title: MOD-4023, a long-acting carboxy-terminal peptide-modified human growth hormone: results of a Phase 2 study in growth hormone-deficient adults.
abstract: OBJECTIVE
  Growth hormone (GH) replacement therapy currently requires daily injections, which may cause distress and low compliance. C-terminal peptide (CTP)-modified growth hormone (MOD-4023) is being developed as a once-weekly dosing regimen in patients with GH deficiency (GHD). This study's objective is to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of MOD-4023 administered once-weekly in GHD adults.
  
  
  METHODS
  54 adults with GHD currently treated with daily GH were normalized and randomized into 4 weekly dosing cohorts of MOD-4023 at 18.5%, 37%, 55.5% or 123.4% of individual cumulative weekly molar hGH dose. The study included 2 stages: Stage A assessed the effectiveness and PK/PD profiles of the 4 dosing regimens of MOD-4023. Stage B was an extension period of once-weekly MOD-4023 administration (61.7% molar hGH content) to collect further safety data and confirm the results from Stage A.
  
  
  RESULTS
  Dose-dependent response was observed for both PK and PD data of weekly MOD-4023 treatment. Insulin-like growth factor I (IGF-I) SDS levels were maintained within normal range. The 18.5% cohort was discontinued due to low efficacy. MOD-4023 was well tolerated and exhibited favorable safety profile in all dose cohorts. The reported adverse events were consistent with known GH-related side effects.
  
  
  CONCLUSIONS
  Once-weekly MOD-4023 administration in GHD adults was found to be clinically effective while maintaining a favorable safety profile and may obviate the need for daily injections. Weekly GH injections may improve compliance and overall outcome. The promising results achieved in this Phase 2 study led to a pivotal Phase 3 trial, which is currently ongoing.
authors.affiliation: Department of Medicine for EndocrinologyDiabetes and Nutritional Medicine, Charité Universitätsmedizin, Berlin, Germany.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Strasburger
authors.affiliation: Department of EndocrinologyNational Institute of Endocrinology and Diabetology, Lubochna, Slovakia.
authors.forename: Peter
authors.initials: P
authors.lastname: Vanuga
authors.affiliation: Department of Internal Medicine VUniversity Hospital Ruzinov, Bratislava, Slovakia.
authors.forename: Juraj
authors.initials: J
authors.lastname: Payer
authors.affiliation: Department of EndocrinologyUniversity Medical Centre Ljubljana, Ljubljana, Slovenia.
authors.forename: Marija
authors.initials: M
authors.lastname: Pfeifer
authors.affiliation: Neuroendocrine UnitClinical Centre of Serbia, Belgrade, Serbia.
authors.forename: Vera
authors.initials: V
authors.lastname: Popovic
authors.affiliation: 1st Department of MedicineUniversity of Pécs, Pécs, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Bajnok
authors.affiliation: 2nd Department of Internal MedicineMilitary Hospital - State Health Center, Budapest, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Góth
authors.affiliation: II Internal Clinic in University Hospital St AnnaBrno, Czech Republic.
authors.forename: Veˇra
authors.initials: V
authors.lastname: Olšovská
authors.affiliation: I Department of Internal MedicineUniversity Hospital Bratislava, Bratislava, Slovakia.
authors.forename: L'udmila
authors.initials: L
authors.lastname: Trejbalová
authors.affiliation: 1st Department of Internal MedicineHetényi Géza Hospital and Out-Patient Clinic, Szolnok, Hungary.
authors.forename: Janos
authors.initials: J
authors.lastname: Vadasz
authors.affiliation: OPKO BiologicsKiryat Gat, Israel.
authors.forename: Eyal
authors.initials: E
authors.lastname: Fima
authors.affiliation: OPKO BiologicsKiryat Gat, Israel.
authors.forename: Ronit
authors.initials: R
authors.lastname: Koren
authors.affiliation: OPKO BiologicsKiryat Gat, Israel.
authors.forename: Leanne
authors.initials: L
authors.lastname: Amitzi
authors.affiliation: Medizinische Klinik - InnenstadtLudwig Maximilian University, Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Bidlingmaier
authors.affiliation: OPKO BiologicsKiryat Gat, Israel.
authors.forename: Oren
authors.initials: O
authors.lastname: Hershkovitz
authors.affiliation: OPKO BiologicsKiryat Gat, Israel.
authors.forename: Gili
authors.initials: G
authors.lastname: Hart
authors.affiliation: Neuroendocrine UnitMassachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Beverly M K
authors.initials: BMK
authors.lastname: Biller
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D020249:Hormone Replacement Therapy / Q000379:methods*; D019382:Human Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use*; D006801:Humans; D007018:Hypopituitarism / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D019382:Human Growth Hormone