Growth FailurePhase 1/2NCT00490100

Treatment for Growth Failure in Patients With X-Linked Severe Combined Immunodeficiency: Phase 2 Study of Insulin-Like Growth Factor-1

A Phase 1/2 study testing Increlex in people with Growth Failure and X-linked Severe Combined Immunodeficiency (XSCID), run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

This study will evaluate the safety and effectiveness of insulin-like growth factor-1 (IGF-1) to treat patients with X-linked severe combined immunodeficiency (XSCID). Those who have XSCID lack white blood cells that protect their bodies from invasion by all types of germs. Read more about this study

Who is it for?: Ages 2 to 20 years
Conditions the study is for: Growth Failure, X-linked Severe Combined Immunodeficiency (XSCID), Growth Hormone Resistence
What is being tested?: Increlex
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 6 participants
Where: 1 siteUnited States
Study dates: Jun 2007to Dec 2012
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 20 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

Participants Must:
Have a diagnosis of XSCID
Be between 2 years to 20 years old and have not completed puberty
Consent to permit blood and/or tissue samples for storage
Demonstrate short stature: height below the 3 rd percentile for chronological age
Have a primary care physician at home

Show all 9Show fewer

Demonstrate growth failure, defined as growth velocity (measured as linear growth) that is less than 5% to 10% of that expected for children of the same age group, over the past 12 months
Willingness to remain hospitalized for several days
Provide evidence of serum IGF-1 level performed within the preceding 6 months and the results fall below normal limits for age

Who cannot join

Participants Must NOT:
Have fusion of epiphyseal plates
Demonstrate any history of anaphylactic reaction or hypersensitivity to mecasermin or any component of the drug's formulation
Have any active or suspected neoplasia
Demonstrate signs of intracranial hypertension as evidenced by papilledema upon examination by fundoscopy
Have any condition that, in the investigator's opinion, places the patient at undue risk by participating in the study
Be unwilling to undergo testing or procedures associated with this protocol

Trial locations and contacts

1 site in 1 country.

United States1 site

National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: Treatment for Growth Failure in Patients With X-Linked Severe Combined Immunodeficiency (XSCID): A Phase 2 Study Assessing Safety and Clinical Response to Treatment With Insulin-like Growth Factor-1 (IGF-1)

Patients ages 2 to 20 who have not yet begun puberty, have a diagnosis of XSCID, and are shorter than the 3rd percentile for their age may be eligible for this study. This study will last about 3 years, and patients' visits will be scheduled at 3-month intervals. Patients will have a physical history and exam, X-rays, electrocardiogram, blood tests, and body measurements.

Patients will take estradiol orally for 2 days, to help avoid false results of growth hormone (GH) levels in blood samples. Then provocation testing is done, with two tests back to back. It determines blood levels of GH and the body's response to testing with drugs called arginine and clonidine. Patients are admitted to the pediatric inpatient unit and will have an intravenous (IV) line placed in the arm. Arginine is given by IV over 30 minutes, and blood samples are taken. Right after arginine testing, the clonidine tablet is given. The IGF-1 generation test is then done to see if the body makes IGF-1 as a product in response to injections of GH for 5 consecutive days. This test does not require that patients are inpatients, but after Day 8, patients must be admitted to the pediatric unit to have blood sampling, start Increlex injections, and start close monitoring of blood sugar levels. They will learn how to do a self-injection and follow other advice. They will complete records about the injection site, symptoms, and side effects-keeping records for at least the first 2 days after going home, with each dose change, and as needed. Patients stick their fingertip and place a small drop of blood on a blood sugar monitoring strip. The strip is put into a glucometer-a small hand-held device to measure the blood sugar level. Patients will be instructed to always have a source of sugar available in case blood sugar is too low.

...

Read the detailed description

This is a Phase 2 protocol evaluating the safety and efficacy of standard dose insulin-like growth factor-1 (IGF-1) for the treatment of growth failure in patients diagnosed with X-linked severe combined immunodeficiency (XSCID). This condition is a fatal inherited immunodeficiency caused by defects in the common cytokine receptor gamma chain (gc), a subunit shared by many cytokine receptors. The common gamma subunit signals through the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, a complex intracellular signaling pathway used by many cytokines and growth factors, including growth hormone (GH). Studies have suggested that the gc defect may result in hyporesponsiveness to GH. This is supported by a report of GH hyporesponsiveness in an XSCID child that was successfully ameliorated following immune reconstitution using bone marrow transplantation (BMT). Haplo-identical BMTs for XSCID children often achieve only partial immune reconstitution, and many BMT recipients experience ongoing problems with growth failure, achieving heights well below 2 standard deviations for their chronological age. It is possible that in these partially corrected conditions, administration of IGF-1, a substance the body produces downstream in response to GH, may achieve an improved growth response.

This study proposes to evaluate the safety and efficacy of Increlex(Trademark) (recombinant human IGF-1) for the treatment of patients with XSCID who have growth failure (children with heights less than 3rd percentile for age). Increlex(Trademark) is a Food and Drug Administration-approved drug for treatment of growth hormone non-responsiveness in the general population of children with growth hormone hyporesponsiveness or primary IGF-1 deficiencies. The scientific objectives are to determine safety and to assess the efficacy of using subcutaneous IGF-1 in XSCID patients with growth failure. The long-term goal of this study is to establish improved treatment regimens for growth failure in children with XSCID.

Conditions: Growth Failure, X-linked Severe Combined Immunodeficiency (XSCID), Growth Hormone Resistence
Being tested: Increlex
Keywords: X-Linked Severe Combined Immune Deficiency (XSCID), Growth Hormone, Insulin-Like Growth Factor 1 (IGF)-1, Bone Age, Growth Failure, XSCID, X-Linked Severe Combined Immunodeficiency
Medical subject headings: Failure to Thrive, X-Linked Combined Immunodeficiency Diseases

What participants receive

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

IncrelexDrug

Study groups in NCT00490100
Study group	Role	What they receive
Treatment	Experimental	Treatment Receives: Drug: Increlex

What is being measured

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

Safety of Study Drug
Rates of adverse events related to study drug
Measured: 1 year
Change in Growth Rate on Study Drug
Growth rate on intervention is compared with growth rate before intervention for each participant.
Measured: During intervention, up to 2 years

Timeline

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

Jun 2007Dec 2012

First posted22 Jun 2007 (estimated)
Study startJun 2007
Primary completionDec 2012
Study completionDec 2012

Why it stopped: Insufficient patient participation

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Growth FailureStudies of the same condition, open and under way.
More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
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 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 6 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00490100
Sponsor's protocol ID: 070171
Other IDs: 07-I-0171
Status last verified: Mar 2014
First submitted: 21 Jun 2007
Last updated: 3 Jul 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Buckley RH, Schiff RI, Schiff SE, Markert ML, Williams LW, Harville TO, Roberts JL, Puck JM. Human severe combined immunodeficiency: genetic, phenotypic, and functional diversity in one hundred eight infants. J Pediatr. 1997 Mar;130(3):378-87. doi: 10.1016/s0022-3476(97)70199-9.
PubMed 9063412
Puck JM, Pepper AE, Henthorn PS, Candotti F, Isakov J, Whitwam T, Conley ME, Fischer RE, Rosenblatt HM, Small TN, Buckley RH. Mutation analysis of IL2RG in human X-linked severe combined immunodeficiency. Blood. 1997 Mar 15;89(6):1968-77.
PubMed 9058718
Leonard WJ, Shores EW, Love PE. Role of the common cytokine receptor gamma chain in cytokine signaling and lymphoid development. Immunol Rev. 1995 Dec;148:97-114. doi: 10.1111/j.1600-065x.1995.tb00095.x.
PubMed 8825284

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Trial Investigating the Efficacy and Safety of Weekly Lonapegsomatropin Compared to Daily Somatropin in Children and Adolescents With Short Stature or Growth Failure Due to Growth Hormone Sufficient Disorders
Turner Syndrome, Short Stature Homeobox Gene Mutation
Active, not recruitingPhase 3
A Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non- Small Cell Lung Cancer After Osimertinib Failure
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Phase III Study of HS-10504 Versus Platinum-Based Doublet Chemotherapy in Patients With C797S+ NSCLC
Advanced or Metastatic NSCLC
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
RecruitingPhase 3
Randomized Clinical Trial of Two Different Initial Growth Hormone Doses in Children
Growth Disorders, Growth Failure

All Growth Failure trials

Study at a glance

From the registry record, last updated by the sponsor on 3 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Treatment for Growth Failure in Patients With X-Linked Severe Combined Immunodeficiency (XSCID): A Phase 2 Study Assessing Safety and Clinical Response to Treatment With Insulin-like Growth Factor-1 (IGF-1)
ClinicalTrials.gov ID: NCT00490100
Acronym / sponsor ID: 070171
Conditions: Growth Failure, X-linked Severe Combined Immunodeficiency (XSCID), Growth Hormone Resistence
Keywords: X-Linked Severe Combined Immune Deficiency (XSCID), Growth Hormone, Insulin-Like Growth Factor 1 (IGF)-1, Bone Age, Growth Failure, XSCID, X-Linked Severe Combined Immunodeficiency
Phase: Phase 1/2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Insufficient patient participation
Enrolment: 6 participants (actual)
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
Study start: Jun 2007
Primary completion: Dec 2012 (actual)
Study completion: Dec 2012 (actual)
First posted: 22 Jun 2007 (estimated)
Results: Posted 3 Jul 2015

Clinical summary

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

...

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Treatment	Experimental	Drug: IncrelexTreatment

Who may qualify

Ages: 2 to 20 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (9 listed)

Have a diagnosis of XSCID
Be between 2 years to 20 years old and have not completed puberty
Consent to permit blood and/or tissue samples for storage
Demonstrate short stature: height below the 3 rd percentile for chronological age
Have a primary care physician at home

Key exclusion criteria (7 listed)

Have fusion of epiphyseal plates
Demonstrate any history of anaphylactic reaction or hypersensitivity to mecasermin or any component of the drug's formulation
Have any active or suspected neoplasia
Demonstrate signs of intracranial hypertension as evidenced by papilledema upon examination by fundoscopy
Have any condition that, in the investigator's opinion, places the patient at undue risk by participating in the study

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
Increlex	Drug	Treatment

Primary outcome

Safety of Study Drug
Time frame: 1 year
Rates of adverse events related to study drug
Change in Growth Rate on Study Drug
Time frame: During intervention, up to 2 years
Growth rate on intervention is compared with growth rate before intervention for each participant.

Results and safety

Results posted to the registry on 3 Jul 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Treatment	6	3

Primary outcome: Safety of Study Drug

Time frame: 1 year. Number. Unit: participants

Measure	Treatment n = 3
Value	0

Primary outcome: Change in Growth Rate on Study Drug

Time frame: During intervention, up to 2 years. Median (Full Range). Unit: cm/year

Measure	Treatment n = 3
Value	5.2 (1.2 to 8.6)

Population analysed: Only participants who completed study

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment	0 of 6 (0%)	4 of 6 (66.7%)	Not reported

Limitations and caveats (from the sponsor): Due to limited subject participation, there is insufficient complete data to generate meaningful statistics for the outcome measures. Instead, this data will be reported as a case series.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 9063412Buckley RH, Schiff RI, Schiff SE, Markert ML, Williams LW, Harville TO, Roberts JL, Puck JM. Human severe combined immunodeficiency: genetic, phenotypic, and functional diversity in one hundred eight infants. J Pediatr. 1997 Mar;130(3):378-87. doi: 10.1016/s0022-3476(97)70199-9.
Background: PubMed 9058718Puck JM, Pepper AE, Henthorn PS, Candotti F, Isakov J, Whitwam T, Conley ME, Fischer RE, Rosenblatt HM, Small TN, Buckley RH. Mutation analysis of IL2RG in human X-linked severe combined immunodeficiency. Blood. 1997 Mar 15;89(6):1968-77.
Background: PubMed 8825284Leonard WJ, Shores EW, Love PE. Role of the common cytokine receptor gamma chain in cytokine signaling and lymphoid development. Immunol Rev. 1995 Dec;148:97-114. doi: 10.1111/j.1600-065x.1995.tb00095.x.
NIH Clinical Center Detailed Web PageLink provided by the sponsor.

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Active, not recruitingPhase 3
A Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non- Small Cell Lung Cancer After Osimertinib Failure
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RecruitingPhase 3
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RecruitingPhase 3
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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.

Suk S De Ravin, M.D. principal investigator

National Institute of Allergy and Infectious Diseases (NIAID)

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

Questions about this trial

What is this clinical trial studying?

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 9 inclusion and 7 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: stopped early, as of the sponsor's last update on 3 Jul 2015. 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 United States. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Yes. Results are posted in the registry (first posted 3 Jul 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Safety of Study Drug (time frame: 1 year). 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 NCT00490100, which also lists 3 linked publications.

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 3 Jul 2015.