Use of Oxandrolone to Promote Growth in Infants With HLHS
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|ClinicalTrials.gov Identifier: NCT04090697|
Recruitment Status : Not yet recruiting
First Posted : September 16, 2019
Last Update Posted : September 16, 2019
|Condition or disease||Intervention/treatment||Phase|
|Hypoplastic Left Heart Congenital Heart Disease||Drug: Oxandrolone||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||100 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Supportive Care|
|Official Title:||Use of Oxandrolone to Promote Growth in Infants With Hypoplastic Left Heart Syndrome: A Phase I/II Pilot Study|
|Estimated Study Start Date :||November 1, 2019|
|Estimated Primary Completion Date :||March 2022|
|Estimated Study Completion Date :||September 2022|
Experimental: Oxandrolone Cohort 1
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.
Oxandrolone 2.5mg tabs will be suspended in multi-chain triglyceride (MCT) oil and administered buccally.
No Intervention: Standard of Care
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.
- Biochemical evidence of hepatic dysfunction [ Time Frame: From date of treatment initiation until the pre-SCPC evaluation or end of study participation, whichever comes first, up to 9 months ]Elevation of serum transaminase levels (alanine transaminase (ALT) and/or aspartate transaminase (AST)) >4 times the local laboratory upper limit of normal
- Virilization [ Time Frame: From date of treatment initiation until the completion of study drug therapy or end of study participation, whichever comes first, up to 28 days ]Standardized physical examination will be performed. Because there are no standard normal values for the various measurements included, each subject will serve as their own control
- SAE probably or definitely related to oxandrolone therapy [ Time Frame: From date of treatment initiation until the pre-SCPC evaluation or end of study participation, whichever comes first, up to 9 months ]Any SAE probably or definitely related to oxandrolone therapy in the opinion of the medical monitor
- Length-for-age z-score [ Time Frame: At the time of completion of study drug therapy, up to 28 days after date of treatment initiation ]The efficacy of buccally administered oxandrolone will be evaluated by measuring length-for-age z-score at the end of study drug therapy
- Weight-for-age z-score [ Time Frame: At the time of completion of study drug therapy, up to 28 days after date of treatment initiation ]The efficacy of buccally administered oxandrolone will be evaluated by measuring weight-for-age z-score at the end of study drug therapy
- Change in Weight-for-age z-score [ Time Frame: From date of pre-Norwood procedure until completion of study drug therapy, up to 28 days ]The efficacy of buccally administered oxandrolone will be evaluated by measuring the change in weight-for-age z-score at the end of study drug therapy
- Change in length-for-age z-score [ Time Frame: From date of pre-Norwood procedure until completion of study drug therapy, up to 28 days ]The efficacy of buccally administered oxandrolone will be evaluated by measuring the change in length-for-age z-score at the end of study drug therapy
- Prealbumin levels [ Time Frame: During the duration of therapy ]Serum prealbumin levels will be measured weekly
- Lean Body Mass [ Time Frame: At the completion of study drug therapy, assessed up to 35 days after initiation of study drug therapy ]Lean body mass will be assessed using dual energy x-ray absorptiometry (DXA)
- Decreased right ventricular systolic function [ Time Frame: At the time of Norwood discharge and at the time of pre-SCPC evaluation, up to 9 months ]Evidence of ≥moderate right ventricular systolic dysfunction or tricuspid valve regurgitation based on qualitative assessment of clinical echocardiograms if performed
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04090697
|Contact: Stephanie Lynch, MPHfirstname.lastname@example.org|
|Contact: Allison Crosby-Thompsonemail@example.com|
|Principal Investigator:||Phillip T Burch, MD||Cook Children's Medical Center|
|Principal Investigator:||Richard V Williams, MD||University of Utah|