Effects of SomatoKine (Iplex)Recombinant Human Insulin-like Growth Factor-1/Recombinant Human Insulin-like Growth Factor-binding Protein-3 (rhIGF-I/rhIGFBP-3) in Myotonic Dystrophy Type 1 (DM1)

NCT00233519 | Completed Phase 1 Results DMC

• 2 other identifiers: 5 U54 NS048843-03 A5U54NS048843-03
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to investigate the safety and feasibility of daily subcutaneous injections of recombinant IGF1 complexed with IGF binding protein 3 (SomatoKine-INSMED) as a treatment for muscle wasting and weakness in myotonic dystrophy type 1.

Conditions

Myotonic Dystrophy

Outcome Measures

Primary Outcomes (1)

• The Number of Study Participants Who Safely Tolerated Somatokine

  Safety and tolerability was measured via interval laboratory studies,electrocardiograms, echocardiograms, ultrasounds of the abdomen and pelvis, dual energy x-ray absorptiometry (DEXA) studies, chest and neck x-rays, and serial physical examinations. The participants had six inpatient evaluations at the University of Rochester General Clinical Research Center (Weeks 0, 8, 16, 24, 28, and 40) and nine outpatient evaluations. Patients also completed side effects diaries to record any adverse events in the interval time between inpatient and outpatient evaluations.

  24 weeks

Study Arms (2)

Cohort 1- Two Escalating Doses of Iplex

EXPERIMENTAL

0.5 and 1.0 mg/kg/day

Drug: SomatoKine/IPLEX

Cohort 2 - Three Escalating Doses of Iplex

ACTIVE COMPARATOR

0.5, 1.0, and 2.0 mg/kg/day

Drug: SomatoKine/IPLEX

Interventions

SomatoKine/IPLEX DRUG

Cohort 1: self-administered subcuteanous injections of 0.5 mg/kg/day of iPlex for 8 weeks, followed by 1.0 mg/kg/day of iPlex for 16 weeks. Cohort 2: consecutive 8 week treatments of 0.5, 1.0, and 2.0 mg/kg/day of iPlex for a total of 24 weeks by self-administered subcuteanous injection.

Cohort 1- Two Escalating Doses of Iplex; Cohort 2 - Three Escalating Doses of Iplex

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• A clinical diagnosis of DM-1 according to accepted clinical research criteria.23 The clinical research criteria require each of the following: (1) clinically evident myotonia; (2) muscle weakness in a characteristic distribution (distal predominant); and (3) similar findings in a first degree relative.
• Age 21 to 60 years (inclusive).
• Ability to walk 30 feet without assistance (cane and leg bracing is permitted).
• Weakness of sufficient severity to justify treatment and provide a reasonable opportunity to observe a therapeutic effect. At the eligibility evaluation, eligible patients must show both of the following:
• muscle strength in a distal muscle group (ankle dorsiflexors or deep flexors of the fingers) which is less than or equal to grade 4 (Medical Research Council grade).
• muscle strength in a proximal or mid-limb muscle group (flexors or extensors of the knee, elbow, shoulder, or hip) which is which is greater than or equal to 4- (Medical Research Council grade).
• For patients that are not within driving distance to Rochester, a local health care provider in their area must be able to complete their home visits.
• Competent, willing, and able to give informed consent.
• Able to self-administer study medication by subcutaneous injection or caregiver available to administer study medication.

You may not qualify if:

• Congenital DM-1. Congenital disease constitutes \~10% of all cases of DM-1. Early in life, the weakness in individuals with congenital DM-1 derives from maldevelopment of skeletal muscle rather than muscle degeneration. Later in life, these individuals are also subject to the added effects of a wasting process similar to classical DM-1. However, it is difficult to determine which of these phenomena are mainly to blame for weakness in a particular patient. Furthermore, more than 75% of patients with congenital DM-1 have mental retardation.
• Prior treatment with glucocorticoids, anabolic steroids, testosterone, growth hormone, or IGF-I within 1 year of entry; or any investigational agent within 60 days of entry.
• Any history of malignancy except for surgically cured skin cancer or pilomatricoma (benign tumor of the hair follicle that is associated with DM-1).
• Women of childbearing potential who are not using effective birth control; women who are pregnant or lactating.
• Known allergy to tetracycline.
• Diaphragmatic weakness such that patients are unable to tolerate supine position, or swallowing impairment such that patients are unable to maintain nutrition without use of gastrostomy.
• Symptomatic liver or kidney disease, insulin requiring diabetes or type 2 diabetes requiring oral anti-diabetic agents.
• Untreated thyroid disease (hypo or hyperthyroidism)
• Major psychiatric illness (major depression, bipolar disorder, or schizophrenia) within twelve months of entry.
• History of non-compliance with other therapies.
• Drug or alcohol abuse within 12 months of enrollment.
• In men, evidence of a mass lesion on clinical examination by their primary care physician within twelve months prior to entry into the study (specifically prostate or testicular mass on clinical exam or other signs of mass lesion) or evidence of mass lesion on chest x-ray. In men 50 years of age or older, prostate specific antigen (PSA) elevation above normal.
• In women, evidence for mass lesion on clinical examination by their primary care physician or gynecologist (specifically breast \& pelvic exam) within 12 months of entry into the study or evidence of mass lesion on chest x-ray. In women 40 years of age or older, evidence of mass lesion on mammogram. Women with Gail Scores \> 1.7 will be excluded due to their increased risk of developing cancer.
• Atrial fibrillation/flutter; 2nd or 3rd degree heart block without pacemaker treatment
• Weight greater than 100 kilograms(kg).

Sponsors & Collaborators

• University of Rochester: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• Imsmed Incorporated: collaborator

Study Sites (1)

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Related Publications (1)

• Heatwole CR, Eichinger KJ, Friedman DI, Hilbert JE, Jackson CE, Logigian EL, Martens WB, McDermott MP, Pandya SK, Quinn C, Smirnow AM, Thornton CA, Moxley RT 3rd. Open-label trial of recombinant human insulin-like growth factor 1/recombinant human insulin-like growth factor binding protein 3 in myotonic dystrophy type 1. Arch Neurol. 2011 Jan;68(1):37-44. doi: 10.1001/archneurol.2010.227. Epub 2010 Sep 13.

  PMID: 20837825 DERIVED

Related Links

• Webpage for the National Registry of Myotonic Dystrophy and Facioscapulohumeral Dystrophy patients and their family members.

MeSH Terms

Conditions

Myotonic Dystrophy

Interventions

somatoKine; IGF-I-IGFBP-3 complex

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Myotonic Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Richard T. Moxley, III MD
• Organization: University of Rochester Medical Center

RichardT_Moxley@urmc.rochester.edu

585-275-5006

Study Officials

• Richard T. Moxley, III, M.D.

  University of Rochester

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology

Study Record Dates

• First Submitted: October 3, 2005
• First Posted: October 5, 2005
• Study Start: November 1, 2005
• Primary Completion: May 1, 2008
• Study Completion: May 1, 2008
• Last Updated: June 25, 2012
• Results First Posted: February 1, 2010

Record last verified: 2012-06

Locations

US (1)