A Six-month Phase 2 Study of Oral hPTH(1-34) (EBP05) in Postmenopausal Women With Low Bone Mass

• Status: Completed
• Trial end date: 2021-05-11
• Target enrollment: 0
• Participant gender: Female

Summary

This is a double-blinded randomized study to determine the effects of treatment on biochemical markers of bone formation and bone resorption, and bone mineral density (BMD) for 6 months of treatment with EBP05 or placebo. Approximately 160 postmenopausal women with low bone mass (BMD T-score lower than or equal to -2.0 in at least one location: Lumbar Spine, Femoral Neck or Total Hip sites) over 50 years of age will receive Study Medication. Protocol Version 3.0 describes the treatment and evaluation of the initial 103 subjects randomized. In Protocol Version 4.0 the treatment phase will consist of 4 different treatment arms as follows:

Oral EBP05 0.5mg x3 tablets (1.5mg), N=6 Oral EBP05 0.5mg x5 tablets (2.5mg), N=36 Oral Placebo for EBP05 0.5mg (split to sub-groups of: 3 or 5 tablets), N=18

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Entera Bio Ltd.
• Treatments: Teriparatide

Criteria

Inclusion criteria:

1. Female subjects above 50 years of age

2. Signed Informed Consent Form

3. Able to adhere to the visit schedule and protocol requirements

4. At least 3 years post menopause (physiological or surgical)

5. Women who are less than 55 years old need to have estradiol and LH in the menopausal range

6. Low bone mass (BMD T-score lower than or equal to -2.0 in at least one location:

Lumbar Spine, Femoral Neck or Total Hip sites)

Exclusion criteria:

7. Active gastrointestinal inflammatory disorder, gastrointestinal motility disorders, and chronic gastritis, such as ulcerative colitis, Crohn's disease, irritable bowel syndrome, short bowel syndrome, celiac disease, gastroparesis, etc. that may affect drug bioavailability

8. Any conditions or factors that, in the judgment of the Investigator, somehow may impact gastrointestinal absorption, distribution or metabolism of parathyroid hormone analogues, or known to potentiate or predispose to undesired effects

9. History of significant gastrointestinal, liver or kidney disease, or surgery (including bariatric surgery) that may affect drug bioavailability

10. Acute illness within 14 days of screening

11. History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder, that may result in either increased risk or limit her ability to comply with Study Medication administration and scheduled clinical evaluations, as judged by the investigator

12. Blood donation (greater than or equal to 500 mL) within 30 days prior to screening

13. History of Paget's disease of bone

14. History of prior external beam or implant radiation therapy involving the skeleton

15. Active urolithiasis

16. Primary hyperparathyroidism

17. History of alcohol or substance abuse within 3 years prior to screening

18. The subject has used an investigational drug within 30 days before the screening visit

19. Any past treatment with Forteo®

20. History of oncologic disease except for past medical history of a) basal cell or squamous cell skin cancer resected for cure or b) papillary or follicular thyroid cancer localized to the thyroid and resected for cure with no evidence of local or distant recurrence ≥ 5 years after surgery.

21. Allergy to soy or known hypersensitivity to PTH

22. Known allergies or sensitivities to components of the Study Medication

23. Abnormal calcium, magnesium, phosphate or alkaline phosphatase (outside of lab reference ranges and clinically significant) on screening visit

24. Significant renal impairment (eGFR <45mL/min/1.73 m2 as measured by MDRD)

25. Any other clinically significant abnormal biochemistry, hematology or urinalysis at screening that are not explained by a disease recorded in the subject's medical history, as judged by the investigator

26. Chronic morning medication that cannot be taken at least 1-hr post-Study Medication dose

27. Any osteoporosis treatment within the last 2 years. Hormone therapy with oral, transdermal or injectable estradiol, estrogen analog or SERM (e.g. raloxifene) is considered an osteoporosis treatment. Topical estrogen for menopausal vaginal symptoms is permitted.

28. Any use of fluoride (dose greater than 1 mg/day) or strontium ranelate

29. Any use of intravenous bisphosphonate in the last 10 years.

30. Any use of denosumab within the last 3 years

31. Any oral bisphosphonate use for more than 6 months (or Risedronate for over 1 year) in the last 5 years.

32. Any oral bisphosphonate except risedronate for more than 3 years ending in the last 5 years; or risedronate for more than 5 years ending in the last 5 years.

33. Systemic glucocorticoids (current use: ≥ 2.5 mg prednisone or equivalent), or prior use ≥ 5 mg per day for more than 1 week in the last year

34. Hyperthyroidism or hypothyroidism not treated with thyroxine replacement to achieve normal TSH

35. Serious medical conditions currently under evaluation or treatment

36. Disorders of bone and mineral metabolism other than osteoporosis, including a known history of Vitamin D deficiency with metabolic significance that has not been treated with Vitamin D for at least 6 months.

37. Severe osteoporosis defined as a BMD below -3.5 or previous osteoporotic (low-energy trauma) fracture(s) that in the investigator's opinion preclude the use of placebo.

38. The Investigator should exclude subjects at his own judgement, who are at very high risk of osteoporotic fracture(s) and require immediate treatment.