PI3K and P110delta Hyperactivation SyndromePhase 2/3NCT06293716

CVL237 Tablets for APDS/PASLI

A Phase 2/3 study testing CVL237 tablets in people with PI3K and P110delta Hyperactivation Syndrome, run by Convalife (Shanghai) Co., Ltd. at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record

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Trial summary

This study was designed to evaluate the efficacy and safety of CVL237 tablets in patients with APDS/PASLI (activated phosphoinositol 3-kinase δ syndrome /p110 delta-activated mutation leading to senescent T cells, lymphadenopathy, and immune deficiency). Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: PI3K and P110delta Hyperactivation Syndrome
What is being tested?: CVL237 tablets
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 35 participants
Where: 1 siteChina
Study dates: 30 Mar 2024to 30 Mar 2026
Phase: Phase 2/3
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male and female patients aged 18-75 years (including boundary values);
Patients with a clinical phenotype consistent with APDS, including a history of recurrent ear, sinus, or lung infections (more frequently than expected in immunoactive individuals), and patients known to have type 1 APDS-related gene PI3K mutations (e.g., E1021K, N334K, E525K, and C416R) or type 2 APDS-related mutations;
In Parts I and II, the patient must have lymph node and/or extranodal lymphocyte proliferation, as well as clinical findings and manifestations consistent with APDS/PASLI, such as a history of recurrent ear - sinus - lung infections and/or organ dysfunction (e.g., lung, liver). In addition, in Part II, patients must have at least one measurable lymph node lesion on a CT or MRI scan.
During screening, vital signs (systolic blood pressure, diastolic blood pressure, and pulse rate) were assessed by sitting position after at least 3 minutes of rest. Seated vital signs should be within the following range:
Systolic blood pressure, 90-139 mm Hg
Diastolic blood pressure, 50-89 mm Hg

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pulse rate, 50-100 bpm; Up to 110 bpm in teenagers
Expected survival ≥3 months;
Pregnant or lactating women or fertile women with a negative pregnancy test at baseline; Men and women with 6) fertility must consent to the use of medically approved contraceptive methods during the study period and within 6 months after the last dosing;
Did not participate in any clinical trials within 1 month before joining the study;
Able to comply with the test protocol (as determined by the investigator);
Volunteer to participate in this clinical trial, understand the study procedure and be able to sign the informed consent in person.

Who cannot join

Previous or concurrent use of immunosuppressive drugs, such as:
Use of mTOR inhibitors (e.g., sirolimus, rapamycin, Everolimus) or PI3kδ inhibitors (selective or non-selective PI3K inhibitors) within 5 half-lives prior to initial medication, but allow short-term use, for a total of no more than 5 days, but only within 1 month prior to enrollment in the study.
Use B cell depleting agents (e.g. Rituximab) within 5 half-lives prior to initial administration; If the patient has previously been treated with B cell depleting agents, the absolute B lymphocyte count in the blood must return to normal.
had taken Belimumab or cyclophosphamide within 5 half-lives before first taking the study drug.
Use of cyclosporin A, nystatin, 6-mercaptopurine, azathioprine, or methotrexate within 5 half-lives prior to first administration of the study drug.
Use more than 25 mg of prednisone or an equivalent dose of glucocorticoids daily for 2 weeks prior to the first dose.

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Other immunosuppressive drugs whose effects are expected to remain at the start of the study.
Being treated with known OATP1B1 and OATP1B3 substrate drugs, CYP3A4/5 substrate drugs, intermediate-acting and potent CYP3A4/5 inhibitors, CYP3A4/5 potent inducers, if treatment cannot be terminated or switched to another drug before initiating investigational therapy;
Drugs currently used that are metabolized by the isoenzyme CYP1A2 and have a narrow therapeutic index (exposure responses indicate that drugs that accompany increasing their exposure levels with the use of powerful inhibitors may cause serious safety concerns (e.g., tip torsion ventricular tachycardia))
Current history of liver disease or chronic disease, unless liver enlargement is determined by their clinicianto be secondary to APDS, or known liver or biliary tract abnormalities (other than Gilbert syndrome or asymptomatic gallstones)
The investigator determined that the patient had clinically significant abnormalities in laboratory results (blood routine, blood biochemical, or urine routine)
Patients with liver disease or liver injury, clinically significant abnormal liver function tests (alanine aminotransferase and aspartate aminotransferase > 2.5 times the upper limit of normal), a history of kidney injury/kidney disease (e.g., kidney trauma, glomerulonephritis, or having only one kidney), or impaired kidney function, The serum creatinine level was >1.5 mg/dL (133 μmol/L). LVEF < 50%, Fridericia corrected QT Interval (QTcF) ≥450 ms for men and 470 ms for women;
If a subject's clinical abnormality or laboratory parameters are not specifically listed in the inclusion or exclusion criteria and are outside the reference range of the studied population, they may be included in the study only if the investigator agrees and records that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedure.
The history of regular alcohol consumption within 6 months of the study was defined as an average weekly intake of > 14 units. One unit is equivalent to 8 grams of alcohol: half a pint (~240 ml) of beer, 1 glass (125 ml) of wine or 1 glass (25 ml) of spirits.
Screen positive for substance abuse. Testing for drugs used for legitimate medical purposes (e.g. benzodiazepines, opioid analgesics) does not necessarily exclude study participation and will be at the discretion of the principal investigator.
A history of sensitivity to any investigational drug or its components (including lactose) or to a history of drug or other allergies (including milk protein allergies) that the investigator deemed unsuitable for participation in the study.
Positive hepatitis B surface antigen (HBsAg) and hepatitis C antibody test results at the time of screening or within 3 months before first receiving the study drug. Patients infected with hepatitis B virus (HBV) or hepatitis C virus (HCV) (defined as Hepatitis B Surface antigen (HbsAg) and/or Hepatitis B core antibody (HbcAb) positive and HBV DNA > 500 IU/mL or > 2500 copies/mL; Positive anti-HCV antibody and HCV-RNA quantification > upper limit of normal test unit).
Have uncontrolled pulmonary fibrosis, acute lung disease, interstitial pulmonary inflammation;
People with active viral, bacterial, fungal or other infections requiring systematic treatment (e.g., active tuberculosis), excluding nail bed fungal infections;
Blood donation/blood loss ≥400 ml or more within 8 weeks before the first dose;
History of immunodeficiency (acquired and congenital), history of organ transplantation, allogeneic bone marrow or hematopoietic stem cell transplantation; Active autoimmune disease or history of autoimmune disease (such as autoimmune enteritis and systemic lupus erythematosus);
There are many factors affecting drug administration and absorption, such as inability to swallow, chronic diarrhea, intestinal obstruction (functional).
Participants participated in a clinical trial and received the investigational drug during the following time period prior to administration of the first investigational drug in this study: 30 days, 5 half-lives, or twice the duration of the investigational drug's biological effect, whichever is older.
Present with difficult or important cardiovascular disease: history of heart or aortic surgery; History of myocardial infarction; Had uncontrollable angina in the 6 months prior to the screening period, or is currently taking anti-angina medication; Grade III/IV congestive heart failure; Arrhythmias requiring clinical intervention; Any other cardiovascular disease that the investigator determines is not suitable for participation in the study;
Live vaccines (including any attenuated live vaccines) were administered within 6 weeks before the first administration of the trial drug, during the study period and within 7 days after the last administration of CVL237 tablets.
Patients who cannot stop taking medications that may cause QT prolongation, such as antiarrhythmic drugs, during the study period.
The patient has a history of malignancy (other than lymphoma) or evidence of residual disease from a previously diagnosed malignancy within 3 years prior to initial dosing;
Subjects deemed unsuitable for this trial for other reasons.

Trial locations and contacts

1 site in 1 country.

Yun Ling, ph.D contact

Ying Lv contact

China1 site

Shanghai Public Health Clinical Center
Shanghai, Shanghai Municipality, 201508
Yun Ling, ph.D, 18121157875, yun.ling@vip.126.com
Ying Lv, 18916099680

Other trials in China

About this study

Official title: An Open, Dose-exploration Study, Followed by a Randomized, Double-blind, Placebo-controlled Study, to Evaluate the Efficacy and Safety of CVL237 Tablets in Patients With APDS/PASLI

Read the detailed description

The study was divided into two parts.

Part I is an open, dose-escalation study planned to enroll five patients with APDS/PASLI to determine the safety, tolerability, pharmacokinetics (PK), and in vivo pharmacodynamics (PD pAkt) of CVL237 tablets at two different dose levels. Patients were given CVL237 tablets, 100 mg/ day, QD, for 4 weeks (28 days), and safety assessment was performed on day 28 of the first cycle. If there was no safety risk, patients could take CVL237 tablets, 200 mg/ day, QD, for 4 weeks (28 days).

Part II is a randomized, double-blind, placebo-controlled study of approximately 30 patients with APDS/PASLI. On day 1, patients were randomly assigned to the trial and placebo groups in a 2:1 ratio to take an oral CVL237 tablet or a placebo CVL237 simulant once daily. Efficacy and safety were evaluated on days 29, 57, and 85. The efficacy of CVL237 tablets in reducing lymphadyopathy will be investigated as measured by changes in the sum of diameter products (SPD) of target lesions selected from MRI or CT imaging according to the Lugano 2014 method, as well as changes in the percentage of naive B cells to total B cells, relative to baseline. The CVL237 tablets will also be evaluated for safety, PK.

Conditions: PI3K and P110delta Hyperactivation Syndrome
Being tested: CVL237 tablets, CVL237 placebo tablets
Keywords: PI3K, P110delta, hyperactivation
Medical subject headings: Hereditary Sensory and Autonomic Neuropathies

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CVL237 tabletsDrug
CVL237 tablets, tablets, specification: 0.1g, Storage condition: not more than 30 ℃ storage.Validity: 72 months tentatively.
CVL237 placebo tabletsDrug
CVL237 tablets, tablets, specification: 0g, Storage condition: not more than 30 ℃ storage.Validity: 72 months tentatively.

Study groups in NCT06293716
Study group	Role	What they receive
part1:treatment group	Experimental	Patients were given CVL237 tablets, 100 mg/ day, QD, for 4 weeks (28 days), and safety assessment was performed on day 28 of the first cycle. If there was no safety risk, patients could take CVL237 tablets, 200 mg/ day, QD, for 4 weeks (28 days). Receives: Drug: CVL237 tablets
part2:treatment group	Experimental	Patients were randomly assigned to the trial and placebo groups in a ratio of 2:1 to take an oral CVL237 tablet once daily. Receives: Drug: CVL237 tablets
part 2:placebo group	Placebo comparator	Patients were randomly assigned to the trial and placebo groups in a ratio of 2:1 to take a placebo CVL237 simulant once daily. Receives: Drug: CVL237 placebo tablets

What is being measured

The primary outcome is the main question the study is designed to answer.

part 1 : Incidence of Treatment-Emergent Adverse Events
Abnormal changes in physical examination, vital signs, electrocardiograph laboratory tests, etc. compared to baseline were reported as AE
Measured: Throughout the study for approximately 84 days
part 2:After 84 days of treatment, changes in the sum of diameter product (SPD) of log10 conversion in target lesions and changes in the percentage of naive B cells to total B cells from baseline were observed
SPD:The maximum diameter of the tumor is multiplied by the longest diameter perpendicular to it
Measured: At baseline (day 0) and at the end of treatment (day 84)

Secondary outcomes (4)

Cmax
Peak concentration: The highest blood concentration after administration
Measured: part 1： Up to day 56；part 2： Up to day 85
t1/2
Terminal elimination half-life: The time required for the terminal phase blood concentration to decrease by half
Measured: part 1： Up to day 56；part 2： Up to day 85
AUC
Area under the drug time curve: The area surrounded by the blood concentration curve to the time axis.
Measured: part 1： Up to day 56；part 2： Up to day 85
Tmax
Peak time: The time required to reach peak concentration after administration
Measured: part 1： Up to day 56；part 2： Up to day 85

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Mar 202430 Mar 2026

First posted5 Mar 2024
Study start30 Mar 2024 (estimated)
Primary completion29 Dec 2025 (estimated)
Study completion30 Mar 2026 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for PI3K and P110delta Hyperactivation SyndromeStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2/3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: CVL237 tablets for APDS/PASLI (Activated phosphoinositol 3-kinase delta syndrome /p110 delta-activated Mutation leading to senescent T cells, lymphadenopathy, and immune deficiency)
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 35 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06293716
Sponsor's protocol ID: CVL237-A2001
Status last verified: Feb 2024
First submitted: 18 Feb 2024
Last updated: 5 Mar 2024
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Study at a glance

From the registry record, last updated by the sponsor on 5 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open, Dose-exploration Study, Followed by a Randomized, Double-blind, Placebo-controlled Study, to Evaluate the Efficacy and Safety of CVL237 Tablets in Patients With APDS/PASLI
ClinicalTrials.gov ID: NCT06293716
Acronym / sponsor ID: CVL237-A2001
Conditions: PI3K and P110delta Hyperactivation Syndrome
Keywords: PI3K, P110delta, hyperactivation
Phase: Phase 2/3
Study type: Interventional
Recruitment status: Unknown status
Enrolment: 35 participants (estimated)
Lead sponsor: Convalife (Shanghai) Co., Ltd.Industry (pharma, biotech, devices)
Study start: 30 Mar 2024 (estimated)
Primary completion: 29 Dec 2025 (estimated)
Study completion: 30 Mar 2026 (estimated)
First posted: 5 Mar 2024 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

The study was divided into two parts.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 3
Model description: CVL237 tablets for APDS/PASLI (Activated phosphoinositol 3-kinase delta syndrome /p110 delta-activated Mutation leading to senescent T cells, lymphadenopathy, and immune deficiency)

Arm	Type	Receives
part1:treatment group	Experimental	Drug: CVL237 tabletsPatients were given CVL237 tablets, 100 mg/ day, QD, for 4 weeks (28 days), and safety assessment was performed on day 28 of the first cycle. If there was no safety risk, patients could take CVL237 tablets, 200 mg/ day, QD, for 4 weeks (28 days).
part2:treatment group	Experimental	Drug: CVL237 tabletsPatients were randomly assigned to the trial and placebo groups in a ratio of 2:1 to take an oral CVL237 tablet once daily.
part 2:placebo group	Placebo comparator	Drug: CVL237 placebo tabletsPatients were randomly assigned to the trial and placebo groups in a ratio of 2:1 to take a placebo CVL237 simulant once daily.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

Male and female patients aged 18-75 years (including boundary values);
Patients with a clinical phenotype consistent with APDS, including a history of recurrent ear, sinus, or lung infections (more frequently than expected in immunoactive individuals), and patients known to have type 1 APDS-related gene PI3K mutations (e.g., E1021K, N334K, E525K, and C416R) or type 2 APDS-related mutations;
In Parts I and II, the patient must have lymph node and/or extranodal lymphocyte proliferation, as well as clinical findings and manifestations consistent with APDS/PASLI, such as a history of recurrent ear - sinus - lung infections and/or organ dysfunction (e.g., lung, liver). In addition, in Part II, patients must have at least one measurable lymph node lesion on a CT or MRI scan.
During screening, vital signs (systolic blood pressure, diastolic blood pressure, and pulse rate) were assessed by sitting position after at least 3 minutes of rest. Seated vital signs should be within the following range:
Systolic blood pressure, 90-139 mm Hg

Key exclusion criteria (28 listed)

Previous or concurrent use of immunosuppressive drugs, such as:
Being treated with known OATP1B1 and OATP1B3 substrate drugs, CYP3A4/5 substrate drugs, intermediate-acting and potent CYP3A4/5 inhibitors, CYP3A4/5 potent inducers, if treatment cannot be terminated or switched to another drug before initiating investigational therapy;
Drugs currently used that are metabolized by the isoenzyme CYP1A2 and have a narrow therapeutic index (exposure responses indicate that drugs that accompany increasing their exposure levels with the use of powerful inhibitors may cause serious safety concerns (e.g., tip torsion ventricular tachycardia))
Current history of liver disease or chronic disease, unless liver enlargement is determined by their clinicianto be secondary to APDS, or known liver or biliary tract abnormalities (other than Gilbert syndrome or asymptomatic gallstones)
The investigator determined that the patient had clinically significant abnormalities in laboratory results (blood routine, blood biochemical, or urine routine)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CVL237 tabletsCVL237 tablets, tablets, specification: 0.1g, Storage condition: not more than 30 ℃ storage.Validity: 72 months tentatively.	Drug	part1:treatment group, part2:treatment group
CVL237 placebo tabletsCVL237 tablets, tablets, specification: 0g, Storage condition: not more than 30 ℃ storage.Validity: 72 months tentatively.	Drug	part 2:placebo group

Primary outcome

part 1 : Incidence of Treatment-Emergent Adverse Events
Time frame: Throughout the study for approximately 84 days
Abnormal changes in physical examination, vital signs, electrocardiograph laboratory tests, etc. compared to baseline were reported as AE
part 2:After 84 days of treatment, changes in the sum of diameter product (SPD) of log10 conversion in target lesions and changes in the percentage of naive B cells to total B cells from baseline were observed
Time frame: At baseline (day 0) and at the end of treatment (day 84)
SPD:The maximum diameter of the tumor is multiplied by the longest diameter perpendicular to it

4 secondary outcomes

Cmax
Time frame: part 1： Up to day 56；part 2： Up to day 85
t1/2
Time frame: part 1： Up to day 56；part 2： Up to day 85
AUC
Time frame: part 1： Up to day 56；part 2： Up to day 85
Tmax
Time frame: part 1： Up to day 56；part 2： Up to day 85

Results and safety

Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2024.
Individual participant dataSharing planned: No

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Yun Ling, ph.D contact

Ying Lv contact

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing CVL237 tablets in people with PI3K and P110delta Hyperactivation Syndrome, run by Convalife (Shanghai) Co., Ltd. at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 5 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Yun Ling, ph.D (18121157875, yun.ling@vip.126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

part 1 : Incidence of Treatment-Emergent Adverse Events (time frame: Throughout the study for approximately 84 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06293716.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2024.