Use of Oxandrolone to Promote Growth in Infants With Hypoplastic Left Heart Syndrome: A Phase I/II Pilot Study
Use of Oxandrolone to Promote Growth in Infants With HLHS
Sponsors
Source
New England Research Institutes
Oversight Info
Has Dmc
Yes
Is Fda Regulated Drug
Yes
Is Fda Regulated Device
No
Brief Summary
The primary aim of this study is to determine if clinically relevant doses of buccally
administered oxandrolone are safe and tolerable in neonates with hypoplastic left heart
syndrome (HLHS) or other single right ventricular anomalies who have undergone a Norwood
procedure. The secondary aim is to evaluate the efficacy of buccally administered oxandrolone
in improving objective indices of growth and nutrition in neonates who have undergone a
Norwood procedure.
Detailed Description
The proposed investigation is a Phase I/II randomized trial of 28 days of open label
oxandrolone vs. no oxandrolone treatment to assess optimal dosing, safety/tolerability, and
preliminary efficacy of this therapy in post-Norwood neonates with HLHS. Control subjects
will receive standard therapy with no placebo and no oxandrolone.
This trial is aimed at cumulative dose finding as well as a preliminary assessment of
safety/tolerability and efficacy. The design and dosing are based upon preliminary phase I
data obtained as part of an ongoing protocol under IND #107706. This trial will initially
include two arms (control and 0.1 mg/kg oxandrolone BID). This initial oxandrolone dose was
chosen based on the preliminary data collected in the background studies conducted for this
trial. There were no adverse safety outcomes in the small cohort of subjects receiving 0.1
mg/kg of oxandrolone BID.
In Cohort 1, subjects will be block randomized into each arm in a 1:4 (control to
oxandrolone) ratio. An interim analysis of the safety data will be performed after the first
25 subjects in Cohort 1 have been randomized and have completed 28 days of oxandrolone
therapy or observation (control group). If there are no significant differences in the
primary safely/tolerability outcome and safety reviews are favorable for BID dosing, then
Cohort 2 (25 subjects) will be randomized in a 1:4 ratio to the control and TID dosing arms.
A similar interim analysis will be performed after Cohort 2 subjects have been randomized and
completed 28 days of oxandrolone therapy. Enrollment will again be suspended during this
second interim analysis to determine if dose escalation is warranted. Cohort 3A, utilizing
0.15 mg/kg oxandrolone TID would be possible if both Cohorts 1 (0.1 mg/kg BID) and 2 (0.1
mg/kg/dose TID) do not demonstrate any differences in the primary safety/tolerability outcome
compared to controls and safety reviews are favorable (Figure 4). If the safety threshold is
crossed, then a dose of 0.1 mg/kg/dose BID will be used for cohort 3B. An interim safety
analysis will be performed after 25 subjects have been enrolled in this highest dosing arm.
If at any point a risk-benefit balance in any cohort is found to be negative, then further
enrollment will proceed at the lower dosing arm determined to be safe/tolerable based on the
primary outcome and safety review with a 1:4 control:oxandrolone ratio and a total subject
number of 100.
If the second interim safety analysis leads to the conclusion that the lower dose (0.1 mg/kg
oxandrolone BID) appears to be safe and well tolerated, while the higher dose (0.1 mg/kg
oxandrolone TID) is not, then the enrollment will proceed in the 0.1 mg/kg BID arm with a 1:4
ratio. If the lowest dose of oxandrolone (0.1 mg/kg BID) is found to be unsafe, then the
trial will be stopped. The benefit of this approach lies in the ability to allocate patients
to the highest safe dose arm thus enriching the relevance of safety/tolerability and efficacy
information obtained. A higher-dose treatment arm will be used if the data reveal the initial
treatment arm is not different from control with regards to the primary outcome. If no
safety/tolerability effect is demonstrated, the trial will, by design, function as a
randomized, controlled trial with dose-escalation. It is anticipated that the study will
conclude with approximately 80 oxandrolone patients (in up to three dosing arms) and 20
control patients.
Overall Status
Not yet recruiting
Start Date
2019-11-01
Completion Date
2022-09-01
Primary Completion Date
2022-03-01
Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Measure |
Time Frame |
|
Biochemical evidence of hepatic dysfunction |
From date of treatment initiation until the pre-SCPC evaluation or end of study participation, whichever comes first, up to 9 months |
|
Virilization |
From date of treatment initiation until the completion of study drug therapy or end of study participation, whichever comes first, up to 28 days |
|
SAE probably or definitely related to oxandrolone therapy |
From date of treatment initiation until the pre-SCPC evaluation or end of study participation, whichever comes first, up to 9 months |
Secondary Outcome
Measure |
Time Frame |
|
Length-for-age z-score |
At the time of completion of study drug therapy, up to 28 days after date of treatment initiation |
|
Weight-for-age z-score |
At the time of completion of study drug therapy, up to 28 days after date of treatment initiation |
|
Change in Weight-for-age z-score |
From date of pre-Norwood procedure until completion of study drug therapy, up to 28 days |
|
Change in length-for-age z-score |
From date of pre-Norwood procedure until completion of study drug therapy, up to 28 days |
|
Prealbumin levels |
During the duration of therapy |
|
Lean Body Mass |
At the completion of study drug therapy, assessed up to 35 days after initiation of study drug therapy |
|
Decreased right ventricular systolic function |
At the time of Norwood discharge and at the time of pre-SCPC evaluation, up to 9 months |
Enrollment
100
Conditions
Intervention
Intervention Type
Drug
Intervention Name
Description
Oxandrolone 2.5mg tabs will be suspended in multi-chain triglyceride (MCT) oil and administered buccally.
Arm Group Label
Oxandrolone Cohort 1
Other Name
Anavar
Oxandrin
Eligibility
Criteria
Inclusion Criteria:
1. HLHS and other single ventricle of right ventricular morphology
2. Age and Norwood procedure ≤14 days of age
3. Informed consent from parent/guardian
Exclusion Criteria:
1. Small for gestational age (birth weight <10th percentile for gestational age)
2. Prematurity, defined as gestational age <37 weeks
3. Intrauterine growth retardation (birth weight ≤2.5 kg and gestational age ≥38 weeks)
4. Chromosomal abnormality, recognizable genetic syndrome or congenital anomalies of more
than minor severity associated with growth failure
5. Moderate or greater right ventricular systolic dysfunction and/or moderate or greater
tricuspid regurgitation prior to the Norwood procedure
6. Extracorporeal membrane oxygenation support (ECMO) prior to or within 24 hours of
Norwood procedure
7. Pre-Norwood interventions (fetal intervention, balloon atrial septostomy for an intact
or restrictive atrial septum)
8. Pre-Norwood pulmonary venous obstruction
9. Pre-Norwood procedure necrotizing enterocolitis and/or other gastrointestinal
syndromes
10. Known contraindication to oxandrolone
11. Planned or current warfarin therapy at screening (warfarin effects are increased by
anabolic drugs)
12. Significant hepatic dysfunction (elevation of serum transaminase levels greater than
two times the upper limit of normal local laboratory standard at screening)
13. Hypercalcemia (>1.5 times upper normal range for lab)
14. Nephrotic syndrome
15. Unwillingness or inability to return to surgical center for follow-up evaluation
16. Participation in another clinical study that may impact growth
Gender
All
Minimum Age
N/A
Maximum Age
14 Days
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
|
Phillip T Burch, MD |
Principal Investigator |
Cook Children's Medical Center |
|
Richard V Williams, MD |
Principal Investigator |
University of Utah |
Overall Contact
Verification Date
2018-11-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Sponsor
Has Expanded Access
No
Condition Browse
Number Of Arms
2
Intervention Browse
Mesh Term
Oxandrolone
Arm Group
Arm Group Label
Oxandrolone Cohort 1
Arm Group Type
Experimental
Description
Participants randomized to Oxandrolone Cohort 1 will receive 0.1mg/kg of oxandrolone suspended in a multi-chain triglyceride (MCT) oil buccally twice per day.
Arm Group Label
Standard of Care
Arm Group Type
No Intervention
Description
Participants randomized to standard of care will receive the standard therapies provided at the institution at which they are being treated. Control subjects will receive standard therapy with no placebo and no oxandrolone.
Firstreceived Results Date
N/A
Overall Contact Backup
Patient Data
Sharing Ipd
No
Firstreceived Results Disposition Date
N/A
Study Design Info
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Supportive Care
Masking
None (Open Label)
Study First Submitted
April 4, 2019
Study First Submitted Qc
September 12, 2019
Study First Posted
September 16, 2019
Last Update Submitted
September 12, 2019
Last Update Submitted Qc
September 12, 2019
Last Update Posted
September 16, 2019
ClinicalTrials.gov processed this data on December 09, 2019
Conditions
Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov,
conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.