Evaluation of the Safety and Efficacy of Eneboparatide (AZP-3601) in Patients With Chronic Hypoparathyroidism

Inclusion Criteria:

1. Males and Females, 18-80 years of age

2. Patients with cHP for ≥12 months at the time of screening

3. Two paired measurements of showing low parathyroid hormone (PTH) and serum calciumeither below normal or within normal under standard of care

4. Requirement for therapy with calcitriol ≥0.5 mcg per day or alphacalcidol ≥1 mcg perday, and requirement for supplemental oral calcium treatment ≥1000 mg per day overand above patient's dietary calcium intake at Day 1 visit

5. Successful completion of the Optimization period based on two consecutivemeasurements of albumin-adjusted serum calcium at least 1 week apart within therange of 7.8 to 9.0 mg/dL and with no more than 25% of change in the daily dose ofany of active vitamin D and oral calcium supplements between the two measurements

6. Thyroid-stimulating hormone (TSH) within the lower limit of normal and 1.5-fold ofthe upper limit of normal at screening; if on suppressive therapy for a history ofthyroid cancer, TSH level must be ≥0.2 mIU/mL and thyroid medication should bestable for at least 6 weeks prior to treatment

7. Prior to start of treatment:

• Magnesium level within laboratory normal limits

• 25(OH) vitamin D levels of 30-70 ng/mL (75-175 nmol/L)

8. eGFR ≥30 mL/min/1.73m² during screening

9. Able to perform daily subcutaneous self-injections of study drug (or have a designeeto perform injections) via a pre-filled injection pen

10. Female patients of non-childbearing potential or using an effective method ofcontraception throughout the study. Women of childbearing potential should have anegative pregnancy test.

11. Able and willing to provide written and signed informed consent in accordance withGCP

Exclusion Criteria:

1. Mental incapacity, unwillingness, or language barriers precluding adequateunderstanding or cooperation

2. Clinically significant abnormal values at screening for hematology, clinicalchemistry, coagulation or urinalysis

3. Abnormal arterial pressure at screening, defined as (1) systolic blood pressure <100mmHg, or (2) systolic blood pressure >150 mmHg, and/or diastolic blood pressure >100mmHg.

4. Heart rate at rest outside the range of 50-100 beats/minute at screening

5. Clinically significant abnormal standard 12-lead electrocardiogram indicative ofsevere cardiac disease

6. Known history of autosomal-dominant hypocalcemia or known pseudohypoparathyroidism (impaired responsiveness to PTH)

7. Any current disease (other than hypoparathyroidism) that might affect calciummetabolism, calcium-phosphate homeostasis or PTH levels

8. Patients with increased risk for osteosarcoma

9. Current uncontrolled active disease processes that may adversely affectgastrointestinal absorption

10. History of cerebrovascular accident within 6 months prior to screening

11. History of active uncontrolled malignancy over the past 2 years at time of screening

12. History of any other cancer other than thyroid cancer (except basal cell skin canceror squamous cell skin cancer) who have not been disease-free for a period of atleast 2 years at the time of screening

13. Acute gout <2 months prior to screening

14. Dependent on parenteral calcium infusions to maintain calcium homeostasis

15. Use of medications such as loop and thiazide diuretics, raloxifene hydrochloride,lithium, methotrexate, cardiac glycosides or systemic corticosteroids within 4 weeksprior to start of treatment

16. Previous treatment with PTH/parathyroid hormone-related protein-like drugs,including PTH(1-84) and PTH(1-34) within 3 months of screening

17. Use of other drugs known to influence calcium and bone metabolism within 4 weeks ofscreening

18. Use of oral bisphosphonates within 6 months of screening or intravenousbisphosphonate within 12 months of screening

19. Use of denosumab within 18 months of screening

20. Seizure disorder/epilepsy with history of a seizure within 6 months of screening

21. History of symptomatic urinary tract calculi within 3 months of screening

22. Irradiation to the skeleton within 2 years of screening

23. Pregnant or breastfeeding female patients

24. Participation in any other interventional study in which the patient received aninvestigational drug or device within 2 months or within 5 times the half-life ofthe investigational drug (whichever comes first) prior to screening

25. Any disease or condition that, in the opinion of the investigator, may requiretreatment or make the subject unlikely to fully complete the trial, or any conditionthat presents undue risk from the study treatment or procedures, including treatedmalignancies that are likely to recur within the approximate duration of the trial

26. Any other reason that in the opinion of the investigator would prevent the subjectfrom completing participation or following the trial schedule

27. Known allergy or sensitivity to PTH or any of the excipients