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Safety, Tolerability, and Efficacy of CLTX-305 in Participants With Autosomal Dominant Hypocalcemia (ADH) Type 1

Sponsor
Calcilytix Therapeutics, Inc., a BridgeBio company (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04581629
Collaborator
(none)
13
Enrollment
1
Location
1
Arm
44.5
Anticipated Duration (Months)
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A Phase 2b open label, dose finding study to evaluate the Safety, Tolerability and Efficacy of CLTX-305 (encaleret) in Autosomal Dominant Hypocalcemia (ADH) Type 1

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

Autosomal dominant hypocalcemia Type 1 is a rare familial genetic form of hypoparathyroidism. Autosomal Dominant Hypocalcemia (ADH) Type 1 is typically passed down from affected parents to their children.

This is a Phase 2b open label, dose finding study to evaluate the safety and tolerability of CLTX-305 (encaleret) in Autosomal Dominant Hypocalcemia (ADH) Type 1 as well as the effects of CLTX-305 (encaleret) on blood calcium concentration.

The estimated duration of this study is 41 months. This study plans to evaluate multiple doses of the investigational drug CLTX-305 (encaleret), in addition to safety and efficacy. CLTX-305 is administered orally.

The study is divided into 3 Periods followed by a Long-Term Extension (LTE):

Periods 1: Up to 8 study participants will be admitted to the NIH Clinical Center for 7 days, where they will be administered different doses of CLTX-305 (encaleret) for up to 5 days.

Period 2: Participants from Period 1, and up to 10 new study participants will be admitted to the NIH Clinical Center for 7 days, where they will be administered different doses of CLTX-305 (encaleret) for up to 5 days.

Period 3: 24 weeks during which eligible study participants who completed Period 2 will take CLTX-305 (encaleret) at home.

LTE: Up to 25 months during which eligible study participants who completed Period 3 will take CLTX-305 (encaleret) at home.

Study participants may:

  • Participate in Period 1

  • Participate in Period 2

  • Participate in both Period 1 and Period 2

  • Participate in Period 3 after completing Period 2

  • Participate in LTE after completing Period 3

Study Design

Study Type:
Interventional
Actual Enrollment :
13 participants
Allocation:
N/A
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2b, Open-label Dose-ranging Study Evaluating the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics, and Efficacy of CLTX-305 (Encaleret) in Autosomal Dominant Hypocalcemia (ADH) Type 1
Actual Study Start Date :
Sep 15, 2020
Actual Primary Completion Date :
Jan 24, 2022
Anticipated Study Completion Date :
Jun 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: CLTX-305

CLTX-305 (encaleret) dose finding study to determine safety, tolerability and dose response during three (3) periods and a long term extension of this study with dose levels at QD and BID; up to 41 months of active treatment per participant

Drug: CLTX-305
Period 1: Once daily, followed by twice daily of CLTX-305 for 5 days Period 2: Twice daily doses of CLTX-305 for 5 days Period 3: Individualized dose titration of CLTX-305 for up to 24 weeks LTE: Individualized dose titration of CLTX-305 for up to 25 months
Other Names:
  • Encaleret

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants with Adverse Events (AEs) [Up to 3 years]

      An Adverse Event (AE) is considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study are reported as adverse events.

    2. Change From baseline in albumin-corrected blood calcium concentrations (cCa) after treatment with CLTX-305 [Period 3; 24 weeks (pre-dose and out to 13 hours post dose) - Period 3 length is 24 weeks]

    3. Change from baseline in 24-hour urinary calcium excretion after treatment with CLTX-305 (encaleret) [Period 3; 24 weeks (pre-dose and out to 24 hours post dose) - Period 3 length is 24 weeks]

    Secondary Outcome Measures

    1. Change From baseline in albumin-corrected blood calcium concentrations (cCa) after treatment with CLTX-305 [LTE; Approximately 2 years (approximately 4 hours post dose) - LTE length is approximately 2 years]

    2. Change from baseline in intact PTH blood concentration profile after treatment with CLTX-305 [Periods 1 and 2, days 1, 2, 3 and 5; up to 17 hours post-dose - Periods 1 and 2 lengths are 7 days each]

    3. Change from baseline in intact PTH blood concentration profile after treatment with CLTX-305 [Period 3; 24 weeks (pre-dose and out to 13 hours post dose) - Period 3 length is 24 weeks]

    4. Change from baseline in intact PTH blood concentration profile after treatment with CLTX-305 [LTE; Approximately 2 years (approximately 4 hours post dose) - LTE length is approximately 2 years]

    5. Change from baseline in urinary calcium clearance fractional excretion [Period 3; 24 weeks (pre-dose and out to 13 hours post dose) - Period 3 length is 24 weeks]

    6. Change from baseline in urinary calcium clearance fractional excretion [LTE; Approximately 2 years (approximately 4 hours post dose) - LTE length is approximately 2 years]

    7. Change from baseline in renal function eGFR [Period 3; 24 weeks (pre-dose and out to 13 hours post dose) - Period 3 length is 24 weeks]

    8. Change from baseline in renal function eGFR [LTE; Approximately 2 years (approximately 4 hours post dose) - LTE length is approximately 2 years]

    9. Change from baseline in Serum levels of 1,25-(OH)2 Vitamin D [Period 3; 24 weeks (pre-dose and out to 13 hours post dose) - Period 3 length is 24 weeks]

    10. Change from baseline in Serum levels of 1,25-(OH)2 Vitamin D [LTE; Approximately 2 years (approximately 4 hours post dose) - LTE length is approximately 2 years]

    11. Change from baseline in blood magnesium levels [Periods 1 and 2, days 1, 2, 3 and 5; up to 17 hours post-dose - Periods 1 and 2 lengths are 7 days each]

    12. Change from baseline in blood magnesium levels [Period 3; 24 weeks (pre-dose and out to 13 hours post dose) - Period 3 length is 24 weeks]

    13. Change from baseline in blood magnesium levels [LTE; Approximately 2 years (approximately 4 hours post dose) - LTE length is approximately 2 years]

    14. Change from baseline in blood phosphate levels [Periods 1 and 2, days 1, 2, 3 and 5; up to 17 hours post-dose - Periods 1 and 2 lengths are 7 days each]

    15. Change from baseline in blood phosphate levels [Period 3; 24 weeks (pre-dose and out to 13 hours post dose) - Period 3 length is 24 weeks]

    16. Change from baseline in blood phosphate levels [LTE; Approximately 2 years (approximately 4 hours post dose) - LTE length is approximately 2 years]

    17. Change from baseline in blood creatinine levels [Periods 1 and 2, days 1, 2, 3 and 5; up to 17 hours post-dose - Periods 1 and 2 lengths are 7 days each]

    18. Change from baseline in blood creatinine levels [Period 3; 24 weeks (pre-dose and out to 13 hours post dose) - Period 3 length is 24 weeks]

    19. Change from baseline in blood creatinine levels [LTE; Approximately 2 years (approximately 4 hours post dose) - LTE length is approximately 2 years]

    20. Change from baseline in urinary content of pH [Periods 1 and 2, days 1, 2, 3 and 5; up to 17 hours post-dose - Periods 1 and 2 lengths are 7 days each]

    21. Change from baseline in urinary content of pH [Period 3; 24 weeks (pre-dose and out to 13 hours post dose) - Period 3 length is 24 weeks]

    22. Change from baseline in urinary content of pH [LTE; Approximately 2 years (approximately 4 hours post dose) - LTE length is approximately 2 years]

    23. Change from baseline in urinary content of magnesium [Periods 1 and 2, days 1, 2, 3 and 5; up to 17 hours post-dose - Periods 1 and 2 lengths are 7 days each]

    24. Change from baseline in urinary content of magnesium [Period 3; 24 weeks (pre-dose and out to 13 hours post dose) - Period 3 length is 24 weeks]

    25. Change from baseline in urinary content of magnesium [LTE; Approximately 2 years (approximately 4 hours post dose) - LTE length is approximately 2 years]

    26. Change from baseline in urinary content of phosphate [Periods 1 and 2, days 1, 2, 3 and 5; up to 17 hours post-dose - Periods 1 and 2 lengths are 7 days each]

    27. Change from baseline in urinary content of phosphate [Period 3; 24 weeks (pre-dose and out to 13 hours post dose) - Period 3 length is 24 weeks]

    28. Change from baseline in urinary content of phosphate [LTE; Approximately 2 years (approximately 4 hours post dose) - LTE length is approximately 2 years]

    29. Change from baseline in urinary content of sodium [Periods 1 and 2, days 1, 2, 3 and 5; up to 17 hours post-dose - Periods 1 and 2 lengths are 7 days each]

    30. Change from baseline in urinary content of sodium [Period 3; 24 weeks (pre-dose and out to 13 hours post dose) - Period 3 length is 24 weeks]

    31. Change from baseline in urinary content of sodium [LTE; Approximately 2 years (approximately 4 hours post dose) - LTE length is approximately 2 years]

    32. Change from baseline in urinary content of potassium [Periods 1 and 2, days 1, 2, 3 and 5; up to 17 hours post-dose - Periods 1 and 2 lengths are 7 days each]

    33. Change from baseline in urinary content of potassium [Period 3; 24 weeks (pre-dose and out to 13 hours post dose) - Period 3 length is 24 weeks]

    34. Change from baseline in urinary content of potassium [LTE; Approximately 2 years (approximately 4 hours post dose) - LTE length is approximately 2 years]

    35. Change from baseline in urinary content of creatinine [Periods 1 and 2, days 1, 2, 3 and 5; up to 17 hours post-dose - Periods 1 and 2 lengths are 7 days each]

    36. Change from baseline in urinary content of creatinine [Period 3; 24 weeks (pre-dose and out to 13 hours post dose) - Period 3 length is 24 weeks]

    37. Change from baseline in urinary content of creatinine [LTE; Approximately 2 years (approximately 4 hours post dose) - LTE length is approximately 2 years]

    38. Change from baseline in urinary content of cAMP [Periods 1 and 2, days 1, 2, 3 and 5; up to 17 hours post-dose - Periods 1 and 2 lengths are 7 days each]

    39. Change from baseline in urinary content of cAMP [Period 3; 24 weeks (pre-dose and out to 13 hours post dose) - Period 3 length is 24 weeks]

    40. Change from baseline in urinary content of cAMP [LTE; Approximately 2 years (approximately 4 hours post dose) - LTE length is approximately 2 years]

    41. Change from baseline in urinary content of citrate [Periods 1 and 2, days 1, 2, 3 and 5; up to 17 hours post-dose - Periods 1 and 2 lengths are 7 days each]

    42. Change from baseline in urinary content of citrate [Period 3; 24 weeks (pre-dose and out to 13 hours post dose) - Period 3 length is 24 weeks]

    43. Change from baseline in urinary content of citrate [LTE; Approximately 2 years (approximately 4 hours post dose) - LTE length is approximately 2 years]

    44. Change from baseline in bone marker - blood collagen cross-linked C-telopeptide (CTx) [Periods 1, 2, 3 and LTE; Approximately 3 years - Periods 1 and 2 lengths are 7 days each, Period 3 length is 24 weeks. LTE length is approximately 2 years.]

    45. Change from baseline in bone marker - blood procollagen type 1 N-propeptide (P1NP) [Periods 1, 2, 3 and LTE; Approximately 3 years - Periods 1 and 2 lengths are 7 days each, Period 3 length is 24 weeks. LTE length is approximately 2 years.]

    46. Maximum Observed Plasma Concentration (Cmax) of CLTX-305 [Period 1; Day 1, 2, 4, and 5 (pre-dose and out to 13 hours post dose) - Period 1 length is 7 days]

    47. Maximum Observed Plasma Concentration (Cmax) of CLTX-305 [Period 2; Day 1, 2, 4, and 5 (pre-dose and out to 13 hours post dose) - Period 2 length is 7 days]

    48. Maximum Observed Plasma Concentration (Cmax) of CLTX-305 [Period 3; week 24 (pre-dose and out to 13 hours post dose) - Period 3 length is 24 weeks]

    49. Area Under the Plasma Concentration Versus Time Curve (AUC) of CLTX-305 [Period 1; Day 1, 2, 4, and 5 (pre-dose and out to 13 hours post dose) - Period 1 length is 7 days]

    50. Area Under the Plasma Concentration Versus Time Curve (AUC) of CLTX-305 [Period 2; Day 1, 2, 4, and 5 (pre-dose and out to 13 hours post dose) - Period 2 length is 7 days]

    51. Area Under the Plasma Concentration Versus Time Curve (AUC) of CLTX-305 [Period 3; week 24 (pre-dose and out to 13 hours post dose) - Period 3 length is 24 weeks]

    52. Apparent Terminal Plasma Half-Life (t1/2) of CLTX-305 [Period 3; week 24 (pre-dose and out to 13 hours post dose) - Period 3 length is 24 weeks]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    16 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Be able to understand and sign a written informed consent or assent form, which must be obtained prior to initiation of study procedures.

    • Age ≥ 16 years

    • Postmenopausal women are allowed to participate in this study

    • Body mass index (BMI) ≥ 18.5 to < 39 kg/m2

    • Have an activating mutation of the CASR gene

    • Participants being treated with thiazide diuretics may be enrolled if they are willing and able to discontinue thiazides

    • Participants being treated with strong CYP3A4 inhibitors should ideally, if clinically appropriate, discontinue these medications during the screening period

    • Participants being treated with magnesium or potassium citrate supplements should discontinue such treatment starting on Day -1 during Period 1 and Period 2 and may be asked to discontinue treatment during Period 3

    Exclusion Criteria:

    • History of treatment with PTH 1-84 or 1-34 within the previous 3 months

    • History of hypocalcemic seizure within the past 3 months

    • Blood 25-OH Vitamin D level < 25 ng/mL

    • Participants with hemoglobin (Hgb) < 13 g/dL for men and < 12 g/dL for women

    • Estimated glomerular filtration rate (eGFR) < 25 mL/minute/1.73 m2 using CKD-EPI (for participants <18 years old the Schwartz equation will be calculated)

    • 12-lead resting electrocardiogram (ECG) with clinically significant abnormalities

    • Participants with positive hepatitis B surface antigen (HBsAg), hepatitis A immunoglobulin M (IgM), or human immunodeficiency virus (HIV) viral serology test results at the Screening Visit

    • Pregnant or nursing (lactating) women

    • History of drug or alcohol dependency within 12 months preceding the Screening Visit

    • History of thyroid or parathyroid surgery

    • Current participation in other investigational drug studies

    • Unwillingness to refrain from blood donation within 12 weeks prior to Screening Visit from the start of the study enrollment through one year after the last dose of the study drug

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 National Institute of Health Bethesda Maryland United States 20892

    Sponsors and Collaborators

    • Calcilytix Therapeutics, Inc., a BridgeBio company

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Calcilytix Therapeutics, Inc., a BridgeBio company
    ClinicalTrials.gov Identifier:
    NCT04581629
    Other Study ID Numbers:
    • CLTX-305-201
    First Posted:
    Oct 9, 2020
    Last Update Posted:
    Jul 22, 2022
    Last Verified:
    Jul 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Arthrogryposis
    Hypocalcemia

    Study Results

    No Results Posted as of Jul 22, 2022