Leigh SyndromePhase 2NCT03747328
ABI-009 (Nab-sirolimus) in Patients With Genetically-confirmed Leigh or Leigh-like Syndrome
A Phase 2 study testing ABI-009 in people with Leigh Syndrome, run by Aadi Bioscience, Inc..
Trial summary
A phase 2a, open-label study to evaluate the safety, tolerability, and clinical activity of ABI-009 (nab-sirolimus) in patients with genetically-confirmed Leigh or Leigh-like syndrome Read more about this study
- Who is it for?
- Ages 2 to 17 years
- Conditions the study is for
- Leigh Syndrome
- What is being tested?
- ABI-009
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 30 Apr 2022to 31 Mar 2025
- Phase
- Phase 2
- 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 2 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- A patient will be eligible for inclusion in this study only if all of the following criteria are met at screening:
- Diagnosis of genetically-confirmed Leigh or Leigh-like syndrome, as well as documented clinical evidence (including demonstrated neurologic manifestations) of the syndrome, as confirmed by the investigator.
- Moderate disease severity based on NPMDS score of >15 on Sections I through III, inclusive.
- Male or female patients, ≥2 and ≤17 years of age at the time of enrollment.
- Body weight ≥5 kg (11 lbs) at the time of enrollment.
- Chronic, stable disease, as determined by the investigator, for a minimum of 3 months prior to enrollment. This includes, but is not limited to, patients without hospitalizations or emergency room visits, or fever <101 F, and/or acute illness.
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- Adequate liver function:
- Total bilirubin ≤1.5 x upper limit of normal (ULN) mg/dL
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <3 x ULN.
- Adequate renal function as defined by serum creatinine <ULN for each individual patient's age category.
- Adequate biological parameters:
- Absolute neutrophil count (ANC) ≥1.5 × 109/L
- Platelet count ≥100,000/mm3 (100 × 109/L)
- Hemoglobin ≥9 g/dL.
- Adequate immunoglobulin levels (IgG, IgA, IgM) that, in the opinion of the investigator, will not place the patient at increased risk for infection.
- Serum amylase and lipase <2 x ULN.
- Non-fasting serum triglyceride ≤300 mg/dL and non-fasting serum cholesterol ≤300 mg/dL, collected within 1 to 4 hours following a meal.
- If receiving prescribed medication to prevent or treat seizures, the patient must be receiving stable doses for at least 1 month prior to screening visit.
- Sexually active males with female partners of child-bearing potential or non-pregnant and non-breast feeding female of child-bearing potential:
- Females of child-bearing potential must agree to use effective contraception without interruption from 28 days prior to starting IP throughout 3 months after last dose of IP and have a negative urine pregnancy test (β-hCG) result at screening and agree to ongoing pregnancy testing during the course of the study, and after the end of study treatment. A second form of birth control is required even if the patient has had a tubal ligation.
- Male patients must practice abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study and throughout 3 months after the last dose of IP. A second form of birth control is required even if the patient has undergone a successful vasectomy.
- The patient (when applicable) or the patient's parent(s) or legal guardian(s) understand(s) and voluntarily signed the informed consent document(s) prior to any study-related assessments/procedures being conducted.
- The patient or parent(s)/guardian(s) is/are willing and able to comply with the study visit schedule and other protocol requirements, in the opinion of the investigator.
Who cannot join
- A patient will not be eligible for inclusion in this study if any of the following criteria apply at screening:
- Renal insufficiency that, in the opinion of the investigator, requires or may require dialysis during the treatment and follow-up periods.
- Cardiac ejection fraction/shortening fraction ≤50 % and/or severe end-organ hypo-perfusion syndrome (secondary to cardiac failure) resulting in lactic acidosis.
- Patients with implanted cardiac assist/medical devices (including pacemakers), unless device was implanted prophylactically, and the patient is clinically asymptomatic.
- In the opinion of the investigator, clinically significant ECG and/or ECHO findings at the time of screening.
- Myocardial infarction within 6 months prior to enrollment.
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- Symptomatic congestive heart failure (CHF), unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension, or unstable coronary artery disease.
- Prior exposure to ABI-009, sirolimus, everolimus, or any other known rapamycin derivative, or previous treatment with any known mTOR inhibitor.
- Patients who are breast feeding or have a confirmed or suspected pregnancy.
- Treatment with any investigational drug (ie, a drug for which there is no approved indication), including an investigational drug for mitochondrial disease within 1 month prior to receiving the first dose of study drug (or within 3 months for a trial with an investigational biologic).
- Disease-related surgical intervention within 1 month prior to the first dose of study drug.
- Use of supplements that are contraindicated in the opinion of investigator, including super-fortified foods and/or beverages that include coenzyme Q10, Vitamin C, Vitamin E, and/or idebenone, etc, unless receiving stable doses for a minimum of 30 days prior to enrollment. Changes to mitochondrial dietary supplements or their doses for 30 days prior to enrollment.
- Known hypersensitivity to ABI-009 (nab-sirolimus; ie, sirolimus and albumin), to any of its excipients, or to any known rapamycin derivative or known mTOR inhibitor.
- Patients with confirmed or suspected increased intracranial pressure, pseudotumor cerebri (PTC)/idiopathic intracranial hypertension, and/or papilledema.
- Any uncontrolled serious illness or psychiatric condition, medical condition, or other medical history, including abnormal laboratory test results which, in the opinion of the investigator, would be likely to interfere with the patient's participation in the study, or with the interpretation of the results of the study.
- Currently active malignancy (other than adequately treated non-melanoma skin cancers [ie, squamous cell and/or basal cell carcinoma], carcinoma in situ of the cervix, or other adequately treated carcinoma in situ) and/or ongoing treatment for malignancy are ineligible. Patients are not considered to have a currently active malignancy if they have completed therapy and are free of disease for ≥1 year.
- Recent infection requiring systemic anti-infective treatment that was completed ≤14 days prior to enrollment.
- Confirmed or suspected immunodeficiency disorder(s), including but not limited to, common variable immune deficiency (CVID), complement deficiency, etc.
- Uncontrolled diabetes mellitus, as defined by HbA1c >8%, despite adequate therapy.
- History of interstitial lung disease and/or pneumonitis, or pulmonary hypertension.
- Use of strong inhibitors and/or inducers of cytochrome P450 (CYP) 3A4 (CYP3A4) and/or p-glycoprotein (p-GP) within the 14 days prior to receiving the first dose of study drug. Additionally, use of any known CYP3A4 substrates with a narrow therapeutic window (eg, fentanyl, alfentanil, astemizole, cisapride, dihydroergotamine, pimozide, quinidine, terfenadine) within the 14 days prior to receiving the first dose of study drug. [All medications will be reviewed by the (Institutional) Investigational Pharmacy to ensure that strong inducers and/or inhibitors of CYP3A4 and/or p-GP, or CYP3A4 substrates with a narrow therapeutic window, have not been administered within 14 days prior to the first dose of study drug; patients receiving anticonvulsant medications within the 14 days prior to receiving the first dose of study drug may be enrolled at the discretion of the investigator].
- Known human immunodeficiency virus (HIV), active hepatitis B or hepatitis C infection(s).
About this study
Official title: A Phase 2a, Open-label Study to Evaluate the Safety, Tolerability, and Clinical Activity of ABI-009 (Nab-sirolimus) in Patients With Genetically-confirmed Leigh or Leigh-like Syndrome
A phase 2a, open-label study to evaluate the safety, tolerability, and clinical activity of ABI-009 (nab-sirolimus) in patients with genetically-confirmed Leigh or Leigh-like syndrome
- Conditions
- Leigh Syndrome
- Being tested
- ABI-009
- Medical subject headings
- Leigh Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ABI-009Drug
nanoparticle albumin bound sirolimus
| Study group | Role | What they receive |
|---|---|---|
| ABI-009 | Experimental | nanoparticle albumin bound sirolimus (ABI-009). Dose levels 1, 2.5, 5 and 10 mg/m2 given weekly for 8 cycles of ABI-009 (each cycle is weekly dosing for 2 weeks followed by a week of rest (qw2/3)) Receives: Drug: ABI-009 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of treatment emergent adverse events in pediatric patients with genetically-confirmed Leigh or Leigh-like syndrome administered ABI-009 intravenously (IV)
Adverse events will be measured according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0.
Measured: Up to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2018
- Study start30 Apr 2022 (estimated)
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Mar 2025 (estimated)
Why it stopped: IND withdrawn
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leigh 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aadi Bioscience, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03747328
- Sponsor's protocol ID
- LS007
- Status last verified
- Jan 2022
- First submitted
- 13 Nov 2018
- Last updated
- 1 Feb 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2a, Open-label Study to Evaluate the Safety, Tolerability, and Clinical Activity of ABI-009 (Nab-sirolimus) in Patients With Genetically-confirmed Leigh or Leigh-like Syndrome
- ClinicalTrials.gov ID
- NCT03747328
- Acronym / sponsor ID
- LS007
- Conditions
- Leigh Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: IND withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Aadi Bioscience, Inc.Industry (pharma, biotech, devices)
- Study start
- 30 Apr 2022 (estimated)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Mar 2025 (estimated)
- First posted
- 20 Nov 2018 (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.
A phase 2a, open-label study to evaluate the safety, tolerability, and clinical activity of ABI-009 (nab-sirolimus) in patients with genetically-confirmed Leigh or Leigh-like syndrome
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ABI-009 | Experimental | Drug: ABI-009nanoparticle albumin bound sirolimus (ABI-009). Dose levels 1, 2.5, 5 and 10 mg/m2 given weekly for 8 cycles of ABI-009 (each cycle is weekly dosing for 2 weeks followed by a week of rest (qw2/3)) |
Who may qualify
- Ages
- 2 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (23 listed)
- A patient will be eligible for inclusion in this study only if all of the following criteria are met at screening:
- Diagnosis of genetically-confirmed Leigh or Leigh-like syndrome, as well as documented clinical evidence (including demonstrated neurologic manifestations) of the syndrome, as confirmed by the investigator.
- Moderate disease severity based on NPMDS score of >15 on Sections I through III, inclusive.
- Male or female patients, ≥2 and ≤17 years of age at the time of enrollment.
- Body weight ≥5 kg (11 lbs) at the time of enrollment.
Key exclusion criteria (22 listed)
- A patient will not be eligible for inclusion in this study if any of the following criteria apply at screening:
- Renal insufficiency that, in the opinion of the investigator, requires or may require dialysis during the treatment and follow-up periods.
- Cardiac ejection fraction/shortening fraction ≤50 % and/or severe end-organ hypo-perfusion syndrome (secondary to cardiac failure) resulting in lactic acidosis.
- Patients with implanted cardiac assist/medical devices (including pacemakers), unless device was implanted prophylactically, and the patient is clinically asymptomatic.
- In the opinion of the investigator, clinically significant ECG and/or ECHO findings at the time of screening.
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 |
|---|---|---|
| ABI-009nanoparticle albumin bound sirolimus | Drug | ABI-009 |
Primary outcome
Incidence of treatment emergent adverse events in pediatric patients with genetically-confirmed Leigh or Leigh-like syndrome administered ABI-009 intravenously (IV)
Time frame: Up to 24 weeks
Adverse events will be measured according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2022.
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ABI-009 in people with Leigh Syndrome, run by Aadi Bioscience, Inc..
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 23 inclusion and 22 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: withdrawn, as of the sponsor's last update on 1 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of treatment emergent adverse events in pediatric patients with genetically-confirmed Leigh or Leigh-like syndrome administered ABI-009 intravenously (IV) (time frame: Up to 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Feb 2022.