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

NCT02636270 | Completed Phase 1 Results DMC

• 1 other identifier: 2015-6218
• Study Type: interventional
• Target: 7
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Short Stature

Outcome Measures

Primary Outcomes (1)

• Height Velocity

  Height velocity in a patient with PAPP-A2 deficiency treated with rhIGF-1 for five years (when the patient elected to discontinue treatment after reviewing growth velocity and skeletal maturation). Ultimately only one patient was treated for the study duration with results reported, as the other recruited participant (sibling of the treated patient) experienced pseudotumor cerebri and discontinued treatment after 51 days. He nevertheless was followed, with height velocity also reported.

  Yearly until participant on treatment stops growing, or discontinues treatment (up to 6 years)

Secondary Outcomes (2)

• Height Standard Deviation Score

  Annually until completion of study, up to 6 years

• Pharmacokinetic/Pharmacodynamic (PK/PD) Relationship

  Yearly until completion of the study, up to 6 years

Other Outcomes (10)

• Glucose Pre- and Post-treatment With Recombinant Human IGF-I

  Yearly until completion of the study, up to 6 years

• Insulin Metabolism Pre- and Post-treatment With Recombinant Human IGF-I

  Annually through completion of the study, up to 6 years

• Body Mass Index at Baseline and on Treatment With rhIGF-I

  Annually until completion of the study, up to 6 years

Study Arms (1)

PAPP-A2 deficient patients

EXPERIMENTAL

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

Drug: Increlex

Interventions

Increlex DRUG

Treat PAPP-A2 deficient patients with Increlex

Also known as: rhIGF-1

PAPP-A2 deficient patients

Eligibility Criteria

• Age: 10 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• None
• Healthy Volunteers
• Between the ages of 18 and 30
• In general good health
• Any medications (with the exception of contraceptives)
• Pregnancy

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead

Related Publications (2)

• 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.

  PMID: 36646053 RESULT

• 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.

  PMID: 29029190 RESULT

MeSH Terms

Conditions

Dwarfism

Interventions

mecasermin

Condition Hierarchy (Ancestors)

Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Endocrine System Diseases

Results Point of Contact

• Title: Philippe Backeljauw
• Organization: Cincinnati Childrens Hospital Medical Center

philippe.backeljauw@cchmc.org

513-636-8444

Study Officials

• Philippe Backeljauw, MD

  Cincinnati Childrens Hospital

  PRINCIPAL INVESTIGATOR

• Gajanathan Muthuvel, MD

  Cincinnati Childrens Hospital Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2015
• First Posted: December 21, 2015
• Study Start: December 21, 2015
• Primary Completion: October 14, 2022
• Study Completion: December 1, 2022
• Last Updated: February 28, 2024
• Results First Posted: February 28, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: The participant data will be available when the treatment trial is actively ongoing. Per study protocol, the study will provide clinical updates to the participants primary Endocrinologist. Should the family request any further information be shared once the study is closed, it can be given to a physician specified by the family.
• Access Criteria: De-identifiable data may be shared with physician that is treating the only other two patients in the world with this genetic mutation.