A Study to Assess the Safety and Efficacy of 3 Doses of ALX1-11 (50, 75, and 100µg) in the Treatment of Postmenopausal Osteoporosis
Condition: Osteoporosis
MeSH terms: Osteoporosis; Osteoporosis, Postmenopausal
Study type: Interventional
Phase: Phase 2

Summary: 
      A double-blind, placebo-controlled, parallel-group study to assess the safety and efficacy of
      3 doses of ALX1-11 (recombinant human parathyroid hormone [rhPTH(1-84)])(50, 75 and 100 µg)
      in the treatment of postmenopausal osteoporosis. The primary objective of this study is to
      compare the efficacy of ALX1-11 (50, 75 and 100 µg) with that of placebo in terms of
      increasing vertebral bone mineral density, when given daily by subcutaneous injection for 12
      months in postmenopausal women with osteoporosis.
    

Detailed description: 
      Human clinical experience with a synthetic human parathyroid hormone fragment (rhPTH 1-34)
      and animal studies with ALX1-11 demonstrate consistent increases in bone mineral density.
      Furthermore, the newly formed bone is normal in structure and composition. Therefore, ALX1-11
      (recombinant human parathyroid hormone [rhPTH 1-84]) has the potential to stimulate new bone
      formation in osteoporotic patients thereby increasing trabecular bone density and preventing
      fractures. The clinical profile for ALX1-11 can be expected to be unique, since none of the
      approved therapies for osteoporosis are able to form the quantities of new bone that ALX1-11
      is potentially capable of. Patients with bone density below the "fracture threshold"
      (osteopenia), as well as those with established vertebral fractures (osteoporosis), would be
      expected to benefit from treatment.

      Animal toxicology studies have been completed and there were no results to indicate any
      restrictions in the clinical usage of the drug. Preliminary human clinical experience with
      ALX1-11 in healthy, postmenopausal females has demonstrated no apparent risk of frank
      hypercalcemia* at single administrations up to 5.0 µg/kg or daily administrations for 7 days
      up to 2.0 µg/kg/day.

      Based on these studies, the anticipated therapeutic range of ALX1-11 is 50-100 µg per day
      (approx. 1.0 - 1.5 µg/kg/day). Therefore, the dose range to be tested in this study will
      include an anticipated minimally effective dose, interim dose and maximally tolerable dose
      (50, 75 and 100 µg). The efficacy of 3 doses of ALX1-11 will be assessed in terms of bone
      mineral density and biochemical markers of bone turnover in postmenopausal women.

      The primary objective of this study is to determine the dose-response relationship of ALX1-11
      in terms of bone mineral density. The efficacy of the 3 doses of ALX1-11 relative to placebo
      will be determined by measurement of bone mineral density (by DXA) at baseline and at 3, 6
      and 12 months.

      Patients will administer a daily subcutaneous injection of 0.5 mL of either 50, 75 or 100 µg
      of ALX1-11 or placebo every morning for 12 months.

      Women will be advised to use the provided calcium supplements (500mg elemental calcium) to
      maintain a total daily intake of 1000-1500 mg/day and vitamin D supplements will also be
      provided (400 IU/day). A dietary questionnaire will be done at visit screen, 6 and 15.

      If a patient's total serum calcium measurement, during the treatment phase, demonstrates
      frank hypercalcemia OR if her pre-dose calcium levels are more than 0.5 mg/dL or 0.125 mmol/L
      above the upper limit of normal (2.78 mmol/L or 11.1 mg/dL), then the patient's serum calcium
      level must be repeated.

      If upon re-test a patient continues to demonstrate frank hypercalcemia OR if her basal
      pre-dose calcium levels continues to be elevated above the upper limit of normal, then the
      patient will be withdrawn from the study.

      *Frank Hypercalcemia: defined as total serum calcium levels above 11.1 mg/dL or 2.78 mmol/L
    

Intervention name(s): ALX1-11 50 mcg; placebo; ALX1-11 75mcg; ALX1-11
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): PTH(1-84) 50 mcg for subcutaneous injection into thigh or abdomen; placebo powder for subcutaneous injection; PTH(1-84)75 mcg for subcutaneous injection; PTH (1-84) 100mcg for subcutaneous injection into thigh or abdomen
Other intervention name(s): PREOS; PREOS; PREOS
Intervention MeSH terms: Parathyroid Hormone
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Post-menopausal; Osteoporosis; Parathyroid Hormone; PTH; ALX1-11