3Kδ inhibitors other than CDZ173 can be enrolled if they meet
the eligibility criteria at the screening visit.
The study will be composed of a screening period of max. 7 days, following by a
treatment period of 6 years during which the subject will take the study drug
twice daily. In total there will be 18 control visits in approx. 6 years and 9
months, including a follow-up period of 3 months (following the treatment
period) and a final control visit. All visits will take approx. 2 hours.
In case patients will be enrolled in this extension study directly at the
end-of-study (EOS) visit of the study CCDZ173X2201, this visit counts as the
screening visit for the extension study. In this case, the total number of
visits comes down to 18.
Intervention
Dosing regime of 70 mg twice daily
Study burden and risks
Study period: circa 6 years and 9 months, 18 visits, approx. 2 hours per visit.
In case patients will be enrolled in this extension study directly at the
end-of-study (EOS) visit of the study CCDZ173X2201, this visit counts as the
screening visit for the extension study. In this case, the total number of
visits comes down to 18.
Based on 18 visits:
Physical examination: 17 times; Blood sampling: 18 times (15-65 ml per draw
(total volume < 200 mL)); Urinalysis: 17 times; Vital signs: 18 times; ECG: 17
times; Optional CT- / MRI-/ US-Scan: 1 time; Assessment disease activity: 16
times, saliva assessment: 4 times
Other: Prohibited concomitant medication.
Darwinweg 24
Leiden 2333CR
NL
Darwinweg 24
Leiden 2333CR
NL
Listed location countries
Age
Inclusion criteria
• Patients must have completed the study CCDZ173X2201 EOT/EOS visit, or were
treated previously with PI3Kδ inhibitors other than CDZ173.
• Patients who are deemed by the Investigator to benefit from PI3K inhibitor
therapy.
• Patients or their legal representatives (for patients under the age of 18
years) must be able to communicate well with the Investigator, to understand
and comply with the requirements of the study.
• Documented APDS/PASLI-associated genetic PI3K delta mutation.
Patients with mutations in either PIK3CD or PIK3R1 can be included.
Other protocol-defined inclusion criteria may apply
Exclusion criteria
• Patients who withdrew consent from the study CCDZ173X2201
• Use of other investigational drugs, except CDZ173, within 5 half -lives of
enrollment, or within 30 days, whichever is longer.
• Concurrent use of immunosuppressive medication
• Administration of any live vaccines (including any attenuated live vaccines)
starting from 6 weeks before study entry, during the study and up to 7 days
after the last dose of CDZ173 should be excluded.
• Pregnant or nursing (lactating) women, where pregnancy is defined as the
state of a female after conception and until the termination of gestation.
• 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 2 days after last dose of study medication.
• Uncontrolled chronic or recurrent infectious disease (with the exception of
those that are considered to be characteristic of APDS/PASLI). , For patients
who did not participate in study CCDZ173X2201 but were treated previously with
PI3Kδ inhibitors other than CDZ173, the following additional exclusion criteria
apply:
• Vital signs (systolic and diastolic blood pressure and pulse rate) will be
assessed in the sitting position after the patient has rested for at least
three minutes.
• Patient must have a minimum body weight of 45 kg
• Evidence of tuberculosis infection as defined by a positive QuantiFERON TB
test (or comparable test) at screening. If presence of latent tuberculosis is
established then treatment according to local
country guidelines must have been completed before patients can be considered
for enrollment.
• Use of unstable dosing regimen with i.v. Ig / s.c. Ig in the last 6 months
before screening. Stable maintenance immunoglobulin regimen, as per local
practice, such as regular injections with a consistent dosing interval (e.g.,
monthly) is acceptable
• History of acquired immunodeficiency diseases, or a positive HIV (ELISA and
Western blot) test result at screening.
• A positive Hepatitis B surface antigen or Hepatitis C test (by PCR) result at
screening.
Other protocol-defined exclusion criteria may apply
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 |
|---|---|
| EudraCT | EUCTR2016-000468-41-NL |
| ClinicalTrials.gov | NCT02859727 |
| CCMO | NL58812.078.16 |