IGF-1 Treatment for Individuals With Short Stature Due to PAPP-A2 Deficiency

NCT ID: NCT02636270

Last Updated: 2024-02-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-21
• Study Completion Date: 2022-12-01

Brief Summary

With this study we want to investigate the pharmacokinetic (PK) effect of a single injection of rhIGF-1 in patients with PAPP-A2 mutations compared to heterozygous carriers and healthy controls. This will be followed by treatment of PAPP-A2 deficient patients with IGF-1 for a period of one-year to assess growth velocity. Additionally, we want to further describe the phenotypic characteristics of patients with PAPP-A2 deficiency.

Detailed Description

The 24-hour pharmacokinetic response of free and total IGF-1 and IGF binding protein-3 (IGFBP-3) to a single dose of rhIGF-1 (120 mcg/kg) in three patients with PAPP-A2 mutation compared to up to four unaffected heterozygous relatives and 2 healthy adult controls.

One-year trial of rhIGF-1 at standard dose given to the two youngest males with PAPP-A2 mutation. The primary end point of this trial will be first year height velocity. Secondary outcomes will include height standard deviation score (SDS), height velocity, and whole body and lumbar spine bone mineral density assessment. The study was amended to extend the treatment period to continue until the subject has stopped growing (or elects to withdraw). All study procedures remain the same. Important note: the treatment phase continues to follow the youngest affected male. The older affected male developed an adverse event that resulted in discontinuation of treatment.

A post-treatment follow up visit (either in-person or remote) will be completed for the study participant who remained on Increlex approximately one-year after their discontinuation of therapy.

Description of additional phenotypic characteristics of patients with PAPP-A2 mutation will be studied by collecting information on glucose and insulin metabolism, body composition, bone geometry and bone density before and after treatment with rhIGF-1. These measures will be collected at the 12-month time period, and every year thereafter until the completion of the study. All three affected siblings will take part in the phenotyping activities.

Conditions

Short Stature

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PAPP-A2 deficient patients

Patients deficient in PAPP-A2 with short stature will be treated with Increlex (rhIGF-1)

Group Type: EXPERIMENTAL

Increlex

Intervention Type: DRUG

Treat PAPP-A2 deficient patients with Increlex

Interventions

Increlex

Treat PAPP-A2 deficient patients with Increlex

Intervention Type: DRUG

Other Intervention Names

rhIGF-1

Eligibility Criteria

Inclusion Criteria

• Defect in PAPP-A2 (heterozygous or homozygous mutation)

• Between the ages of 18 and 30
• In general good health

Exclusion Criteria

• None

Healthy Volunteers

• Any medications (with the exception of contraceptives)
• Pregnancy

• Minimum Eligible Age: 10 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Children's Hospital Medical Center, Cincinnati

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philippe Backeljauw, MD

Role: PRINCIPAL_INVESTIGATOR

Cincinnati Childrens Hospital

Gajanathan Muthuvel, MD

Role: PRINCIPAL_INVESTIGATOR

Cincinnati Childrens Hospital Medical Center

References

Muthuvel G, Dauber A, Alexandrou E, Tyzinski L, Andrew M, Hwa V, Backeljauw P. Five-Year Therapy with Recombinant Human Insulin-Like Growth Factor-1 in a Patient with PAPP-A2 Deficiency. Horm Res Paediatr. 2023;96(5):449-457. doi: 10.1159/000529071. Epub 2023 Jan 16.

Reference Type: RESULT

PMID: 36646053 (View on PubMed)

Cabrera-Salcedo C, Mizuno T, Tyzinski L, Andrew M, Vinks AA, Frystyk J, Wasserman H, Gordon CM, Hwa V, Backeljauw P, Dauber A. Pharmacokinetics of IGF-1 in PAPP-A2-Deficient Patients, Growth Response, and Effects on Glucose and Bone Density. J Clin Endocrinol Metab. 2017 Dec 1;102(12):4568-4577. doi: 10.1210/jc.2017-01411.

Reference Type: RESULT

PMID: 29029190 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

2015-6218

Identifier Type: -

Identifier Source: org_study_id