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Protocol Details

An open-label, non-randomized extension study to evaluate the long term safety, tolerability, efficacy and pharmacokinetics of CDZ173 (leniolisib) in patients with APDS/PASLI (Activated phosphoinositide 3-kinase delta syndrome/p110 delta-activating mutation causing senescent T cells, lymphadenopathy and immunodeficiency)

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: No longer recruiting/follow-up only
Gender: Male & Female
Min Age: 12 Years
Max Age: 75 Years

Referral Letter Required


Population Exclusion(s)

Pregnant Women



Recruitment Keyword(s)




Investigational Drug(s)

CDZ173 (Leniolisib)

Investigational Device(s)



Drug: CDZ173 70 mg

Supporting Site

National Institute of Allergy and Infectious Diseases

APDS/PASLI is a rare immune system disease. That system fights diseases and infections in the body. The current treatment for APDS/PASLI only helps with the symptoms. These include recurrent infections. Researchers want to see if the new drug CDZ173, also known as Leniolisib, can also treat the disease itself.


To learn more about how safe, effective, and well tolerated CDZ173 is in treating APDS/PASLI.


People ages 16-75 with APDS/PASLI who completed study NIH-15-I-0135 and would benefit from CDZ173.


Participants will be screened with medical history, physical exam, and a scan. The scan could be ultrasound or magnetic resonance imaging (MRI). For MRI, participants lie in a machine that takes pictures. They will give blood and urine samples. They will have an electrocardiogram (EKG). This measures heart electrical activity using sticky pads on the arms, legs, and chest.

Participants will answer questions about how the disease affects their daily life and activities. They will have more blood tests.

Participants will take capsules of the study drug twice a day.

While taking the study drug, participants will have 6 study visits in a year, then approximately every 6 months for the remainder of your participation, up to 5 years.

During visits, participants will have a physical exam. Blood and urine will be collected. Participants will have another EKG.

Participants may have a scan every 3 months.

Participants will return to the clinic about 4 weeks after finishing the study drug. They will have a physical evaluation. Blood and urine will be collected. They may have a scan.

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Patients eligible for inclusion in this study must fulfill all of the following criteria:

-Written informed consent must be obtained before any assessment is performed.

-Patients must have participated in study CCDZ173X2201 or were treated previously with PI3K delta inhibitors other than CDZ173.

-Patients who are deemed by the Investigator to benefit from PI3K delta 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.


Patients fulfilling any of the following criteria are not eligible for inclusion in this study.

-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.

-History of hypersensitivity to any of the study treatments or excipients or to drugs of similar chemical classes.

-History or current diagnosis of ECG abnormalities indicating significant risk of safety for patients participating in the study such as:

--History of familial long QT syndrome or known family history of Torsades de Pointes.

--Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, and clinically significant second or third degree atrioventricular (AV) block without a pacemaker.

--Resting QTcF (Fridericia preferred, but Bazett acceptable) > 450 msec in male patients of the age group 16 - 75 years, > 460 msec in female patients of the age group 16 - 75 years and > 440 msec in patients of the age group 12 - 15 years, if the measurement is confirmed with an additional ECG repeated as soon as possible. Concomitant use of agents known to prolong the QT interval unless it can be permanently discontinued for the duration of the study.

-Current use of medication known to be strong inhibitors, or moderate or strong inducers of isoenzyme CYP3A and the treatment cannot be discontinued or switched to a different medication prior to starting study treatment.

-Current use of medications that are metabolized by isoenzyme CYP1A2 and have a narrow therapeutic index (drugs whose exposure-response indicates that increases in their exposure levels by the concomitant use of potent inhibitors may lead to serious safety concerns (e.g. Torsades de Pointes).

-Previous or concurrent use of immunosuppressive medication such as:

--mTOR inhibitor (e.g. sirolimus, rapamycin, everolimus) or a PI3K delta inhibitor (selective or non-selective PI3K inhibitors) within 6 weeks prior to first dosing, however short-term use for up to a total of 5 days is allowed but only up to

1 month prior to enrollment in the study.

-B cell depleters (e.g. rituximab) within 6 months prior to first dosing of study medication; if patients have received prior treatment with a B cell depleter, absolute B lymphocyte counts in the blood must have regained normal values.

--Belimumab or cyclophosphamide within 6 months prior to first dosing of study medication.

--Cyclosporine A, mycophenolate, 6-mercaptopurine, azathioprine or methotrexate within 3 months prior to first dosing of study medication.

--Glucocorticoids above 25 mg prednisone or equivalent per day within 2 weeks prior to first dosing of study medication.

-Other immunosuppressive medication where effects are expected to persist at start of dosing of study medication.

-Donation or loss of 400 mL or more of blood within 8 weeks before Day 1.

-Administration of 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. Highly effective contraception methods include:

--Total abstinence (when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post- ovulation methods) and withdrawal are not acceptable methods of contraception.

--Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or total hysterectomy or tubal ligation at least 6 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 months prior to screening). For female patients on the study, the vasectomized male partner should be the sole partner for that patient.

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 stable on the same pill for a minimum of 3 months before taking study treatment.

Women are considered post-menopausal and not in of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment she is considered not of child bearing potential.

-Patients who were non-compliant or demonstrated a serious protocol deviation in the study CCDZ173X2201.

-History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, regardless of whether there is evidence of local recurrence or metastases.

-Any surgical or medical condition, which may jeopardize the patient in case of participation in the study or which might significantly alter the absorption, distribution, metabolism, or excretion of drugs. Conditions due to APDS/PASLI are permitted. The Investigator should make this determination in consideration of the patient s medical history and/or clinical or laboratory evidence (e.g. assessed at the end of treatment or EOT/EOS visit of the study CCDZ173X2201):

--Uncontrolled hypertension (>= 140/90 mmHg).

--Congestive heart failure (New York Heart Association status of class III or IV).

--Chronic obstructive pulmonary disease (GOLD stage 3-4).

--Inflammatory bowel disease, peptic ulcers, gastrointestinal including rectal bleeding.

--Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection.

--Pancreatic injury or pancreatitis.

--Liver disease or liver injury as indicated by clinically significant abnormal liver function tests. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) greater than 2.5 times upper limit of normal (ULN).

--History of renal injury/renal disease (e.g. renal trauma, glomerulonephritis, or one kidney only) or presence of impaired renal function as indicated by a serum creatinine level exceeding 1.5 mg/dL (133 micro mol/L).

--Evidence of urinary obstruction or difficulty in voiding at screening.

--Uncontrolled diabetes (insulin dependent or non-insulin dependent).

--Uncontrolled chronic or recurrent infectious disease (with the exception of those that are considered to be characteristic of APDS/PASLI)

Note: In the case where a safety laboratory assessment at screening or at the CCDZ173X2201 EOT/EOS visit is outside of the range specified above, the assessment may be repeated. Values should be within specified ranges prior to treatment.

For patients who did not participate in study CCDZ173X2201 but were treated previously with PI3K delta 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. Sitting vital signs should be within the following ranges:

--Systolic blood pressure, 90-139 mm Hg

--Diastolic blood pressure, 50-89 mm Hg

--Pulse rate, 50 - 100 bpm; up to 110 bpm for adolescents

--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.

-Intentionally blank; exclusion criterion removed in this protocol amendment.

-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. No additional exclusions may be applied by the Investigator, in order to ensure that the study population will be representative of all eligible patients.

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Not Provided

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Principal Investigator

Referral Contact

For more information:

V. Koneti Rao, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
BG 10 RM 12C106
(301) 496-6502

Alanvin D. Orpia, R.N.
National Institute of Allergy and Infectious Diseases (NIAID)
National Institutes of Health
Building 10
Room 12C106
10 Center Drive
Bethesda, Maryland 20892
(240) 669-2935

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: TTY Users Dial 7-1-1

Clinical Trials Number:


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