Use of Oxandrolone to Promote Growth in Infants With HLHS

Use of Oxandrolone to Promote Growth in Infants With Hypoplastic Left Heart Syndrome: A Phase I/II Pilot Study

Sponsors

Lead Sponsor: HealthCore-NERI

Source HealthCore-NERI
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 Recruiting
Start Date December 20, 2019
Completion Date May 2023
Primary Completion Date November 2022
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
Condition
Intervention

Intervention Type: Drug

Intervention Name: Oxandrolone

Description: Oxandrolone 2.5mg tabs will be suspended in multi-chain triglyceride (MCT) oil and administered buccally.

Arm Group Label: Oxandrolone Cohort 1

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
Overall Contact

Last Name: Stephanie Lynch, MPH

Phone: 617-972-3288

Email: [email protected]

Location
Facility: Status: Contact: Contact Backup:
Children's Hospital of Atlanta | Atlanta, Georgia, 30322, United States Not yet recruiting Timothy Slesnick, MD 404-256-2593 [email protected]
Boston Children's Hospital | Boston, Massachusetts, 02115, United States Recruiting Kimberly Mills, MD 617-355-5427 [email protected]
University of Michigan Health System, Ann Arbor | Ann Arbor, Michigan, 48109, United States Not yet recruiting Mark Russell, MD 734-615-2369 [email protected]
Cincinnati Children's Hospital Medical Center | Cincinnati, Ohio, 45229, United States Recruiting Wonshill Koh, MD 513-636-3865 [email protected]
Children's Hospital of Philadelphia | Philadelphia, Pennsylvania, 19104, United States Not yet recruiting Chitra Ravishankar, MD 267-425-6116 [email protected]
Medical University of South Carolina | Charleston, South Carolina, 29425, United States Not yet recruiting Sinai Zyblewski, MD 843-876-0444 [email protected]
Cook Children's Medical Center | Fort Worth, Texas, 76104, United States Not yet recruiting Phillip Burch, MD 682-885-6400 [email protected]
Texas Children's Hospital | Houston, Texas, 77030, United States Not yet recruiting Rinna (Elena) Ocampo, MD 832-826-5915 [email protected]
Primary Children's Medical Center | Salt Lake City, Utah, 84113, United States Recruiting Richard Williams, MD 801-213-7641 [email protected]
The Hospital for Sick Children | Toronto, Ontario, M5G 1X8, Canada Not yet recruiting Steven Schwartz, MD 416-819-7654 206186 [email protected]
Location Countries

Canada

United States

Verification Date

January 2020

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Oxandrolone Cohort 1

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.

Label: Standard of Care

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.

Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Supportive Care

Masking: None (Open Label)

Source: ClinicalTrials.gov